A Mo(VI) based coordination polymer as an antiproliferative agent against cancer cells.
Metal ions being an important part of biological systems are of great interest in the designing of new drugs. Molybdenum is an essential trace element for humans, animals, and plants and naturally present in many enzymes hence its complexes can be expected to serve as potential candidates for biomedical applications. A novel molybdenum-based coordination polymer, [Mo2(μ2-O)O4(2-pyc)2(H2O)], is synthesized by a hydrothermal route and structurally characterized by using single crystal X-Ray diffraction. The structure consists of molybdenum octahedra connected by a bridging oxo ligand and 2-pyc forming a one-dimensional coordination polymer. This Mo coordination polymer was found to show a considerable inhibitory effect with IC50 values of 22.63 μmol L-1, 28.19 μmol L-1, and 20.97 μmol L-1, against HepG2 (human liver cancer), A549 (human lung cancer), and MCF-7 (human breast cancer) cell lines respectively. This is the first attempt at exploring the molybdenum-based coordination polymer for antitumor applications. The cell cytotoxicity analysis revealed that the anti-tumor potential of the compound is governed by arresting of the A549, HepG2, and MCF-7 cancer cells in the S phase of the cell cycle. UV-Visible absorption spectroscopy further revealed the binding interaction between the Mo coordination polymer and ctDNA and the binding constant was found to be 5.9 × 103 L mol-1, which is in agreement with those of well-known groove binders. This binding interaction in turn induces apoptosis and necrosis pathways leading to the death of the cancer cells.


Phase transfer catalysts drive diverse organic solvent solubility of single-walled carbon nanotubes helically wrapped by ionic, semiconducting polymers.
Use of phase transfer catalysts such as 18-crown-6 enables ionic, linear conjugated poly[2,6-{1,5-bis(3-propoxysulfonicacidsodiumsalt)}naphthylene]ethynylene (PNES) to efficiently disperse single-walled carbon nanotubes (SWNTs) in multiple organic solvents under standard ultrasonication methods. Steady-state electronic absorption spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy (TEM) reveal that these SWNT suspensions are composed almost exclusively of individualized tubes. High-resolution TEM and AFM data show that the interaction of PNES with SWNTs in both protic and aprotic organic solvents provides a self-assembled superstructure in which a PNES monolayer helically wraps the nanotube surface with periodic and constant morphology (observed helical pitch length = 10 ± 2 nm); time-dependent examination of these suspensions indicates that these structures persist in solution over periods that span at least several months. Pump-probe transient absorption spectroscopy reveals that the excited state lifetimes and exciton binding energies of these well-defined nanotube-semiconducting polymer hybrid structures remain unchanged relative to analogous benchmark data acquired previously for standard sodium dodecylsulfate (SDS)-SWNT suspensions, regardless of solvent. These results demonstrate that the use of phase transfer catalysts with ionic semiconducting polymers that helically wrap SWNTs provide well-defined structures that solubulize SWNTs in a wide range of organic solvents while preserving critical nanotube semiconducting and conducting properties.


[Aquatic animals of medical importance in Brazil].
The injuries caused by venomous and poisonous aquatic animals may provoke important morbidity in the victim. The cnidarians (jellyfishes, especially cubomedusas and Portuguese-Man-of-War) caused nearly 25% of 236 accidents by marine animals, while sea urchins were responsible for about 50% and catfish, stingrays and scorpionfish nearly 25%). In freshwater, stingrays and catfish cause injuries with a very similar mechanism to the poisoning and the effects of the toxins of marine species. In a series of about 200 injuries observed among freshwater fishermen, nearly 40% were caused by freshwater catfish, 5% freshwater stingrays and 55% by traumatogenic fish, such as piranhas and traíras. The author presents the aquatic animals that cause injuries to humans in Brazil, the clinical aspects of the envenoming and the first measures for the control of the severe pain observed mainly in the accidents caused by cnidarians and venomous fishes.


Measuring the diurnal pattern of leaf hyponasty and growth in Arabidopsis - a novel phenotyping approach using laser scanning.
Plants forming a rosette during their juvenile growth phase, such as Arabidopsis thaliana (L.) Heynh., are able to adjust the size, position and orientation of their leaves. These growth responses are under the control of the plants circadian clock and follow a characteristic diurnal rhythm. For instance, increased leaf elongation and hyponasty - defined here as the increase in leaf elevation angle - can be observed when plants are shaded. Shading can either be caused by a decrease in the fluence rate of photosynthetically active radiation (direct shade) or a decrease in the fluence rate of red compared with far-red radiation (neighbour detection). In this paper we report on a phenotyping approach based on laser scanning to measure the diurnal pattern of leaf hyponasty and increase in rosette size. In short days, leaves showed constitutively increased leaf elevation angles compared with long days, but the overall diurnal pattern and the magnitude of up and downward leaf movement was independent of daylength. Shade treatment led to elevated leaf angles during the first day of application, but did not affect the magnitude of up and downward leaf movement in the following day. Using our phenotyping device, individual plants can be non-invasively monitored during several days under different light conditions. Hence, it represents a proper tool to phenotype light- and circadian clock-mediated growth responses in order to better understand the underlying regulatory genetic network.


PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients.
AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced β cell stress, and promoted β cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro- and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.


European Society of Trauma and Emergency Surgery (ESTES) recommendations for trauma and emergency surgery preparation during times of COVID-19 infection.
A series of recommendations regarding hospital perioperative preparation for the COVID-19 pandemic were compiled to inform surgeons worldwide on how to provide emergency surgery and trauma care during enduring times.The recommendations are divided into eight domains: (1) General recommendation for surgical services; (2) Emergency Surgery for critically ill COVID-19 positive or suspected patients -Preoperative planning and case selection; (3) Operating Room setup; (4) patient transport to the OR; (5) Surgical staff preparation; (6) Anesthesia considerations; (7) Surgical approach; and (8) Case Completion.The European Society of Emergency Surgery board endorsed these recommendations.


Sleep in children with autistic spectrum disorder.
Children and adolescents with autistic spectrum disorders (ASD) suffer from sleep problems, particularly insomnia, at a higher rate than typically developing children, ranging from 40% to 80%. Sleep problems in ASD might occur as a result of complex interactions between biological, psychological, social/environmental, and family factors, including child rearing practices that are not conducive to good sleep. Interestingly, children with a history of developmental regression have a more disturbed sleep pattern than children without regression. Even though regulation of sleep in children with ASD is still poorly understood, circadian abnormalities in autism might be the result of genetic abnormalities related to melatonin synthesis and melatonin's role in modulating synaptic transmission. Recently a bifurcation of the sleep/wake cycle with increased sensitivity to external noise and short sleep duration causing irregular sleep onset and wake up times has been suggested. Identifying and treating sleep disorders may result not only in improved sleep, but also impact favorably on daytime behavior and family functioning. Several studies have also demonstrated effectiveness of behavioral interventions for sleep onset and maintenance problems in these populations. When behavioral interventions are not effective or lead only to a partial response, pharmacological treatment options should be considered. Studies of melatonin use in children with ASD provide evidence for its effectiveness and safety in the long run. The clinician assessing a child with an ASD should screen carefully for sleep disorders and make referrals as indicated.


Tuning Intramolecular Förster Resonance Energy Transfer and Activating Intramolecular Singlet Fission.
The synergy of panchromatic absorption throughout most of the visible range of the solar spectrum and intramolecular singlet fission (SF) has been realized in a series of conjugates featuring different light-harvesting subphthalocyanines (SubPcs) and an energy accepting pentacene dimer (Pnc2 ). At the focal point was a modular SubPc approach, which was based on decorating the SubPc core with different peripheral substituents to tailor and fine-tune their optical properties. Transient absorption measurements assisted in corroborating that the SubPcs act as energy-transfer antennas by means of unidirectional and quantitative intramolecular Förster resonance energy transfer (FRET) to the Pnc2 , where an intramolecular SF affords triplet quantum yields reaching unity.


Combined effect of coffee ingestion and repeated bouts of low-intensity exercise on fat oxidation.
We investigated the effect of the combination of coffee ingestion and repeated bouts of low-intensity exercise on fat oxidation. Subjects were seven young, healthy male adults. They performed four trials: a single 30-min bout of exercise following ingestion of plain hot water (WS) or coffee (CS); a trial with three 10-min bouts of exercise separated by 10-min periods of rest following ingestion of plain hot water (WR) or coffee (CR). The coffee contained 5 mg kg-1 of caffeine. All trials were performed on a cycle ergometer at 40% maximal oxygen uptake for each subject an hour after beverage ingestion. Oxygen uptake in the CS and CR trials was higher compared with the WS and WR trials at 90 min after exercise (P<0·05). Respiratory exchange ratio (RER) in the CS and CR trials was decreased during the whole recovery period compared with baseline (P<0·05), whereas no significant decreases were observed in either the WS or WR trials. Moreover, RER was significantly lower at 30 min after exercise in the CR trial than in either the WS or WR trials (P<0·05 each). Similarly, it is notable that fat oxidation rate in the CR trial was significantly higher at 30 min after exercise compared to that in the WS and WR trials (P<0·05). These results suggest that the combination of coffee intake and repeated bouts of low-intensity exercise enhances fat oxidation in the period after exercise.


Effects of visual rehabilitation on a child with severe visual impairment.
We examined the effects of visual rehabilitation, including a chromatic luminance discrimination program and a fixation training program, on a 6-yr-old boy with severe visual impairment. Single-subject ABA and AB designs were used. The programs were conducted 2×/wk and included 6 to 7 sessions for the baseline phase and 10 to 11 sessions for the intervention phase. Play was integrated into the visual training programs. Goggle visual evoked potential (VEP) testing was used to evaluate neural activity in the primary visual cortex. Correct responses increased and response times were shortened after training in luminance discrimination. The total and maximum fixation time also improved, as did P100 latency and amplitude of VEPs. While walking, the boy was able to detect obstacles he had not noticed before training. The results indicate the value of visual training and the possibility of brain plasticity in a child with severe visual impairment.


Deaf perceptions about treatment for alcohol use and mental health.
Recent research suggests that alcohol use disorder may be more prevalent in the Deaf community, a diverse sociolinguistic minority group. However, rates of treatment-seeking among Deaf individuals are even lower than in the general society. This study used the Theory of Planned Behavior to identify Deaf adults' beliefs about treatment that may prevent their treatment-seeking behaviors. This study conducted elicitation interviews with 16 Deaf adults. The study team recruited participants from across the U.S. and conducted interviews on Zoom. Participant ages ranged from 27 to 67 years (M = 40, SD =10.8). Seventy-five percent of the sample was male, 75 % were White, and 12.5 % were Hispanic/Latine. The study conducted interviews in American Sign Language, subsequently interpreted into English by a nationally certified interpreter, and transcribed for data analyses. The study analyzed transcripts using the Framework Method. The study team coded the interviews in groups and assessed for saturation (≤ 5 % new themes) of themes throughout the analysis. This study reached saturation in the third group (six total groups). Identified themes followed the Theory of Planned Behavior constructs. The study identified nine Behavioral Beliefs with four advantages and five disadvantages of seeking treatment, four Normative Beliefs with one support and three oppositions to seeking treatment, and thirteen Control Beliefs with five facilitators and eight barriers to seeking treatment. Overall, the Deaf participants reported several unique beliefs based on their cultural and linguistic perspectives, including a concern about unqualified providers, experiencing stress in treatment with hearing providers, stigma within the Deaf community, less access to cultural information about alcohol and mental health, less encouragement of traditional treatment in marginalized communities, and additional barriers (e.g., communication, limited Deaf treatment options, discrimination, etc.). A thorough understanding of individual beliefs about treatment is necessary to develop interventions that may increase treatment-seeking behaviors. Previous research has demonstrated that individual beliefs may be modified using Cognitive Behavioral Therapy techniques to increase treatment-seeking behaviors among hearing individuals. Similar interventions may be useful with Deaf individuals; however, they must consider the unique cultural and linguistic perspectives of the community.


Effectiveness of percutaneous coronary intervention in patients with silent myocardial ischemia (post hoc analysis of the COURAGE trial).
Previous studies have suggested that percutaneous coronary intervention (PCI) decreases long-term mortality in patients with silent myocardial ischemia (SMI), but whether PCI specifically decreases mortality when added to intensive medical therapy is unknown. We performed a post hoc analysis of clinical outcomes in patients in the COURAGE trial based on the presence or absence of anginal symptoms at baseline. Asymptomatic patients were classified as having SMI by electrocardiographic ischemia at rest or reversible stress perfusion imaging (exercise-induced or pharmacologic). Study end points included the composite primary end point (death or myocardial infarction [MI]); individual end points of death, MI, and hospitalization for acute coronary syndrome; and need for revascularization. Of 2,280 patients 12% (n = 283) had SMI and 88% were symptomatic (n = 1,997). There were no between-group differences in age, gender, cardiac risk factors, previous MI or revascularization, extent of angiographic disease, or ischemia by electrocardiogram or imaging. Compared to symptomatic patients, those with SMI had fewer subsequent revascularizations (16% vs 27%, p <0.001) regardless of treatment assignment and fewer hospitalizations for acute coronary syndrome (7% vs 12%, p <0.04). No significant differences in outcomes were observed between the 2 treatment groups, although there was a trend toward fewer deaths in the PCI group (n = 7, 5%) compared to the optimal medical therapy (OMT) group (n = 16, 11%, p = 0.12). In conclusion, addition of PCI to OMT did not decrease nonfatal cardiac events in patients with SMI but showed a trend toward fewer deaths. Although underpowered, given similar outcomes in other small studies, these findings suggest the need for an adequately powered trial of revascularization versus OMT in SMI patients.


Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a.
To evaluate visual impairment in Usher syndrome 1b (USH1b) and Usher syndrome 2a (USH2a). We carried out a retrospective study of 19 USH1b patients and 40 USH2a patients. Cross-sectional regression analyses of the functional acuity score (FAS), functional field score (FFS) and functional vision score (FVS) related to age were performed. Statistical tests relating to regression lines and Student's t-test were used to compare between (sub)groups of patients. Parts of the available individual longitudinal data were used to obtain individual estimates of progressive deterioration and compare these to those obtained with cross-sectional analysis. Results were compared between subgroups of USH2a patients pertaining to combinations of different types of mutations. Cross-sectional analyses revealed significant deterioration of the FAS (0.7% per year), FFS (1.0% per year) and FVS (1.5% per year) with advancing age in both patient groups, without a significant difference between the USH1b and USH2a patients. Individual estimates of the deterioration rates were substantially and significantly higher than the cross-sectional estimates in some USH2a cases, including values of about 5% per year (or even higher) for the FAS (age 35-50 years), 3-4% per year for the FFS and 4-5% per year for the FVS (age > 20 years). There was no difference in functional vision score behaviour detected between subgroups of patients pertaining to different biallelic combinations of specific types of mutations. The FAS, FFS and FVS deteriorated significantly by 0.7-1.5% per year according to cross-sectional linear regression analysis in both USH1b and USH2a patients. Higher deterioration rates (3-5% per year) in any of these scores were attained, according to longitudinal data collected from individual USH2a patients. Score behaviour was similar across the patient groups and across different biallelic combinations of various types of mutations. However, more elaborate studies, preferably covering longitudinal data, are needed to obtain conclusive evidence.


Detailed Chemical Prospecting of Volatile Organic Compounds Variations from Adriatic Macroalga Halopteris scoparia.
The present study aimed to isolate volatile organic compounds (VOCs) from fresh (FrHSc) and air-dried (DrHSc) Halopteris scoparia (from the Adriatic Sea) by headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD) and to analyse them by gas chromatography and mass spectrometry (GC-MS). The impact of the season of growth (May-September) and air-drying on VOC composition was studied for the first time, and the obtained data were elaborated by principal component analysis (PCA). The most abundant headspace compounds were benzaldehyde, pentadecane (a chemical marker of brown macroalgae), and pentadec-1-ene. Benzaldehyde abundance decreased after air-drying while an increment of benzyl alcohol after drying was noticed. The percentage of pentadecane and heptadecane increased after drying, while pentadec-1-ene abundance decreased. Octan-1-ol decreased from May to September. In HD-FrHSc, terpenes were the most abundant in June, July, and August, while, in May and September, unsaturated aliphatic compounds were dominant. In HD-DrHSc terpenes, unsaturated and saturated aliphatic compounds dominated. (E)-Phytol was the most abundant compound in HD-FrHSc through all months except September. Its abundance increased from May to August. Two more diterpene alcohols (isopachydictyol A and cembra-4,7,11,15-tetraen-3-ol) and sesquiterpene alcohol gleenol were also detected in high abundance. Among aliphatic compounds, the dominant was pentadec-1-ene with its peak in September, while pentadecane was present with lower abundance. PCA (based on the dominant compound analyses) showed distinct separation of the fresh and dried samples. No correlation was found between compound abundance and temperature change. The results indicate great seasonal variability of isolated VOCs, as well among fresh and dried samples, which is important for further chemical biodiversity studies.


The direct cellular target of topically applied pimecrolimus may not be infiltrating lymphocytes.
Topically applied calcineurin inhibitors have been shown to be effective in the treatment of atopic dermatitis. When systemically administered, these agents cause immunosuppression via inhibition of calcineurin in lymphocytes. As topical agents, the mechanism of action is poorly defined. To test the hypothesis that skin-infiltrating lymphocytes are directly targeted when calcineurin inhibitors are applied to the skin. Ten patients with atopic dermatitis were treated with 1% pimecrolimus cream twice daily to target lesions. Skin biopsies were performed before and 48 h after beginning therapy. We assessed the cellular localization of NFAT1 and NFAT2 as a surrogate measure of intracellular calcineurin activity (e.g. increasing cytoplasmic localization with increasing calcineurin inhibition). All patients showed a clinical response, at both 48 h and 2 weeks. As previously described, NFAT2 localized to the follicular keratinocytes, and its activation was partially inhibited by topical pimecrolimus. NFAT1 was found to be expressed by follicular and interfollicular keratinocytes, and its mostly nuclear localization was not affected by topical pimecrolimus therapy. Both NFAT1 and NFAT2 were found in the infiltrating lymphocytes. However, using both manual counting as well as an automated method to assess nuclear intensity of NFAT staining, we found that the proportion of infiltrating leucocytes with nuclear ('activated') NFAT did not change following therapy with pimecrolimus. Our results suggest that topical pimecrolimus does not act primarily by inhibiting the calcineurin/NFAT axis in lymphocytes but may instead act by other mechanisms, possibly by decreasing NFAT2 activity in follicular keratinocytes.


Impact of steel slag on the ammonium adsorption by zeolite and a new configuration of zeolite-steel slag substrate for constructed wetlands.
The CaO dissolution from slag, as well as the effects of influencing parameters (i.e. pH and Ca2+ concentration) on the ammonium adsorption onto zeolite, was systematically studied in this paper. Modeling results of Ca2+ and OH- release from slag indicated that pseudo-second-order reaction had a better fitness than pseudo-first-order reaction. Changing pH value from 7 to 12 resulted in a drastic reduction of the ammonium adsorption capacity on zeolite, from the peak adsorption capacity at pH 7. High Ca2+ concentration in solution also inhibited the adsorption of ammonium onto zeolite. There are two proposed mechanisms for steel slag inhibiting the ammonium adsorption capacity of zeolite. On the one hand, OH- released from steel slag can react with ammonium ions to produce the molecular form of ammonia (NH3·H2O), which would cause the dissociation of NH4+ from zeolite. On the other hand, Ca2+ could replace the NH4+ ions to adhere onto the surface of zeolite. An innovative substrate filling configuration with zeolite placed upstream of the steel slag was then proposed to eliminate the disadvantageous effects of steel slag. Experimental results showed that this novel filling configuration was superior to two other filling configurations in terms of ammonium removal.


[Serum urate and gout in 4663 young male workers (author's transl)].
Serum urate levels and history of gout were observed from 4663 men aged 20-44 who were employed by a Parisian government agency. Serum urate levels, mean value 62,8 mg/l (374 mu mol/l), did not vary with age but were strongly correlated with weight. For constant weight, urate levels decreased with age. By our definition: typical history of gout and either efficacity of colchicine during an attack or serum urate level over 70 mg/l (417 mu mol/l) at examination, there were 57 cases of gout, giving a prevalence of 1,1% among men 35-39 and 2,0% among men 40-44 years old. Using the definition by the New York criteria which do not include serum urate level, there were 51 cases of gout, giving a prevalence of 1,5% in the 35-44 year age group. This is about 3 times the prevalence found by O'Sullivan, using the same criteria, in an American town. the higher serum urate levels in the present study may account for much of this difference. The incidence of new cases of gout was estimated to be 1,6% over 5 years for men 40-44 years old. The site was the great toe in 57% of gouty men with only one attack and in 92% of those with more than one attack. It was not related to the amount of standing or activity at work. Comparison with a study made 7 years earlier showed an augmentation in serum urate values and probably in prevalence of gout. These results are discussed in terms of dietary modification over this time period.


Synthesis and characterization of chitosan-grafted-polycaprolactone micelles for modulate intestinal paclitaxel delivery.
In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis (1H NMR), and contact angle evaluation. Micelles were produced by solvent evaporation method, and the critical micelle concentration was investigated by conductimetry. The obtained micelles were of 408-nm mean particle size, narrow size distribution (polydispersity index of 0.335) and presented positive surface charge around 30 mV. The morphology of micelles assessed by transmission electron microscopy (TEM) revealed round and smooth surface, in agreement with dynamic light scattering measurements. The association efficiency determined by high-performance liquid chromatography (HPLC) was as high as 82%. The in vitro cytotoxicity of the unloaded and PTX-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cells, resulting in the absence of cell toxicity for all formulations. Moreover, the permeability of PTX-loaded micelles in Caco-2 monolayer and Caco-2/HT29-MTX co-culture model was determined. Results showed that the permeability of PTX was higher in Caco-2/HT29-MTX co-culture model compared with Caco-2 monolayer due to the mucoadhesive character of micelles, acting as a platform to deliver PTX at the sites of absorption. Therefore, it can be concluded that the PTX-loaded CS-g-PCL micelles, employed for the first time as PTX carriers, may be a potential drug carrier for the intestinal delivery of hydrophobic drugs, particularly anticancer agents.


Growth-inhibitory and cell cycle-arresting properties of the rice bran constituent tricin in human-derived breast cancer cells in vitro and in nude mice in vivo.
Tricin, a flavone found in rice bran, inhibits the growth of human-derived malignant MDA-MB-468 breast tumour cells at submicromolar concentrations. As part of the exploration of tricin as a potential cancer chemopreventive agent, we investigated the duration and cell cycle specificity of growth inhibition elicited by tricin in vitro and the effect of tricin on the development of MDA-MB-468 tumours grown in immune-compromised MF-1 mice in vivo. Preincubation of MDA-MB-468 cells with tricin (1-40 microM) for 72 h compromised cell growth after tricin removal, and such irreversibility was not observed in human breast-derived nonmalignant HBL-100 cells. Tricin (>/=5 microM) arrested MDA-MB-468 cells in the G2/M phase of the cell cycle without inducing apoptosis as adjudged by annexin V staining. In nude mice consumption of tricin with the diet (0.2%, w w(-1)) from 1 week prior to MDA-MB-468 cell implantation failed to impede tumour development. Steady-state levels of tricin in plasma, breast tumour tissue and intestinal mucosa, as measured by HPLC, were 0.13 microM and 0.11 and 63 nmol g(-1), respectively. Cells were exposed to tricin (0.11, 1.1 or 11 microM) in vitro for 72 h and then implanted into mice. The volume of tumours in animals bearing cells pre-exposed to 11 microM tricin was less than a third of that in mice with control cells, while tumours from cells incubated with 0.1 or 1.1 microM tricin were indistinguishable from controls. These results suggest that the potent breast tumour cell growth-inhibitory activity of tricin in vitro does not directly translate into activity in the nude mouse bearing the MDA MB-468 tumour. While the results do not support the notion that tricin is a promising candidate for breast cancer chemoprevention, its high levels in the gastrointestinal tract after dietary intake render exploration of its ability to prevent colorectal carcinogenesis propitious.


Variation in caries treatment proposals among dentists in Norway: the best interest of the child.
To explore variation in treatment-related-decisions for severe caries in children among dentists in the Public Dental Service (PDS) in Norway. It was also to evaluate the treatment choices in relation to the best interest of children and a child's rights to enjoy the highest standard of health care. A pre-coded questionnaire was sent electronically to all general dental practitioners (GDPs) working in the PDS in eight counties in Norway (n = 611). The questionnaire included two case scenarios to reflect common dental conditions related to severe caries among 5-year-old children. Paediatric dentists and paediatric students were invited to validate the different treatment options. Frequency distributions and statistical analyses were carried out using Chi square statistics. The response rate was 65% (n = 391) among the GDPs. A majority of the GDPs preferred a new appointment with behaviour management techniques (BMT) to a child presenting pulpitis and pain. Dentists educated outside the Nordic region would use restraint more often as a treatment alternative when the child was in pain than Nordic-educated dentists (p\0.05). Dentists with less than 10 years of experience preferred BMT and sedation more often when the child was in pain than their older colleagues, who, however, preferred a waiting approach and no immediate treatment if the child was not in pain(p\0.05) [corrected]. Use of BMT and sedation is related to region of education and years of experience. Awareness of ethical principles with the child´s best interest in mind, should receive increased attention.


Urbanicity, social adversity and psychosis.
In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts - indexed by area-level exposures such as population density, social fragmentation and deprivation - on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date.


The health fair as an effective health promotion strategy.
1. Effective health fairs must provide appropriate health education. 2. Screenings must have associated education and be performed by qualified screeners with properly calibrated equipment. 3. Environmental stress reduction and privacy are important factors to consider when planning a health fair or screening. 4. All fairs and screenings are important and should not be coordinated haphazardly.


Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth.
The chemokine receptor, CXCR4 signaling regulates cell growth, invasion, and metastasis to the bone-marrow niche in prostate cancer (PCa). Previously, we established that CXCR4 interacts with phosphatidylinositol 4-kinase IIIα (PI4KIIIα encoded by PI4KA) through its adaptor proteins and PI4KA overexpressed in the PCa metastasis. To further characterize how the CXCR4-PI4KIIIα axis promotes PCa metastasis, here we identify CXCR4 binds to PI4KIIIα adaptor proteins TTC7 and this interaction induce plasma membrane PI4P production in prostate cancer cells. Inhibiting PI4KIIIα or TTC7 reduces plasma membrane PI4P production, cellular invasion, and bone tumor growth. Using metastatic biopsy sequencing, we found PI4KA expression in tumors correlated with overall survival and contributes to immunosuppressive bone tumor microenvironment through preferentially enriching non-activated and immunosuppressive macrophage populations. Altogether we have characterized the chemokine signaling axis through CXCR4-PI4KIIIα interaction contributing to the growth of prostate cancer bone metastasis.


Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis.
The secreted polypeptide noggin (encoded by the Nog gene) binds and inactivates members of the transforming growth factor beta superfamily of signalling proteins (TGFbeta-FMs), such as BMP4 (ref. 1). By diffusing through extracellular matrices more efficiently than TGFbeta-FMs, noggin may have a principal role in creating morphogenic gradients. During mouse embryogenesis, Nog is expressed at multiple sites, including developing bones. Nog-/- mice die at birth from multiple defects that include bony fusion of the appendicular skeleton. We have identified five dominant human NOG mutations in unrelated families segregating proximal symphalangism (SYM1; OMIM 185800) and a de novo mutation in a patient with unaffected parents. We also found a dominant NOG mutation in a family segregating multiple synostoses syndrome (SYNS1; OMIM 186500); both SYM1 and SYNS1 have multiple joint fusion as their principal feature. All seven NOG mutations alter evolutionarily conserved amino acid residues. The findings reported here confirm that NOG is essential for joint formation and suggest that NOG requirements during skeletogenesis differ between species and between specific skeletal elements within species.


Management of pelvic giant cell tumours involving the acetabular bone.
The purpose of this study was to establish the optimal surgical treatment in patients with a Giant Cell Tumour (GCT) involving the acetabular bone. The surgical outcome in 10 patients with GCT involving the acetabular bone was reviewed. Patients were divided into two groups: group 1 in which 5 patients were primarily treated by curettage, and group 2, in which 5 patients were treated by resection and pelvic reconstruction. In group 1, local recurrence occurred in two cases. The functional outcome was excellent or good in 4, and poor in one case. There were no recurrences in group 2, in which the functional outcome was excellent or good in 4 and poor in one patient. The optimal surgical treatment modality should be based upon the tumour extension. Tumours located primarily in the ischiopubic region and not extending proximally beyond the supra-acetabular line can be adequately treated by extended curettage while those with further proximal extension are better treated by en-bloc resection. However, the possible complications of the different methods of pelvic reconstruction should always be considered.


Toxicity of white snakeroot (Ageratina altissima) and chemical extracts of white snakeroot in goats.
White snakeroot (Ageratina altissima) is a sporadically toxic plant that causes trembles in livestock and milk sickness in humans that drink tainted milk. The putative toxin in white snakeroot is tremetone and possibly other benzofuran ketones, even though it has not been demonstrated in vivo. Toxic white snakeroot was dosed to goats, and they developed clinical signs of poisoning, exercise intolerance, significant increases in serum enzyme activities, and histological changes. Tremetone and the other benzofuran ketones were extracted with hexane; the extracts and residues were analyzed for tremetone and dosed to goats at tremetone and benzofuran ketone concentrations similar to the original plant material. However, none of the dosed goats developed the disease. The results demonstrate for the first time that white snakeroot is a potent myotoxin in goats and that other compound(s), which may be lost or modified during the extraction process, could be involved in causing trembles and milk sickness.


Improved abnormal Pap smear triage using cervical cancer biomarkers.
The current system of Pap smear screening and management of abnormal cytology has resulted in a marked reduction in invasive cervical cancer. Many women, however, are not found to have significant precursor lesions. This is due to the poor specificity of high-risk human papillomavirus (HPV) triage. More specific cervical cancer biomarkers may be more effective triage tools than hr-HPV. We evaluated whether a dual stain for p16 and Ki-67 might improve the triage of abnormal Pap smears. p16/Ki-67 immunostaining was performed on additional slides prepared from 515 women with abnormal Pap smears (301 atypical squamous cells of undetermined significance [ASCUS], 169 low-grade squamous intraepithelial lesion [LSIL], 29 atypical squamous cells-cannot exclude high-grade lesion [ASC-H], 16 high-grade squamous intraepithelial lesion [HSIL]). High-risk HPV typing was performed on all cases. Immunostaining and hr-HPV were compared in relation to their diagnostic accuracy for the detection of biopsy-proven cervical intraepithelial neoplasia (CIN) 2/3. A cost analysis comparing hr-HPV versus immunostaining as the initial triage tool used for abnormal Pap smears was also performed. High-risk HPV was positive in 127 (42.2%) ASCUS, 129 (76.3%) LSIL, 20 (69.0%) ASC-H, and 15 (93.8%) HSIL. p16/Ki-67 was positive in 54 (17.9%) ASCUS, 73 (43.2%) LSIL, 19 (65.5%) ASC-H, and 15 (93.8%) HSIL. For detection of CIN 2/3, sensitivity/specificity of hr-HPV and p16/Ki-67 was 89.29%/14.94% and 96.43%/60.92%, respectively. Overall, diagnostic accuracy was statistically significantly higher for p16/Ki-67 compared with hr-HPV. Compared to HPV, immunostain triage could have generated approximately $46,000 savings in the study population. The triage of abnormal Pap smears by p16/Ki-67 immunostaining shows comparable sensitivity, improved specificity, and significantly improved diagnostic performance when compared to hr-HPV. Immunostaining is of value in triaging LSIL and ASC-H Pap smears in addition to ASCUS. The widespread utilization of biomarker triage could result in significant health care cost savings without compromising the detection of significant cervical cancer precursors.


A robust route to enzymatically functional, hierarchically self-assembled peptide frameworks.
The addition of enzyme biofunctionality to self-assembling peptide nanofibers is challenging since such additions can inhibit functionality or self-assembly. We introduce a method for peptide nanofiber enzyme functionalization, demonstrated by the attachment of a polymerization synthase to peptide nanofibers. The enzyme generates a biocompatible, biodegradable biopolyester coat on the fibers with applicablity in medical engineering. This approach provides a template for generation of functional bionanomaterials.


N-formyl peptide receptors internalize but do not recycle in the absence of arrestins.
Arrestins mediate phosphorylation-dependent desensitization, internalization, and initiation of signaling cascades for the majority of G protein-coupled receptors (GPCRs). Many GPCRs undergo agonist-mediated internalization through arrestin-dependent mechanisms, wherein arrestin serves as an adapter between the receptor and endocytic proteins. To understand the role of arrestins in N-formyl peptide receptor (FPR) trafficking, we stably expressed the FPR in a mouse embryonic fibroblast cell line (MEF) that lacked endogenous arrestin 2 and arrestin 3 (arrestin-deficient). We compared FPR internalization and recycling kinetics in these cells to congenic wild type MEF cell lines. Internalization of the FPR was not altered in the absence of arrestins. Since the FPR remains associated with arrestins following internalization, we investigated whether the rate of FPR recycling was altered in arrestin-deficient cells. While the FPR was able to recycle in the wild type cells, receptor recycling was largely absent in the arrestin double knockout cells. Reconstitution of the arrestin-deficient line with either arrestin 2 or arrestin 3 restored receptor recycling. Confocal fluorescence microscopy studies demonstrated that in arrestin-deficient cells the FPR may become trapped in the perinuclear recycling compartment. These observations indicate that, although the FPR can internalize in the absence of arrestins, recycling of internalized receptors to the cell surface is prevented. Our results suggest a novel role for arrestins in the post-endocytic trafficking of GPCRs.


Complete Genome Sequence of Sulfitobacter sp. Strain D7, a Virulent Bacterium Isolated from an Emiliania huxleyi Algal Bloom in the North Atlantic.
A Rhodobacterales bacterium, Sulfitobacter sp. strain D7, was isolated from an Emiliania huxleyi bloom in the North Atlantic and has been shown to act as a pathogen and induce cell death of E. huxleyi during lab coculturing. We report here its complete genome sequence comprising one chromosome and five low-copy-number plasmids.


Irinotecan and uridine diphosphate glucuronosyltransferase 1A1 pharmacogenetics: to test or not to test, that is the question.
Pharmacogenetic research indicates a relationship between a polymorphism in the gene encoding uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and irinotecan inactivation, in that degradation of SN-38, the active metabolite of irinotecan, correlates inversely with the number of TA repeats in the TATA element of the UGT1A1 promoter region. Individuals who are homozygous for the UGT1A1*28 allele (7 repeats) may exhibit reduced degradation of SN-38 and increased probability of severe toxicities. Clinical study results, as reported in the literature, have not been uniform, however, in showing a relation between genotype and the development of toxicities. Even when correlations are statistically significant, confidence intervals are wide, rendering assessment of individual risk difficult at best. Irinotecan labeling recommends testing for the UGT1A1*28 allele and reducing irinotecan dosing in patients who are positive to reduce the likelihood of dose-limiting neutropenia only, but not diarrhea. Importantly, both dose-limiting neutropenia and diarrhea are dependent on numerous known and unknown factors, such as the specific regimen used, duration of therapy, doses, cycle of treatment, and complexities of irinotecan pharmacodynamics and pharmacokinetics, including other key enzymes and drug transporters. Guidance on how to modify irinotecan dosing or how to incorporate the impact of multiple variables into clinical decision-making does not exist. Furthermore, pharmacogenomic test results at this time can only provide an estimate of risk for subsets of populations rather than a risk-benefit estimate for an individual. Consequently, these test results are supplementary to clinical judgment, which requires assessing multiple variables that contribute to phenotype to arrive at individual dosing decisions.


Recovery of memory from infantile amnesia is developmentally constrained.
Episodic memories formed during infancy are rapidly forgotten, a phenomenon associated with infantile amnesia, the inability of adults to recall early-life memories. In both rats and mice, infantile memories, although not expressed, are actually stored long term in a latent form. These latent memories can be reinstated later in life by certain behavioral reminders or by artificial reactivations of neuronal ensembles activated at training. Whether the recovery of infantile memories is limited by developmental age, maternal presence, or contingency of stimuli presentation remains to be determined. Here, we show that the return of inhibitory avoidance memory in rats following a behavioral reactivation consisting of an exposure to the context (conditioned stimuli [CS]) and footshock (unconditioned stimuli [US]) given in a temporally unpaired fashion, is evident immediately after US and is limited by the developmental age at which the reactivations are presented; however, it is not influenced by maternal presence or the time interval between training and reactivation. We conclude that one limiting factor for infantile memory reinstatement is developmental age, suggesting that a brain maturation process is necessary to allow the recovery of a "lost" infantile memory.


[Subcellular distribution of the phosphate-activated glutaminase activity in the visual analyzer of the brain during postnatal ontogenesis in dogs].
The level of general activity of phosphate-activated glutaminase (PAG) on the 1st postnatal day was higher in heavy and light synaptosomes of the exterior geniculate body (EGB) and lower--in the superior colliculus (SC) and visual cortex (field 17); in the subfractions of synaptic mitochondria (E) the general activity of the enzyme was higher in EGB and lower in the visual cortex (field 17) and SC. The level of general activity of the enzyme in the subcellular formations and certain formations of the visual analyzer on the 1st postnatal day was different. This difference varied in the course of postnatal development of the visual system in dogs. The PAG general activity in the subfractions of light (C), heavy (D) synaptosomes, synaptic mitochondria of the membranous enzymes and small synaptosomes sharply enhanced in the visual cortex (field 17) of SC and EGB from the 1st to the 12-14th postnatal days, the subfractions C and D of the visual cortex (field 17) showing the highest degree of the enzyme activity up to the 45th day. SC and EGB subfractions showed a considerable decrease in the enzyme activity of dogs aged 3 months; this peculiarity persisted up to the 6-month age in the above formations, especially in the subfractions B, C, D and E. Dogs aged 1 year exhibited a sharper decrease in the general activity of the enzyme of formations C, D, E in EGB and SC. It was established that with an advance of age the general activity of the enzyme in myelin subfractions (A) mostly increased, especially in the visual cortex (field 17) and EGB of dogs aged 1 year and in SC of dogs aged 6 months.


In vitro cytotoxic evaluation of some synthesized COX-2 inhibitor derivatives against a panel of human cancer cell lines.
Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) developed as a selective inhibitor of cyclooxygenase-2 (COX-2) for the treatment of rheumatoid arthritis disease. Recently some other mechanisms have been identified for anti cancer activity of these agents including induction of apoptosis, inhibition of tumor vascularization, stimulation of antitumor immune responses and inhibition of cellular protein synthesis. The cytotoxic effects of four synthesisized analogues of celecoxib (coded as D, E, F and G) were evaluated against Hela, MDA-MB-231, A-2780-s and HT-29 cancer cells, using MTT assay; Also their induction of apoptosis using DNA fragmentation analysis were studied. MTT assay showed that cell survival percent of COX-2 positive cell lines (HT-29, MDA-MB-231 and Hela; p≤0.05) were decreased significantly after exposure to the tested COX-2 inhibitors while little effect was observed on the COX-2 negative cell line (A-2780-s). Results also showed that A-2780-s and Hela were the most resistant and the most sensitive cell lines to these compounds, respectively. Moreover, in DNA fragmentation assay, induction of apoptosis was confirmed by electrophoretic pattern of separated DNA fragments in Hela cell line. Compounds E and G in comparison with D and F exerted more cytotoxic effect on COX-2 positive cell lines (Hela, HT-29 and MDA-MB-231). This could be due to the hydrophobic substituent (Cl, CH3) located at the para position of phenyl ring leading to more lipophilicity and cell uptake. In addition, these COX-2 inhibitors induced apoptosis on Hela cell-line, which could be considered as one of the cytotoxic mechanisms of these compounds as potential anti cancer agents.


Can we improve the nutritional quality of meat?
The nutritional value of meat is an increasingly important factor influencing consumer preferences for poultry, red meat and processed meat products. Intramuscular fat content and composition, in addition to high quality protein, trace minerals and vitamins are important determinants of nutritional value. Fat content of meat at retail has decreased substantially over the past 40 years through advances in animal genetics, nutrition and management and changes in processing techniques. Evidence of the association between diet and the incidence of human non-communicable diseases has driven an interest in developing production systems for lowering total SFA and trans fatty acid (TFA) content and enrichment of n-3 PUFA concentrations in meat and meat products. Typically, poultry and pork has a lower fat content, containing higher PUFA and lower TFA concentrations than lamb or beef. Animal genetics, nutrition and maturity, coupled with their rumen microbiome, are the main factors influencing tissue lipid content and relative proportions of SFA, MUFA and PUFA. Altering the fatty acid (FA) profile of lamb and beef is determined to a large extent by extensive plant and microbial lipolysis and subsequent microbial biohydrogenation of dietary lipid in the rumen, and one of the major reasons explaining the differences in lipid composition of meat from monogastrics and ruminants. Nutritional strategies can be used to align the fat content and FA composition of poultry, pork, lamb and beef with Public Health Guidelines for lowering the social and economic burden of chronic disease.


Biomechanical analysis of structural deformation in living cells.
Most tissues are subject to some form of physiological mechanical loading which results in deformation of the cells triggering intracellular mechanotransduction pathways. This response to loading is generally essential for the health of the tissue, although more pronounced deformation may result in cell and tissue damage. In order to determine the biological response of cells to loading it is necessary to understand how cells and intracellular structures deform. This paper reviews the various loading systems that have been adopted for studying cell deformation both in situ within tissue explants and in isolated cell culture systems. In particular it describes loading systems which facilitate visualisation and subsequent quantification of cell deformation. The review also describes the associated microscopy and image analysis techniques. The review focuses on deformation of chondrocytes with additional information on a variety of other cell types including neurons, red blood cells, epithelial cells and skin and muscle cells.


The Impact of Initial Misdiagnosis of Ruptured Abdominal Aortic Aneurysms on Lead Times, Complication Rate, and Survival.
To investigate the frequency of initial misdiagnosis and the clinical consequences of an initial misdiagnosis of ruptured abdominal aortic aneurysms (rAAA). This was a retrospective cohort study. Data from the Swedish National Registry for Vascular Surgery (Swedvasc) and medical charts were extracted for patients treated for rAAA in the West of Sweden in the period 2008-14. Initially misdiagnosed patients were compared with correctly diagnosed patients. In all, 261 patients were included in the study. Patients with rAAA were initially misdiagnosed in 33% (n = 86) of the cases and this caused a 4.8 hour (median time) additional delay to surgical intervention. There were no differences in 30 day mortality between initially misdiagnosed patients and correctly diagnosed patients (27.9% vs. 28.0%; p = 1.00). The adjusted odds ratio for mortality in initially misdiagnosed patients compared with correctly diagnosed patients was 0.78 (95% confidence interval 0.38-1.60). No difference was observed between the groups regarding 90 day mortality, length of intensive care, need for post-operative ventilator support, need of haemodialysis support, and length of hospital stay. Misdiagnosis is common in patients with rAAA, and treatment is significantly delayed in misdiagnosed patients. The study did not show any survival disadvantage or increased frequency of post-operative complications in misdiagnosed patients despite the delayed treatment. However, only patients who reached surgical intervention were included in the analysis.


Current and Future Directions for Targeting Lipoxin A4 in Alzheimer's Disease.
Neuroinflammation has been implicated in Alzheimer's disease onset and progression. Chronic neuroinflammation is initiated by amyloid-β-activated microglial cells that secrete immuno-modulatory molecules within the brain and into the vasculature. Inflammation is normally self-limiting and actively resolves by "switching off" the generation of pro-inflammatory mediators and by non-phlogistic clearance of spent cells and their debris to restore tissue homeostasis. Deficits in these anti-inflammatory/pro-resolution pathways may predispose to the development of chronic inflammation. The synthesis of endogenous lipid mediators from arachidonic acid, lipoxins via cyclooxygenase 2 and lipoxygenases, and conversion of exogenous polyunsaturated fatty acids, namely docosahexaenoic acid and eicosapentaenoic acid, to resolvins contributes to effective, timely resolution of acute inflammation. Work by Xiuzhe et al., 2020 in the Journal of Alzheimer's Disease reported that plasma level of LXA4 is related to cognitive status in ischemic stroke patients suggesting that decreased LXA4 may be a potential risk factor for post post-stroke cognitive impairment. As evident by recent clinical trials and development of drug analogues, there is recent drive to search for lipoxin analogues as therapeutics for inflammatory diseases. Understanding how bioactive lipid signaling is involved in resolution will increase our understanding of controlling inflammation and may facilitate the discovery of new classes of therapeutic pro-resolution agents for evaluation in AD prevention studies.


[Nitric oxide in the physiopathology of myocardial dysfunction in heart failure].
Nitric oxide (NO) modulates several parameters of myocardial function at the autocrine and paracrine level. Various studies have demonstrated that endogenously NO, regulates myocardial contractility, distensibility, heart rate, coronary vasodilation, myocardial oxygen consumption, mitochondrial respiration and apoptosis. In pathological situations, particularly heart failure (HF), NO synthesis and activity are altered and its effects are controversial. Thus, NO can have beneficial or deleterious actions, depending on: (i) the cellular and enzymatic source, (ii) the amount produced and/or released, (iii) the presence of reactive oxygen species, (iv) interactions with neurohumoral and other stimuli, (v) the tanget issue and (vi) the activation of different cyclic GMP (cGMP)-dependent and independent subcellular signal transduction pathways. In this paper we review the main physiological actions of NO in normal myocardial function and its role in the pathophysiology of HF, as well as the cellular and molecular mechanisms underlying these effects. We also include a brief mention of therapeutic approaches are which directly or indirectly related with the bioavailability of this mediator.


Measles-virus-persistent infection in BGM cells. Modification of the incorporation of [3H]arachidonic acid and [14C]stearic acid into lipids.
In BGM cells chronically infected with measles virus, although the composition of the phospholipids is unaltered, the fatty acid composition is modified. Uninfected, lytic and persistently infected cells were labelled with [3H]arachidonic acid and [14C]stearic acid and their metabolic fate analysed. No difference in the total incorporation was observed in the different systems. However, the [14C]stearic acid and [3H]arachidonic acid were incorporated up to 2-fold and 13-fold respectively greater into the neutral lipid of persistently infected compared with that of uninfected cells. Both radioactive fatty acids were specifically accumulated in the triacylglycerol and non-esterified fatty acids fractions. Lytically infected cells were similar to uninfected cells. Although there was no significant difference in the incorporation of radioactivity into the total phospholipid in either system, there was a large decrease in [3H]arachidonic acid incorporated into phosphatidylethanolamine and to a lesser extent phosphatidylcholine and phosphatidylinositol in persistently infected cells. [14C]Stearic acid incorporation was also reduced in phosphatidylcholine and phosphatidylethanolamine fractions of persistently infected cells.


Accurate reading of morphogen concentrations by nuclear receptors: a formal model of complex transduction pathways.
Signal transduction in development follows multiple, interactive, and overlapping pathways. How does this contribute to accuracy and stability? I show that a formal model of retinoic acid receptors, based on the details of their molecular biology, demonstrates striking precision and robustness while converting a graded morphogen distribution into gene transcription patterns. Thus, transcription can be reliably established in a single row of cells, despite the absence, in the model, of intercellular signalling mechanisms. The subtle interplay of two nuclear receptor types is fundamental for this achievement: one of them ubiquitous, the other controlled itself by morphogen, they act as homodimers or heterodimers, ensuring that many errors cancel out by affecting both activation and repression pathways; regulatory molecular "reservoirs" are also formed. In spite of this robustness, some shifts in gene regulation may well have interesting evolutionary consequences. These conclusions regarding precision in transduction will remain of interest whether retinoic acid turns out to be a morphogen or not, and generalize easily to other experimental situations.


Organic long persistent luminescence.
Long persistent luminescence (LPL) materials-widely commercialized as 'glow-in-the-dark' paints-store excitation energy in excited states that slowly release this energy as light. At present, most LPL materials are based on an inorganic system of strontium aluminium oxide (SrAl2O4) doped with europium and dysprosium, and exhibit emission for more than ten hours. However, this system requires rare elements and temperatures higher than 1,000 degrees Celsius during fabrication, and light scattering by SrAl2O4 powders limits the transparency of LPL paints. Here we show that an organic LPL (OLPL) system of two simple organic molecules that is free from rare elements and easy to fabricate can generate emission that lasts for more than one hour at room temperature. Previous organic systems, which were based on two-photon ionization, required high excitation intensities and low temperatures. By contrast, our OLPL system-which is based on emission from excited complexes (exciplexes) upon the recombination of long-lived charge-separated states-can be excited by a standard white LED light source and generate long emission even at temperatures above 100 degrees Celsius. This OLPL system is transparent, soluble, and potentially flexible and colour-tunable, opening new applications for LPL in large-area and flexible paints, biomarkers, fabrics, and windows. Moreover, the study of long-lived charge separation in this system should advance understanding of a wide variety of organic semiconductor devices.


Acute and chronic toxicity of Nigella sativa fixed oil.
We investigated the toxicity of the fixed oil of Nigella sativa L seeds in mice and rats through determination of LD50 values and examination of possible biochemical, hematological and histopathological changes. The acute toxicity of Nigella sativa fixed oil was investigated in mice. LD50 values, obtained by single doses, orally and intraperitoneally administered in mice, were 28.8 ml/kg body wt. p.o. [26.2-31.6] and 2.06 ml/kg body wt. i.p. [1.86-2.26], respectively. Chronic toxicity was studied in rats treated daily with an oral dose of 2 ml/kg body wt. for 12 weeks. Changes in key hepatic enzymes levels, including aspartate-aminotransferase, alanine-aminotranferase, and gamma-glutamyltransferase and histopathological modifications (heart, liver, kidneys and pancreas) were not observed in rats treated with Nigella sativa after 12 weeks of treatment. The serum cholesterol, triglyceride and glucose levels and the count of leukocytes and platelets decreased significantly, compared to control values, while hematocrit and hemoglobin levels increased significantly. A slowing of body weight gain was also observed in Nigella sativa treated rats, as compared to control animals. The low toxicity of Nigella sativa fixed oil, evidenced by high LD50 values, key hepatic enzyme stability and organ integrity, suggests a wide margin of safety for therapeutic doses of Nigella sativa fixed oil, but the changes in hemoglobin metabolism and the fall in leukocyte and platelet count must be taken into consideration.


Functionalized defects through solvent-assisted linker exchange: synthesis, characterization, and partial postsynthesis elaboration of a metal-organic framework containing free carboxylic acid moieties.
Intentional incorporation of defect sites functionalized with free carboxylic acid groups was achieved in a paddlewheel-based metal-organic framework (MOF) of rht topology, NU-125. Solvent-assisted linker exchange (SALE) performed on a mixed-linker derivative of NU-125 containing isophthalate (IPA) linkers (NU-125-IPA) led to the selective replacement of the IPA linkers in the framework with a conjugate base of trimesic acid (H3BTC). Only two of the three carboxylic acid moieties offered by H3BTC coordinate to the Cu2 centers in the MOF, yielding a rare example of a MOF decorated with free -COOH groups. The presence of the -COOH groups was confirmed by diffuse reflectance infrared Fourier-transformed spectroscopy (DRIFTS); moreover, these groups were found to be available for postsynthesis elaboration (selective monoester formation). This work constitutes an example of the use of SALE to obtain otherwise challenging-to-synthesize MOFs. The resulting MOF, in turn, can serve as a platform for accomplishing selective organic transformations, in this case, exclusive monoesterification of trimesic acid.


Initial experiences of family caregivers of survivors of a traumatic brain injury.
There seems to be a paucity of research on the initial subjective experiences of family caregivers of survivors of a traumatic brain injury (TBI). To explore the challenges that family caregivers face during the initial stages of recovery of a relative who has sustained a TBI. Thematic analysis was used to explore the findings from semi-structured interviews that were conducted with 12 female family caregivers of relatives who had sustained a TBI. Family caregivers recalled their initial experiences of the shock at hearing the news about their relative's TBI, negative experiences in hospital and frustrating interactions with healthcare professionals as particularly challenging. The findings of this study emphasise caregivers' need for support, information and psycho-education, especially from healthcare professionals, from the very beginning stages of recovery from a TBI. Practical and physical needs with regard to admission to and care in the hospital were also highlighted. This research will hopefully contribute to creating awareness amongst healthcare professionals on how they can contribute to improvement of the services provided by the healthcare system based on the experiences of the caregivers who participated in this study.


Speciation and fate of toxic cadmium in contaminated paddy soils and rice using XANES/EXAFS spectroscopy.
The present study was conducted to determine the Cd distribution and speciation in contaminated paddy soils and rice kernels using XANES/EXAFS spectroscopy. The morphology and crystallization of rice and soils were investigated using FE-SEM and XRD techniques. The EXAFS spectra of Cd in soil and rice kernels showed that cadmium oxides (CdO) in soil and rice kernels formed Cd clusters with Cd-O bond distances of 2.35 Å and 2.83 Å (coordination numbers of 2.3 and 4.2), respectively. The XRD patterns show that silica oxide (SiO2, 2θ = 24.2) and aluminum oxide (Al2O3, 2θ = 35.7) were the main components detected. The FE-SEM analysis revealed that the surface characteristics and sizes of the rice kernels are smooth and uneven with particle sizes of 0.5-4 μm, while the soil particles are not uniform and aggregated. Furthermore, the distribution of toxic metals/metalloid (Cd, Pb, Cr, Ni, As, Cu, and Zn) accumulated in the contaminated paddy soils and rice crops were also examined. Interestingly, these results offered an insight into the accumulation mechanism and distribution of heavy metals in contaminated rice farming soils and rice crops.


Porosity and mechanical properties relationship in PCL porous scaffolds.
Scaffold design plays a pivotal role in tissue engineering and regenerative medicine approaches for creating biological alternatives for implants. The crucial aspect in scaffold design consists of the development of highly porous scaffolds, with strict control of porosity features (porosity degree and pore sizes), continuing to provide an adequate mechanical response, mainly in compressive loading, both in vitro and in vivo conditions. A study was undertaken of three-dimensional (3D) porous scaffolds obtained from poly epsilon-caprolactone solution through the phase inversion/salt leaching technique. In particular, the influence of structural porosity features on mechanical response was investigated to establish the correlation between structural parameters and compressive response. Scaffold porosity features can be controlled by changing the amount and size of the porogen agent used. Mechanical response in compression is consistent with porosity features: elastic modulus calculated in the toe region range (0-0.1 of total strain) shows an increase from 0.24-1.85 MPa coherently, with a reduction in pore volume fraction from 84.9 to 45.7%. Such behavior can be predicted by using analytical models for the determination of the elastic modulus of cellular solids based on the morphological assumption of cubic cell structure (cubic open cell (COC) and cubic closed cells (CCC)). Compressive behavior prediction offered by the proposed models is in agreement with the experimental results in the case of higher pore volume fractions according to the theoretical results of other investigators.


Ultrasensitive detection of drug-resistant pandemic 2009 (H1N1) influenza A virus by rare-variant-sensitive high-resolution melting-curve analysis.
Oseltamivir (Tamiflu), an oral neuraminidase inhibitor, has been widely used to treat pandemic 2009 (H1N1) influenza A. Although a majority of 2009 (H1N1) influenza A virus remains oseltamivir susceptible, the threat of resistance due to the His275Tyr mutation is highlighted by the limitations of alternative therapies and the potential for rapid, global fixation of this mutation in the circulating influenza A virus population. In order to better understand the emergence of resistance, we developed a rare-variant-sensitive high-resolution melting-curve analysis method (RVS-HRM) that is able to detect the His275Tyr oseltamivir resistance mutation to 0.5% in a background of susceptible virus. We applied RVS-HRM to clinical specimens from patients who developed oseltamivir resistance and demonstrated the ultrasensitive detection of influenza A virus N1 neuraminidase quasispecies. Interestingly, we were unable to detect the oseltamivir resistance mutation in pretreatment samples, suggesting that resistant virus does not reach even this very low detection threshold until exposed to selective drug pressure. Thus, patients naive to oseltamivir are most likely to be susceptible when this drug is used as a first-line treatment modality.


Three frames of reference in work-related occupational therapy programs.
This paper discusses the relationship of a theoretical frame of reference to the implementation of a work-oriented program. Three frames of reference in occupational therapy are reviewed, and work-related theories and approaches available to therapists are categorized under each. Examples of the application of various frames of reference are given through an analysis of work programs described in the occupational therapy literature. We recommend that therapists select and apply frames of reference systematically when developing work programs to facilitate the development of a body of knowledge in this area.


Technical note: Effects of rumen passage on fluoxetine bioavailability in serum and effects of fluoxetine on serum prolactin concentration and demeanor in ewes.
Sheep are becoming increasingly important in medical research. The objective of the present study was to identify changes in bioactivity of fluoxetine during ruminal passage in ewes, and to examine the effects of fluoxetine administration on demeanor and serum prolactin concentration. Twelve mature ewes were administered saline (control), daily oral fluoxetine (40 mg), or alternate-day oral fluoxetine for 10 d. Four additional ewes were fitted with rumen cannulas and administered daily fluoxetine by abomasal deposition. Serum samples were collected daily for 15 d. Serum fluoxetine concentrations (ELISA) were greater (P < 0.001) in ewes in all fluoxetine treatments compared with controls on d 2. Serum fluoxetine concentrations in ewes receiving daily abomasal dosages were greater (P < 0.007) than those in controls on d 2 to 12 and were greater than those in ewes receiving daily or alternate-day oral fluoxetine on d 3 to 12. Serum prolactin concentration (RIA) did not differ (P = 0.137) among treatments and was only weakly correlated with serum fluoxetine concentration (r = 0.20, P = 0.041), and regression analysis revealed that very little variation in serum prolactin concentration was due to serum fluoxetine concentration (R(2) = 0.04, P = 0.082). Demeanor ratings on d 1 to 12 remained at normal in all treatment groups (P > 0.362). However, in ewes that had received an abomasal dosage of fluoxetine, demeanor scores decreased (P < 0.029) on d 13 and 14 before returning to normal on d 15 (P = 0.397). This study indicates that mature ewes may provide a suitable model for the study of fluoxetine, but that a larger oral dosage may be required relative to the human dosage to overcome partial loss of bioactivity during ruminal passage.


Acute NMDA toxicity in cultured rat cerebellar granule neurons is accompanied by autophagy induction and late onset autophagic cell death phenotype.
Autophagy, an intracellular response to stress, is characterized by double membrane cytosolic vesicles called autophagosomes. Prolonged autophagy is known to result in autophagic (Type II) cell death. This study examined the potential role of an autophagic response in cultured cerebellar granule neurons challenged with excitotoxin N-methyl-D-aspartate (NMDA). NMDA exposure induced light chain-3 (LC-3)-immunopositive and monodansylcadaverine (MDC) fluorescent dye-labeled autophagosome formation in both cell bodies and neurites as early as 3 hours post-treatment. Elevated levels of Beclin-1 and the autophagosome-targeting LC3-II were also observed following NMDA exposure. Prolonged exposure of the cultures to NMDA (8-24 h) generated MDC-, LC3-positive autophagosomal bodies, concomitant with the neurodegenerative phase of NMDA challenge. Lysosomal inhibition studies also suggest that NMDA-treatment diverted the autophagosome-associated LC3-II from the normal lysosomal degradation pathway. Autophagy inhibitor 3-methyladenine significantly reduced NMDA-induced LC3-II/LC3-I ratio increase, accumulation of autophagosomes, and suppressed NMDA-mediated neuronal death. ATG7 siRNA studies also showed neuroprotective effects following NMDA treatment. Collectively, this study shows that autophagy machinery is robustly induced in cultured neurons subjected to prolonged exposure to excitotoxin, while autophagosome clearance by lysosomal pathway might be impaired. Our data further show that prolonged autophagy contributes to cell death in NMDA-mediated excitotoxicity.


Impact of the economic crisis on the health of older persons in Spain: research clues based on an analysis of mortality. SESPAS report 2014.
Older adults are seldom considered in studies on the health impact of economic recessions or crises. However, they constitute a population group that is highly vulnerable to decreases in investment in health and social services and social security. Our aim is to examine the relationship between the economic crisis starting in 2008 and the health status of older adults in Spain. More specifically, we analyze changes in trends of mortality in relation to the crisis, the specific impact of winter on mortality and gender differences in the crisis' impact on mortality. Using data from the National Institute of Statistics of Spain on people over 60 years of age, the number of monthly deaths by age and sex from January 2005 to December 2012 was analyzed. Interrupted time series analyses and the "difference in differences" method were used. During the crisis, for adults 60 years and older: 1) the observed mortality seems to be decreasing at a slower rate than what would have been expected in the absence of the crisis; 2) there has been an increase in winter mortality; 3) the impact of the crisis has been greater for female than for male mortality. These results suggest sizable effects of the economic crisis on the mortality of older adults and argue for research done using more detailed analyses integrating economic indicators.


The Pelvic and Sacral Splanchnic Nerves - Identification by Dissection, Trajectory.
The modern principles in pelvic surgery imply the preservation of the nervous structures that are involved in the physiological functioning of the pelvic and genital organs. The main pelvic nervous element is represented by the inferior hypogastric plexus. This plexus receives sympathetic afferent fibres from the hypogastric nerve, parasympathetic afferent fibres from the pelvic splanchnic nerves and also sympathetic afferent fibres coming from the sympathetic sacral chain via the sacral splanchnic nerves. We aimed to demonstrate the anatomy of these structures through dissection and we exposed the origins, pathway and manner of distribution of the splanchnic nerves of the pelvis. We managed to clarify the main anatomical relations of these nerves, among which we highlighted the relation to the branches of the internal iliac artery. The parasympathetic fibres reach the pelvis by running through the anterior rami of the spinal nerves, which are the origin of the sacral plexus. We managed to exhibit the way in which the parasympathetic fibres emerge from the sacral nerves and form the pelvic splanchnic nerves. Pelvic surgery nowadays is focused on nerve-sparing, which essentially means the conservation of the integrity of splanchnic nerves, hypogastric nerves and inferior hypogastric plexuses in order to maintain the normal functioning of the anatomical sphincters and genital organs. In this respect, it is crucial for the surgeon who performs pelvic procedures to be more than well-acquainted to the anatomy of the pelvic splanchnic nerves, which are considered to be the erectile nerves, and to that of the sacral splanchnic nerves.


Are Grasses Really Useful for the Phytoremediation of Potentially Toxic Trace Elements? A Review.
The pollution of soil, water, and air by potentially toxic trace elements poses risks to environmental and human health. For this reason, many chemical, physical, and biological processes of remediation have been developed to reduce the (available) trace element concentrations in the environment. Among those technologies, phytoremediation is an environmentally friendly in situ and cost-effective approach to remediate sites with low-to-moderate pollution with trace elements. However, not all species have the potential to be used for phytoremediation of trace element-polluted sites due to their morpho-physiological characteristics and low tolerance to toxicity induced by the trace elements. Grasses are prospective candidates due to their high biomass yields, fast growth, adaptations to infertile soils, and successive shoot regrowth after harvest. A large number of studies evaluating the processes related to the uptake, transport, accumulation, and toxicity of trace elements in grasses assessed for phytoremediation have been conducted. The aim of this review is (i) to synthesize the available information on the mechanisms involved in uptake, transport, accumulation, toxicity, and tolerance to trace elements in grasses; (ii) to identify suitable grasses for trace element phytoextraction, phytostabilization, and phytofiltration; (iii) to describe the main strategies used to improve trace element phytoremediation efficiency by grasses; and (iv) to point out the advantages, disadvantages, and perspectives for the use of grasses for phytoremediation of trace element-polluted soils.


[Radiation exposure of patients from diagnostic and interventional X-ray procedures. Facts, assessment and trends].
Man-made radiation exposure to the German population predominantly results from the medical use of ionizing radiation. According to the most recent evaluation, the mean effective dose per inhabitant and year from X-ray procedures increased from 1.6 to 1.8 mSv between 1996 and 2001. This rise is mainly caused by the expanding use of CT and reflects the growing importance of this imaging modality. Besides actual data on the frequency and dose of various types of X-ray examinations, patient-specific factors will be highlighted which have to be considered in the assessment of the associated individual and collective radiation risk. Moreover, different concepts to reduce radiation exposure of patients will be discussed as well as some current trends in health service that may affect radiation hygiene -- such as diagnosis-related groups for inpatients and CT screening.


Human genital tissues containing DNA of adeno-associated virus lack DNA sequences of the helper viruses adenovirus, herpes simplex virus or cytomegalovirus but frequently contain human papillomavirus DNA.
The detection of DNA of the helper virus-dependent adeno-associated virus type 2 (AAV-2) in biopsies of material from spontaneous abortion and in tissue samples from the uterus raises the question of whether sequences of known helper viruses can be detected simultaneously within the same specimen despite the lack of histological evidence for the presence of lytic viruses. Therefore, we performed PCR analyses with primers detecting DNA sequences of viruses (adenovirus, herpes simplex virus and human cytomegalovirus) known for their helper activity in the replication of adeno-associated viruses. In addition, PCR was performed to detect DNA of human papillomaviruses (HPV), which were recently shown to be able to help AAV replication in vitro. In no cases were sequences of the known helper viruses found. However, HPV DNA was detected in approximately 60% of paraffin sections from uterus biopsies and cervical lesions containing AAV DNA and in approximately 70% of material from early miscarriage. This finding suggests that HPV may be a helper virus for AAV.


Clinical features of Graves' ophthalmopathy in an incidence cohort.
To determine the clinical characteristics of an incidence cohort of patients with Graves' ophthalmopathy. We reviewed the community medical records of 120 patients residing in Olmsted County, Minnesota, in whom Graves' ophthalmopathy was diagnosed between 1976 and 1990. Among 120 patients with Graves' ophthalmopathy, 108 (90%) patients had Graves' hyperthyroidism, one (1%) had primary hypothyroidism, four (3%) had Hashimoto's thyroiditis, and seven (6%) were euthyroid. At some point in their clinical course, eyelid retraction was present in 108 patients, whereas the approximate frequency of exophthalmos was 62% (73 patients); restrictive extraocular myopathy, 43% (51 patients); and optic nerve dysfunction, 6% (seven patients). Only six (5%) patients had eyelid retraction, exophthalmos, optic nerve dysfunction, extraocular muscle involvement, and hyperthyroidism. At the time of diagnosis of ophthalmopathy, upper eyelid retraction and eyelid lag were documented in 85 and 52 patients, respectively, and the most frequent ocular symptom was pain (36 patients, 30%). Diplopia was noted at the initial examination by 20 patients, lacrimation was present in 25 patients, 19 patients had photophobia, and nine patients had blurred vision. Decreased vision from optic neuropathy was present in less than 2% of eyes at the time of diagnosis. Thyroid dermopathy and acropachy accompanied Graves' ophthalmopathy in five patients (4%) and one (1%) patient, respectively. Myasthenia gravis occurred in only one patient. Eyelid retraction is the most common clinical sign of Graves' ophthalmopathy. The complete constellation of typical features (hyperthyroidism, eyelid retraction, exophthalmos, restrictive extraocular myopathy, and optic nerve dysfunction) occurs relatively infrequently.


Efficacy of topical 10% urea-based lotion in patients with ichthyosis vulgaris: a two-center, randomized, controlled, single-blind, right-vs.-left study in comparison with standard glycerol-based emollient cream.
Ichthyoses are genetic disorders of keratinization which are uncomfortable due to their conspicuous scaling, itching and cosmetic problems. Ichthyoses can lead to social discrimination and psychological problems. Ichthyosis vulgaris (IV) is the most common form of these geno-dermatoses. IV is a chronic disorder that often requires continuous therapy. Emollient and keratolytic products are the mainstay treatments of IV. It is important that efficient, safe and well tolerated therapies should be available. Direct comparative data regarding efficacy of different emollient products in IV patients are very few. The aim of the study was to investigate the keratolytic and moisturizing properties as well as the tolerance of a new urea topical formulation (Ureadin Rx10) when applied to hyperkeratotic and dry skin in patients with (IV) in comparison with a standard emollient cream. The study was conducted as a two-center, randomized, controlled, single-blind, intra-patient (right-vs.-left) trial design. A total of 30 patients with IV between 8 and 65 (mean age: 25 years) treated with a 10% urea-based lotion, Ureadin Rx 10 * *Ureadin RX 10 is a registered trade name of ISDIN, Spain. (URx), for 4 weeks or a glycerol-based emollient cream, Dexeryl † †Dexeryl is a registered trade name of Pierre Fabre Dermatologie. (DC), in a right-vs.-left study design. Primary outcome was a 5-point SRRC Index score (evaluating scaling roughness, redness and cracks) evaluated at baseline and after 2 and 4 weeks of treatment. As secondary endpoints patients evaluated also the global efficacy (GE) and global tolerability (GT) scores with the help of a 10 cm visual analogue scale (0 = no efficacy at all/very bad tolerability; 10: excellent efficacy/excellent tolerability). At baseline the mean (SD) SRRC score was 9.5 (1.9) in the URx treated sites and 9.5 (1.9) in the DC treated sites. A total of 27 patients (90%) concluded the study period. Three patients were withdrawn prematurely because of itching and burning sensation after DC application (1 patient) or URx application (2 patients). At week 4, in comparison with baseline values, both treatments were shown to be clinically effective: SRRC significantly (p = 0.0001) decreased to 3.3 (1.8) after URx (a 65% relative reduction) and to 5.7 (2.5) after DC (a 40% relative reduction). SRRC was significantly lower in URx treated regions in comparison with DC both after 2 and 4 weeks of treatment (p = 0.0005). Mean GE score in areas treated with URx was significantly (p = 0.0001) higher than in the areas treated with the DC (8.9 vs.7.3). Both treatments were in general well tolerated. GT score was 8.1 (range 10 to 3) with URx and 8.4 (range 10 to 3) with DC application (p = ns). The two main limitations of this trial are the study design (single blind), and the small sample size which is not adequate for an evaluation of safety. Ureadin Rx 10 lotion has shown a greater efficacy on ichthyosis vulgaris in term of reduction of scaling, roughness, redness and cracking in comparison with a glycerol-based emollient cream. Tolerability of the two topical treatments was comparable. Further studies with larger sample sizes are needed for the evaluation of safety and tolerability of urea 10% lotion in this clinical setting.


Costs of a public health model to increase receipt of hepatitis-related services for persons with mental illness.
This study examined the costs and impact on receipt of hepatitis and HIV testing and hepatitis immunization services of a public health intervention model that was designed for use by persons with serious mental illness and co-occurring substance use disorders. Between 2006 and 2008, a random sample of 202 nonelderly, predominantly African-American males with a psychotic or major depressive disorder and a co-occurring substance use disorder was recruited at four community mental health outpatient programs in a large metropolitan area. Participants were randomly assigned at each site to enhanced treatment as usual (N=97), including education about blood-borne diseases and referrals for testing and vaccinations, or to an experimental intervention (N=105) that provided on-site infectious disease education, screening of risk level, pretest counseling, testing for HIV and hepatitis B and C, vaccination for hepatitis A and B, and personalized risk-reduction counseling. The authors compared the two study groups to assess the average costs of improving hepatitis and HIV testing and hepatitis A and B vaccination in this population. The average cost per participant was $423 for the intervention and $24 for the comparison condition (t=52.7, df=201, p<.001). The costs per additional person tested was $706 for hepatitis C, $776 for hepatitis B, and $3,630 for HIV, and the cost per additional person vaccinated for hepatitis was $561. Delivery of hepatitis and HIV public health services to persons with serious mental illness in outpatient mental health settings can be as cost-effective as similar interventions for other at-risk populations.


Neuroendocrine and pharmacological manipulations to assess how caloric restriction increases life span.
As part of an effort to review current understanding of the mechanisms by which caloric restriction (CR) extends maximum life span, the authors of the present review were requested to develop a list of key issues concerning the potential role of neuroendocrine systems in mediating these effects. It has long been hypothesized that failure of specific neuroendocrine functions during aging leads to key age-related systemic and physiological failures, and more recently it has been postulated that physiological neuroendocrine responses to CR may increase life span. However, although the acute neuroendocrine responses to fasting have been well studied, it is not clear that these responses are necessarily identical to those observed in response to the chronic moderate (30% to 50% reduction) CR that increases maximum life span. Therefore the recommendations of this panel fall into two categories. First, further characterization of neuroendocrine responses to CR over the entire life span is needed. Second, rigorous interventional studies are needed to test the extent to which neuroendocrine responses to CR mediate the effects of CR on life span, or alternatively if CR protects the function of essential neuroendocrine cells whose impairment reduces life span. Complementary studies using rodent models, nonhuman primates, and humans will be essential to assess the generality of elucidated mechanisms, and to determine if such mechanisms might apply to humans.


Contribution of murine IgG Fc regions to antibody binding to the capsule of Burkholderia pseudomallei.
Immunoglobulin G3 (IgG3) is the predominant IgG subclass elicited in response to polysaccharide antigens in mice. This specific subclass has been shown to crosslink its fragment crystallizable (Fc) regions following binding to multivalent polysaccharides. Crosslinking leads to increased affinity through avidity, which theoretically should lead to more effective protection against bacteria and yeast displaying capsular polysaccharides on their surface. To investigate this further we have analyzed the binding characteristics of 2 IgG monoclonal antibody (mAb) subclass families that bind to the capsular polysaccharide (CPS) of Burkholderia pseudomallei. The first subclass family originated from an IgG3 hybridoma cell line (3C5); the second family was generated from an IgG1 cell line (2A5). When the Fc region of the 3C5 IgG3 is removed by proteolytic cleavage, the resulting F(ab')2 fragments exhibit decreased affinity compared to the full-length mAb. Similarly, when the parent IgG3 mAb is subclass-switched to IgG1, IgG2b, and IgG2a, all of these subclasses exhibit decreased affinity. This decrease in affinity is not seen when the 2A5 IgG1 mAb is switched to an IgG2b or IgG2a, strongly suggesting the drop in affinity is related to the IgG3 Fc region.


Stability of coping and the role of self-efficacy in the first year following mild traumatic brain injury.
Coping, the psychological adaptation to stressors and serious life events, has been found to have a great influence on the development and persistence of posttraumatic complaints. Coping has received much attention for having been found to be modifiable in treatment following mild traumatic brain injury (mTBI) and for its potential to identify the Patients who are at risk of suffering from long-term complaints. Currently, coping styles are assumed to be stable over time. Although interventions to facilitate adaptive coping are given at different time intervals after the injury, little is known about spontaneous changes in preferred strategies over time following mTBI. This study aimed to investigate the stability of different coping styles over a one-year period following mTBI (at two weeks', six and twelve months' post-injury) and to investigate the relation between coping styles and feelings of self-efficacy. We included 425 mTBI patients (Glasgow Coma Scale [GCS] score 13-15) admitted to three Level-1 trauma centers in the Netherlands as part of a prospective follow-up study. All participants filled out The Utrecht Coping List (UCL) to determine their position on seven coping subscales. Most coping styles showed a decrease over time, except for positive reframing, which showed a decrease and then increased. Interestingly, the passive coping style was found to stabilize over time within the year after injury. High feelings of self-efficacy were related to a high active coping style (r = 0.36), and low feelings of self-efficacy with passive coping (r = -0.32). These results hold important possibilities for the use of the passive coping strategy as an inclusion criterion for intervention studies and an entry point for treatment itself. Considering the intertwinement of coping with self-efficacy, improving feelings of self-efficacy could form an effective part of an intervention to improve outcome.


Is goniometry suitable for measuring ankle range of motion in female ballet dancers? An initial comparison with radiographic measurement.
Female ballet dancers require extreme ankle motion to attain the demi-plié (weight-bearing full dorsiflexion [DF]) and en pointe (weight-bearing full plantar flexion [PF]) positions of ballet. However, techniques for assessing this amount of motion have not yet received sufficient scientific scrutiny. Therefore, the purpose of this study was to examine possible differences between weight-bearing goniometric and radiographic ankle range of motion measurements in female ballet dancers. Ankle range of motion in 8 experienced female ballet dancers was assessed by goniometry and 2 radiographic measurement methods. The latter were performed on 3 mediolateral x-rays, in demi-plié, neutral, and en pointe positions; one of them used the same landmarks as goniometry. DF values were not significantly different among the methods, but PF values were (P < .05). Not only was PF of the talocrural joint significantly less than the other 2 measurements (P < .001), PF from the goniometric method applied to the x-rays was significantly less than PF obtained from clinical goniometry (P < .05). These data provide insight into the extreme ankle and foot motion, particularly PF, required in female ballet dancers and suggest that goniometry may not be ideal for assessing ankle range of motion in these individuals. Therefore, further research is needed to standardize how DF and PF are measured in ballet dancers. Diagnostic, Level I.


Long-Term Nephrotoxicity of 177Lu-PSMA Radioligand Therapy.
β-emitting 177Lu targeting prostate-specific membrane antigen (PSMA) is an approved treatment option for metastatic castration-resistant prostate cancer. Data on its long-term nephrotoxicity are sparse. This study aimed to retrospectively evaluate post-177Lu-PSMA estimated glomerular filtration rate (eGFR) dynamics for at least 12 mo in a cohort of metastatic castration-resistant prostate cancer patients. Methods: The institutional databases of 3 German tertiary referral centers identified 106 patients who underwent at least 4 cycles of 177Lu-PSMA and had at least 12 mo of eGFR follow-up data. eGFR (by the Chronic Kidney Disease Epidemiology Collaboration formula) at 3, 6, and 12 mo after 177Lu-PSMA radioligand therapy was estimated using monoexponentially fitted curves through available eGFR data. eGFR changes were grouped (≥15%-<30%, moderate; ≥30%-<40%, severe; and ≥40%, very severe). Associations between eGFR changes (%) and nephrotoxic risk factors, prior treatment lines, and number of 177Lu-PSMA cycles were analyzed using multivariable linear regression. Results: At least moderate eGFR decreases were present in 45% (48/106) of patients; of those, nearly half (23/48) had a severe or very severe eGFR decrease. A higher number of risk factors at baseline (-4.51, P = 0.03) was associated with a greater eGFR decrease. Limitations of the study were the retrospective design, lack of a control group, and limited number of patients with a follow-up longer than 1 y. Conclusion: A considerable proportion of patients may experience moderate or severe decreases in eGFR 1 y from initiation of 177Lu-PSMA. A higher number of risk factors at baseline seems to aggravate loss of renal function. Further prospective trials are warranted to estimate the nephrotoxic potential of 177Lu-PSMA.


Fabrication of a novel magnetic topological heterostructure and temperature evolution of its massive Dirac cone.
Materials that possess nontrivial topology and magnetism is known to exhibit exotic quantum phenomena such as the quantum anomalous Hall effect. Here, we fabricate a novel magnetic topological heterostructure Mn4Bi2Te7/Bi2Te3 where multiple magnetic layers are inserted into the topmost quintuple layer of the original topological insulator Bi2Te3. A massive Dirac cone (DC) with a gap of 40-75 meV at 16 K is observed. By tracing the temperature evolution, this gap is shown to gradually decrease with increasing temperature and a blunt transition from a massive to a massless DC occurs around 200-250 K. Structural analysis shows that the samples also contain MnBi2Te4/Bi2Te3. Magnetic measurements show that there are two distinct Mn components in the system that corresponds to the two heterostructures; MnBi2Te4/Bi2Te3 is paramagnetic at 6 K while Mn4Bi2Te7/Bi2Te3 is ferromagnetic with a negative hysteresis (critical temperature ~20 K). This novel heterostructure is potentially important for future device applications.