Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence.
Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2). Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis. In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3-7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI. Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.


The role of angiotensin II type 1 receptor antagonists in elderly patients with hypertension.
Hypertension is a major risk factor for stroke and coronary events in elderly people and clinical trials have shown that treatment of hypertension with various drugs can result in a substantial reduction in cerebrovascular and cardiovascular events. The angiotensin II type 1 (AT1) receptor antagonists are the newest class of antihypertensive agents to be used widely in clinical practice. AT1 receptor antagonists can generally be given once-daily. They are also extremely well tolerated with minimal first-dose hypotension and an incidence of adverse effects similar to that seen with placebo. Adverse event rates are significantly lower than with other classes of antihypertensive drugs including ACE inhibitors. These factors result in improved compliance and increased rates of continuance on therapy. AT1 receptor antagonists show similar efficacy in lowering blood pressure to other classes of antihypertensive agents and their antihypertensive effect is potentiated when they are given concomitantly with low-dose thiazide diuretics. AT1 receptor antagonists are eliminated predominantly by the hepatic route but most are not subject to extensive metabolism and interactions with other drugs are uncommon. This is an advantage in the elderly, who are often receiving multiple medications which increases the risk for adverse drug interactions. Dose adjustments are not usually required in the elderly unless there is plasma volume depletion. Although plasma AT1 receptor antagonist concentrations are generally higher in the elderly than in younger subjects, this pharmacokinetic difference may be balanced by decreased activation of the circulating renin-angiotensin-aldosterone system in the elderly. Recent clinical studies in high-risk hypertensive patients with left ventricular hypertrophy or in patients with diabetic nephropathy or heart failure have demonstrated that AT1 receptor antagonists can improve clinical outcomes to a similar or sometimes greater extent than other antihypertensive agents. Many of these studies have included large numbers of older patients and have confirmed the excellent tolerability profile of these drugs. Thus, AT1 receptor antagonists should be considered as a possible first-line treatment or as a component of combination therapy in patients with type 2 diabetes mellitus and microalbuminuria or nephropathy and as an alternative or additional treatment to ACE inhibitors in patients with heart failure or left ventricular dysfunction. AT1 receptor antagonists also appear to reduce the onset of new diabetes compared with some other antihypertensive drugs. The benefits in terms of organ protection have mainly been seen in studies using higher doses of particular AT1 receptor antagonists and it is not certain at present whether these results can be extrapolated to other members of the class. As the elderly are more likely to have developed organ damage related to hypertension or to have heart failure or diabetes as concomitant conditions, AT1 receptor antagonists represent an appropriate option for many elderly patients. The main disadvantage of these drugs is the cost of the medication but this may be offset by their improved tolerability with fewer adverse reactions and thus increased compliance, resulting in better blood pressure control and fewer clinical events. Overall, AT1 receptor antagonists are well tolerated and efficacious for blood pressure-lowering when given as a single daily dose in elderly patients and have many potential benefits in high-risk hypertensive subjects.


Disclose or not? Effect of impression management tactics on hireability of persons with epilepsy.
The purpose of this study is to determine the effect of assertive impression management (IM) tactics, such as personal storytelling and self-promotion, on job interview outcomes of people with epilepsy. Specifically, the effect of IM on interviewers' subjective impressions and evaluation of hireability of job candidates with epilepsy were examined. Ninety-nine master's level graduate students majoring in business or human resources were randomly assigned to three experimental conditions to view one of three 15-min video clips of a job applicant interviewing for a technical computer sales position. The three experimental conditions were (1) job applicant who did not disclose any disability, (2) job applicant with epilepsy who did not use IM tactics, and (3) job applicant with epilepsy who used IM tactics. After watching the job interview video portraying the experimental conditions, participants were asked to rate the job applicant in terms of general impression and hireability for the described position. The use of IM was found to have a significant effect on job interview outcomes (p < 0.01). Post hoc comparisons indicated that the average rating of business/human resources students on both general impression and hireability for the job applicant with epilepsy and IM condition were significantly higher than for the job applicant with epilepsy who did not use IM condition. Furthermore, mediation analysis revealed that general impression is a mediator for the relationship between IM and interview outcomes. This study demonstrates that IM has a significant and positive effect on job interview outcomes for persons with epilepsy. IM can be used as a powerful strategy for empowering people with epilepsy to combat disability stigma, and offset negative perceptions of employers about the potential of this population to be productive workers.


Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.
Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown. Here we identify Heterochromatin Protein 1β (HP1β) as an essential protein for proper differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs. In pluripotent and differentiated cells HP1β is differentially localized and differentially associated with chromatin. Deletion of HP1β, but not HP1α, in ESCs provokes a loss of the morphological and proliferative characteristics of embryonic pluripotent cells, reduces expression of pluripotency factors and causes aberrant differentiation. However, in differentiated cells, loss of HP1β has the opposite effect, perturbing maintenance of the differentiation state and facilitating reprogramming to an induced pluripotent state. Microscopy, biochemical fractionation and chromatin immunoprecipitation reveal a diffuse nucleoplasmic distribution, weak association with chromatin and high expression levels for HP1β in ESCs. The minor fraction of HP1β that is chromatin-bound in ESCs is enriched within exons, unlike the situation in differentiated cells, where it binds heterochromatic satellite repeats and chromocenters. We demonstrate an unexpected duality in the role of HP1β: it is essential in ESCs for maintaining pluripotency, while it is required for proper differentiation in differentiated cells. Thus, HP1β function both depends on, and regulates, the pluripotent state.


Ameliorative Effect of Beta vulgaris Root Extract on Chlorpyrifos-Induced Oxidative Stress, Inflammation and Liver Injury in Rats.
Exposure to organophosphorus insecticides causes several health problems to animals and humans. Red beetroot (RBR) is rich in antioxidant ingredients and possesses a promising hepatoprotective activity. This study evaluated the potential of RBR extract to prevent chlorpyrifos (CPF)-induced liver injury, with an emphasis on oxidative stress, inflammation and apoptosis. Rats received 10 mg/kg CPF and were treated with 300 mg/kg RBR extract for 28 days. CPF caused liver injury evidenced by elevated serum levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin, along with several histological alterations. Hepatic lipid peroxidation (LPO) and nitric oxide (NO) levels, as well as inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines were increased in CPF-intoxicated rats. RBR prevented CPF-induced histological alterations, and ameliorated liver function, LPO, NO, iNOS and pro-inflammatory cytokines. RBR boosted glutathione and antioxidant enzymes, and increased Nrf2 expression. In addition, RBR diminished Bax and caspase-3, and increased Bcl-2 expression. In conclusion, RBR prevented CPF-induced liver injury via attenuation of oxidative stress, inflammation and apoptosis. RBR enhanced antioxidant defenses, suggesting that it could be used as a potential therapeutic intervention to minimize CPF hepatotoxicity.


Low Molecular Weight Heparin-Coated and Dendrimer-Based Core-Shell Nanoplatform with Enhanced Immune Activation and Multiple Anti-Metastatic Effects for Melanoma Treatment.
High-efficiency treatment for tumor is not easy to achieve owing to the existence of metastasis, which remains the arch-criminal of most tumor deaths. Conventional chemotherapy exhibits insufficient inhibitory efficiency on tumor metastasis and more powerful strategies to conquer metastatic tumors are urgently needed. In this study, a rational chemoimmunotherapy strategy was adopted to treat highly aggressive melanoma based on a newly developed multifunctional nanoplatform. Firstly, immunoadjuvant cytosine-phosphate-guanine oligonucleotides (CpG ODNs) were used to boost the doxorubicin (DOX)-elicited immune responses, which synergistically suppressed tumor growth and metastasis. And the anti-metastatic low molecular weight heparin (LMWH) was also integrated, thus multiple anti-metastatic effects to against tumor metastasis were achieved. Methods: G4 PAMAM was serving as the main support to conjugate DOX by pH-sensitive hydrazone bond (PPD) and the synthesized conjugates were confirmed by 1H-NMR spectra, IR spectra and HRMS. Immunoadjuvant CpG ODNs were loaded by electrostatic adsorption to formulate PPD/CpG. After the coating of anti-metastatic LMWH, the designed LMWH/PPD/CpG was fabricated and characterized. The platelets-related and platelets-unrelated anti-metastatic mechanisms were investigated on B16F10 the immune activation effects, anti-tumor and anti-metastatic efficacy of LMWH/PPD/CpG were evaluated on a B16F10 melanoma xenograft model. Results: DOX elicited tumor-specific immune responses by ICD, and the immunological effects could be further promoted by CpG ODNs, exhibiting enhanced maturation of dendritic cells (DCs) and increased level of cytolytic T lymphocytes (CTLs) in vivo. Owing to the coating of LMWH, the platelets-induced epithelial-mesenchymal-like transition of tumor cells was hindered and the actin cytoskeletal arrangement of tumor cells was affected, thus the migration ability of tumor cells was further inhibited. This multifunctional nanoplatform showed enhanced treatment efficiency on melanoma primary tumor and pulmonary metastasis. Conclusion: The immune activation and multiple anti-metastatic effects of LMWH/PPD/CpG establish a novel therapeutic strategy for melanoma. This anti-metastatic nanoplatform could be broadly applied for the co-delivery of other nucleic acids and chemotherapeutic drugs to treat highly aggressive tumors.


Quantitative peel test for thin films/layers based on a coupled parametric and statistical study.
The adhesion strength of thin films is critical to the durability of micro and nanofabricated devices. However, current testing methods are imprecise and do not produce quantitative results necessary for design specifications. The most common testing methods involve the manual application and removal of unspecified tape. This overcome many of the challenges of connecting to thin films to test their adhesion properties but different tapes, variation in manual application, and poorly controlled removal of tape can result in wide variation in resultant forces. Furthermore, the most common tests result in a qualitative ranking of film survival, not a measurement with scientific units. This paper presents a study into application and peeling parameters that can cause variation in the peeling force generated by tapes. The results of this study were then used to design a test methodology that would control the key parameters and produced repeatable quantitative measurements. Testing using the resulting method showed significant improvement over more standard methods, producing measured results with reduced variation. The new method was tested on peeling a layer of paint from a PTFE backing and was found to be sensitive enough to register variation in force due to differing peeling mechanisms within a single test.


Dietary factors and the risk of thyroid cancer: a review.
In the past few decades, the incidence of thyroid cancer has rapidly increased worldwide. Thyroid cancer incidence is relatively high in regions where the population's daily iodine intake is insufficient. While low dietary iodine has been considered as a risk factor for thyroid cancer development, previous studies found controversial results across different food types. Among different ethnic groups, dietary factors are influenced by various dietary patterns, eating habits, life-styles, nutrition, and other environmental factors. This review reports the association between dietary factors and thyroid cancer risk among ethnic groups living in different geologic regions. Iodine-rich food such as fish and shellfish may provide a protective role in populations with insufficient daily iodine intake. The consumption of goitrogenic food, such as cruciferous vegetables, showed a positive association with risk. While considered to be a risk factor for other cancers, alcohol intake showed a protective role against thyroid cancer. High consumption of meat such as chicken, pork, and poultry showed a positive association with the risk, but dairy products showed no significant association. Regular use of multivitamins and dietary nitrate and nitrite also showed a positive association with thyroid cancer risk. However, the study results are inconsistent and investigations into the mechanism for how dietary factors change thyroid hormone levels and influence thyroid function are required.


Effect of alteration in organic material of the occlusal caries on DIAGNOdent readings.
DIAGNOdent is a laser fluorescence device used for dental caries diagnosis in occlusal and smooth surfaces. Despite the promising preliminary results, the molecules involved in the increase of fluorescence in carious lesions remain unclear. The aim of this study was to compare the laser fluorescence readings before and after changes in the organic material of occlusal carious lesions in primary teeth. Twenty-four primary molars stored in saline solution with at least one site with occlusal caries were divided into two groups. The control group had 17 sites with caries and the experimental one had 16 sites. The carious lesions were measured with laser fluorescence. The experimental samples were then removed from the storage solution and immersed in a 2% sodium hypochlorite solution for 24 hours. After washing with water, the teeth were measured again with the laser fluorescence device. The teeth of the control group were submitted to the same procedures, but saline solution was used instead of the sodium hypochlorite solution. A statistically significant reduction in the mean of the readings after immersion in the two tested solutions compared with the initial readings was observed in both groups, but the decrease was statistically higher in the experimental group (p < 0.0001). In this study, the data indicate that changes in the fluorescence of carious lesions measured by the laser fluorescence are mainly due to the organic content alterations rather than to the mineral loss.


Effects of material, coating, design and plaque composition on stent deployment inside a stenotic artery--finite element simulation.
Finite-element simulations have been carried out to study the effects of material choice, drug eluting coating and cell design on the mechanical behaviour of stents during deployment inside a stenotic artery. Metallic stents made of materials with lower yield stress and weaker strain hardening tend to experience higher deformation and stronger dogboning and recoiling, but less residual stresses. Drug eluting coatings have limited effect on stent expansion, recoiling, dogboning and residual stresses. Stent expansion is mainly controlled by the radial stiffness of the stent which is closely associated with the stent design. In particular, open-cell design tends to have easier expansion and higher recoiling than closed-cell design. Dogboning is stronger for slotted tube design and open-cell sinusoidal design, but reduced significantly for designs strengthened with longitudinal connective struts. After deployment, the maximum von Mises stress appears to locate at the U-bends of stent cell struts, with varying magnitude that depends on the materials and severity of plastic deformation. For the artery-plaque system, the stresses, especially in the plaque which is in direct contact with the stent, appear to be distinctly different for different stent designs and materials in terms of both distribution and magnitude. The plaque composition also strongly affects the expansion behaviour of the stent-artery system and modifies the stresses on the plaque.


Chromosomal number aberrations and transformation in adult mouse retinal stem cells in vitro.
The potential of stem cells (SCs) as a source for cell-based therapy on a wide range of degenerative diseases and damaged tissues such as retinal degeneration has been recognized. Generation of a high number of retinal stem cells (RSCs) in vitro would thus be beneficial for transplantation in the retina. However, as cells in prolonged cultivation may be unstable and thus have a risk of transformation, it is important to assess the stability of these cells. Chromosomal aberrations were analyzed in mouse RSC lines isolated from adult and from postnatal day (PN)1 mouse retinas. Moreover, selected cell lines were tested for anchorage-dependent proliferation, and SCs were transplanted into immunocompromised mice to assess the possibility of transformation. Marked aneuploidy occurred in all adult cell lines, albeit to different degrees, and neonatal RSCs were the most stable and displayed a normal karyotype until at least passage 9. Of interest, the level of aneuploidy of adult RSCs did not necessarily correlate with cell transformation. Only the adult RSC lines passaged for longer periods and with a higher dilution ratio underwent transformation. Furthermore, we identified several cell cycle proteins that might support the continuous proliferation and transformation of the cells. Adult RSCs rapidly accumulated severe chromosomal aberrations during cultivation, which led to cell transformation in some cell lines. The culture condition plays an important role in supporting the selection and growth of transformed cells.


Potential oscillators and keystone modules in food webs.
Food web theory suggests that the placement of a weak interaction is critical such that under some conditions even one well-placed weak interaction can stabilise multiple strong interactions. This theory suggests that complex stable webs may be built from pivotal weak interactions such that the removal of even one to a few keystone interactions can have significant cascading impacts on whole system diversity and structure. However, the connection between weak interactions, derived from the theory of modular food web components, and keystone species, derived from empirical results, is not yet well understood. Here, we develop numerical techniques to detect potential oscillators hidden in complex food webs, and show that, both in random and real food webs, keystone consumer-resource interactions often operate to stabilise them. Alarmingly, this result suggests that nature frequently may be dangerously close to precipitous change with even the loss of one or a few weakly interacting species.


Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.
We review our experience with Melanotan II, a non-selective melanocortin receptor agonist, in human subjects with erectile dysfunction (ED). Melanotan II was administered to 20 men with psychogenic and organic ED using a double-blind placebo-controlled crossover design. Penile rigidity was monitored for 6 h using RigiScan. Level of sexual desire and side effects were reported with a questionnaire. In the absence of sexual stimulation, Melanotan II led to penile erection in 17 of 20 men. Subjects experienced a mean of 41 min Rigiscan tip rigidity>80%. Increased sexual desire was reported after 13/19 (68%) doses of Melanotan II vs 4/21 (19%) of placebo (P<0.01). Nausea and yawning were frequently reported side effects due to Melanotan II; at a dose of 0.025 mg/kg, 12.9% of subjects had severe nausea. We conclude that Melanotan II is a potent initiator of penile erection in men with erectile dysfunction. Our findings warrant further investigation of melanocortin agonists and antagonists on penile erection. International Journal of Impotence Research (2000) 12, Suppl 4, S74-S79.


A comparative study of coagulation, granular- and powdered-activated carbon for the removal of perfluorooctane sulfonate and perfluorooctanoate in drinking water treatment.
Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are persistent organic pollutants in the environment and their occurrence causes toxicological effects on humans. We examined different conventional coagulant treatments such as alum, ferric chloride and polyaluminium chloride in removing these compounds. These were then compared with a natural coagulant (Moringa oleifera). We also investigated the powdered-activated carbon (PAC) and granular-activated carbon (GAC) for removing these compounds. At an initial dose of 5 mg/L, polyaluminium chloride led to a higher reduction of PFOS/PFOA compared with alum which in turn was higher than ferric. The removal efficiency increased with the increase in coagulant dose and decrease in pH. M. oleifera was very effective in reducing PFOS and PFOA than conventional coagulants, with a reduction efficiencies of 65% and 72%, respectively, at a dose of 30 mg/L. Both PAC and GAC were very effective in reducing these compounds than coagulations. PAC led to a higher reduction in PFOS and PFOA than GAC due to its greater surface area and shorter internal diffusion distances. The addition of PAC (10 min contact time) with coagulation (at 5 mg/L dosage) significantly increased the removal efficiency, and the maximum removal efficiency was for M. oleifera with 98% and 94% for PFOS and PFOA, respectively. The reduction efficiency of PFOS/PFOA was reduced with the increase in dissolved organic concentration due to the adsorption competition between organic molecules and PFOS/PFOA.


The adolescent and young adult with cancer: state of the art -- psychosocial aspects.
Adolescents and young adults with cancer are a distinct subgroup of patients within oncology. From the onset of symptoms until the completion of therapy and beyond, they face physical, psychological, and social challenges that are significantly different from those of adults and children. Survival rates and quality of life outcomes for this population have not improved to the same extent that have for younger and older patients. Improvements in quality of care, overall survival and quality of life for these patients require access to specialized care and participation in clinical trials; assistance with management of disease and treatment effects (especially fertility and body image issues); assessment of psychosocial needs; facilitated transition to off-treatment care; and referral to age-appropriated information and support services. Staff team caring for young patients must be dedicated to working with this age group and should have specialist knowledge and training to support their specific needs.


Association between body mass index and pregnancy outcome in a randomized trial of cerclage for short cervix.
To evaluate whether increasing body mass index (BMI) alters the efficacy of ultrasound-directed cerclage in women with a history of preterm birth. This was a planned secondary analysis of a multicenter trial in which women with a singleton gestation and prior spontaneous preterm birth (17 to 33 + 6 weeks' gestation) were screened for a short cervix by serial transvaginal ultrasound evaluations between 16 and 22 + 6 weeks. Women with a short cervix (cervical length < 25 mm) were randomly assigned to cerclage or not. Linear and logistic regression were used to assess the relationship between BMI and continuous and categorical variables, respectively. Overall, in the screened women (n = 986), BMI was not associated with cervical length (P = 0.68), gestational age at delivery (P = 0.12) or birth at < 35 weeks (P = 0.68). For the cerclage group (n = 148), BMI had no significant effect. For the no-cerclage group (n = 153), BMI was associated with a decrease in gestational age at delivery, with an estimated slope of - 0.14 weeks per kg/m(2) (P = 0.03; including adjustment for cervical length). This result was driven primarily by several women with BMI > 47 kg/m(2) . In women at high risk for recurrent preterm birth, BMI was not associated with cervical length or gestational age at birth. BMI did not appear to adversely affect ultrasound-indicated cerclage.


The external aldimine form of serine palmitoyltransferase: structural, kinetic, and spectroscopic analysis of the wild-type enzyme and HSAN1 mutant mimics.
Sphingolipid biosynthesis begins with the condensation of L-serine and palmitoyl-CoA catalyzed by the PLP-dependent enzyme serine palmitoyltransferase (SPT). Mutations in human SPT cause hereditary sensory autonomic neuropathy type 1, a disease characterized by loss of feeling in extremities and severe pain. The human enzyme is a membrane-bound hetereodimer, and the most common mutations are located in the enzymatically incompetent monomer, suggesting a "dominant" or regulatory effect. The molecular basis of how these mutations perturb SPT activity is subtle and is not simply loss of activity. To further explore the structure and mechanism of SPT, we have studied the homodimeric bacterial enzyme from Sphingomonas paucimobilis. We have analyzed two mutants (N100Y and N100W) engineered to mimic the mutations seen in hereditary sensory autonomic neuropathy type 1 as well as a third mutant N100C designed to mimic the wild-type human SPT. The N100C mutant appears fully active, whereas both N100Y and N100W are significantly compromised. The structures of the holoenzymes reveal differences around the active site and in neighboring secondary structure that transmit across the dimeric interface in both N100Y and N100W. Comparison of the l-Ser external aldimine structures of both native and N100Y reveals significant differences that hinder the movement of a catalytically important Arg(378) residue into the active site. Spectroscopic analysis confirms that both N100Y and N100W mutants subtly affect the chemistry of the PLP. Furthermore, the N100Y and R378A mutants appear less able to stabilize a quinonoid intermediate. These data provide the first experimental insight into how the most common disease-associated mutations of human SPT may lead to perturbation of enzyme activity.


Effect of temperature on the structure and phase behavior of water confined by hydrophobic, hydrophilic, and heterogeneous surfaces.
We perform molecular dynamics simulations of water confined between atomically detailed hydrophobic, hydrophilic, and heterogeneous (patchy) nanoscale plates. We study the effects of temperature 220 <or= T <or= 300 K on confined water's behavior at various pressures -0.2 <or= P <or= 0.2 GPa and plate separations 0.5 <or= d <or= 1.6 nm. Combining this with our earlier results on the same system [Giovambattista, N.; Rossky, P. J.; Debenedetti, P. G. Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys. 2006, 73, 041604; Giovambattista, N.; Rossky, P. J.; Debenedetti, P. G. J. Phys. Chem. C, 2007, 11, 1323], where pressure was varied at constant temperature, allows us to compare water's behavior in nanoscale confinement, upon isobaric cooling and isothermal compression, corresponding to paths of interest in protein denaturation. At a fixed temperature, water confined between hydrophobic plates can form vapor, liquid, or crystal (bilayer ice) phases, depending on the values of P and d. The P-d phase diagrams at T = 300 K and T = 220 K show that cooling suppresses the vapor phase and stabilizes the liquid and crystal phases. The critical separation d(c)(P), below which vapor forms, shifts to lower values of d and P upon cooling. The density profiles show that, upon cooling, water approaches the hydrophobic plates. Hence, the effective hydrophobicity of the plate decreases as T decreases, consistent with the suppression of the vapor phase upon cooling. However, both the orientation of water's molecules at the interface and the water contact angle on the hydrophobic surface show practically no temperature dependence. Simulations of water confined by heterogeneous plates decorated with hydrophobic and hydrophilic patches reveal that cooling leads to appreciable blurring of the differences between water densities at hydrophobic and hydrophilic surfaces. This observation, together with remarkable similarities in confined water's response to isobaric cooling and to isothermal compression, suggests that the invasion of hydrophobic cavities by water is an important mechanism underlying both pressure and cold denaturation of proteins.


Bicarbonate therapy and intracellular acidosis.
1. The correction of metabolic acidosis with sodium bicarbonate remains controversial. Experiments in vitro have suggested possible deleterious effects after alkalinization of the extracellular fluid. Disequilibrium of carbon dioxide and bicarbonate across cell membranes after alkali administration, leading to the phenomenon of 'paradoxical' intracellular acidosis, has been held responsible for some of these adverse effects. 2. Changes in intracellular pH in suspensions of leucocytes from healthy volunteers were monitored using a fluorescent intracellular dye. The effect in vitro of increasing extracellular pH with sodium bicarbonate was studied at different sodium bicarbonate concentrations. Lactic acid and propionic acid were added to the extracellular buffer to mimic conditions of metabolic acidosis. 3. The addition of a large bolus of sodium bicarbonate caused intracellular acidification as has been observed previously. The extent of the intracellular acidosis was dependent on several factors, being most evident at higher starting intracellular pH. When sodium bicarbonate was added as a series of small boluses the reduction in intracellular pH was small. Under conditions of initial acidosis this was rapidly followed by intracellular alkalinization. 4. Although intracellular acidification occurs after addition of sodium bicarbonate to a suspension of human leucocytes in vitro, the effect is minimal when the conditions approximate those seen in clinical practice. We suggest that the observed small and transient lowering of intracellular pH is insufficient grounds in itself to abandon the use of sodium bicarbonate in human acidosis.


Pseudocapacitance-boosted ultrafast Na storage in a pie-like FeS@C nanohybrid as an advanced anode material for sodium-ion full batteries.
In order to develop promising anode materials for sodium-ion batteries (SIBs), a novel pie-like FeS@C (P-FeS@C) nanohybrid, in which all ultrasmall FeS nanocrystals (NCs) are completely embedded into the carbon network and sealed by a protective carbon shell, has been prepared. The unique pie-like structure can effectively speed up the kinetics of electrode reactions, while the carbon shell stabilizes the FeS NCs inside. Studies show that the electrochemical reaction processes of P-FeS@C electrodes are dominated by the pseudocapacitive behavior, leading to an ultrafast Na+-insertion/extraction reaction. Hence, the prepared P-FeS@C nanohybrid exhibits superior Na-storage properties especially high rate capability in half cells. For example, it can deliver reversible capacities of 555.1 mA h g-1 at 0.2 A g-1 over 150 cycles and about 60.4 mA h g-1 at 80 A g-1 (an ultrahigh current density even higher than that of the capacitor test). Furthermore, an advanced P-FeS@C//Na3V2(PO4)2O2F full cell has been assembled out, which delivers a stable specific capacity of 441.2 mA h g-1 after 80 cycles at 0.5 A g-1 with a capacity retention of 91.8%.


The use of leukocyte cell line culture supernatant for skin reaction testing in malignant melanoma.
A study was conducted to determine some of the potential applications of a human leukocyte culture supernatant or "lymphokine" preparation in cancer patients. The application evaluated in this study was the use of this preparation as a skin test reagent for evaluation of the inflammatory response following intradermal injection. The preparation was derived from the supernatant of a long-term cultured lymphoblastoid cell line with migration inhibition factor (MIF) and other lymphokine activities. Dose response, histology and toxicity studies were done in 53 patients with malignant melanoma stage IIIB and IV. A dose response curve was observed for both erythema and induration at 12 and 24 hours, but not at 48 hours. An optimal intradermal dose for eliciting inflammation was determined and found to be five units. Histopathological evaluation of biopsy specimens showed a mixed cell reaction including granulocytes, eosinophils, lymphocytes and monocytes differing in lymphocyte content from the classical delayed type hypersensitivity (DTH) reaction in man. Compared with the response to recall antigens, only a weak correlation with the DTH response to the recall antigens was found. Our results support the conclusion that lymphokines may be used in the future to evaluate the ability to develop nonspecific inflammation in cancer patients, and that this inflammatory response can be obtained in a number of patients no longer capable of responding to recall antigens.


A new perspective for stem-cell mechanobiology: biomechanical control of stem-cell behavior and fate.
Biomechanics is known to play an important role in cell metabolism. Cell phenotype, tissue-specific functions, and fate critically depend on the extracellular mechanical environment. The mechanical properties of the cell itself, such as cytoskeleton elasticity, membrane tension, and adhesion strength, may also play an important role in cell homeostasis and differentiation. Pluripotent bone marrow-derived human mesenchymal stem cells, for example, can be differentiated into many tissue-specific lineages. While cellular biomechanical properties are significantly altered during stem-cell specification to a particular phenotype, the complexity of events associated with transformation of these precursor cells leaves many questions unanswered about morphological, structural, proteomic, and functional changes in differentiating stem cells. A thorough understanding of stem-cell behavior would allow the development of more effective approaches to the expansion of stem cells in vitro and the regulation of their commitment to a specific phenotype. Control of cell behaviors might be feasible through manipulation of the cellular biomechanical properties using various external physical stimuli, including electric fields, mechanical stimuli, and genetic manipulation of the expression of particular genes. Biomechanical regulation of stem-cell differentiation can greatly minimize the number of chemicals and growth factors that would otherwise be required for composite tissue engineering. Determination and the appropriate use of the known physicochemical cues will facilitate current research effort toward designing and engineering functional tissue constructs.


The distinct metabolism between large and small HDL indicates unique origins of human apolipoprotein A4.
Apolipoprotein A4's (APOA4's) functions on HDL in humans are not well understood. A unique feature of APOA4 is that it is an intestinal apolipoprotein secreted on HDL and chylomicrons. The goal of this study was to gain a better understanding of the origin and function of APOA4 on HDL by studying its metabolism across 6 HDL sizes. Twelve participants completed a metabolic tracer study. HDL was isolated by APOA1 immunopurification and separated by size. Tracer enrichments for APOA4 and APOA1 were determined by targeted mass spectrometry, and metabolic rates were derived by compartmental modeling. APOA4 metabolism on small HDL (alpha3, prebeta, and very small prebeta) was distinct from that of APOA4 on large HDL (alpha0, 1, 2). APOA4 on small HDL appeared in circulation by 30 minutes and was relatively rapidly catabolized. In contrast, APOA4 on large HDL appeared in circulation later (1-2 hours) and had a much slower catabolism. The unique metabolic profiles of APOA4 on small and large HDL likely indicate that each has a distinct origin and function in humans. This evidence supports the notion that APOA4 on small HDL originates directly from the small intestine while APOA4 on large HDL originates from chylomicron transfer.


Radiology services in emergency medicine residency programs: a national survey.
To determine who reads plain film radiographs, how quickly radiologists' interpretations are available, how many initial readings require correction, and how satisfied emergency physicians (EPs) are with radiology in emergency departments (EDs) with emergency medicine (EM) residency programs. A questionnaire was sent to the chairs of all U.S. EM residencies, asking about EM radiology services. Of 120 sites surveyed, 97 (81%) responded. Respondents reported that, on weekday days, EM attendings or residents performed the radiograph interpretation used for clinical decision making at 66% of sites; on nights and weekends, EPs performed the clinically relevant readings at 79% of sites. Twenty-one percent of sites reported that no radiologist reviewed images before patients left the ED on nights and weekends. Only 39% of sites reported that all images were read within four hours on weekday days, and only 19% of sites reported readings within this time frame on nights and weekends. Median misinterpretation rates were reported as 1% on weekday days and 1.5% at other times. Overall, EPs were satisfied with their interactions with radiology at 63% of EDs. This study summarizes the perceptions of EPs regarding radiology services; the findings must be interpreted with caution, given the lack of external validation. Nevertheless, EPs report that many EM residency programs depend on EPs' interpretations of radiographs. Emergency physicians report that attending radiologists rarely read images on nights and weekends and that images are misread more frequently at these times. Although EPs were satisfied with many aspects of radiology, EPs expressed the most dissatisfaction with turnaround times and misreads.


Comparison of negative and positive ion electrospray ionization mass spectra of calmodulin and its complex with trifluoperazine.
The protein calmodulin (apoCaM) undergoes a conformational change when it binds calcium. This structure of the protein (Ca4CaM) is a dumbbell-shaped molecule that undergoes a further profound conformational change on binding of the antipsychotic drug trifluoperazine (TFP). Experimental conditions were developed to prepare samples of apoCaM, Ca4CaM and Ca4CaM/TFP that were substantially free of sodium. The effects of the conformational changes of calmodulin on the charge-state distributions observed in positive ion and negative ion electrospray ionization (ESI) mass spectra were examined. Conversion of apoCaM into Ca4CaM was concomitant with a change in the negative ion ESI mass spectrum whereby the 16- ion was the most abundant ion observed for the apo form and the 8- ion was the most abundant for the complex. In contrast, in the positive ion ESI mass spectra of apoCaM and Ca4CaM, the most abundant species in each case was the 8+ ion. When a complex of Ca4CaMwith TFP was prepared, the most abundant species was the 5+ ion. This is consistent with a conformational change of Ca4CaM that rendered some basic sites inaccessible to ionization in the ESI process. Using the same Ca4CaM/TFP mixture, no complex with TFP was observed in negative ion ESI mass spectra. These observations are discussed in the context of the structural changes that are known to occur in calmodulin, and suggestions are made to explain the apparently conflicting data. The results reported here reflect on the validity of using differences in charge-state distributions observed in ESI mass spectra to assess conformational changes in proteins.


The Occupational Therapy Practice Checklist for adult physical rehabilitation.
Although the practice of occupational therapy is described in textbooks, research, and professional standards, a tool for outcomes research is needed. The Occupational Therapy Practice Checklist (OTPC), based on the Model of Occupational Performance (Pedretti, 1996), includes domains of adjunctive, enabling, purposeful, and occupational performance. Practices are also identified by phase of therapy (early, middle, late). The OTPC was piloted with 40 adults in an outpatient physical rehabilitation center. The Kuder Richardson 20 coefficient of internal consistency was .91. Practices on the OTPC discriminated between clients with and without neurological disorders. The OTPC has potential for yielding knowledge about occupational therapy practice. Results of the pilot show that occupational therapy practice was not linear, as theorized, but rather a complex integration of techniques.


What stabilizes close arginine pairing in proteins?
Close stacking of arginine residues are often observed in protein structures despite the highly repulsive nature of the close like-charged groups. Physical factors stabilizing the close guanidinium ions of arginine side-chains have been previously studied in water and in protein-like environments, and the hydration free energy has been emphasized to be an important factor. However, how close arginine pairs are stabilized in real proteins has not been fully understood yet. In this paper, we show that arginine pairs are more frequently found in the protein interior than expected from the frequency of unpaired arginines buried inside protein through a statistical analysis of the protein structure database. We then confirm that 4 selected arginine pairs buried in the protein are indeed positively charged rather than neutralized, by molecular dynamics simulations and pKa estimation with molecular mechanics-Poisson-Boltzmann calculations. Further energy decomposition analysis shows that the hydration free energy may not be strong enough to overcome the repulsive Coulomb interaction between the positively charged arginine residues buried inside the protein. Instead, a highly polar interaction network is identified around each buried arginine pair, and the electrostatic interactions within such network are strong enough to stabilize the repulsive interaction of the buried arginine pair for the 4 selected cases. The polar interaction network is highly conserved evolutionarily in some proteins, implicating their roles in protein stabilization or biochemical function.


Ocular aberrations with ray tracing and Shack-Hartmann wave-front sensors: does polarization play a role?
Ocular aberrations were measured in 71 eyes by using two reflectometric aberrometers, employing laser ray tracing (LRT) (60 eyes) and a Shack-Hartmann wave-front sensor (S-H) (11 eyes). In both techniques a point source is imaged on the retina (through different pupil positions in the LRT or a single position in the S-H). The aberrations are estimated by measuring the deviations of the retinal spot from the reference as the pupil is sampled (in LRT) or the deviations of a wave front as it emerges from the eye by means of a lenslet array (in the S-H). In this paper we studied the effect of different polarization configurations in the aberration measurements, including linearly polarized light and circularly polarized light in the illuminating channel and sampling light in the crossed or parallel orientations. In addition, completely depolarized light in the imaging channel was obtained from retinal lipofuscin autofluorescence. The intensity distribution of the retinal spots as a function of entry (for LRT) or exit pupil (for S-H) depends on the polarization configuration. These intensity patterns show bright corners and a dark area at the pupil center for crossed polarization, an approximately Gaussian distribution for parallel polarization and a homogeneous distribution for the autofluorescence case. However, the measured aberrations are independent of the polarization states. These results indicate that the differences in retardation across the pupil imposed by corneal birefringence do not produce significant phase delays compared with those produced by aberrations, at least within the accuracy of these techniques. In addition, differences in the recorded aerial images due to changes in polarization do not affect the aberration measurements in these reflectometric aberrometers.


Lysophospholipids are potential biomarkers of ovarian cancer.
To determine whether lysophosphatidic acid (LPA) and other lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of ovarian cancer in a controlled setting. Plasma samples were collected from ovarian cancer patients and healthy control women in Hillsborough and Pinellas counties, Florida, and processed at the University of South Florida H. Lee Moffitt Cancer Center and Research Institute (Moffitt). Case patients with epithelial ovarian cancer (n = 117) and healthy control subjects (n = 27) participated in the study. Blinded LPL analysis, including 23 individual LPL species, was performed at the Cleveland Clinic Foundation using an electrospray ionization mass spectrometry-based method. LPL levels were transmitted to Moffitt, where clinical data were reviewed and statistical analyses were performed. There were statistically significant differences between preoperative case samples (n = 45) and control samples (n = 27) in the mean levels of total LPA, total lysophosphatidylinositol (LPI), sphingosine-1-phosphate (S1P), and individual LPA species as well as the combination of several LPL species. The combination of 16:0-LPA and 20:4-LPA yielded the best discrimination between preoperative case samples and control samples, with 93.1% correct classification, 91.1% sensitivity, and 96.3% specificity. In 22 cases with both preoperative and postoperative samples, the postoperative levels of several LPL, including S1P, total LPA, and lysophosphatidylcholine (LPC) levels and some individual species of LPA and LPC, were significantly different from preoperative levels. LPA, LPI, LPC, and S1P appear useful as diagnostic and prognostic biomarkers of ovarian cancer.


Sexual intercourse, age of initiation and contraception among adolescents in Ireland: findings from the Health Behaviour in School-aged Children (HBSC) Ireland study.
The need to tackle sexual health problems and promote positive sexual health has been acknowledged in Irish health policy. Young people's sexual behaviour however remains under-researched with limited national data available. This study presents the first nationally representative and internationally comparable data on young people's sexual health behaviours in Ireland. Self-complete questionnaire data were collected from 4494 schoolchildren aged 15-18 years as part of a broader examination of health behaviour and their context. The prevalence of sexual initiation, very early sexual initiation (< 14 years) and non-condom use at last intercourse are reported and used as outcomes in separate multilevel logistic regression models examining associations between sociodemographic characteristics, lifestyle characteristics and young people's sexual behaviours. Overall, 25.7% of boys and 21.2% of girls were sexually initiated. Older age was consistently predictive of initiation for both boys and girls, as were alcohol, tobacco and cannabis involvement, living in poorer neighbourhoods and having good communication with friends. Involvement in music and drama was protective. Very early sexual initiation (< 14 years) was reported by 22.8% of sexually initiated boys and 13.4% of sexually initiated girls, and was consistently associated with rural living, cannabis involvement and bullying others for both. Boys' very early initiation was predicted by alcohol involvement, receiving unhealthy food from parents and taking medication for psychological symptoms, whereas better communication with friends and more experience of negative health symptoms were protective. Girls' very early initiation was predicted by being bullied and belonging to a non-Traveller community, whereas taking medication for physical symptoms and attending regular health checks was protective. Condom use was reported by 80% of sexually initiated students at last intercourse. Boys' condom use was associated with older age, higher family affluence, bullying others, more frequent physical activity and health protective behaviours. For girls, condom use was predicted by belonging to a non-Traveller community, healthy food consumption, higher quality of life and being bullied, whereas taking medication for physical and psychological symptoms was associated with non-condom use. These nationally representative research findings highlight the importance of focusing on young people as a distinct population subgroup with unique influences on their sexual health requiring targeted interventions and policy.


Chronic amphetamine administration to cats: behavioral and neurochemical evidence for decreased central serotonergic function.
Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors, e.g., limb flick and abortive groom, characteristic of the action of hallucinogenic drugs and dependent on a depression of central serotonergic neurotransmission. This drug treatment produced large decreases (-40 to -60%) in central nervous system serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), when measured either 6 or 24 hr after the last amphetamine injection. The rate of limb flicking returned to a predrug level approximately 5 days after drug withdrawal, at which time 5-HT and 5-HIAA levels had returned to within 30 to 40% of base line. Both 5-HT and 5-HIAA returned to base-line levels within 14 days after drug withdrawal. Norepinephrine (NE), dopamine (DA) and DA metabolites were decreased 60 to 95% by chronic amphetamine treatment and showed little recovery within the 14 days after drug withdrawal. A second experiment examined the latency to onset of the behavioral and neurochemical changes with a constant dose of amphetamine (7.5 mg/kg, twice daily). Limb flicking was significantly increased above base-line levels following 3 days of amphetamine administration, at which time 5-HT and 5-HIAA levels were decreased 30 to 40%. NE, DA and DA metabolites were decreased approximately 50 to 90% by this treatment regimen. A third experiment examined the effects of a low dose of amphetamine (3.75 mg/kg), injected more frequently (every 6 hr for 6 days), to approximate the administration pattern in human amphetamine abuse. This treatment produced significant increases in limb flicking and abortive grooming on days 5 and 6 and resulted in 30 to 40% depletions of 5-HT and 5-HIAA. NE, DA and DA metabolites were decreased by approximately 50 to 90%. These data are discussed in relation to a role for serotonin in amphetamine psychosis and schizophrenia.


Hematodinium infection seasonality in the Firth of Clyde (Scotland) Nephrops norvegicus population: a re-evaluation.
Hematodinium infections in Norway lobster Nephrops norvegicus from the Clyde Sea area (CSA) population, Scotland, UK, have previously been undetected in summer. This study aimed to establish if the CSA is actually devoid of infected N. norvegicus in this season. Two PCR assays, an ELISA and 2 tests that detect only patent infection (pleopod and body colour methods) were applied in a 21 mo study. Patent infection was seasonal, appearing predominantly in spring, while subpatent infection diagnosed by ELISA and PCR was highly prevalent in all seasons. Generalised linear modelling supported this assertion, as sampling in September and February significantly increased the probability of finding infected N. norvegicus (p < 0.01); infections were predominantly subpatent and patent respectively, at these times. Therefore, Hematodinium seasonality in N. norvegicus populations is likely to have been an artefact of insensitive diagnostic tests. Light Hematodinium infections were found using PCR assays when patent infections were at their most prevalent and intense, suggesting that infection develops at different rates in different N. norvegicus individuals and that only a portion of the total number of infected N. norvegicus die within a single year. These new data were added to a long-term data series for the CSA (1990 to 2008), which showed that after an initial 5 yr epidemic period, prevalence stabilised at 20 to 25%. Comparisons with 'susceptible-infected-recovered/removed' (SIR) models suggest that this high prevalence is maintained through high birth rates of susceptible host N. norvegicus.


Identification of a novel nuclear localization signal sequence in Chlamydia trachomatis-secreted hypothetical protein CT311.
We previously reported that Chlamydia trachomatis hypothetical protein CT311 was secreted out of chlamydial inclusion and into host cell cytosol. We now found that CT311 further entered host cell nucleus at the late stage of infection and continued to accumulate in the nucleus of C. trachomatis-infected cells. When CT311 was expressed via a transgene in mammalian cells, CT311 protein was exclusively detected in the nucleus, suggesting that CT311 by itself is sufficient for nuclear targeting. However, preexisting nuclear CT311 did not affect subsequent chlamydial infection. Using deletion constructs, we mapped a nuclear localization signal sequence of CT311 to residues 21 to 63 ((21)AVEGKPLSRAAQLRERRKDLHVSGKPSPRYALKKRALEAKKNK(63)). This sequence was sufficient for targeting a heterologous protein into mammalian cell nucleus and it contains two independent clusters of basic residues ((34)RERRK(38) and (53)KKRALEAKKNK(63) respectively). Deletion or alanine substitution of the basic residues in either cluster led to loss of nuclear targeting activity, suggesting that both clusters are critical for the nuclear targeting function. These observations have demonstrated that the hypothetical protein CT311 possesses a novel nuclear localization signal sequence with dual modules of basic residues for targeting host cell nucleus during Chlamydia trachomatis infection.


The development of a reliable amateur boxing performance analysis template.
The aim of this study was to devise a valid performance analysis system for the assessment of the movement characteristics associated with competitive amateur boxing and assess its reliability using analysts of varying experience of the sport and performance analysis. Key performance indicators to characterise the demands of an amateur contest (offensive, defensive and feinting) were developed and notated using a computerised notational analysis system. Data were subjected to intra- and inter-observer reliability assessment using median sign tests and calculating the proportion of agreement within predetermined limits of error. For all performance indicators, intra-observer reliability revealed non-significant differences between observations (P > 0.05) and high agreement was established (80-100%) regardless of whether exact or the reference value of ±1 was applied. Inter-observer reliability was less impressive for both analysts (amateur boxer and experienced analyst), with the proportion of agreement ranging from 33-100%. Nonetheless, there was no systematic bias between observations for any indicator (P > 0.05), and the proportion of agreement within the reference range (±1) was 100%. A reliable performance analysis template has been developed for the assessment of amateur boxing performance and is available for use by researchers, coaches and athletes to classify and quantify the movement characteristics of amateur boxing.


Improved Joint Mobility Associated with Reduced Inflammation Related to Consumption of Nopal Cactus Fruit Juice: Results from a Placebo-Controlled Trial Using Digital Inclinometry to Objectively Document Mobility of All Major Joints.
To evaluate the effects of daily consumption of Nopal cactus fruit juice (NFJ) on joint mobility in a population experiencing chronic pain but otherwise in good health. A double-blind, placebo-controlled study design was used to enroll 40 people after written informed consent, randomized to consume 3 oz/day of NFJ versus placebo. At baseline and 8 weeks, joint range of motion (ROM) was examined by digital inclinometry along the vertical weight-bearing axis of the body from neck to knees and the shoulders. Blood samples were tested for cytokines and C-reactive protein (CRP). Questionnaires addressed wellness, pain, and reliance on pain medications. After 8 weeks of consuming NFJ, participants showed improved ROM beyond that of participants consuming placebo. Cervical and thoracic/lumbar ROM for the NFJ group was significantly improved when compared to placebo (cervical: P<0.03, thoracic/lumbar: P<0.04). People consuming NFJ relied less on pain medication to complete daily activities (P<0.1) and experienced reduced interference from pain and breathing issues (not significant). Serum levels of Eotaxin, involved in airway inflammation, showed significant differences between placebo and NFJ groups after 8 weeks (P<0.048). Changes in CRP levels showed a larger reduction in the NFJ group (-13%) than in the placebo group (-4%) (not significant). In the subgroup with CRP levels between 1 and 9.9 mg/L at baseline, CRP levels decreased in the NFJ group (-30%) but increased in the placebo group (31%) (P<0.015). Consumption of NFJ for 8 weeks was associated with statistically significant improvements in joint mobility and physical functioning compared to the placebo group, allowing participants in the NFJ group to be more physically active; daily activities were easier, including walking, sitting, and lying. This was associated with reduced use of pain medication, possibly associated with anti-inflammatory properties of NFJ, as suggested by reduced Eotaxin and CRP levels.


Trophic niche, capture efficiency and venom profiles of six sympatric ant-eating spider species (Araneae: Zodariidae).
The arms race between specialist predators and their prey has resulted in the evolution of a variety of specific adaptations. In venomous predators, this can include venom composition, particularly if predators are specialized on dangerous prey. Here, we performed an integrative study using six species of highly specialized ant-eating spiders of the genus Zodarion to investigate their phylogeny, realized trophic niche, efficacy in the capture of various ant species and venom composition. Data on natural diet obtained by next-generation sequencing and field observations showed that the six Zodarion species exploit different ant species. Their phylogeny, based on mitochondrial and nuclear genes, correlated with the composition of their natural prey, indicating that closely related Zodarion species specialize on similar ant species. Prey-capture parameters differed among Zodarion species suggesting prey-specific efficacy. Similarly, the venom profiles of both low and high molecular compounds differed among species. Only the profiles of low molecular compounds were correlated with capture efficacy parameters, suggesting that the venom of Zodarion spiders contains prey-specific components. Our study suggests that Iberian Zodarion spiders are specialized on particular ant species.


Biogeography and evolution of Asian Gesneriaceae based on updated taxonomy.
Based on an updated taxonomy of Gesneriaceae, the biogeography and evolution of the Asian Gesneriaceae are outlined and discussed. Most of the Asian Gesneriaceae belongs to Didymocarpoideae, except Titanotrichum was recently moved into Gesnerioideae. Most basal taxa of the Asian Gesneriaceae are found in the Indian subcontinent and Indo-China Peninsula, suggesting Didymocarpoideae might originate in these regions. Four species diversification centers were recognized, i.e. Sino-Vietnam regions, Malay Peninsula, North Borneo and Northwest Yunnan (Hengduan Mountains). The first three regions are dominated by limestone landscapes, while the Northwest Yunnan is well-known for its numerous deep gorges and high mountains. The places with at least 25% species are neoendemics (newly evolved and narrowly endemic) which were determined as evolutionary hotspots, including Hengduan Mountains, boundary areas of Yunnan-Guizhou-Guangxi in Southwest China, North Borneo, Pahang and Terengganu in Malay Peninsula, and mountainous areas in North Thailand, North Sulawesi Island. Finally, the underlying mechanisms for biogeographical patterns and species diversification of the Asian Gesneriaceae are discussed.


Feeding and dispersal behavior of the cotton leafworm, Alabama argillacea (Hübner) (Lepidoptera: Noctuidae), on Bt and non-Bt cotton: implications for evolution and resistance management.
The host acceptance of neonate Alabama argillacea (Hübner) (Lepidoptera: Noctuidae) larvae to Bt cotton plants exerts a strong influence on the potential risk that this pest will develop resistance to Bt cotton. This will also determine the efficiency of management strategies to prevent its resistance such as the "refuge-in-the-bag" strategy. In this study, we assessed the acceptance of neonate A. argillacea larvae to Bt and non-Bt cotton plants at different temperatures during the first 24 h after hatching. Two cotton cultivars were used in the study, one a Bt DP 404 BG (Bollgard) cultivar, and the other, an untransformed isoline, DP 4049 cultivar. There was a greater acceptance by live neonate A. argillacea larvae for the non-Bt cotton plants compared with the Bt cotton plants, especially in the time interval between 18 and 24 h. The percentages of neonate A. argillacea larvae found on Bt or non-Bt plants were lower when exposed to temperatures of 31 and 34 °C. The low acceptance of A. argillacea larvae for Bt cotton plants at high temperatures stimulated the dispersion of A. argillacea larvae. Our results support the hypothesis that the dispersion and/or feeding behavior of neonate A. argillacea larvae is different between Bt and non-Bt cotton. The presence of the Cry1Ac toxin in Bt cotton plants, and its probable detection by the A. argillacea larvae tasting or eating it, increases the probability of dispersion from the plant where the larvae began. These findings may help to understand how the A. argillacea larvae detect the Cry1Ac toxin in Bt cotton and how the toxin affects the dispersion behavior of the larvae over time. Therefore, our results are extremely important for the management of resistance in populations of A. argillacea on Bt cotton.


Prediction of Sepsis in the Intensive Care Unit With Minimal Electronic Health Record Data: A Machine Learning Approach.
Sepsis is one of the leading causes of mortality in hospitalized patients. Despite this fact, a reliable means of predicting sepsis onset remains elusive. Early and accurate sepsis onset predictions could allow more aggressive and targeted therapy while maintaining antimicrobial stewardship. Existing detection methods suffer from low performance and often require time-consuming laboratory test results. To study and validate a sepsis prediction method, InSight, for the new Sepsis-3 definitions in retrospective data, make predictions using a minimal set of variables from within the electronic health record data, compare the performance of this approach with existing scoring systems, and investigate the effects of data sparsity on InSight performance. We apply InSight, a machine learning classification system that uses multivariable combinations of easily obtained patient data (vitals, peripheral capillary oxygen saturation, Glasgow Coma Score, and age), to predict sepsis using the retrospective Multiparameter Intelligent Monitoring in Intensive Care (MIMIC)-III dataset, restricted to intensive care unit (ICU) patients aged 15 years or more. Following the Sepsis-3 definitions of the sepsis syndrome, we compare the classification performance of InSight versus quick sequential organ failure assessment (qSOFA), modified early warning score (MEWS), systemic inflammatory response syndrome (SIRS), simplified acute physiology score (SAPS) II, and sequential organ failure assessment (SOFA) to determine whether or not patients will become septic at a fixed period of time before onset. We also test the robustness of the InSight system to random deletion of individual input observations. In a test dataset with 11.3% sepsis prevalence, InSight produced superior classification performance compared with the alternative scores as measured by area under the receiver operating characteristic curves (AUROC) and area under precision-recall curves (APR). In detection of sepsis onset, InSight attains AUROC = 0.880 (SD 0.006) at onset time and APR = 0.595 (SD 0.016), both of which are superior to the performance attained by SIRS (AUROC: 0.609; APR: 0.160), qSOFA (AUROC: 0.772; APR: 0.277), and MEWS (AUROC: 0.803; APR: 0.327) computed concurrently, as well as SAPS II (AUROC: 0.700; APR: 0.225) and SOFA (AUROC: 0.725; APR: 0.284) computed at admission (P<.001 for all comparisons). Similar results are observed for 1-4 hours preceding sepsis onset. In experiments where approximately 60% of input data are deleted at random, InSight attains an AUROC of 0.781 (SD 0.013) and APR of 0.401 (SD 0.015) at sepsis onset time. Even with 60% of data missing, InSight remains superior to the corresponding SIRS scores (AUROC and APR, P<.001), qSOFA scores (P=.0095; P<.001) and superior to SOFA and SAPS II computed at admission (AUROC and APR, P<.001), where all of these comparison scores (except InSight) are computed without data deletion. Despite using little more than vitals, InSight is an effective tool for predicting sepsis onset and performs well even with randomly missing data.


Formation and reinforcement of clusters composed of C60 molecules.
We carry out two experiments: (1) the formation of clusters composed of C60 molecules via self-assembly and (2) the reinforcement of the clusters. Firstly, clusters such as fibres and helices composed of C60 molecules are produced via self-assembly in supercritical carbon dioxide. However, C60 molecules are so weakly bonded to each other in the clusters that the clusters are broken by the irradiation of electron beams during scanning electron microscope observation. Secondly, UV photons are irradiated inside a chamber in which air is filled at 1 atm and the above clusters are placed, and it was found that the clusters are reinforced; that is, they are not broken by electron beams any more. C60 molecules located at the surface of the clusters are oxidised, i.e. C60On molecules, where n = 1, 2, 3 and 4, are produced according to time-of-flight mass spectroscopy. It is supposed that oxidised C60 molecules at the surface of the clusters may have an important role for the reinforcement, but the actual mechanism of the reinforcement of the clusters has not yet been clearly understood and therefore is an open question.


The use of anthropometric measures in the prediction of incident gout: results from a Swedish community-based cohort study.
Objectives: To study associations between different anthropometric measures and incident gout, and to find the best predictive measure. Method: We used the baseline investigation from the Malmö Diet and Cancer study, excluding cases of prevalent gout (n = 28 081). Cox regression for each anthropometric measurement was calculated per standard deviation increment for men and women, with hazard ratios (HRs) and 95% confidence intervals (CIs), using a hospital diagnosis of incident gout (M10) during follow-up as the outcome. Incremental C-statistics for each anthropometric measure were used to determine the measure with the best predictive capacity, in models adjusted for age, socio-economic data, lifestyle factors, comorbidities, and antihypertensive medications. Results: The study population included 11 049 men and 17 032 women, with 633 incident gout cases, 393 in men (3.6%) and 240 in women (1.4%). For both men and women, the five anthropometric measurements with highest C-statistics were weight, body mass index (BMI), waist circumference (WC), hip circumference, and waist-to-height ratio; in men, the measurement with the highest C-statistic was BMI (0.7361; fully adjusted HR 1.52, 95% CI 1.39-1.68), and in women WC (0.8085; fully adjusted HR 1.62, 95% CI 1.46-1.81). The increment in C-statistic with anthropometric measures was good, around 0.035. Waist-to-hip ratio, waist-to-hip-to-height ratio, body fat percentages, and especially A Body Shape Index had lower C-statistics. Conclusions: Both BMI and WC showed good predictive ability for incident gout. The clinically used cut-offs for BMI and WC appeared to be relevant in the assessment of increased risk of gout.


Suicide in the global chinese aging population: a review of risk and protective factors, consequences, and interventions.
As one of the leading causes of death around the world, suicide is a global public health threat. In the Chinese population, suicides constitute one-fifth of all recorded suicides in the world. Despite the factual data on suicide rates, the understanding of various causal factors behind suicide, including risk and protective factors and adverse health care, remained incomplete among the global Chinese aging population. To fill in the knowledge void, this paper reviews the epidemiology of suicide among Chinese older adults globally as well as explores the existing intervention strategies. Using the PRISMA statement, we performed a systematic review of exiting research on the topic, including studies describing suicide among Chinese older adults in communities outside of Asia. A literature search was conducted online by using both medical and social science data-bases. Our findings highlighted that elderly suicide in Chinese populations is significantly affected by the social, cultural, and familial contexts within which the individual lived prior to committing suicide. Reviewing such research indicated that while reducing risk factors may contribute to lowering suicides amongst Chinese older adults, measures to improve protective factors are also critical. Support through ongoing family and community care relationships is necessary to improve resilience in older adults and positive aging. Future longitudinal studies on the risk factors and protective factors, and adverse health consequences are called for to devise culturally and linguistically appropriate prevention and intervention programs in global Chinese aging populations.


Metacognition as a Predictor of Improvements in Personality Disorders.
Personality Disorders (PDs) are particularly hard to treat and treatment drop-out rates are high. Several authors have agreed that psychotherapy is more successful when it focuses on the core of personality pathology. For this reason, therapists dealing with PDs need to understand the psychopathological variables that characterize this pathology and exactly what contributes to maintaining psychopathological processes. Moreover, several authors have noted that one key problem that characterizes all PDs is an impairment in understanding mental states - here termed metacognition - which could also be responsible for therapy failures. Unfortunately, a limited number of studies have investigated the role of mentalization in the process of change during psychotherapy. In this paper, we assume that poor metacognition corresponds to a core element of the general pathology of personality, impacts a series of clinical variables, generates symptoms and interpersonal problems, and causes treatment to be slower and less effective. We explored whether changes in metacognition predicted an improvement among different psychopathological variables characterizing PDs; 193 outpatients were treated at the Third Center of Cognitive Psychotherapy in Rome, Italy, and followed a structured path tailored for the different psychopathological variables that emerged from a comprehensive psychodiagnostic assessment that considered patients' symptoms, metacognitive abilities, interpersonal relationships, personality psychopathology, and global functioning. The measurements were repeated after a year of treatment. The results showed that changes in metacognitive abilities predicted improvements in the analyzed variables.


ChiMS: Open-source instrument control software platform on LabVIEW for imaging/depth profiling mass spectrometers.
ChiMS is an open-source data acquisition and control software program written within LabVIEW for high speed imaging and depth profiling mass spectrometers. ChiMS can also transfer large datasets from a digitizer to computer memory at high repetition rate, save data to hard disk at high throughput, and perform high speed data processing. The data acquisition mode generally simulates a digital oscilloscope, but with peripheral devices integrated for control as well as advanced data sorting and processing capabilities. Customized user-designed experiments can be easily written based on several included templates. ChiMS is additionally well suited to non-laser based mass spectrometers imaging and various other experiments in laser physics, physical chemistry, and surface science.


Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen.
Glycogen-targeting subunits of protein phosphatase-1, such as protein targeting to glycogen (PTG), direct the phosphatase to the glycogen particle, where it stimulates glycogenesis. We have investigated the metabolic impact of overexpressing PTG in liver of normal rats. After administration of PTG cDNA in a recombinant adenovirus, animals were fasted or allowed to continue feeding for 24 hours. Liver glycogen was nearly completely depleted in fasted control animals, whereas glycogen levels in fasted or fed PTG-overexpressing animals were 70% higher than in fed controls. Nevertheless, transgenic animals regulated plasma glucose, triglycerides, FFAs, ketones, and insulin normally in the fasted and fed states. Fasted PTG-overexpressing animals receiving an oral bolus of [U-(13)C]glucose exhibited a large increase in hepatic glycogen content and a 70% increase in incorporation of [(13)C]glucose into glycogen. However, incorporation of labeled glucose accounted for only a small portion of the glycogen synthesized in PTG-overexpressing animals, consistent with our earlier finding that PTG promotes glycogen synthesis from gluconeogenic precursors. We conclude that hepatic PTG overexpression activates both direct and indirect pathways of glycogen synthesis. Because of its ability to enhance glucose storage without affecting other metabolic indicators, the glycogen-targeting subunit may prove valuable in controlling blood glucose levels in diabetes.


Diagnosing suspected scaphoid fractures: a systematic review and meta-analysis.
Imaging protocols for suspected scaphoid fractures among investigators and hospitals are markedly inconsistent. We performed a systematic review and meta-analysis to assess and compare the diagnostic performance of bone scintigraphy, MRI, and CT for diagnosing suspected scaphoid fractures. Twenty-six studies were included. Sensitivity, specificity, and diagnostic odds ratio were pooled separately and summary receiver operating characteristic curves were fitted for each modality. Meta-regression analyses were performed to compare these modalities. We obtained likelihood ratios derived from the pooled sensitivity and specificity and, using Bayes' theorem, calculated the posttest probability by application of the tests. The pooled sensitivity, specificity, natural logarithm of the diagnostic odds ratio, and the positive and negative likelihood ratios were, respectively, 97%, 89%, 4.78, 8.82, and 0.03 for bone scintigraphy; 96%, 99%, 6.60, 96, and 0.04 for MRI; and 93%, 99%, 6.11, 93, and 0.07 for CT. Bone scintigraphy and MRI have equally high sensitivity and high diagnostic value for excluding scaphoid fracture; however, MRI is more specific and better for confirming scaphoid fracture. We believe additional studies are needed to assess diagnostic performance of CT, especially paired design studies or randomized controlled trials to compare CT with MRI or bone scintigraphy. Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.


Commentary: the quest for women's prophylactic methods--hopes vs science.
The companion article by Rosenberg and Gollub in this issue summarizes data from 10 observational studies and concludes that female-controlled contraceptive methods, under typical conditions, are comparable to condoms in preventing sexually transmitted diseases and should be merchandized as such. While we agree that chemical and mechanical contraceptives provide protection against some sexually transmitted diseases, we think the authors have overstated the scientific case for these methods, especially in comparison with the condom. We think the current data remain inconclusive regarding the absolute protection of spermicides against the human immunodeficiency virus and their level of protection--relative to that of the condom--against other sexually transmitted diseases. Three reasons account for our differences: the limitations in the comparative data; the reported adverse effects of spermicides on vaginal conditions, including genital ulcers; and the relative value of condoms, even under typical conditions, in preventing sexually transmitted diseases. For these reasons, we would currently counsel both women and men who practice high-risk sexual behaviors to use condoms as their first line of defense. If this is unacceptable, the female barriers become a fallback position to protect against bacterial sexually transmitted diseases.


Nanomolar binding of peptides containing noncanonical amino acids by a synthetic receptor.
This paper describes the molecular recognition of phenylalanine derivatives and their peptides by the synthetic receptor cucurbit[7]uril (Q7). The 4-tert-butyl and 4-aminomethyl derivatives of phenylalanine (tBuPhe and AMPhe) were identified from a screen to have 20-30-fold higher affinity than phenylalanine for Q7. Placement of these residues at the N-terminus of model tripeptides (X-Gly-Gly), resulted in no change in affinity for tBuPhe-Gly-Gly, but a remarkable 500-fold increase in affinity for AMPhe-Gly-Gly, which bound to Q7 with an equilibrium dissociation constant (K(d)) value of 0.95 nM in neutral phosphate buffer. Structure-activity studies revealed that three functional groups work in a positively cooperative manner to achieve this extraordinary stability (1) the N-terminal ammonium group, (2) the side chain ammonium group, and (3) the peptide backbone. Addition of the aminomethyl group to Phe substantially improved the selectivity for peptide versus amino acid and for an N-terminal vs nonterminal position. Importantly, Q7 binds to N-terminal AMPhe several orders of magnitude more tightly than any of the canonical amino acid residues. The high affinity, single-site selectivity, and small modification in this system make it attractive for the development of minimal affinity tags.


Genome-wide analysis of macrosatellite repeat copy number variation in worldwide populations: evidence for differences and commonalities in size distributions and size restrictions.
Macrosatellite repeats (MSRs), usually spanning hundreds of kilobases of genomic DNA, comprise a significant proportion of the human genome. Because of their highly polymorphic nature, MSRs represent an extreme example of copy number variation, but their structure and function is largely understudied. Here, we describe a detailed study of six autosomal and two X chromosomal MSRs among 270 HapMap individuals from Central Europe, Asia and Africa. Copy number variation, stability and genetic heterogeneity of the autosomal macrosatellite repeats RS447 (chromosome 4p), MSR5p (5p), FLJ40296 (13q), RNU2 (17q) and D4Z4 (4q and 10q) and X chromosomal DXZ4 and CT47 were investigated. Repeat array size distribution analysis shows that all of these MSRs are highly polymorphic with the most genetic variation among Africans and the least among Asians. A mitotic mutation rate of 0.4-2.2% was observed, exceeding meiotic mutation rates and possibly explaining the large size variability found for these MSRs. By means of a novel Bayesian approach, statistical support for a distinct multimodal rather than a uniform allele size distribution was detected in seven out of eight MSRs, with evidence for equidistant intervals between the modes. The multimodal distributions with evidence for equidistant intervals, in combination with the observation of MSR-specific constraints on minimum array size, suggest that MSRs are limited in their configurations and that deviations thereof may cause disease, as is the case for facioscapulohumeral muscular dystrophy. However, at present we cannot exclude that there are mechanistic constraints for MSRs that are not directly disease-related. This study represents the first comprehensive study of MSRs in different human populations by applying novel statistical methods and identifies commonalities and differences in their organization and function in the human genome.


Characterising paediatric mortality during and after acute illness in Sub-Saharan Africa and South Asia: a secondary analysis of the CHAIN cohort using a machine learning approach.
A better understanding of which children are likely to die during acute illness will help clinicians and policy makers target resources at the most vulnerable children. We used machine learning to characterise mortality in the 30-days following admission and the 180-days after discharge from nine hospitals in low and middle-income countries (LMIC). A cohort of 3101 children aged 2-24 months were recruited at admission to hospital for any acute illness in Bangladesh (Dhaka and Matlab Hospitals), Pakistan (Civil Hospital Karachi), Kenya (Kilifi, Mbagathi, and Migori Hospitals), Uganda (Mulago Hospital), Malawi (Queen Elizabeth Central Hospital), and Burkina Faso (Banfora Hospital) from November 2016 to January 2019. To record mortality, children were observed during their hospitalisation and for 180 days post-discharge. Extreme gradient boosted models of death within 30 days of admission and mortality in the 180 days following discharge were built. Clusters of mortality sharing similar characteristics were identified from the models using Shapley additive values with spectral clustering. Anthropometric and laboratory parameters were the most influential predictors of both 30-day and post-discharge mortality. No WHO/IMCI syndromes were among the 25 most influential mortality predictors of mortality. For 30-day mortality, two lower-risk clusters (N = 1915, 61%) included children with higher-than-average anthropometry (1% died, 95% CI: 0-2), and children without signs of severe illness (3% died, 95% CI: 2-4%). The two highest risk 30-day mortality clusters (N = 118, 4%) were characterised by high urea and creatinine (70% died, 95% CI: 62-82%); and nutritional oedema with low platelets and reduced consciousness (97% died, 95% CI: 92-100%). For post-discharge mortality risk, two low-risk clusters (N = 1753, 61%) were defined by higher-than-average anthropometry (0% died, 95% CI: 0-1%), and gastroenteritis with lower-than-average anthropometry and without major laboratory abnormalities (0% died, 95% CI: 0-1%). Two highest risk post-discharge clusters (N = 267, 9%) included children leaving against medical advice (30% died, 95% CI: 25-37%), and severely-low anthropometry with signs of illness at discharge (46% died, 95% CI: 34-62%). WHO clinical syndromes are not sufficient at predicting risk. Integrating basic laboratory features such as urea, creatinine, red blood cell, lymphocyte and platelet counts into guidelines may strengthen efforts to identify high-risk children during paediatric hospitalisations. Bill & Melinda Gates FoundationOPP1131320.


Colloidal-sized metal-organic frameworks: synthesis and applications.
Colloidal metal-organic frameworks (CMOFs), nanoporous colloidal-sized crystals that are uniform in both size and polyhedral shape, are crystals composed of metal ions and organic bridging ligands, which can be used as building blocks for self-assembly in organic and aqueous liquids. They stand in contrast to conventional metal-organic frameworks (MOFs), which scientists normally study in the form of bulk crystalline powders. However, powder MOFs generally have random crystal size and shape and therefore do not possess either a definite mutual arrangement with adjacent particles or uniformity. CMOFs do have this quality, which can be important in vital uptake and release kinetics. In this Account, we present the diverse methods of synthesis, pore chemistry control, surface modification, and assembly techniques of CMOFs. In addition, we survey recent achievements and future applications in this emerging field. There is potential for a paradigm shift, away from using just bulk crystalline powders, towards using particles whose size and shape are regulated. The concept of colloidal MOFs takes into account that nanoporous MOFs, conventionally prepared in the form of bulk crystalline powders with random crystal size, shape, and orientation, may also form colloidal-sized objects with uniform size and morphology. Furthermore, the traditional MOF functions that depend on porosity present additional control over those MOF functions that depend on pore interactions. They also can enable controlled spatial arrangements between neighboring particles. To begin, we discuss progress regarding synthesis of MOF nano- and microcrystals whose crystal size and shape are well regulated. Next, we review the methods to modify the surfaces with dye molecules and polymers. Dyes are useful when seeking to observe nonluminescent CMOFs in situ by optical microscopy, while polymers are useful to tune their interparticle interactions. Third, we discuss criteria to assess the stability of CMOFs for various applications. In another section of this Account, we give examples of supracrystal assembly in liquid, on substrates, at interfaces, and under external electric fields. We end this Account with discussion of possible future developments, both conceptual and technological.


Manual Muscle Testing-Force Profiles and Their Reproducibility.
The manual muscle test (MMT) is a flexible diagnostic tool, which is used in many disciplines, applied in several ways. The main problem is the subjectivity of the test. The MMT in the version of a "break test" depends on the tester's force rise and the patient's ability to resist the applied force. As a first step, the investigation of the reproducibility of the testers' force profile is required for valid application. The study examined the force profiles of n = 29 testers (n = 9 experiences (Exp), n = 8 little experienced (LitExp), n = 12 beginners (Beg)). The testers performed 10 MMTs according to the test of hip flexors, but against a fixed leg to exclude the patient's reaction. A handheld device recorded the temporal course of the applied force. The results show significant differences between Exp and Beg concerning the starting force (padj = 0.029), the ratio of starting to maximum force (padj = 0.005) and the normalized mean Euclidean distances between the 10 trials (padj = 0.015). The slope is significantly higher in Exp vs. LitExp (p = 0.006) and Beg (p = 0.005). The results also indicate that experienced testers show inter-tester differences and partly even a low intra-tester reproducibility. This highlights the necessity of an objective MMT-assessment. Furthermore, an agreement on a standardized force profile is required. A suggestion for this is given.


Universal crossed beam imaging studies of polyatomic reaction dynamics.
The marriage between high level quantum calculations and experimental advances in laser technology, quantum state control, and detection techniques have opened the door to the study of molecular collision dynamics at a new level of detail. However, one current challenge lies in adapting these powerful strategies to address questions beyond the scope of the small ground state systems that have largely been the focus of reaction dynamics investigations to-date. For molecules with intermediate or large size (more than 6 atoms), lack of spectroscopic information and spectral congestion limit quantum state preparation, control and detection for experiment, and the large number of degrees of freedom of the system makes accurate quantum dynamics calculations prohibitively expensive. Nevertheless, studies of the chemical dynamics of such systems can reveal novel aspects of reactivity not anticipated based upon the behavior of smaller model systems. This Perspective will highlight applications of soft vacuum ultraviolet photoionization at 157 nm as a universal probe in combination with crossed beams and DC slice velocity map ion imaging to study bimolecular reaction dynamics of molecules of intermediate or large size, illuminated with support of high-level ab initio calculations. Here, we report on the chemical dynamics of atomic oxygen or chlorine reactions with organic compounds: propanol isomers, alkylamines (N(CH3)3 and NH(CH3)2), and isobutene ((CH3)2CCH2) studied using this approach. The polyatomic radical products from the hydrogen abstraction process have been detected by 157 nm photoionization and their slice ion images embody translational energy and angular information that directly reflect the underlying collision dynamics. Various reaction mechanisms (such as direct abstraction and addition-elimination) along with the involvement of roaming dynamics and novel intersystem crossing pathways are presented. These demonstrate the power of this technique to reveal fundamentally new aspects of reaction dynamics that arise in larger reaction systems.


Trends in smoking and quitting in China from 1993 to 2003: National Health Service Survey data.
China has about 350 million smokers, more commonly men. Using data from National Health Service Surveys conducted in 1993, 1998 and 2003, we (i) estimated trends in smoking prevalence and cessation according to sociodemographic variables and (ii) analysed cessation rates, quitting intentions, reasons for quitting and reasons for relapsing. Data were collected from approximately 57 000 households and 200 000 individuals in each survey year. Household members > 15 years of age were interviewed about their smoking habits, quitting intentions and attitudes towards smoking. We present descriptive data stratified by age, sex, income level and rural versus urban residence. In China, current smoking in those > 15 years old declined 60-49% in men and 5-3.2% in women over 1993-2003. The decline was more marked in urban areas. However, heavy smoking (≥ 20 cigarettes daily) increased substantially overall and doubled in men. The average age of uptake also dropped by about 3 years. In 2003, 7.9% of smokers reported intending to quit, and 6% of people who had ever smoked reported having quit. Of former smokers, 40.6% quit because of illness, 26.9% to prevent disease and 10.9% for financial reasons. Smoking prevalence declined in China over the study period, perhaps due to the combined effect of smoking cessation, reduced uptake in women and selective mortality among men over 40 years of age. However, heavy smoking increased. People in China rarely quit or intend to quit smoking, except at older ages. Further tobacco control efforts are urgently needed, especially in rural areas.


Functional desensitization due to stimulation of cyclic AMP-phosphodiesterase in human mononuclear leukocytes.
We have previously demonstrated heterologous desensitization of human mononuclear leukocytes (MNL) by incubation of low (e.g., 10(-6)M) concentrations of histamine, isoproterenol and prostaglandin E1. Subsequent exposure of the cells to stimulating (e.g., 10(-3) to 10(-5)M) concentrations of any one of the three agonists shows reduced cAMP responses. Possible mechanisms for the subnormal responsiveness include rapid degradation of cAMP. In this report we demonstrated time-dependent elevation of cAMP-phosphodiesterase (PDE) activity following agonist desensitization. The increased enzyme activity was accompanied by a mirror-image decrease in cAMP responsiveness. The effect was rapid and prolonged, with recovery time proportional to desensitization time. Cycloheximide failed to inhibit the increase of cAMP-PDE activity caused by short-term histamine exposure, but partially diminished the elevation as the result of chronic histamine desensitization. We observed three different kinetic forms of cAMP-PDE in MNL, designated as I, II and III, each with distinctive Km and Vmax. Histamine desensitization increased the activity of form II and drastically reduced that of form I. Also we observed a possible conversion of lymphocyte cAMP-PDE from form I to the form II more characteristic of monocytes. Agonist-induced increases in cAMP-PDE activity and changes in enzyme kinetic characteristics represent a potentially important mechanism of functional desensitization. This may have significant effects on biological regulation of cyclic nucleotides.


A summary and appraisal of existing evidence of antimicrobial resistance in the Syrian conflict.
Antimicrobial resistance (AMR) in populations experiencing war has yet to be addressed, despite the abundance of contemporary conflicts and the protracted nature of twenty-first century wars, in combination with growing global concern over conflict-associated bacterial pathogens. The example of the Syrian conflict is used to explore the feasibility of using existing global policies on AMR in conditions of extreme conflict. The available literature on AMR and prescribing behaviour in Syria before and since the onset of the conflict in March 2011 was identified. Overall, there is a paucity of rigorous data before and since the onset of conflict in Syria to contextualize the burden of AMR. However, post onset of the conflict, an increasing number of studies conducted in neighbouring countries and Europe have reported AMR in Syrian refugees. High rates of multidrug resistance, particularly Gram-negative organisms, have been noted amongst Syrian refugees when compared with local populations. Conflict impedes many of the safeguards against AMR, creates new drivers, and exacerbates existing ones. Given the apparently high rates of AMR in Syria, in neighbouring countries hosting refugees, and in European countries providing asylum, this requires the World Health Organization and other global health institutions to address the causes, costs, and future considerations of conflict-related AMR as an issue of global governance.