Spontaneously hierarchical self-assembly of nanofibres into fluorescent spherical particles: a leap from organogels to macroscopic solid spheres.
The spontaneous hierarchical self-assembly of organic small molecules into macroscopic architectures with excellent photophysical properties and highly-ordered structures has rarely been reported to date. In this work, we find that the organogel of SY1 formed in ethyl acetate could spontaneously assemble into macroscopic spherical particles with a unique morphology and photophysical properties. Upon increasing the aging time, the gel gradually collapsed and then transformed into many macroscopic spheres (SY1-balls) with an average diameter of ca. 500 μm and strong yellow emission. In view of the emission properties and the porous structure of the SY1-balls, they were successfully applied in the adsorption and detection of heavy metal ions. More interestingly, SY1 shows different assembly behaviours in toluene solution when mixed with a triphenylamine derivative (TPA1). Macroscopic particles (ST-balls) with a core-shell structure were obtained, which were quite different from the SY1-balls in morphology and emission colour. So far as we know, many studies have focused on the change of the micromorphology of a gel, while the spontaneous self-assembly of organogels into macroscopic particles has been reported in this work for the first time. This work enriches the present study on organogels and plays an important role in further understanding the hierarchical self-assembly of organogels.


Developing structure-activity relationships for the prediction of hepatotoxicity.
Drug-induced liver injury is a major issue of concern and has led to the withdrawal of a significant number of marketed drugs. An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems. This process can be supported by the use of existing toxicity data and mechanistic understanding of the biological processes for related compounds. In the published literature, this information is often spread across diverse sources and can be varied and unstructured in quality and content. The current work has explored whether it is feasible to collect and use such data for the development of new SARs for the hepatotoxicity endpoint and expand upon the limited information currently available in this area. Reviews of hepatotoxicity data were used to build a structure-searchable database, which was analyzed to identify chemical classes associated with an adverse effect on the liver. Searches of the published literature were then undertaken to identify additional supporting evidence, and the resulting information was incorporated into the database. This collated information was evaluated and used to determine the scope of the SARs for each class identified. Data for over 1266 chemicals were collected, and SARs for 38 classes were developed. The SARs have been implemented as structural alerts using Derek for Windows (DfW), a knowledge-based expert system, to allow clearly supported and transparent predictions. An evaluation exercise performed using a customized DfW version 10 knowledge base demonstrated an overall concordance of 56% and specificity and sensitivity values of 73% and 46%, respectively. The approach taken demonstrates that SARs for complex endpoints can be derived from the published data for use in the in silico toxicity assessment of new compounds.


Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature.
Presently alpha-linolenic acid (ALA) is the most widely used vegetarian LC3PUFA, but only marginal amounts are converted into eicosapentaenoic (EPA) and docosahexaenoic acid (DHA); both of which are strongly related to human health. Currently, fish oils represent the most prominent dietary sources of EPA and DHA; however, these are unsuitable for vegetarians. Alternative sources include flaxseed, echium, walnut, and algal oil but their conversion to EPA and DHA must be considered. The present systematic review sets out to collate information from intervention studies examining the bioavailability of alternative vegetarian long chain omega-3 (n-3) polyunsaturated fatty acids (LC3PUFA) sources. Ten key papers published over the last 10 years were identified with seven intervention studies reporting that ALA from nut and seed oils was not converted to DHA at all. Three studies showed that ingestion of micro-algae oil led to significant increases in blood erythrocyte and plasma DHA. Further work is now needed to identify optimal doses of alternative vegetarian LC3PUFAs and how these can be integrated within daily diets. The potential role of algal oils appears to be particularly promising and an area in which further research is warranted.


Respiratory Mechanical and Cardiorespiratory Consequences of Cycling with Aerobars.
Aerobars place a cyclist in a position where the trunk is flexed forward and the elbows are close to the midline of the body. This position is known to improve cycling aerodynamics and time trial race performance compared with upright cycling positions. However, the aggressive nature of this position may have important cardiorespiratory and metabolic consequences. The purpose of this investigation was to examine the respiratory mechanical, ventilatory, metabolic, and sensory consequences of cycling while using aerobars during laboratory-based cycling. Eleven endurance-trained male cyclists (age, 26 ± 9 yr; V˙O2peak, 55 ± 5 mL·kg·min) were recruited. Visit 1 consisted of an incremental cycling test to determine peak power output. Visit 2 consisted of 6-min bouts of constant load cycling at 70% of peak incremental power output in the aerobar position, drop position, and upright position while grasping the brake hoods. Metabolic and ventilatory responses were measured using a commercially available metabolic cart, and respiratory pressures were measured using an esophageal catheter. Cycling in the aerobar position significantly increased the work of breathing (Wb), power of breathing (Pb), minute ventilation, ventilatory equivalent for oxygen and carbon dioxide, and transdiaphragmatic pressure compared with the upright position. Increases in the Wb and Pb in the aerobars relative to the upright position were strongly correlated with the degree of thoracic restriction, measured as the shoulder-to-aerobar width ratio (Wb: r = 0.80, P = 0.01; Pb: r = 0.69, P = 0.04). Aerobars significantly increase the mechanical cost of breathing and leads to greater ventilatory inefficiency compared with upright cycling. Future work is needed to optimize aerobar width to minimize the respiratory mechanical consequences while optimizing aerodynamics.


Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats.
Ventricular pressure-volume relationships have become well established as the most rigorous and comprehensive ways to assess intact heart function. Thanks to advances in miniature sensor technology, this approach has been successfully translated to small rodents, allowing for detailed characterization of cardiovascular function in genetically engineered mice, testing effects of pharmacotherapies and studying disease conditions. This method is unique for providing measures of left ventricular (LV) performance that are more specific to the heart and less affected by vascular loading conditions. Here we present descriptions and movies for procedures employing this method (anesthesia, intubation and surgical techniques, calibrations). We also provide examples of hemodynamics measurements obtained from normal mice/rats, and from animals with cardiac hypertrophy/heart failure, and describe values for various useful load-dependent and load-independent indexes of LV function obtained using different types of anesthesia. The completion of the protocol takes 1-4 h (depending on the experimental design/end points).


The effect of exercise training on biventricular myocardial strain in heart failure with preserved ejection fraction.
High-intensity interval training (HIIT) improves peak oxygen uptake and left ventricular diastology in patients with heart failure with preserved ejection fraction (HFpEF). However, its effects on myocardial strain in HFpEF remain unknown. We explored the effects of HIIT and moderate-intensity aerobic continuous training (MI-ACT) on left and right ventricular strain parameters in patients with HFpEF. Furthermore, we explored their relationship with peak oxygen uptake (VO2peak ). Fifteen patients with HFpEF (age = 70 ± 8.3 years) were randomized to either: (i) HIIT (4 × 4 min, 85-90% peak heart rate, interspersed with 3 min of active recovery; n = 9) or (ii) MI-ACT (30 min at 70% peak heart rate; n = 6). Patients were trained 3 days/week for 4 weeks and underwent VO2peak testing and 2D echocardiography at baseline and after completion of the 12 sessions of supervised exercise training. Left ventricular (LV) and right ventricular (RV) average global peak systolic longitudinal strain (GLS) and peak systolic longitudinal strain rate (GSR) were quantified. Paired t-tests were used to examine within-group differences and unpaired t-tests used for between-group differences (α = 0.05). Right ventricular average global peak systolic longitudinal strain improved significantly in the HIIT group after training (pre = -18.4 ± 3.2%, post = -21.4 ± 1.7%; P = 0.02) while RV-GSR, LV-GLS, and LV-GSR did not (P > 0.2). No significant improvements were observed following MI-ACT. No significant between-group differences were observed for any strain measure. ΔLV-GLS and ΔRV-GLS were modestly correlated with ΔVO2peak (r = -0.48 and r = -0.45; P = 0.1, respectively). In patients with HFpEF, 4 weeks of HIIT significantly improved RV-GLS.


Ecological half-life of 137Cs in fish from a stream contaminated by nuclear reactor effluents.
Radiocesium (137Cs) concentrations were determined during 1974, 1981 and 1998 for seven species of fish inhabiting a stream (Steel Creek) contaminated by effluents from a nuclear reactor to examine the decline of this radionuclide in a natural ecosystem. Median 137Cs concentrations were highest in Micropterus salmoides (largemouth bass) during each year of the investigation (1974 = 6.67 Bq g(-1) dry wt. of whole body; 1981 = 3.72 Bq g(-1); 1998 = 0.35 Bq g(-1)), but no patterns of differences were observed among Aphredoderus sayanus (pirate perch), Esox americanus (redfin pickerel), Lepomis auritus (redbreast sunfish), L. gulosus (warmouth), L. punctatus (spotted sunfish), and Notropis cummingsae (dusky shiner). Results demonstrated a rapid decline in 137Cs within fish from Steel Creek during the 24-year period. For example, 137Cs concentrations in all fish species declined significantly among years, even after accounting for radioactive decay. The observed percent declines in 137Cs concentrations of individual species were 3-4 times greater between 1974 and 1981 compared to that expected by physical decay alone, and 2-3 times greater during 1981-1998. Ecological half-lives (EHLs) of 137Cs in fish ranged from 4.43 years in A. sayanus to 6.53 years in L. gulosus. The EHL for 137Cs in all fish species combined was 5.54 years. Current levels of 137Cs in fish from Steel Creek (1.16 Bq g(-1) dry wt. of whole body to below detection limits) indicate that the consumption of fish from this ecosystem poses little risk to humans and sensitive wildlife species. These results demonstrate the importance of incorporating the concept of ecological half-life into determinations concerning the length and severity of potential risks associated with radiocontaminants.


Primary care monitoring of long-term opioid therapy among veterans with chronic pain.
To characterize long-term opioid prescribing and monitoring practices in primary care. Retrospective medical record review. Primary care clinics associated with a large Veterans Affairs (VA) medical center. Adult patients who filled ≥6 prescriptions for opioid medications from the outpatient VA pharmacy between May 1, 2006 and April 30, 2007. Indicators of potential opioid misuse, documentation of guideline-recommended opioid-monitoring processes. Ninety-six patients (57%) received a long-acting opioid, 122 (72%) received a short-acting opioid, and 50 (30%) received two different opioids. Indicators of some form of potential opioid misuse were present in the medical records of 55 (33%) patients. Of the seven guideline-recommended opioid-monitoring practices we examined, the mean number documented within 6 months was 1.7 (standard deviation [SD] 1.5). Pain reassessment was the most frequently documented process (N = 105, 52%), and use of an opioid treatment agreement was the least frequent (N = 19, 11%). Patients with indicators of potential opioid misuse had more documented opioid-monitoring processes than those without potential misuse indicators (2.4 vs 1.3, P < 0.001). After adjustment, potential opioid misuse was positively associated with the number of documented guideline-recommended processes (mean = 1.0 additional process, 95% confidence interval [CI] 0.4, 1.5). Guideline-recommended opioid management practices were infrequently documented overall but were documented more often for higher risk patients who had indicators of potential opioid misuse. The relationship between guideline-concordant opioid management and high-quality care has not been established, so our findings should not be interpreted as evidence of poor quality opioid management. Research is needed to determine optimal methods of monitoring opioid therapy in primary care.


Methotrexate stimulates lung fibroblasts and epithelial cells to release eosinophil chemotactic activity.
To determine if methotrexate (MTX) induces human lung fibroblast (HFL-1) and epithelial (BEAS 2B) cell lines to release eosinophil chemotactic activity (ECA). HFL-1 and BEAS 2B cell supernatant fluids were evaluated for ECA by a blind well chamber technique. HFL-1 and BEAS-2B cells released ECA in a dose and time dependent manner in response to MTX. Partial characterization revealed that ECA was partly heat labile, trypsin sensitive, and ethylacetate extractable. Thus the culture supernatant fluids were evaluated for known eosinophil chemotactic factors. Although several were released constitutively, granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly increased in response to MTX from both cell types. Consistent with these observations, ECA from both cell types was inhibited by GM-CSF antibodies. These data suggest that lung fibroblasts and epithelial cells may modulate eosinophil recruitment into the lung by releasing ECA in response to MTX.


Review of osteoimmunology and the host response in endodontic and periodontal lesions.
Both lesions of endodontic origin and periodontal diseases involve the host response to bacteria and the formation of osteolytic lesions. Important for both is the upregulation of inflammatory cytokines that initiate and sustain the inflammatory response. Also important are chemokines that induce recruitment of leukocyte subsets and bone-resorptive factors that are largely produced by recruited inflammatory cells. However, there are differences also. Lesions of endodontic origin pose a particular challenge since that bacteria persist in a protected reservoir that is not readily accessible to the immune defenses. Thus, experiments in which the host response is inhibited in endodontic lesions tend to aggravate the formation of osteolytic lesions. In contrast, bacteria that invade the periodontium appear to be less problematic so that blocking arms of the host response tend to reduce the disease process. Interestingly, both lesions of endodontic origin and periodontitis exhibit inflammation that appears to inhibit bone formation. In periodontitis, the spatial location of the inflammation is likely to be important so that a host response that is restricted to a subepithelial space is associated with gingivitis, while a host response closer to bone is linked to bone resorption and periodontitis. However, the persistence of inflammation is also thought to be important in periodontitis since inflammation present during coupled bone formation may limit the capacity to repair the resorbed bone.


Comparison of CT and MR angiography in evaluation of peripheral arterial disease before endovascular intervention.
Multidetector computed tomography angiography (MDCTA) and magnetic resonance angiography (MRA) are accurate techniques for selecting patients with peripheral arterial disease for surgical and endovascular treatment. No studies in the literature have directly compared MDCTA and MRA to establish which one should be employed, in patients suitable for both techniques, before endovascular treatment. To compare diagnostic performance of MDCTA vs MRA before endovascular intervention. We prospectively compared MDCTA (64 slices scanner) and MRA (1.5 T scanner; 3D gadolinium-enhanced bolus-chase acquisition plus time resolved acquisition on calves) to stratify 35 patients according to the TASC II score and a runoff severity score. We also evaluated the accuracy of both techniques in each arterial segment. Selective angiography performed during the treatment was the standard of reference. MDCTA and MRA accurately classify disease in the aorto-iliac (accuracy 0.92 for MDCTA and MRA) and femoro-popliteal (MDCTA 0.94, MRA 0.90) segments. MDCTA was more accurate in stratifying disease in the infrapopliteal segments (0.96 vs. 0.9) and in assessing the impairment of runoff arteries (0.92 vs. 0.85) at per-segment analysis. MDCTA showed a higher confidence and a shorter examination time. Our results suggest that MDCTA can be considered as a first-line investigation in patients being candidates for endovascular procedures when clinical history or duplex sonographic evaluation are indicative of severe impairment of the infrapopliteal segment.


Diluting the resistance of built-in electric fields in oxygen vacancy-enriched Ru/NiMoO4-x for enhanced hydrogen spillover in alkaline seawater splitting.
Recently, hydrogen spillover based binary (HSBB) catalysts have received widespread attention due to the sufficiently utilized reaction sites. However, the specific regulation mechanism of spillover intensity is still unclear. Herein, we have fabricated oxygen vacancies enriched Ru/NiMoO4-x to investigate the internal relationship between electron supply and mechanism of hydrogen spillover enhancement. The DFT calculations cooperates with in-situ Raman spectrum to uncover that the H* spillover from NiMoO4-x to Ru. Meanwhile, oxygen vacancies weakened the electron supply from Ru to NiMoO4-x, which contributes to dilute the resistance of built-in electric field (BEF) for hydrogen spillover. In addition, the higher ion concentration in electrolyte will promote the H* adsorption step obviously, which is demonstrated by in-situ EIS test. As a result, the Ru/NiMoO4-x exhibits a low overpotential of 206 mV at 3.0 A cm-2, a small Tafel slope of 28.8 mV dec-1, and an excellent durability of 550 h at the current density of 0.5 A cm-2 for HER in 1.0 M KOH seawater.


Are normally sighted, visually impaired, and blind pedestrians accurate and reliable at making street crossing decisions?
The purpose of this study is to measure the accuracy and reliability of normally sighted, visually impaired, and blind pedestrians at making street crossing decisions using visual and/or auditory information. Using a 5-point rating scale, safety ratings for vehicular gaps of different durations were measured along a two-lane street of one-way traffic without a traffic signal. Safety ratings were collected from 12 normally sighted, 10 visually impaired, and 10 blind subjects for eight different gap times under three sensory conditions: (1) visual plus auditory information, (2) visual information only, and (3) auditory information only. Accuracy and reliability in street crossing decision-making were calculated for each subject under each sensory condition. We found that normally sighted and visually impaired pedestrians were accurate and reliable in their street crossing decision-making ability when using either vision plus hearing or vision only (P > 0.05). Under the hearing only condition, all subjects were reliable (P > 0.05) but inaccurate with their street crossing decisions (P < 0.05). Compared to either the normally sighted (P = 0.018) or visually impaired subjects (P = 0.019), blind subjects were the least accurate with their street crossing decisions under the hearing only condition. Our data suggested that visually impaired pedestrians can make accurate and reliable street crossing decisions like those of normally sighted pedestrians. When using auditory information only, all subjects significantly overestimated the vehicular gap time. Our finding that blind pedestrians performed significantly worse than either the normally sighted or visually impaired subjects under the hearing only condition suggested that they may benefit from training to improve their detection ability and/or interpretation of vehicular gap times.


Synthesis and molecular structure of a plutonium(IV) coordination complex: [Pu(NO3)2(2,6-[(C6H5)2P(O)CH2]2C5H3NO)2](NO3)2x1.5H2Ox0.5MeOH.
The trifunctional ligand 2,6-[(C6H5)2P(O)CH2]2 C5H3NO (1), in a mixed EtOH/MeOH solvent system, when combined with an aqueous nitric acid solution of Pu(IV), produces a 2:1 coordination complex, [Pu(1)2(NO3)2](NO3)2. A single crystal of [Pu(NO3)2(2,6-[(C6H5)2P(O)CH2]2C5H3NO)2](NO3)2x1.5H2Ox0.5MeOH was characterized by X-ray diffraction analysis. The crystal is monoclinic, space group P2(1)/n, with a = 19.1011(9) A, b = 18.2873(9) A, c = 21.507(1) A, alpha = gamma = 90 degrees, beta = 108.64(1) degrees, and Z = 4. Two neutral ligands (1) are bonded to the Pu(IV) ion in a tridentate fashion. Two nitrate ions also occupy inner sphere coordination positions, while two additional NO3- ions reside in the outer sphere. Comparison of the solution optical absorbance and solid diffuse reflectance spectra shows the same Pu(IV) chromophore exists in both solid and solution states.


Construction of a cleavable linker chemistry-based HBEXO-Chip to isolate circulating exosomes for breast cancer diagnosis.
Breast cancer is presently the most common form of malignant tumour globally, and its precise diagnosis is vital for enhancing patient survival rates and their quality of life. Exosomes, which are small extracellular vesicles containing proteins and nucleic acid molecules, have emerged as ideal cancer markers for liquid biopsy-based diagnostics. Nevertheless, the current methods for isolating exosomes present challenges for clinical implementation. Although immunoaffinity-based microfluidics hold potential for exosome-based cancer diagnostics, existing microfluidic chips struggle to capture and release intact, high-purity, and highly specific exosomes effectively. To surmount these obstacles, we developed the HBEXO-Chip, an innovative immunoaffinity microfluidic device that employs cleavable linker chemistry technology. This chip enables rapid isolation and detection of breast cancer-derived exosomes in peripheral blood. The fishbone-like microfluidic chip design of the HBEXO-Chip heightens the binding likelihood between specific exosomes and antibodies, significantly augmenting capture efficiency. Furthermore, the gentle reaction conditions of the cleavable linker chemistry retain the exosomes' membrane structure's integrity during the release process, which is advantageous for downstream experimental analysis. Our study demonstrated the effectiveness of the HBEXO-Chip in distinguishing breast cancer patients, patients with benign breast tumours, and healthy controls. By quantitatively analysing Epcam+ exosomes in clinical plasma samples, this technology platform provides a quick, user-friendly, highly sensitive, and specific assay for detecting tumour exosomes in peripheral blood, making it a valuable liquid biopsy tool for clinicians to diagnose breast cancer.


A putative polypeptide N-acetylgalactosaminyltransferase/Williams-Beuren syndrome chromosome region 17 (WBSCR17) regulates lamellipodium formation and macropinocytosis.
We previously identified a novel polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) gene, which is designated Williams-Beuren syndrome chromosome region 17 (WBSCR17) because it is located in the chromosomal flanking region of the Williams-Beuren syndrome deletion. Recent genome-scale analysis of HEK293T cells treated with a high concentration of N-acetylglucosamine (GlcNAc) demonstrated that WBSCR17 was one of the up-regulated genes possibly involved in endocytosis (Lau, K. S., Khan, S., and Dennis, J. W. (2008) Genome-scale identification of UDP-GlcNAc-dependent pathways. Proteomics 8, 3294-3302). To assess its roles, we first expressed recombinant WBSCR17 in COS7 cells and demonstrated that it was N-glycosylated and localized mainly in the Golgi apparatus, as is the case for the other GalNAc-Ts. Assay of recombinant WBSCR17 expressed in insect cells showed very low activity toward typical mucin peptide substrates. We then suppressed the expression of endogenous WBSCR17 in HEK293T cells using siRNAs and observed phenotypic changes of the knockdown cells with reduced lamellipodium formation, altered O-glycan profiles, and unusual accumulation of glycoconjugates in the late endosomes/lysosomes. Analyses of endocytic pathways revealed that macropinocytosis, but neither clathrin- nor caveolin-dependent endocytosis, was elevated in the knockdown cells. This was further supported by the findings that the overexpression of recombinant WBSCR17 stimulated lamellipodium formation, altered O-glycosylation, and inhibited macropinocytosis. WBSCR17 therefore plays important roles in lamellipodium formation and the regulation of macropinocytosis as well as lysosomes. Our study suggests that a subset of O-glycosylation produced by WBSCR17 controls dynamic membrane trafficking, probably between the cell surface and the late endosomes through macropinocytosis, in response to the nutrient concentration as exemplified by environmental GlcNAc.


The third age in the Third World in the third millennium.
The international community is coming to the realization that in Third World countries the aging population is not a burden but a resource to aid society in many ways. In the Dominican Republic one program has tapped elders' resources to fill a need otherwise left gaping.


National assessment and variability of blue carbon in seagrass ecosystems in Thailand.
Seagrass ecosystems are important organic carbon (Corg) sinks with great potential to contribute to climate change mitigation strategies. However, the high spatial and temporal variability is a barrier to the accurate assessment of national Corg stocks. This study provides a national assessment of Corg within seagrass meadows, including spatial and temporal variations. The highest Corg stocks were within mangrove-associated (44.3 ± 8.27 Mg ha-1), while near-surface sediments were highest in reef-associated meadows (10.20 ± 3.69 Mg ha-1). Regionally, the highest stocks were in the Upper Andaman coast in monospecific meadows (51.7 ± 7.14 Mg ha-1). Corg stocks in near-surface sediments were significantly different across historical trends (p < 0.001), with the highest stocks in stable meadows (9.28 ± 3.39 Mg ha-1). The national Corg stock within seagrass meadows sediment was 40.45 ± 11.59 Mg C ha-1. The results of this study highlighted the complexity of blue carbon in seagrass meadows and the associated impacts on national Corg assessments, carbon accounting, and conservation strategies.


Brain Abscess in Children: A Rare but Serious Infection.
Brain abscess is a rare disease in childhood requiring prompt medical and/or surgical treatment. The objective was to review presentation, management, and outcome of brain abscess in children. We reviewed the clinical and radiological features and outcomes of 18 children (10 females, 8 males), with a median age of 48 months (range 1-182), that presented with brain abscesses and admitted to a tertiary pediatric infectious department between December 2010 and January 2017. One (5.5%) patient underwent craniotomy and 14 (77.7%) had burr hole aspirations. The most common localization was the frontal lobe (33.3%). The survival rate was 94.4%, and long-term neurological sequelae affected 27.7% of the patients. Empiric treatment choices require knowledge of common pathogens and local resistance. The most predominant infections were still upper respiratory infections. Clinicians may treat the children with appropriate choice and duration of antibiotic treatment for upper respiratory tract infections.


A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions.
Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T(g)) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T(g) from the predicted values calculated using the Couchman-Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.


Photocatalytic Production of Ethanolamines and Ethylenediamines from Bio-Polyols over a Cu/TiO2 Catalyst.
Valorization of biomass-derived polyols into high-value-added ethanolamines and ethylenediamines is highly attractive. Herein, we report a one-step photocatalytic protocol to convert bio-polyols into a 60% yield of ethanolamines and ethylenediamines over a multifunctional Cu/TiO2 catalyst. This catalyst enables a tandem process of photocatalytic polyol C-C bond cleavage and reductive amination in one pot at room temperature, and also allows the selective conversion of various bio-polyols and amines. Mechanistic studies revealed that photogenerated holes in TiO2 promote the retro-aldol C-C bond cleavage or oxidative dehydrogenation of polyols, and photogenerated electrons accumulate on small-sized Cu clusters, which facilitate the reductive amination via hydrogen transfer and prevent the H2 generation. This strategy provides new opportunities for the development of non-noble metal photocatalysts and methods of biomass conversion under mild conditions.


Can transient elastography replace liver histology for determination of advanced fibrosis in alcoholic patients: a real-life study.
Consensus is lacking whether cut-off values for different fibrosis stages using transient elastography (TE, FibroScan) are universally applicable to all liver diseases. We evaluated the performance of TE in predicting severe fibrosis (> or =F3) in alcoholic patients using cut-off values validated for chronic hepatitis C. Patients admitted for alcohol withdrawal were prospectively evaluated by TE and biochemistry for aspartate aminotransferase to platelet ratio index (APRI) and Forns score calculations. If TE revealed severe fibrosis (> or =F3), hepatic venous pressure gradient measurements and transjugular liver biopsy were proposed results of which were correlated and compared with TE measurements or APRI and Forns scores. Among 239 patients, 72 had liver TE scores > or =F3 and 23 declined liver biopsy leaving a final study population of 49 patients. Compared with biopsy, 32 patients were correctly classified by TE, whereas 16 patients differed by 2 fibrosis stages yielding a positive predictive value of 65% for liver fibrosis > or =F3 at TE. Specificity and sensitivity of TE improved beyond 75% and 70%, respectively, with modified cut-offs of 17 (F3) and 21.1 kPa (F4). Areas under the receiver operating characteristic curves were 0.766 and 0.864 for severe fibrosis (> or =F3) and cirrhosis, respectively. APRI and Forns scores performed less well than TE regarding sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic values. A significant correlation was found between hepatic venous pressure gradients and liver stiffness values at TE. TE with modified cut-offs has the potential to predict advanced fibrosis and significant portal hypertension in alcoholic patients. APRI and Forns scores are of limited usefulness in alcoholics.


Chitosan-based delivery system enhances antimicrobial activity of chlorhexidine.
Infected chronic skin wounds and other skin infections are increasingly putting pressure on the health care providers and patients. The pressure is especially concerning due to the rise of antimicrobial resistance and biofilm-producing bacteria that further impair treatment success. Therefore, innovative strategies for wound healing and bacterial eradication are urgently needed; utilization of materials with inherent biological properties could offer a potential solution. Chitosan is one of the most frequently used polymers in delivery systems. This bioactive polymer is often regarded as an attractive constituent in delivery systems due to its inherent antimicrobial, anti-inflammatory, anti-oxidative, and wound healing properties. However, lipid-based vesicles and liposomes are generally considered more suitable as delivery systems for skin due to their ability to interact with the skin structure and provide prolonged release, protect the antimicrobial compound, and allow high local concentrations at the infected site. To take advantage of the beneficial attributes of the lipid-based vesicles and chitosan, these components can be combined into chitosan-containing liposomes or chitosomes and chitosan-coated liposomes. These systems have previously been investigated for use in wound therapy; however, their potential in infected wounds is not fully investigated. In this study, we aimed to investigate whether both the chitosan-containing and chitosan-coated liposomes tailored for infected wounds could improve the antimicrobial activity of the membrane-active antimicrobial chlorhexidine, while assuring both the anti-inflammatory activity and cell compatibility. Chlorhexidine was incorporated into three different vesicles, namely plain (chitosan-free), chitosan-containing and chitosan-coated liposomes that were optimized for skin wounds. Their release profile, antimicrobial activities, anti-inflammatory properties, and cell compatibility were assessed in vitro. The vesicles comprising chitosan demonstrated slower release rate of chlorhexidine and high cell compatibility. Additionally, the inflammatory responses in murine macrophages treated with these vesicles were reduced by about 60% compared to non-treated cells. Finally, liposomes containing both chitosan and chlorhexidine demonstrated the strongest antibacterial effect against Staphylococcus aureus. Both chitosan-containing and chitosan-coated liposomes comprising chlorhexidine could serve as excellent platforms for the delivery of membrane-active antimicrobials to infected wounds as confirmed by improved antimicrobial performance of chlorhexidine.


Genetic assessment of the effects of streamscape succession on coho salmon Oncorhynchus kisutch colonization in recently deglaciated streams.
Measures of genetic diversity within and among populations and historical geomorphological data on stream landscapes were used in model simulations based on approximate Bayesian computation (ABC) to examine hypotheses of the relative importance of stream features (geomorphology and age) associated with colonization events and gene flow for coho salmon Oncorhynchus kisutch breeding in recently deglaciated streams (50-240 years b.p.) in Glacier Bay National Park (GBNP), Alaska. Population estimates of genetic diversity including heterozygosity and allelic richness declined significantly and monotonically from the oldest and largest to youngest and smallest GBNP streams. Interpopulation variance in allele frequency increased with increasing distance between streams (r = 0·435, P < 0·01) and was inversely related to stream age (r = -0·281, P < 0·01). The most supported model of colonization involved ongoing or recent (<10 generations before sampling) colonization originating from large populations outside Glacier Bay proper into all other GBNP streams sampled. Results here show that sustained gene flow from large source populations is important to recently established O. kisutch metapopulations. Studies that document how genetic and demographic characteristics of newly founded populations vary associated with successional changes in stream habitat are of particular importance to and have significant implications for, restoration of declining or repatriation of extirpated populations in other regions of the species' native range.


An exploration of food and the lived experience of individuals after treatment for colorectal cancer using a phenomenological approach.
There is a paucity of qualitative literature investigating people's experiences of food and nutrition after treatment for cancer. The present study aimed to explore people's relationships with food and nutrition throughout their colorectal cancer journey. In-depth semi-structured interviews were conducted with 25 participants who had undergone surgery for colorectal cancer. The study design was informed by principles of phenomenology. Data were collected then transcribed and analysed using an inductive coding process and a thematic analysis to allow the themes to highlight people's lived experiences. Data enabled five primary themes to be drawn including: 'appetite swings', 'emotions on a changing physicality', 'the medicalisation of food', 'taking control of symptom management' and a cross-cutting theme 'drivers and vehicles for action'. Feelings and emotions described by participants around their relationship with food and nutritional status often guided decisions on what was eaten more than objective nutritional measure or dietary advice. Participants used weight changes, appetite and food as barometers to measure their overall recovery. Food was an area over which people exhibited control of their lives and they could quantify, in measurable units, their overall well-being and rehabilitation. They did this either by using the currency of body weight in pounds or the size of portions eaten. Appetite, weight and symptoms influenced dietary intake substantially and were poignant issues affecting people's lives. The relationship people have with food determines their eating habits and an understanding of the essences and nuances of their experiences is essential to enable the delivery of patient-centred care.


Absidia parricida plays a dominant role in biotrophic fusion parasitism among mucoralean fungi (Zygomycetes): Lentamyces, a new genus for A. parricida and A. zychae.
Within the order Mucorales (Zygomycetes), the facultative parasites Parasitella parasitica, Chaetocladium brefeldii, Chaetocladium jonesii and Absidia parricida are known to initiate biotrophic fusion parasitic interactions on a wide variety of other mucoralean hosts. Their phylogenetic relationship within the Mucorales and their ability to form parasitic structures with several known host species was examined. Together with interspecific reactions between the mycoparasites, this study found: (i) no evident differences in the spectrum of non-parasitic hosts tested within the study; (ii) A. parricida parasitises all other fusion parasites; (iii) A. parricida is ancestral to all other parasites; (iv) A. parricida is reported for the first time as phylogenetically basal to all other mucoralean fungi except the Umbelopsidaceae and (v) based on phylogenetic analyses and physiological and morphological characteristics, the slow-growing species A. parricida and Absidia zychae are removed from the genus Absidia and reclassified in the newly described genus Lentamyces.


Diffusive mixing of polymers investigated by Raman microspectroscopy and microrheology.
Diffusive mixing in a model polymer blend of limited miscibility (i.e., the pair polydimethylsiloxane/polyisobutene) is investigated. The diffusion process is followed in the actual droplet-based microstructure of the polymer blend, as opposed to the ideal planar geometry used in previous studies (Brochard et al. Macromolecules 1983, 16, 1638; Composto et al. Nature 1987, 328, 234). In our experiments we combine Raman microspectroscopy and video particle-tracking microrheology. The first technique allows us to monitor local concentration of the two polymers with high spatial resolution both inside and outside a micrometer-size droplet of the dispersed phase. In addition, microrheology enables to follow how the local viscosity inside the droplet changes during the diffusion. The polymer viscosity inside the droplet is determined by video tracking the Brownian motion of a polystyrene bead microinjected into the droplet. The microspectroscopic and microrheological data are combined to estimate the concentration dependence of the monomer friction factor of the two species, which is a key parameter to calculate the interdiffusion coefficient D. Numerical calculations based on such concentration-dependent interdiffusion coefficient D and several alternative models of the polymer diffusion are compared to the experimental concentration profiles. A satisfactory agreement is found for the so-called "slow theory" (Brochard et al.). A phenomenological model improving the agreement of the model with the experimental data is also presented.


Sugars, organic acids, and phenolic compounds of ancient grape cultivars (Vitis vinifera L.) from Igdir province of Eastern Turkey.
The Eurasian grapevine (Vitis vinifera L.) is the most widely cultivated and economically important horticultural crop in the world. As a one of the origin area, Anatolia played an important role in the diversification and spread of the cultivated form V. vinifera ssp. vinifera cultivars and also the wild form V. vinifera ssp. sylvestris ecotypes. Although several biodiversity studies have been conducted with local cultivars in different regions of Anatolia, no information has been reported so far on the biochemical (organic acids, sugars, phenolic acids, vitamin C) and antioxidant diversity of local historical table V. vinifera cultivars grown in Igdir province. In this work, we studied these traits in nine local table grape cultivars viz. 'Beyaz Kismis' (synonym name of Sultanina or Thompson seedless), 'Askeri', 'El Hakki', 'Kirmizi Kismis', 'Inek Emcegi', 'Hacabas', 'Kerim Gandi', 'Yazen Dayi', and 'Miskali' spread in the Igdir province of Eastern part of Turkey. Variability of all studied parameters is strongly influenced by cultivars (P < 0.01). Among the cultivars investigated, 'Miskali' showed the highest citric acid content (0.959 g/l) while 'Kirmizi Kismis' produced predominant contents in tartaric acid (12.71 g/l). The highest glucose (16.47 g/100 g) and fructose (15.55 g/100 g) contents were provided with 'Beyaz Kismis'. 'Kirmizi Kismis' cultivar had also the highest quercetin (0.55 mg/l), o-coumaric acid (1.90 mg/l), and caffeic acid (2.73 mg/l) content. The highest ferulic acid (0.94 mg/l), and syringic acid (2.00 mg/l) contents were observed with 'Beyaz Kismis' cultivar. The highest antioxidant capacity was obtained as 9.09 μmol TE g(-1) from 'Inek Emcegi' in TEAC (Trolox equivalent Antioxidant Capacity) assay. 'Hacabas' cultivar had the highest vitamin C content of 35.74 mg/100 g. Present results illustrated that the historical table grape cultivars grown in Igdir province of Eastern part of Turkey contained diverse and valuable sugars, organic acids, phenolic acids, Vitamin C values and demonstrated important antioxidant capacity for human health benefits. Further preservation and use of this gene pool will be helpful to avoid genetic erosion and to promote continued agriculture in the region.


Differential regulation of granulocyte-macrophage colony-stimulating factor mRNA and protein expression in human thyrocytes and thyroid-derived fibroblasts by interleukin-1 alpha and tumor necrosis factor-alpha.
In this study, we provide the first report on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human thyroid epithelial cells. Primary cultures of highly purified thyrocytes and thyroid-derived fibroblasts (n = 3) and three thyroid anaplastic and one largely papillary carcinoma cell lines were exposed to different potent GM-CSF stimulators, employing interleukin 1 alpha (Il-1 alpha) and tumour necrosis factor-alpha (TNF-alpha). Cytokine mRNA levels were monitored by semi-quantitative reverse transcriptase-PCR including an internal heterologous competitor fragment after 3, 6 and 18 h of culture. Culture supernatants were assayed for GM-CSF using a highly sensitive ELISA (detection limit < or = 0.5 pg/ml) after 24 h. Basal GM-CSF mRNA expression was higher in fibroblasts and SW 1736 cells compared with thyrocytes, C 634, 8505 C and HTh 74 cells. GM-CSF was spontaneously secreted by fibroblasts (means +/- S.E.M.; 43 +/- 15 pg/ml), SW 1736 (59 +/- 4 pg/ml), HTh 74 (34 +/- 4 pg/ml) and C 643 cells (12 +/- 1 pg/ml) but not by thyrocytes and 8505 C cells. Treatment with Il-1 alpha (10 U/ml) resulted in a marked increase of GM-CSF mRNA within 3 h and an increase or induction of protein expression in thyrocyte (2350 +/- 214 pg/ml), fibroblast (5242 +/- 1400 pg/ml), SW 1736 (20016 +/- 280 pg/ml) and C 643 cultures (1285 +/- 79 pg/ml). Stimulation with TNF-alpha (10 U/ml) yielded divergent results. No significant increase of GM-CSF mRNA or protein expression was found in thyrocytes although TNF-alpha receptor expression in these cells is well documented. Stimulation with TNF-alpha resulted in an increased GM-CSF production in fibroblasts (361 +/- 14 pg/ml), HTh 74 (148 +/- 51 pg/ml) and SW 1736 cultures (235 +/- 43 pg/ml). TSH (10 mU/ ml) did not stimulate GM-CSF secretion in thyrocytes and HTh 74 cells, both expressing the TSH receptor. Phorbol 12-myristate 13-acetate (10 ng/ml) enhanced GM-CSF mRNA and protein levels in all cell types investigated. Our data suggest that both thyrocytes and fibroblasts synthesize GM-CSF in response to Il-1 alpha, but only fibroblasts respond to TNF-alpha with a significant increase in GM-CSF. Anaplastic thyroid carcinomas are potential GM-CSF producers.


School Quality and the Development of Cognitive Skills between Age Four and Six.
This paper studies the extent to which young children develop their cognitive ability in high and low quality schools. We use a representative panel data set containing cognitive test scores of 4-6 year olds in Dutch schools. School quality is measured by the school's average achievement test score at age 12. Our results indicate that children in high-quality schools develop their skills substantially faster than those in low-quality schools. The results remain robust to the inclusion of initial ability, parental background, and neighborhood controls. Moreover, using proximity to higher-achieving schools as an instrument for school choice corroborates the results. The robustness of the results points toward a causal interpretation, although it is not possible to erase all doubt about unobserved confounding factors.


Variation in plastic responses to light results from selection in different competitive environments-A game theoretical approach using virtual plants.
Phenotypic plasticity is a vital strategy for plants to deal with changing conditions by inducing phenotypes favourable in different environments. Understanding how natural selection acts on variation in phenotypic plasticity in plants is therefore a central question in ecology, but is often ignored in modelling studies. Here we present a new modelling approach that allows for the analysis of selection for variation in phenotypic plasticity as a response strategy. We assess selection for shade avoidance strategies of Arabidopsis thaliana in response to future neighbour shading signalled through a decrease in red:far-red (R:FR) ratio. For this, we used a spatially explicit 3D virtual plant model that simulates individual Arabidopsis plants competing for light in different planting densities. Plant structure and growth were determined by the organ-specific interactions with the light environment created by the vegetation structure itself. Shade avoidance plastic responses were defined by a plastic response curve relating petiole elongation and lamina growth to R:FR perceived locally. Different plasticity strategies were represented by different shapes of the response curve that expressed different levels of R:FR sensitivity. Our analyses show that the shape of the selected shade avoidance strategy varies with planting density. At higher planting densities, more sensitive response curves are selected for than at lower densities. In addition, the balance between lamina and petiole responses influences the sensitivity of the response curves selected for. Combining computational virtual plant modelling with a game theoretical analysis represents a new step towards analysing how natural selection could have acted upon variation in shade avoidance as a response strategy, which can be linked to genetic variation and underlying physiological processes.


RHOBTB2 Mutations Expand the Phenotypic Spectrum of Alternating Hemiplegia of Childhood.
To explore the phenotypic spectrum of RHOBTB2-related disorders and specifically to determine whether patients fulfill criteria for alternating hemiplegia of childhood (AHC), we report the clinical features of 11 affected individuals. Individuals with RHOBTB2-related disorders were identified through a movement disorder clinic at a specialist pediatric center, with additional cases identified through collaboration with other centers internationally. Clinical data were acquired through retrospective case-note review. Eleven affected patients were identified. All had heterozygous missense variants involving exon 9 of RHOBTB2, confirmed as de novo in 9 cases. All had a complex motor phenotype, including at least 2 different kinds of movement disorder, e.g., ataxia and dystonia. Many patients demonstrated several features fulfilling the criteria for AHC: 10 patients had a movement disorder including paroxysmal elements, and 8 experienced hemiplegic episodes. In contrast to classic AHC, commonly caused by mutations in ATP1A3, these events were reported later only in RHOBTB2 mutation-positive patients from 20 months of age. Seven patients had epilepsy, but of these, 4 patients achieved seizure freedom. All patients had intellectual disability, usually moderate to severe. Other features include episodes of marked skin color change and gastrointestinal symptoms, each in 4 patients. Although heterozygous RHOBTB2 mutations were originally described in early infantile epileptic encephalopathy type 64, our study confirms that they account for a more expansive clinical phenotype, including a complex polymorphic movement disorder with paroxysmal elements resembling AHC. RHOBTB2 testing should therefore be considered in patients with an AHC-like phenotype, particularly those negative for ATPA1A3 mutations.


Extended Taylor frozen-flow hypothesis and statistics of optical phase in aero-optics.
We present an extended Taylor frozen-flow model for the statistics of the spatiotemporal disturbances of the index of refraction of air and the phase of an optical beam propagated through the turbulent boundary and shear layers in a high-Reynolds-number flow. By incorporating rapid random fluctuations of the flow velocity about a mean convection velocity and an anisotropic spatial power spectrum for the index of refraction, we calculate both the short-delay temporal structure function and the power spectral density of these disturbances. We discuss the predicted scaling behaviors for these quantities in the context of existing experimental observations, showing specifically the agreement of these predictions with some optical phase data obtained by the Airborne Aero-Optical Laboratory.


Prevalence of afebrile parasitaemia due to Plasmodium falciparum & P. vivax in district Balaghat (Madhya Pradesh): Implication for malaria control.
Balaghat district in Central India is a highly malarious district where both Plasmodium falciparum and P. vivax are prevalent. In this district, the persistence of malaria was on an increase and not responsive to intervention measures even though there was no drug resistance. This study was undertaken by conducting mass screening to determine the prevalence of malaria among particularly vulnerable tribe of Balaghat, for developing evidence-based intervention measures for malaria control in hard to reach areas. This prospective study was carried out during 2013-2014 by conducting mass survey of the population in 10 villages of Birsa community health centre (CHC) and 12 villages of Baihar CHC. Finger-pricked blood smears were collected from all consenting individuals with or without fever for microscopic examination. In the febrile group, the slide positivity rate (SPR) and slide falciparum rate (SFR) were 32.4 and 28.9 per cent, respectively, with 89.4 per cent P. falciparum, while in the afebrile individuals also, the SPR and SFR were high (29 and 26%, respectively), but these were significantly lower than that of febrile group. The gametocyte carriers were significantly higher (odds ratio 1.67, 95% confidence interval 1.25-2.25, P=0.0004) in afebrile patients when compared with febrile group. Vector incrimination showed the presence of four sporozoite-positive Anopheles culicifacies out of 1953 assayed. Plasmodium falciparum malaria was high in young children (up to 8 years) as compared to the adult in both afebrile and febrile group in Balaghat district. High prevalence of gametocyte was observed in all age groups among the afebrile cases. The identification of afebrile malaria parasitaemia is an important challenge for the malaria elimination initiatives. A strong malaria surveillance system is fundamental to both programme design and implementation.


The inhibitory GABA system as a therapeutic target for cognitive symptoms in schizophrenia: investigational agents in the pipeline.
Cognitive impairments associated with schizophrenia include neuropsychological deficits in attention, working memory, learning and executive function. Because these cognitive deficits precede the onset of psychosis, are present in non-affected relatives and constitute the best predictor of functional outcome, they are a cardinal clinical feature in schizophrenia. Currently, no effective treatment for the cognitive symptoms in schizophrenia exists. There is evidence that the inhibitory GABA system is affected in schizophrenia, suggesting that cognitive impairments associated with schizophrenia may be effectively treated by drugs that modulate the GABA(A) receptor. However, classical benzodiazepines produce cognitive impairments and are associated with numerous side effects. The recent development of compounds with selective efficacy for different α subunits at the benzodiazepine site of the GABA(A) receptor has renewed interest for the therapeutic potential of GABAergic drugs. This review summarizes the involvement of the inhibitory GABA system in the cognitive abnormalities of schizophrenia and discusses putative (selective) GABAergic cognition-enhancing drugs for schizophrenia. If cognitive abnormalities in schizophrenic individuals are the result of GABAergic dysfunction, selectively modulating the GABA system could comprise a promising therapeutic intervention for cognitive symptoms in schizophrenia.


Localized expression of the atrial natriuretic factor gene during cardiac embryogenesis.
Expression of the gene encoding atrial natriuretic factor (ANF) during mouse cardiac embryogenesis was studied using in situ hybridization to histologic sections. ANF mRNA was first detected in a subpopulation of myocardial cells at day 8 of embryogenesis. During day 9, abundant hybridization of the ANF probe to the atrium and the primitive ventricle was found. At day 14, strong labeling of cells in both atria and the trabeculated regions of the left ventricle was seen, whereas fewer cells in the right ventricle expressed the ANF gene. The developmental regulation of ANF gene expression in atrial and ventricular cells suggests an important role for this peptide hormone in the embryo. Localized expression of the ANF gene provides a marker for discerning subpopulations of cardiac cells during embryogenesis. Identification of embryonic ventricular ANF mRNA transcripts may have implications with respect to pathologic reexpression of the ANF gene in adult ventricles.


Scoping Review on Brain-Computer Interface-Controlled Electrical Stimulation Interventions for Upper Limb Rehabilitation in Adults: A Look at Participants, Interventions, and Technology.
While current rehabilitation practice for improving arm and hand function relies on physical/occupational therapy, a growing body of research evaluates the effects of technology-enhanced rehabilitation. We review interventions that combine a brain-computer interface (BCI) with electrical stimulation (ES) for upper limb movement rehabilitation to summarize the evidence on (1) populations of study participants, (2) BCI-ES interventions, and (3) the BCI-ES systems. After searching seven databases, two reviewers identified 23 eligible studies. We consolidated information on the study participants, interventions, and approaches used to develop integrated BCI-ES systems. The included studies investigated the use of BCI-ES interventions with stroke and spinal cord injury (SCI) populations. All studies used electroencephalography to collect brain signals for the BCI, and functional electrical stimulation was the most common type of ES. The BCI-ES interventions were typically conducted without a therapist, with sessions varying in both frequency and duration. Of the 23 eligible studies, only 3 studies involved the SCI population, compared to 20 involving individuals with stroke. Future BCI-ES interventional studies could address this gap. Additionally, standardization of device and rehabilitation modalities, and study-appropriate involvement with therapists, can be considered to advance this intervention towards clinical implementation.


Prenatal Coke: What's Behind the Smoke?: Prenatal Cocaine/Alcohol Exposure and School-Age Outcomes: The SCHOO-BE Experiencea.
Despite media reports and educators' concerns, little substantive data have been published to document or refute the emerging reports that children prenatally exposed to cocaine have serious behavioral problems in school. Recent pilot data from this institution have indeed demonstrated teacher-reported problem behaviors following prenatal cocaine exposure after controlling for the effects of prenatal alcohol use and cigarette exposure. Imperative in the study of prenatal exposure and child outcome is an acknowledgment of the influence of other control factors such as postnatal environment, secondary exposures, and parenting issues. We report preliminary evaluation from a large ongoing historical prospective study of prenatal cocaine exposure on school-age outcomes. The primary aim of this NIDA-funded study is to determine if a relationship exists between prenatal cocaine/alcohol exposures and school behavior and, if so, to determine if the relationship is characterized by a dose-response relationship. A secondary aim evaluates the relationship between prenatal cocaine/alcohol exposures and school achievement. Both relationships will be assessed in a black, urban sample of first grade students using multivariate statistical techniques for confounding as well as mediating and moderating prenatal and postnatal variables. A third aim is to evaluate the relationship between a general standardized classroom behavioral measure and a tool designed to tap the effects thought to be specific to prenatal cocaine exposure. This interdisciplinary research team can address these aims because of the existence of a unique, prospectively collected Perinatal Database, funded in part by NIAAA and NICHD. The database includes repeated measures of cocaine, alcohol, and other substances for over 3,500 births since 1986. Information from this database is combined with information from the database of one of the largest public school systems in the nation. The final sample will be composed of over 600 first grade students for whom the independent variables, prenatal cocaine/alcohol exposures, were prospectively assessed and quantified at the university maternity center. After informed consent, the primary dependent variable, school behavior, is assessed, using the PROBS-14 (a teacher consensus developed instrument), the Child Behavior Check List, and the Conners' Teacher Rating Scale. The secondary dependent measure, school achievement, is measured by the Metropolitan Achievement Text and the Test of Early Reading Ability. Control variables, such as the environment and parenting, are measured by several instruments aimed at capturing the child and family ecology since birth. All analyses will be adjusted as appropriate for prospectively gathered control variables such as perinatal risk, neonatal risk, and other prenatal drug and cigarette exposures. Further adjustment will be made for postnatal social risk factors which may influence outcome. Of particular concern are characteristics of the home (adaptation of HOME), parent (depression, stress), and neighborhood (violence exposure). Finally, postnatal exposure to lead and other drugs is being considered.


The effect of human-mattress interface's temperature on perceived thermal comfort.
In recent years, methods that allow for an objective evaluation of perceived comfort, in terms of postural, physiological, cognitive and environmental comfort, have received a great deal of attention from researchers. This paper focuses on one of the factors that influences physiological comfort perception: the temperature difference between users and the objects with which they interact. The first aim is to create a measuring system that does not affect the perceived comfort during the temperatures' acquisition. The main aim is to evaluate how the temperature at the human-mattress interface can affect the level of perceived comfort. A foam mattress has been used for testing in order to take into account the entire back part of the human body. The temperature at the interface was registered by fourteen 100 Ohm Platinum RTDs (Resistance Temperature Detectors) placed on the mattress under the trunk, the shoulders, the buttocks, the legs, the thighs, the arms and the forearms of the test subject. 29 subjects participated in a comfort test in a humidity controlled environment. The test protocol involved: dress-code, anthropometric-based positioning on mattress, environment temperature measuring and an acclimatization time before the test. At the end of each test, each of the test subject's thermal sensations and the level of comfort perception were evaluated using the ASHRAE (American Society of Heating, Refrigerating and Air-Conditioning Engineers) scale. The data analyses concerned, in the first instance, correlations between the temperature at the interface and comfort levels of the different parts of the body. Then the same analyses were performed independently of the body parts being considered. The results demonstrated that there was no strong correlation among the studied variables and that the total increase of temperature at interface is associated with a reduction in comfort.


Subchondral route for nutrition to articular cartilage in the rabbit. Measurement of diffusion with hydrogen gas in vivo.
The route of nutrients going to articular cartilage was studied by determining the diffusion of hydrogen molecules from the subchondral circulation to the articular cartilage in rabbits. In all immature animals there was diffusion of hydrogen from subchondral bone into articular cartilage, while in the older immature animals the results were variable. None of the mature animals showed any diffusion of hydrogen into articular cartilage. The rate of diffusion of hydrogen was significantly lower in the articular cartilage than in the subchondral bone in the immature animals while the concentrations of hydrogen in the articular cartilage were only fractions of those in the subchondral bone at the same instant. Histologically, the deep layers of immature cartilage are penetrated extensively by vascular buds from the ossified portion of the epiphysis, while in adults the articular cartilage is separated from subchondral vascular spaces by an end-plate of bone. Blood vessels penetrating into the basilar layer of articular cartilage in immature animals appear to play an important role in the nutrition of articular cartilage coming from the subchondral region.


[Photochromism of visual pigments. II. Kinetics of photoconversion of frog rhodopsin].
A kinetic scheme is suggested of reversible processes of rhodopsin phototransformation at --22 degrees C under light effect with lambda 579 and 435 mm. On the basis of this scheme quantum yields of certain stages are calculated from initial rates of transformations. Dependence of the quantum yield of photolysis of rhodopsin transformation on the wavelength of light and temperature is studied. The scheme of frog rhodopsin transformation is compared with the similar scheme of bovine rhodopsin phototransformation.


Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes.
Bupropion is primarily metabolized in human liver by cytochrome P450 (CYP) 2B6, an isoform that shows high interindividual variability in expression and catalysis. The aim of this study was to identify mechanisms underlying this variability through comprehensive phenotype-genotype analysis of a well-characterized human liver bank (n = 54). There was substantial variability in microsomal bupropion hydroxylation activities (over 45-fold) and CYP2B6 protein content (over 288-fold), with excellent correlation between protein and activity values (rs = 0.88). CYP2B6 mRNA levels showed less variability (13-fold) and poorer correlation (rs = 0.44) to CYP2B6 protein resulting from 20-30% of livers that contained substantial CYP2B6 mRNA, but low CYP2B6 protein. Livers were genotyped for the common coding polymorphisms (Q172H, K262R and R487C) and 14 additional variations identified by sequencing of the gene promoter to -3000 bp. Of 14 haplotypes that were inferred, *1A (reference), *1H (-2320t>c; -750t>c) and *6B (-1456t>c; -750t>c; Q172H; K262R) were most common with frequencies of 0.28, 0.20 and 0.26, respectively. Alcohol use history (P = 0.011) and *6B haplotype (P = 0.011) were identified as significant predictors of bupropion hydroxylation. A consideration of the effects of these variables on CYP2B6 mRNA and protein levels suggests that alcohol use is associated with enhanced CYP2B6 gene transcription, but the presence of at least one *6B allele reduces this effect on bupropion hydroxylation at the post-transcriptional level. In conclusion, the results of this study indicate that interindividual variability in bupropion hydroxylation is a consequence of interactions between environmental and genetic influences on CYP2B6 gene function.


Traumatic posterior luxation of the hip.
The long-term outcome of treatment of posterior hip dislocations was studied in 60 patients. Thirty-two patients had concomitant fractures of the acetabular rim and seven had also femoral head fractures. Treatment consisted of immediate reduction, followed by gentle traction during one week and progressive weight-bearing over six weeks. Thirteen patients needed internal fixation of the acetabular fracture. Fourty-six patients could be followed for a median of 6.5 years. Fifteen patients, all with associated fractures, had late complications: peri-articular ossifications (5), avascular necrosis of the femoral head (1), mild osteo-arthrosis (5) and pain of unknown origin (4). No complications were noted in patients with simple posterior dislocation of the hip. Simple traumatic posterior hip dislocation has an excellent prognosis. Poor results only occur in case of associated fractures.


The conserved core of a human SIR2 homologue functions in yeast silencing.
Silencing is a universal form of transcriptional regulation in which regions of the genome are reversibly inactivated by changes in chromatin structure. Sir2 (Silent Information Regulator) protein is unique among the silencing factors in Saccharomyces cerevisiae because it silences the rDNA as well as the silent mating-type loci and telomeres. Discovery of a gene family of Homologues of Sir Two (HSTs) in organisms from bacteria to humans suggests that SIR2's silencing mechanism might be conserved. The Sir2 and Hst proteins share a core domain, which includes two diagnostic sequence motifs of unknown function as well as four cysteines of a putative zinc finger. We demonstrate by mutational analyses that the conserved core and each of its motifs are essential for Sir2p silencing. Chimeras between Sir2p and a human Sir2 homologue (hSir2Ap) indicate that this human protein's core can substitute for that of Sir2p, implicating the core as a silencing domain. Immunofluorescence studies reveal partially disrupted localization, accounting for the yeast-human chimeras' ability to function at only a subset of Sir2p's target loci. Together, these results support a model for the involvement of distinct Sir2p-containing complexes in HM/telomeric and rDNA silencing and that HST family members, including the widely expressed hSir2A, may perform evolutionarily conserved functions.


Photoinitiated coupling of unmodified monosaccharides to iron oxide nanoparticles for sensing proteins and bacteria.
We report a versatile approach for the immobilization of unmodified monosaccharides onto iron oxide nanoparticles. Covalent coupling of the carbohydrate onto iron oxide nanoparticle surfaces was accomplished by the CH insertion reaction of photochemically activated phosphate-functionalized perfluorophenylazides (PFPAs), and the resulting glyconanoparticles were characterized by IR, TGA, and TEM. The surface-bound d-mannose showed the recognition ability toward Concanavalin A and Escherichia coli strain ORN178 that possesses mannose-specific receptor sites. Owing to the simplicity and versatility of the technique, together with the magnetic property of iron oxide nanoparticles, the methodology developed in this study serves as a general approach for the preparation of magnetic glyconanoparticles to be used in clinical diagnosis, sensing, and decontamination.


Structure and innervation of the third axillary muscle of Manduca relative to its role in turning flight.
The morphology, ultrastructure, innervation and physiology of the third axillary muscle in Manduca sexta were examined to investigate the role of this muscle in flight. The muscle consists of three parts: the upper bundle, which originates on the episternum, and the middle and lower bundles, which originate on the epimeron; all three parts insert on the tip of a projection from the third axillary sclerite. The middle bundle is composed of tonic fibres, and is innervated by a single slow axon, while the other two bundles consist of intermediate fibres and are each innervated by a single fast axon. The shape and position of the third axillary sclerite within the wing hinge are such that its primary function appears to be remotion of the wing. The length of the third axillary muscle determines the amount of remotion, independency of the degree of elevation or depression of the wing and independently of the amount of remotion of the contralateral wing. Electrophysiological recordings from the three parts of the muscle during tethered flight indicate that they may each function independently of each other and in different ways. The tonic (middle) bundle is capable of maintaining tension to hold the wings in the folded position at rest and is active when the wings are folded at the end of flight. The intermediate (upper and lower) bundles are activated phasically with impulses that may occur with various relationships to the timing of activation of a direct depressor, the subalar, or of several of the elevators. The findings are consistent with the hypothesis that the third axillary muscles on both sides are important in determining the asymmetric degrees of remotion observed in turning flight.


Upregulation of eIF-5A1 in the paralyzed muscle after spinal cord transection associates with spontaneous hindlimb locomotor recovery in rats by upregulation of the ErbB, MAPK and neurotrophin signal pathways.
It is well known that trauma is frequently accompanied by spontaneous functional recovery after spinal cord injury (SCI), but the underlying mechanisms remain elusive. In this study, BBB scores showed a gradual return of locomotor functions after SCT. Proteomics analysis revealed 16 differential protein spots in the gastrocnemius muscle between SCT and normal rats. Of these differential proteins, eukaryotic translation initiation factor 5A1 (elf-5A1), a highly conserved molecule throughout eukaryotes, exhibited marked upregulation in the gastrocnemius muscle after SCT. To study the role of eIF-5A1 in the restoration of hindlimb locomotor functions following SCT, we used siRNA to downregulate the mRNA level of eIF-5A1. Compared with untreated SCT control rats, those subjected to eIF-5A1 knockdown exhibited impaired functional recovery. Moreover, gene expression microarrays and bioinformatic analysis showed high correlation between three main signal pathways (ErbB, MAPK and neurotrophin signal pathways) and eIF-5A1. These signal pathways regulate cell proliferation, differentiation and neurocyte growth. Consequently, eIF-5A1 played a pivotal role via these signal pathways in hindlimb locomotor functional recovery after SCT, which could pave the way for the development of a new strategy for the treatment of spinal cord injury in clinical trials.


Development of a scale to measure symptoms of anxiety and depression in the general UK population: the psychiatric symptom frequency scale.
The psychiatric symptom frequency (PSF) scale was developed to assess symptoms of anxiety and depression (i.e. affective symptoms) experienced over the past year in the general population. This study aimed to examine the distribution of PSF scores, internal consistency, and factor structure and to investigate relationships between total scores for this scale and other indicators of poor mental health. The Medical Research Council national survey of health and development, a class stratified cohort study of men and women followed up from birth in 1946, with the most recent interview at age 43 when the PSF scale was administered. The PSF scale showed high internal consistency between the 18 items (Cronbach's alpha = 0.88). Ratings on items of the scale reflected one predominant factor, incorporating both depression and anxiety, and two additional factors of less statistical importance, one reflecting sleep problems and the other panic and situational anxiety. Total scores were calculated by adding 18 items of the scale, and high total scores were found to be strongly associated with reports of contact with a doctor or other health professional and use of prescribed medication for "nervous or emotional trouble or depression," and with suicidal ideas. The PSF is a useful and valid scale for evaluating affective symptoms in the general population. It is appropriate for administration by lay interviewers with minimal training, is relatively brief, and generates few missing data. The total score is a flexible measure which can be used in continuous or binary form to suit the purposes of individual investigations, and provides discrimination at lower as well as upper levels of symptom severity.


The limiting mechanism in tarsal chemoreception.
Rejection thresholds of eight primary alcohols applied to the tarsal chemoreceptors of the blowfly Phormia regina Meigen and the ovipositor of Gryllus assimilis Fab. have been determined. Three different solvents for the alcohols have been used: water, ethylene glycol, and mineral oil. The comparative stimulating effectiveness of the alcohols assumes a different aspect with each different solvent. In oil the range of thresholds from methanol to octanol extends over less than one log unit as compared with the corresponding thresholds in water which extend over four log units. In glycol the thresholds extend over two and one half log units only. When water is employed as a solvent, the line which describes the relationship between threshold concentration and chain length of the compound exhibits a sharp break at or near butanol. No such discontinuity is evident when glycol or oil is employed as solvent. This is offered as evidence supporting the hypothesis that the limiting mechanism in tarsal chemoreception involves a two phase system whereby highly water-soluble compounds gain access to the receptor through an aqueous phase and the larger lipoid-soluble molecules chiefly through a lipoid phase. Additional facts which support this idea are gained from data which show that the inflection in the curve occurs at different points with different species of insects and is conspicuously absent in the case of man. When thresholds in aqueous solutions are converted from molar concentrations to activities, it is clear that the relation of equal physiological effect at equal thermodynamic activities does not apply here. The lower members of the series stimulate at progressively increasing activities up to pentanol and then at progressively decreasing activities. Furthermore, the ratio of water threshold to oil threshold exhibits no obvious agreement with the water/oil partition coefficients determined experimentally. These results indicate either that the limiting process of chemoreception in these insects does not depend upon the establishment of an equilibrium or that some kinetic effect is obscuring an underlying relationship which does so depend.


Hypnotic suggestibility predicts the magnitude of the imaginative word blindness suggestion effect in a non-hypnotic context.
The present study investigated how the magnitude the word blindness suggestion effect on Stroop interference depended on hypnotic suggestibility when given as an imaginative suggestion (i.e. not post-hypnotic suggestion) and under conditions in which hypnosis was not mentioned. Hypnotic suggestibility is shown to be a significant predictor of the magnitude of the imaginative word blindness suggestion effect under these conditions. This is therefore the first study to show a linear relationship between the imaginative word blindness suggestion effect and hypnotic suggestibility across the whole hypnotizability spectrum. The results replicate previous findings showing that highs respond to the word blindness suggestion to a greater extent than lows but extend previous work by showing that the advantage for those higher on the hypnotizability spectrum occurs even in a non-hypnotic context. Negative attitudes about hypnosis may not explain the failure to observe similar effects of the word blindness suggestion in less hypnotizable individuals.


Re-infused autologous graft natural killer cells correlates with absolute lymphocyte count recovery after autologous stem cell transplantation.
Early absolute lymphocyte count (ALC) has been reported to be a powerful prognostic indicator of survival after autologous stem cell transplantation (ASCT). One possible source affecting ALC recovery includes the re-infused autologous graft lymphocytes (AGL). To assess if the re-infused AGL correlate with ALC recovery post-ASCT, we conducted a pilot study to identify which of the re-infused AGL subsets is most associated with day 15 ALC recovery in three patients with multiple myeloma and four patients with non-Hodgkin's lymphoma. Using the Spearman rank correlation coefficient analysis (r), we compared absolute numbers of CD3, CD4, CD8, CD19, and CD16+/CD56+ cells/kg of body weight from the apheresis product with ALC (cells/microl) at day 15 post-ASCT. The main lymphocyte subsets identified in the apheresis product were T cells and NK cells. There was no strong correlation between T or B cells from the apheresis product compared with the ALC at day 15 post-ASCT (CD3, r = 0.21; CD4, r = 0.32; CD8, r = 0.39; and CD19, r = 0.14). However, there was good correlation between NK cells from the apheresis product compared with ALC at day 15 post-ASCT (CD16+/CD56+/CD3-, r = 0.77). These data provide preliminary evidence that the number of re-infused autologous graft NK cells in the apheresis product significantly affect ALC recovery early post-ASCT. However, given the small sample size, our results are primarily hypothesis generating and subject of further research.


Oligoclonal bands and increased cytokine levels in idiopathic intracranial hypertension.
The pathogenesis of idiopathic intracranial hypertension (IIH) is currently unknown and there are speculations about the contribution of some immunologic factors. The aim of this study is to investigate the presence of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) and/or serum cytokine levels in patients with IIH. Patients fulfilling revised diagnostic criteria for IIH were included. Their demographic, clinical, ophthalmologic and laboratory features were examined. Serum and CSF samples were detected by isoelectric focusing and immunoblotting for OCBs. The samples of IIH patients and control groups were investigated by ELISA for cytokine levels. We detected OCBs in eight (30.77%) patients diagnosed with IIH. There were no other obvious clinical and laboratory differences of IIH profiles between the patients with and without OCBs, but frequency of vision loss was significantly higher in the group with OCBs in comparison to OCB negatives (p = 0.038). Patients with IIH had highly elevated TNF-α, IFN-γ, IL-4, IL-10, IL-12, IL-17 in their sera compared to patients with multiple sclerosis (MS) and healthy controls. Furthermore, all cytokines except TNF-α in the CSF were found significantly higher in IIH patients compared to MS controls. The presence of OCBs and elevated cytokine levels in IIH patients may support an immunologic background in the pathophysiological pathway of this disorder.


Evidence-based medicine in a nutshell. A guide to finding and using the best evidence in caring for patients.
Evidence-based medicine is the use of the best current evidence in making decisions about the care of individual patients. Practicing EBM requires recognition that in most encounters with patients, questions arise that should be answered to provide the patient with the best available medical care. Asking well-built clinical questions that contain 4 elements--a patient or problem, an intervention, a comparison intervention (if necessary), and an outcome--is an important step in practicing EMB. Once appropriate questions have been formulated, the best source for finding most types of best evidence is by searching the MEDLINE database by computer. MEDLINE searches have inherent software and operator limitations that make their reliability quite variable. One should be aware of these limitations and improve one's skills in searching. The Cochrane Collaboration Controlled Clinical Trials Registry contains more than 190,000 controlled clinical trials and is the best source of evidence about treatment. The quality (strength) of evidence is based on a hierarchy of evidence: results of systematic reviews of well-designed clinical studies, results of 1 or more well-designed clinical studies, results of large case series, expert opinion, and personal experience. Once the best evidence has been found, the EBM approach involves critically appraising the quality of the evidence, determining its magnitude and precision, and applying it to the specific patient. Guidelines to critically appraise and apply evidence are available. The clinical question, best evidence, and its critical appraisal should be saved in a format that can be easily retrieved for future use.


Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer.
In current clinical practice, photodynamic therapy (PDT) is carried out with prescribed drug doses and light doses as well as fixed drug-light intervals and illumination fluence rates. This approach can result in undesirable treatment outcomes of either overtreatment or undertreatment because of biological variations between different lesions and patients. In this study, we explore the possibility of improving PDT dosimetry by monitoring drug photobleaching and photoproduct formation. The study involved 60 mice receiving the same drug dose of a novel verteporfin-like photosensitizer, QLT0074, at 0.3 mg/kg body weight, followed by different light doses of 5, 10, 20, 30, 40 or 50 J/cm2 at 686 nm and a fluence rate of 70 mW/cm2. Photobleaching and photoproduct formation were measured simultaneously, using fluorescence spectroscopy. A ratio technique for data processing was introduced to reliably detect the photoproduct formed by PDT on mouse skin in vivo. The study showed that the QLT0074 photoproduct is stable and can be reliably quantified. Three new parameters, photoproduct score (PPS), photobleaching score (PBS) and percentage photobleaching score (PBS%), were introduced and tested together with the conventional dosimetry parameter, light dose, for performance on predicting PDT-induced outcome, skin necrosis. The statistical analysis of experimental results was performed with an ordinal logistic regression model. We demonstrated that both PPS and PBS improved the prediction of skin necrosis dramatically compared to light dose. PPS was identified as the best single parameter for predicting the PDT outcome.


Photoemission sources and beam blankers for ultrafast electron microscopy.
Observing atomic motions as they occur is the dream goal of ultrafast electron microscopy (UEM). Great progress has been made so far thanks to the efforts of many scientists in developing the photoemission sources and beam blankers needed to create short pulses of electrons for the UEM experiments. While details on these setups have typically been reported, a systematic overview of methods used to obtain a pulsed beam and a comparison of relevant source parameters have not yet been conducted. In this report, we outline the basic requirements and parameters that are important for UEM. Different types of imaging modes in UEM are analyzed and summarized. After reviewing and analyzing the different kinds of photoemission sources and beam blankers that have been reported in the literature, we estimate the reduced brightness for all the photoemission sources reviewed and compare this to the brightness in the continuous and blanked beams. As for the problem of pulse broadening caused by the repulsive forces between electrons, four main methods available to mitigate the dispersion are summarized. We anticipate that the analysis and conclusions provided in this manuscript will be instructive for designing an UEM setup and could thus push the further development of UEM.


Interferon-alpha inhibits proliferation in human T lymphocytes by abrogation of interleukin 2-induced changes in cell cycle-regulatory proteins.
IFN-alpha exerts prominent regulatory functions on the immune system. One such effect is the inhibition of proliferation of in vitro stimulated T lymphocytes. The exact physiological function of this activity is not known, but it has been implicated in the antiviral effects of IFN, its antitumor action in T-cell malignancies, and the regulation of the in vivo T-cell response. Here, we have investigated the mechanism underlying the IFN-alpha-mediated growth inhibition of normal human PHA- and IL-2-stimulated T lymphocytes by an analysis of how IFN-alpha treatment influences known molecular events that normally accompany the transition from quiescence to proliferation in these cells. IFN-alpha treatment was found to profoundly block S-phase entry of stimulated T lymphocytes. This correlated with a strong inhibition of IL-2-induced changes in G1-regulatory proteins, including the prevented up-regulation of G1 cyclins and cyclin-dependent kinases as well as an abrogation of mitogen-induced reduction of p27Kip1 levels. This latter effect was due to a maintained stability of the p27Kip1 protein in the IFN-alpha-treated cells. In line with these findings, phosphorylation of the pocket proteins was abrogated in IFN-alpha-treated cells. Furthermore, our data indicate that IFN-alpha has selective effects on the pathways that emerge from the IL-2 receptor because IFN-alpha treatment does not block IL-2-induced up-regulation of c-myc or Cdc25A.


Determination of fat in vegetable foods.
The fat in vegetable foods--tree nuts, peanuts, sunflower seeds, avocado, and olives--can be determined volumetrically by acid digestion of the material and separation of the fat. The assay can be performed conveniently by using the equipment developed for fat determination of milk (Gerber method). The results agree well with those obtained by Soxhlet extraction. The advantages of using the Gerber method for vegetable foods are simplicity, speed, low operation cost, and elimination of the use of inflammable solvents.


Biostorage and quality control for human peripheral blood leukocytes.
Peripheral blood leukocytes (PBLs) are the main source of DNA in blood samples. A common protocol is to store buffy coat specimens for future DNA isolation, and such samples may remain in frozen storage for years. However, the currently available methods to maintain buffy coat specimens can be optimized for better quality and cost efficiency. Seventeen donors (aged 24-34 years) were enrolled in this study. Initially, five centrifugal speeds were chosen to examine the distribution of PBLs in the cell layer; the buffy coat was then harvested to evaluate the cell quantity and viability after storing at 4°C for various times. Finally, the buffy coat was isolated, snap frozen, and kept at -80°C for 1 hour, 1 week, or 4 weeks until the DNA was extracted. Agarose gel electrophoresis and multiplex PCR were used to verify DNA integrity and amplifiability. There was a linear positive correlation between the amount of fresh PBLs and the DNA yield. At least 70% of PBLs were collected in the uppermost 40% of the cellular material when the centrifugal force was over 800 g compared to 400 g. Storing blood at 4°C for no more than 24 hours did not have an effect on the amount of PBLs or their viability. In addition, the amount of extracted DNA was decreased in the frozen buffy coat that was stored for more than 7 days, though the DNA quality was acceptable. DNA should be extracted from fresh buffy coat samples as soon as possible after collection, especially for very important samples. Retaining the upper 40% of the cell pack of blood instead of whole blood could improve the storage efficiency of biobanking such samples. Our study provides a recommended option for blood collection and processing protocols in biobanking.


Long-term patient-reported back and shoulder function after delayed breast reconstruction with a latissimus dorsi flap: case-control cohort study.
Sacrifice of the latissimus dorsi (LD) muscle might entail donor site morbidity when used in delayed breast reconstruction. Previous studies are small, have short follow-up, and demonstrate diverging results. The aims of this study were to evaluate long-term patient-reported effects on shoulder and back function following LD flap harvest, and to investigate predictors for a worse outcome. This is a retrospective observational case-control cohort study. Cases were all patients who had undergone an LD flap reconstruction during the years 2007-2017. Controls were patients reconstructed with a deep inferior epigastric perforator (DIEP) flap during the same time period. Participants completed two validated questionnaires; the BREAST-Q reconstruction LD domains and the Western Ontario Shoulder Osteoarthritis Index (WOOS). A total of 135 cases (75 per cent) and 118 controls (60 per cent) responded to the questionnaires. The mean follow-up time was 7 years. Patients reconstructed with a LD flap were significantly less satisfied with their back and shoulder function when compared to the DIEP controls, as measured with BREAST-Q and WOOS. Predictors for a poor patient-reported back and shoulder function included axillary surgery and axillary radiotherapy, especially when combined, as well as higher age at reconstruction. Patients who have undergone LD flap for delayed breast reconstruction had a lower satisfaction with back and shoulder function, when compared to patients who had undergone a DIEP reconstruction. Delayed LD reconstruction should be used with care, especially in patients who have undergone axillary surgery and axillary radiotherapy.


A Novel Strategy for Surface Modification of Superparamagnetic Iron Oxide Nanoparticles for Lung Cancer Imaging.
Superparamagnetic iron oxide (SPIO) nanoparticles are widely used in magnetic resonance imaging (MRI) as versatile ultra-sensitive nanoprobes for cellular and molecular imaging of cancer. In this study, we report a one-step procedure for the surface functionalization of SPIO nanoparticles with a lung cancer-targeting peptide. The hydrophobic surfactants on the as-synthesized SPIO are displaced by the peptide containing a poly(ethylene glycol)-tethered cysteine residue through ligand exchange. The resulting SPIO particles are biocompatible and demonstrate high T(2) relaxivity. The nanoprobes are specific in targeting α(v)β(6)-expressing lung cancer cells as demonstrated by MR imaging and Prussian blue staining. This facile surface chemistry and the functional design of the proposed SPIO system may provide a powerful nanoplatform for the molecular diagnosis of lung cancer.


Neurochemicals involved in medullary control of common carotid blood flow.
The common carotid artery (CCA) supplies intra- and extra-cranial vascular beds. An area in the medulla controlling CCA blood flow is defined as the dorsal facial area (DFA) by Kuo et al. in 1987. In the DFA, presynaptic nitrergic and/or glutamatergic fibers innervate preganglionic nitrergic and/or cholinergic neurons which give rise to the preganglionic fibers of the parasympathetic 7th and 9th cranial nerves. Released glutamate from presynaptic nitrergic and/or glutamatergic fibers can activate N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors on preganglionic nitrergic and/or cholinergic neurons. By modulating this glutamate release, several neurochemicals including serotonin, arginine, nitric oxide, nicotine, choline and ATP in the DFA regulate CCA blood flow. Understanding the neurochemical regulatory mechanisms can provide important insights of the physiological roles of the DFA, and may help develop therapeutic strategies for diseases involving CCA blood flow, such as migraine, hypertensive disease, Alzheimer's disease and cerebral ischemic stroke.


The important role of primary care providers in the detection of alpha-1 antitrypsin deficiency.
Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder that can cause chronic obstructive pulmonary disease (COPD) and liver cirrhosis, two clinical conditions commonly seen by primary care physicians. AATD is estimated to affect 1/4000-1/5000 people in the United States and 1-2% of all COPD cases. PubMed was searched for relevant articles using AAT/AATD-related terms. Unfortunately, <10% of symptomatic individuals have been properly diagnosed primarily due to the underdiagnosis of COPD and the lack of awareness of AATD as a possible underlying cause. Because primary care providers are most likely to be the first to encounter symptomatic individuals, their role in the identification and early diagnosis of AATD patients is instrumental, particularly since therapy to slow lung disease progression is available. The diagnosis of AATD is laboratory-based rather than clinical. Testing for AATD should be part of the reflex testing that follows any COPD diagnosis or unexplained liver disease and can be performed by determining the AAT phenotype or genotype along with serum AAT levels. Both nonpharmacological and pharmacological approaches are recommended for treatment of lung disease, including smoking cessation, bronchodilators or supplemental oxygen as needed. Specific augmentation of AAT levels with regular purified AAT infusions has been found to slow lung function decline and emphysema progression in patients with moderate airflow obstruction and severely low serum AAT levels. Improving primary care provider awareness and promoting regular reflex testing all COPD patients for AATD may significantly improve the care of COPD patients.