Optically pumped distributed feedback dye lasing with slide-coated TiO₂ inverse-opal slab as Bragg reflector.
We demonstrate an optical amplification of organic dye within a TiO2 inverse-opal (IO) distributed feedback (DFB) reflector prepared by a slide-coating method. Highly reflective TiO2 IO film was fabricated by slide coating the binary aqueous dispersions of polystyrene microspheres and charge-stabilized TiO2 nanoparticles on a glass slide and subsequently removing the polymer-opal template. TiO2 IO film was infiltrated, in turn, with the solutions of DCM, a fluorescent dye in various solvents with different indices of refraction. Optical pumping by frequency-doubled Nd:YAG laser resulted in amplified spontaneous emission in each dye solution. In accordance with the semi-empirical simulation by the FDTD method, DCM in ethanol showed the best emission/stopband matching for the TiO2 IO film used in this study. Therefore, photo excitation of a DCM/ethanol cavity showed a single-mode DFB lasing at 640 nm wavelength at moderate pump energy.


Lipopolysaccharide-inducible and salicylate-sensitive nuclear factor(s) on human tumor necrosis factor alpha promoter.
Lipopolysaccharide (LPS) is one of the most potent trigger substances for monocytes and macrophages causing secretion of tumor necrosis factor alpha (TNF-alpha) and other inflammatory mediators. The nature of the nuclear factors involved in human TNF-alpha gene regulation is still unknown. Nuclear factor kappa B (NF-kappa B) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with LPS. However, it remains unclear whether these nuclear factors are the only ones involved in human TNF-alpha gene regulation. In this report, to further the identification of nuclear factor(s) involved in TNF-alpha gene regulation, human monocytic THP-1 cells were transfected with a series of truncated versions of human TNF-alpha promoter. A 98-bp region located from nucleotides -584 to -487 demonstrated strong promoter activity. Electrophoretic mobility shift assays demonstrated that a 64-bp fragment located within the 98-bp region and lacking any potential NF-kappa B-binding sites avidly bound LPS-challenged THP-1 nuclear protein. Although this binding was inhibited in salicylate-treated cells, as was binding of NF-kappa B, the pattern of binding was found to differ from that noted for NF-kappa B. Analysis of this 64-bp fragment disclosed the absence of an NF-kappa B consensus sequence, suggesting a novel nuclear DNA-binding protein necessary for the initiation of human TNF-alpha transcription other than, or in addition to, NF-kappa B.


Identification of stroke in the community: a comparison of three methods.
Evidence concerning secondary prevention of cerebrovascular disease is not optimally used in clinical practice. A necessary first step is to identify those eligible for treatment. In primary care, this equates to setting up a register of prevalent stroke. To compare three different methods for identifying prevalent cases of cerebrovascular disease in the community: general practice-based computer systems; population surveys; and hospital-based routine information systems. Comparison of results of each method applied to a defined population and then assessed against reference criteria for cerebrovascular disease. A total of 5801 people aged 65 years or over, resident in seven practices situated within the South Birmingham Primary Care Trust area. The sensitivity, specificity, and predictive value of each method of identification were calculated against reference criteria applied by two investigators independently of each other. The prevalence of reference criteria-validated cerebrovascular disease in patients aged 65 years or over was 8.2%. Overall, general practice-based computer systems had a sensitivity of 81.0%, a specificity of 97.2% and a positive predictive value (PPV) of 71.8%, but there was a wide range of sensitivity (33% to 90%) and PPV (42% to 92%) between practices. Patient survey and hospital information systems were less sensitive (75.7% and 28.4%, respectively) but had higher PPVs (77.5% and 89.2%, respectively). Thirty-nine per cent of patients with a history of cerebrovascular disease had not been admitted to hospital. General practice-based computer systems can produce reasonably accurate prevalent stroke registers. In areas where these are poorly developed, patient survey is an alternative.


Quantitative evaluation of Coulombic interactions in the oriented-attachment growth of nanotubes.
The Coulombic interaction in the oriented attachment growth of one-dimensional nanotubes is evaluated via a newly-derived analytical expression of the Coulombic interactions between a spherical attaching nanoparticle and a growing nanotube. The correlation between the interaction and the important growth parameters, including nanoparticle/nanotube size, aspect ratio, and nanoparticle-nanotube separation has been analyzed. Our work provides, for the first time, an efficient platform to investigate the growth kinetics and mechanisms of oriented attachment growth of nanotubes.


Preoperative Falls and Their Association with Functional Dependence and Quality of Life.
No study has rigorously explored the characteristics of surgical patients with recent preoperative falls. Our objective was to describe the essential features of preoperative falls and determine whether they are associated with preoperative functional dependence and poor quality of life. This was an observational study involving 15,060 surveys from adult patients undergoing elective surgery. The surveys were collected between January 2014 and August 2015, with a response rate of 92%. In the 6 months before surgery, 26% (99% CI, 25 to 27%) of patients fell at least once, and 12% (99% CI, 11 to 13%) fell at least twice. The proportion of patients who fell was highest among patients presenting for neurosurgery (41%; 99% CI, 36 to 45%). At least one fall-related injury occurred in 58% (99% CI, 56 to 60%) of those who fell. Falls were common in all age groups, but surprisingly, they did not increase monotonically with age. Middle-aged patients (45 to 64 yr) had the highest proportion of fallers (28%), recurrent fallers (13%), and severe fall-related injuries (27%) compared to younger (18 to 44 yr) and older (65+ yr) patients (P < 0.001 for each). A fall within 6 months was independently associated with preoperative functional dependence (odds ratio, 1.94; 99% CI, 1.68 to 2.24) and poor physical quality of life (odds ratio, 2.18; 99% CI, 1.88 to 2.52). Preoperative falls might be common and are possibly often injurious in the presurgical population, across all ages. A history of falls could enhance the assessment of preoperative functional dependence and quality of life.


Does Early Psychological Intervention Promote Recovery From Posttraumatic Stress?
In the wake of the terrorist attacks at the World Trade Center, more than 9,000 counselors went to New York City to offer aid to rescue workers, families, and direct victims of the violence of September 11, 2001. These mental health professionals assumed that many New Yorkers were at high risk for developing posttraumatic stress disorder (PTSD), and they hoped that their interventions would mitigate psychological distress and prevent the emergence of this syndrome. Typically developing in response to horrific, life-threatening events, such as combat, rape, and earthquakes, PTSD is characterized by reexperiencing symptoms (e.g., intrusive recollections of the trauma, nightmares), emotional numbing and avoidance of reminders of the trauma, and hyperarousal (e.g., exaggerated startle, difficulty sleeping). People vary widely in their vulnerability for developing PTSD in the wake of trauma. For example, higher cognitive ability and strong social support buffer people against PTSD, whereas a family or personal history of emotional disorder heightens risk, as does negative appraisal of one's stress reactions (e.g., as a sign of personal weakness) and dissociation during the trauma (e.g., feeling unreal or experiencing time slowing down). However, the vast majority of trauma survivors recover from initial posttrauma reactions without professional help. Accordingly, the efficacy of interventions designed to mitigate acute distress and prevent long-term psychopathology, such as PTSD, needs to be evaluated against the effects of natural recovery. The need for controlled evaluations of early interventions has only recently been widely acknowledged. Psychological debriefing-the most widely used method-has undergone increasing empirical scrutiny, and the results have been disappointing. Although the majority of debriefed survivors describe the experience as helpful, there is no convincing evidence that debriefing reduces the incidence of PTSD, and some controlled studies suggest that it may impede natural recovery from trauma. Most studies show that individuals who receive debriefing fare no better than those who do not receive debriefing. Methodological limitations have complicated interpretation of the data, and an intense controversy has developed regarding how best to help people in the immediate wake of trauma. Recent published recommendations suggest that individuals providing crisis intervention in the immediate aftermath of the event should carefully assess trauma survivors' needs and offer support as necessary, without forcing survivors to disclose their personal thoughts and feelings about the event. Providing information about the trauma and its consequences is also important. However, research evaluating the efficacy of such "psychological first aid" is needed. Some researchers have developed early interventions to treat individuals who are already showing marked stress symptoms, and have tested methods of identifying those at risk for chronic PTSD. The single most important indicator of subsequent risk for chronic PTSD appears to be the severity or number of posttrauma symptoms from about 1 to 2 weeks after the event onward (provided that the event is over and that there is no ongoing threat). Cognitive-behavioral treatments differ from crisis intervention (e.g., debriefing) in that they are delivered weeks or months after the trauma, and therefore constitute a form of psychotherapy, not immediate emotional first aid. Several controlled trials suggest that certain cognitive-behavioral therapy methods may reduce the incidence of PTSD among people exposed to traumatic events. These methods are more effective than either supportive counseling or no intervention. In this monograph, we review risk factors for PTSD, research on psychological debriefing, recent recommendations for crisis intervention and the identification of individuals at risk of chronic PTSD, and research on early interventions based on cognitive-behavioral therapy. We close by placing the controversy regarding early aid for trauma survivors in its social, political, and economic context.


Model-Based Quantification of the Systemic Interplay between Glucose and Fatty Acids in the Postprandial State.
In metabolic diseases such as Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, the systemic regulation of postprandial metabolite concentrations is disturbed. To understand this dysregulation, a quantitative and temporal understanding of systemic postprandial metabolite handling is needed. Of particular interest is the intertwined regulation of glucose and non-esterified fatty acids (NEFA), due to the association between disturbed NEFA metabolism and insulin resistance. However, postprandial glucose metabolism is characterized by a dynamic interplay of simultaneously responding regulatory mechanisms, which have proven difficult to measure directly. Therefore, we propose a mathematical modelling approach to untangle the systemic interplay between glucose and NEFA in the postprandial period. The developed model integrates data of both the perturbation of glucose metabolism by NEFA as measured under clamp conditions, and postprandial time-series of glucose, insulin, and NEFA. The model can describe independent data not used for fitting, and perturbations of NEFA metabolism result in an increased insulin, but not glucose, response, demonstrating that glucose homeostasis is maintained. Finally, the model is used to show that NEFA may mediate up to 30-45% of the postprandial increase in insulin-dependent glucose uptake at two hours after a glucose meal. In conclusion, the presented model can quantify the systemic interactions of glucose and NEFA in the postprandial state, and may therefore provide a new method to evaluate the disturbance of this interplay in metabolic disease.


Self-harm and self-regulation in urban ethnic minority youth: a pilot application of dialectical behavior therapy for adolescents.
Difficulties in coping with stress and regulating emotions are transdiagnostic risk factors for self-harming behavior. Due to sociocultural stressors, ethnic minority adolescents may be at greater risk for self-regulation difficulties and self-harm. Dialectical behavior therapy for adolescents (DBT-A) frames adaptive skill acquisition as a mechanism of change, but few studies have investigated its impact on ethnic minority adolescents' self-regulation (i.e. coping, emotion regulation). Therefore, this pilot study examined relations between self-regulation and self-harm among ethnic minority adolescents and investigated changes in their self-regulation upon completing DBT-A. A clinically referred sample of 101 ethnic minority adolescents (Mage = 14.77; female = 69.3%) completed questionnaires about a history of self-harm, coping (DBT Ways of Coping Checklist), and emotion regulation (Difficulties in Emotion Regulation Scale). Of the initial sample, 51 adolescents (Mage = 14.73; female = 80.4%) entered a 20-week DBT-A program due to self-harm and/or Borderline Personality features. In a pretreatment sample, the frequency of dysfunctional coping, but not of adaptive coping, differentiated self-injurers from non-self-injurers. Full information maximum likelihood estimation was used to address high attrition (60.8%) from DBT-A. Those who completed DBT-A (n = 20) reported significantly improved emotion regulation. Adaptive coping at pretreatment predicted increased DBT skills use at post-treatment. This non-randomized pilot study highlights dysfunctional coping and emotion dysregulation as risk factors for self-harm and suggests that 20-week DBT-A may help improve emotion regulation. Future research should employ a randomized design to further examine the effect of DBT-A on these transdiagnostic processes of psychopathology. Due to cultural and environmental stressors, ethnic minority adolescents may be at greater risk for developing self-regulatory difficulties - transdiagnostic mechanisms known to underly self-harming behaviors; however, we know little about whether empirically supported treatments for self-harm will improve youth's coping and emotion regulation. In a clinically referred, pretreatment sample of ethnic minority youth, levels of BPD symptomatology, emotion dysregulation, and dysfunctional coping, but not of adaptive coping, differentiated teens who self-harmed from those who did not. Self-harming ethnic minority youth who participated in an uncontrolled, pilot trial of dialectical behavior therapy for adolescents (DBT-A) at an urban mental health clinic reported improved emotion regulation at post-treatment. Baseline emotion regulation skills were not predictive of treatment-related changes, suggesting that other factors, such as DBT-A, may have played a decisive role in improving teens' emotion regulation. In contrast, adaptive coping skills at pretreatment were linked to increased DBT skills use at post-treatment, indicating that patients' baseline coping skills may play a predictive role in psychotherapy outcomes. Future research should employ a randomized control trial to examine the effect of DBT-A on vulnerable ethnic minority youth's development of self-regulation. It should also investigate the hypothesized mediating role of self-regulation in effecting lasting clinical gains.


Introduction of hypermatrix and operator notation into a discrete mathematics simulation model of malignant tumour response to therapeutic schemes in vivo. Some operator properties.
The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code). However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators' commutativity and outline the "summarize and jump" strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83-02, thus strengthening the reliability of the model developed.


The tracer gas technique--a useful tool for industrial hygiene.
The tracer gas technique was applied in industrial hygiene surveys. Carbon dioxide, nitrous oxide, and sulfur hexafluoride were used to elicit ventilation rates and determine spreading routes of dilution air in the work environment. The continuous monitoring of nitrous oxide with an infrared spectrophotometer was found to be the most practicable choice for ventilation testing, whereas plastic bag sampling of nitrous oxide or sulfur hexafluoride with subsequent analysis by gas chromatography appeared to be a good method for emission spreading studies. The local flow rates of dilution air and the percentages of make-up air present were the most important information gained in the ventilation studies.


Polydopamine Nanostructures as Biomaterials for Medical Applications.
Polydopamine is a versatile and organic material that can be deposited as a conformal film with nanometer thickness on virtually any substrate. Much of the initial foundational work regarding polydopamine synthesis and processing was reported during the 2000s. Latter years have witnessed increasing interest and widespread adoption of polydopamine as a material for many applications including medicine. Conformal polydopamine coatings confer unique chemical and physical properties to many substrate materials including metals, ceramics, polymers, and beyond. Polydopamine-modified surfaces permit facile bioconjugation of many biomedical materials for potential use as bioadhesives, contrast agents, drug delivery systems, and protein-adsorption resistant interfaces. Polydopamine-based materials and interfaces may improve the performance of biomedical devices used in neurotechnology, diagnostics, and cardiovascular applications. This highlight article reviews recent advances in polydopamine processing capabilities. The use of polydopamine as a material in various biomedical applications is also discussed. Finally, challenges and opportunites in translating polydopamine for future biomedical technologies are summarized.


The importance of the role of the patient in the outcome of schizophrenia.
The Family Interpersonal Perception Test (FIPT) was used to explore the relationships between schizophrenic patients and their parents, and how these related both to relapse in the year after discharge and to improvement in social functioning. Forty schizophrenic patients and their parents were tested during their first ever admission to hospital and again two years later. Parents' and patient's views of each other were more negative in those with worse outcome, but what most significantly distinguished groups with different outcomes was how patients expected their parents to see them. The FIPT, therefore, reveals patterns of interaction in which the patient's role in outcome is at least as important as that of the parents, and can aid the identification of specific features with which to work in therapy.


The Dark Side of the Force - Constraints and Complications of Cell Therapies for Stroke.
Cell therapies are increasingly recognized as a promising option to augment the limited therapeutic arsenal available to fight ischemic stroke. During the last two decades, cumulating preclinical evidence has indicated a substantial efficacy for most cell treatment paradigms and first clinical trials are currently underway to assess safety and feasibility in patients. However, the strong and still unmet demand for novel stroke treatment options and exciting findings reported from experimental studies may have drawn our attention away from potential side effects related to cell therapies and the ways by which they are commonly applied. This review summarizes common and less frequent adverse events that have been discovered in preclinical and clinical investigations assessing cell therapies for stroke. Such adverse events range from immunological and neoplastic complications over seizures to cell clotting and cell-induced embolism. It also describes potential complications of clinically applicable administration procedures, detrimental interactions between therapeutic cells, and the pathophysiological environment that they are placed into, as well as problems related to cell manufacturing. Virtually each therapeutic intervention comes at a certain risk for complications. Side effects do therefore not generally compromise the value of cell treatments for stroke, but underestimating such complications might severely limit therapeutic safety and efficacy of cell treatment protocols currently under development. On the other hand, a better understanding will provide opportunities to further improve existing therapeutic strategies and might help to define those circumstances, under which an optimal effect can be realized. Hence, the review eventually discusses strategies and recommendations allowing us to prevent or at least balance potential complications in order to ensure the maximum therapeutic benefit at minimum risk for stroke patients.


Roles of Hypoxia Response in Retinal Development and Pathophysiology.
The hypoxia response is a fundamental phenomenon mainly regulated by hypoxia-inducible factors (HIFs). For more than a decade, we have investigated and revealed the roles of the hypoxia response in the development, physiology, and pathophysiology of the retina by generating and utilizing cell-type-specific conditional knockout mice. To investigate the functions of genes related to the hypoxia response in cells composing the retina, we generated various mouse lines that lack HIFs and/or related genes specifically in retinal neurons, astrocytes, myeloid cells, or retinal pigment epithelium cells. We found that these genes in the different types of retinal cells contribute in various ways to the homeostasis of ocular vascular and visual function. We hypothesized that the activation of HIFs is likely involved in the development and progress of retinal diseases, and we subsequently confirmed the pathological roles of HIFs in animal models of neovascular and atrophic ocular diseases. Currently, anti-vascular endothelial growth factor (anti-VEGF) therapy is a first-line treatment widely used for neovascular retinal diseases. However, alternative or additional targets are now required because several recent large-scale clinical trials and animal studies, including our own research, have indicated that VEGF antagonism may induce retinal vascular and neuronal degeneration. We have identified and confirmed a microRNA as a candidate for an alternative target against neovascular retinal diseases, and we are now working to establish a novel HIF inhibitor for clinical use based on the disease mechanism that we identified.


Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT.
BUSTER-TNT is a maximum-likelihood macromolecular refinement package. BUSTER assembles the structural model, scales observed and calculated structure-factor amplitudes and computes the model likelihood, whilst TNT handles the stereochemistry and NCS restraints/constraints and shifts the atomic coordinates, B factors and occupancies. In real space, in addition to the traditional atomic and bulk-solvent models, BUSTER models the parts of the structure for which an atomic model is not yet available ('missing structure') as low-resolution probability distributions for the random positions of the missing atoms. In reciprocal space, the BUSTER structure-factor distribution in the complex plane is a two-dimensional Gaussian centred around the structure factor calculated from the atomic, bulk-solvent and missing-structure models. The errors associated with these three structural components are added to compute the overall spread of the Gaussian. When the atomic model is very incomplete, modelling of the missing structure and the consistency of the BUSTER statistical model help structure building and completion because (i) the accuracy of the overall scale factors is increased, (ii) the bias affecting atomic model refinement is reduced by accounting for some of the scattering from the missing structure, (iii) the addition of a spatial definition to the source of incompleteness improves on traditional Luzzati and sigmaA-based error models and (iv) the program can perform selective density modification in the regions of unbuilt structure alone.


Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.
Despite best current therapy, up to 20% of pediatric patients with acute lymphoblastic leukemia (ALL) have a relapse. Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined. We studied a cohort of 221 children with high-risk B-cell-progenitor ALL with the use of single-nucleotide-polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis. Children with known very-high-risk ALL subtypes (i.e., BCR-ABL1-positive ALL, hypodiploid ALL, and ALL in infants) were excluded from this cohort. A copy-number abnormality was identified as a predictor of poor outcome, and it was then tested in an independent validation cohort of 258 patients with B-cell-progenitor ALL. More than 50 recurring copy-number abnormalities were identified, most commonly involving genes that encode regulators of B-cell development (in 66.8% of patients in the original cohort); PAX5 was involved in 31.7% and IKZF1 in 28.6% of patients. Using copy-number abnormalities, we identified a predictor of poor outcome that was validated in the independent validation cohort. This predictor was strongly associated with alteration of IKZF1, a gene that encodes the lymphoid transcription factor IKAROS. The gene-expression signature of the group of patients with a poor outcome revealed increased expression of hematopoietic stem-cell genes and reduced expression of B-cell-lineage genes, and it was similar to the signature of BCR-ABL1-positive ALL, another high-risk subtype of ALL with a high frequency of IKZF1 deletion. Genetic alteration of IKZF1 is associated with a very poor outcome in B-cell-progenitor ALL.


An update of Coenzyme Q10 implications in male infertility: biochemical and therapeutic aspects.
This review is focused upon the role of coenzyme Q(10) in male infertility in the light of a broader issue of oxidative damage and antioxidant defence in sperm cells and seminal plasma. Reactive oxygen species play a key pathogenetic role in male infertility besides having a well-recognized physiological function. The deep involvement of coenzyme Q(10) in mitochondrial bioenergetics and its antioxidant properties are at the basis of its role in seminal fluid. Following the early studies addressing its presence in sperm cells and seminal plasma, the relative distribution of the quinone between these two compartments was studied in infertile men, with special attention to varicocele. The reduction state of CoQ(10) in seminal fluid was also investigated. After the first in vitro experiments CoQ(10) was administered to a group of idiopathic asthenozoospermic infertile patients. Seminal analysis showed a significant increase of CoQ(10) both in seminal plasma and in sperm cells, together with an improvement in sperm motility. The increased concentration of CoQ(10) in seminal plasma and sperm cells, the improvement of semen kinetic features after treatment, and the evidence of a direct correlation between CoQ(10) concentrations and sperm motility strongly support a cause/effect relationship. From a general point of view, a deeper knowledge of these molecular mechanisms could lead to a new insight into the so-called unexplained infertility.


Influence of recent bark beetle outbreak on fire severity and postfire tree regeneration in montane Douglas-fir forests.
Understanding how disturbances interact to shape ecosystems is a key challenge in ecology. In forests of western North America, the degree to which recent bark beetle outbreaks and subsequent fires may be linked (e.g., outbreak severity affects fire severity) and/ or whether these two disturbances produce compound effects on postfire succession is of widespread interest. These interactions remain unresolved, largely because field data from actual wildfires following beetle outbreaks are lacking. We studied the 2008 Gunbarrel Fire, which burned 27 200 ha in Douglas-fir (Pseudotsuga menziesii) forests that experienced a bark beetle outbreak 4-13 years prefire ("gray stage," after trees have died and needles have dropped), to determine whether outbreak severity influenced subsequent fire severity and postfire tree regeneration. In 85 sample plots we recorded prefire stand structure and outbreak severity; multiple measures of canopy and forest-floor fire severity; and postfire tree seedling density. Prefire outbreak severity was not related to any measure of fire severity except for mean bole scorch, which declined slightly with increasing outbreak severity. Instead, fire severity varied with topography and burning conditions (proxy for weather at time of fire). Postfire Douglas-fir regeneration was low, with tree seedlings absent in 65% of plots. Tree seedlings were abundant in plots of low fire severity that also had experienced low outbreak severity (mean = 1690 seedlings/ha), suggesting a dual filter on tree regeneration. Although bark beetles and fire collectively reduced live basal area to < 5% and increased snag density to > 2000% of pre-outbreak levels, the lack of relationship between beetle outbreak and fire severity suggests that these disturbances were not linked. Nonetheless, effects on postfire tree regeneration suggest compound disturbance interactions that contribute to the structural heterogeneity characteristic of mid/lower montane forests.


Ultra-highly diluted plant extracts of Hydrastis canadensis and Marsdenia condurango induce epigenetic modifications and alter gene expression profiles in HeLa cells in vitro.
Methylation-specific epigenetic process and gene expression profiles of HeLa cells treated with ultra-high dilutions (HDs) of two plant extracts, Hydrastis canadensis (HC-30) and Marsdenia condurango (Condu-30), diluted 1060 times, were analyzed against placebo 30C (Pl-30) for alterations in gene profiles linked to epigenetic modifications. Separate groups of cells were subjected to treatment of Condu-30, HC-30, and Pl-30 prepared by serial dilutions and succussions. Global microarray data recorded on Affymetrix platform, using 25-mer probes were provided by iLifeDiscoveries, India. Slides were scanned with 3000 7G microarray scanner and raw data sets were extracted from Cel (raw intensity) files. Analyses of global microarray data profile, differential gene expression, fold change and clusters were made using GeneSpring GX12.5 software and standard normalization procedure. Before microarray study, concentration of RNA (ng/μL), RIN value and rRNA ratio for all the samples were analysed by Agilant Bioanalyzer 2100. Reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative RT-PCR were done for analyzing SMAD-4 expression. Fluorescence-activated cell sorting study was further made to elucidate fate of cells at divisional stages. Methylation-specific restriction enzyme assay was conducted for ascertaining methylation status of DNA at specific sites. HDs of HC-30 and Condu-30 differentially altered methylation in specific regions of DNA and expression profiles of certain genes linked to carcinogenesis, as compared to Pl-30. Two separate cut sites were found in genomic DNA of untreated and placebo-treated HeLa cells when digested with McrBC, compared to a single cut observed in Condu-30-treated genomic DNA. SMAD-4 gene expression validated the expression pattern observed in microarray profile. Methylation-specific restriction enzyme assay elucidated differential epigenetic modifications in drug-treated and control cells. HDs triggered epigenetic modifications and alterations in microarray gene expression profiles of many genes associated with carcinogenesis in HeLa cells in vitro.


Mechanism of Triplet Energy Transfer in Photosynthetic Bacterial Reaction Centers.
In purple bacterial reaction centers, triplet excitation energy transfer occurs from the primary donor P, a bacteriochlorophyll dimer, to a neighboring carotenoid to prevent photodamage from the generation of reactive oxygen species. The BB bacteriochlorophyll molecule that lies between P and the carotenoid on the inactive electron transfer branch is involved in triplet energy transfer between P and the carotenoid. To expand the high-resolution spectral and kinetic information available for describing the mechanism, we investigated the triplet excited state formation and energy transfer pathways in the reaction center of Rhodobacter sphaeroides using pump-probe transient absorption spectroscopy over a broad spectral region on the nanosecond to microsecond time scale at both room temperature and at 77 K. Wild-type reaction centers were compared with a reaction center mutant (M182HL) in which BB is replaced by a bacteriopheophytin (Φ), as well as to reaction centers that lack the carotenoid. In wild-type reaction centers, the triplet energy transfer efficiency from P to the carotenoid was essentially unity at room temperature and at 77 K. However, in the M182HL mutant reaction centers, both the rate and efficiency of triplet energy transfer were decreased at room temperature, and at 77 K, no triplet energy transfer was observed, attributable to a higher triplet state energy of the bacteriopheophytin that replaces bacteriochlorophyll in this mutant. Finally, detailed time-resolved spectral analysis of P, carotenoid, and BB (Φ in the M182HL mutant) reveals that the triplet state of the carotenoid is coupled fairly strongly to the bridging intermediate BB in wild-type and Φ in the M182HL mutant, a fact that is probably responsible for the lack of any obvious intermediate 3BB/3Φ transient formation during triplet energy transfer.


Synthetic lethality screen identifies a novel yeast myosin I gene (MYO5): myosin I proteins are required for polarization of the actin cytoskeleton.
The organization of the actin cytoskeleton plays a critical role in cell physiology in motile and nonmotile organisms. Nonetheless, the function of the actin based motor molecules, members of the myosin superfamily, is not well understood. Deletion of MYO3, a yeast gene encoding a "classic" myosin I, has no detectable phenotype. We used a synthetic lethality screen to uncover genes whose functions might overlap with those of MYO3 and identified a second yeast myosin 1 gene, MYO5. MYO5 shows 86 and 62% identity to MYO3 across the motor and non-motor regions. Both genes contain an amino terminal motor domain, a neck region containing two IQ motifs, and a tail domain consisting of a positively charged region, a proline-rich region containing sequences implicated in ATP-insensitive actin binding, and an SH3 domain. Although myo5 deletion mutants have no detectable phenotype, yeast strains deleted for both MYO3 and MYO5 have severe defects in growth and actin cytoskeletal organization. Double deletion mutants also display phenotypes associated with actin disorganization including accumulation of intracellular membranes and vesicles, cell rounding, random bud site selection, sensitivity to high osmotic strength, and low pH as well as defects in chitin and cell wall deposition, invertase secretion, and fluid phase endocytosis. Indirect immunofluorescence studies using epitope-tagged Myo5p indicate that Myo5p is localized at actin patches. These results indicate that MYO3 and MYO5 encode classical myosin I proteins with overlapping functions and suggest a role for Myo3p and Myo5p in organization of the actin cytoskeleton of Saccharomyces cerevisiae.


Functional interaction between trace amine-associated receptor 1 and dopamine D2 receptor.
The ability of dopamine receptors to interact with other receptor subtypes may provide mechanisms for modulating dopamine-related functions and behaviors. In particular, there is evidence suggesting that the trace amine-associated receptor 1 (TAAR1) affects the dopaminergic system by regulating the firing rate of dopaminergic neurons or by altering dopamine D2 receptor (D2R) responsiveness to ligands. TAAR1 is a Gα(s) protein-coupled receptor that is activated by biogenic amines, "trace amines," such as β-phenylethylamine (β-PEA) and tyramine that are normally found at low concentrations in the mammalian brain. In the present study, we investigated the biochemical mechanism of interaction between TAAR1 and D2R and the role this interaction plays in D2R-related signaling and behaviors. Using a bioluminescence resonance energy transfer biosensor for cAMP, we demonstrated that the D2R antagonists haloperidol, raclopride, and amisulpride were able to enhance selectively a TAAR1-mediated β-PEA increase of cAMP. Moreover, TAAR1 and D2R were able to form heterodimers when coexpressed in human embryonic kidney 293 cells, and this direct interaction was disrupted in the presence of haloperidol. In addition, in mice lacking TAAR1, haloperidol-induced striatal c-Fos expression and catalepsy were significantly reduced. Taken together, these data suggest that TAAR1 and D2R have functional and physical interactions that could be critical for the modulation of the dopaminergic system by TAAR1 in vivo.


Joint-position sense and kinesthesia in cerebral palsy.
To examine joint-position sense and kinesthesia in all extremities in participants with diplegic or hemiplegic cerebral palsy (CP). Survey of joint-position sense and kinesthesia differences between aged-matched controls and 2 groups with CP. University movement assessment laboratory. Population-based sample of participants with CP, diplegia (n=21), hemiplegia (n=17), and age-matched volunteers (n=21) without neurologic disease. Not applicable. Joint-position sense and kinesthesia were measured in the transverse plane (forearm pronation/supination and hip internal/external rotation) using a custom-built device. For joint-position sense, participants actively rotated the tested limb to align the distal end with 10 target positions first with the limb and targets visible to assess their ability to perform the task motorically. The task was then repeated with vision of the limb occluded, with targets remaining visible. Joint-position sense error was determined by the magnitude and direction of the rotation errors for each limb in the vision and no vision conditions. Kinesthesia was evaluated by the ability to detect passive limb rotation without vision. No group differences were detected in the vision condition. Indicative of joint-position sense deficits, a significant increase in errors was found in the no vision condition in all limbs except the dominant upper limb for both groups with CP. Joint-position sense errors were systematically biased toward the direction of internal rotation. Kinesthesia deficits were evident on the nondominant upper limb in diplegia and hemiplegia, and bilaterally in the lower limbs in hemiplegia. In hemiplegia, joint-position sense and kinesthesia deficits were noted on the dominant limbs, but were significantly worse on the nondominant limbs. These results indicate that people with CP have proprioception deficits in all limbs.


Reliability and Validity of the Pediatric Quality of Life Inventory With Individuals With Intellectual and Developmental Disabilities.
The Pediatric Quality of Life Inventory (PedsQL) measures health-related quality of life, a growing area of research, particularly among individuals with disabilities. This research is necessary to fully understand the varied needs of the population and, ultimately, ensure that those needs are being met. The current study assessed the reliability and validity of the PedsQL in individuals with intellectual and developmental disabilities, including individuals with autism spectrum disorder. Participants included 359 caregivers of children, youth, and young adults with IDD. Caregivers completed the PedsQL 4.0 Generic Core Scales questions regarding the individual's physical health and the Strengths and Difficulties Questionnaire. The PedsQL achieved excellent reliability across scales, and distinguished healthy individuals from those with chronic health conditions, as well as individuals with ASD from those without. Factor analysis confirmed a 5-factor model, with moderate to high criterion validity. The PedsQL shows sound psychometric properties and may be a useful tool to measure psychosocial functioning in this population.


Evaluation of a Program to Improve Linkage to and Retention in Care Among Refugees with Hepatitis B Virus Infection - Three U.S. Cities, 2006-2018.
An estimated 257 million persons worldwide have chronic hepatitis B virus (HBV) infection (1). CDC recommends HBV testing for persons from countries with intermediate to high HBV prevalence (≥2%), including newly arriving refugees (2). Complications of chronic HBV infection include liver cirrhosis and hepatocellular carcinoma, which develop in 15%-25% of untreated adults infected in infancy or childhood (3). HBV-infected patients require regular monitoring for both infection and sequelae. Several studies have evaluated initial linkage to HBV care for both refugee and nonrefugee immigrant populations (4-9), but none contained standardized definitions for either linkage to or long-term retention in care for chronic HBV-infected refugees. To assess chronic HBV care, three urban sites that perform refugee domestic medical examinations and provide primary care collaborated in a quality improvement evaluation. Sites performed chart reviews and prospective outreach to refugees with positive test results for presumed HBV infection during domestic medical examinations. Linkage to care (29%-53%), retention in care (11%-21%), and outreach efforts (22%-71% could not be located) demonstrated poor access to initial and ongoing HBV care. Retrospective outreach was low-yield. Interventions that focus on prospective outreach and addressing issues related to access to care might improve linkage to and retention in care.


Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies.
Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.


The spinobulbar system in lamprey.
Locomotor networks in the spinal cord are controlled by descending systems which in turn receive feedback signals from ascending systems about the state of the locomotor networks. In lamprey, the ascending system consists of spinobulbar neurons which convey spinal network signals to the two descending systems, the reticulospinal and vestibulospinal neurons. Previous studies showed that spinobulbar neurons consist of both ipsilaterally and contralaterally projecting cells distributed at all rostrocaudal levels of the spinal cord, though most numerous near the obex. The axons of spinobulbar neurons ascend in the ventrolateral spinal cord and brainstem to the caudal mesencephalon and within the dendritic arbors of reticulospinal and vestibulospinal neurons. Compared to mammals, the ascending system in lampreys is more direct, consisting of excitatory and inhibitory monosynaptic inputs from spinobulbar neurons to reticulospinal neurons. The spinobulbar neurons are rhythmically active during fictive locomotion, representing a wide range of timing relationships with nearby ventral root bursts including those in phase, out of phase, and active during burst transitions between opposite ventral roots. The spinobulbar neurons are not simply relay cells because they can have mutual synaptic interactions with their reticulospinal neuron targets and they can have synaptic outputs to other spinal neurons. Spinobulbar neurons not only receive locomotor inputs but also receive direct inputs from primary mechanosensory neurons. Due to the relative simplicity of the lamprey nervous system and motor control system, the spinobulbar neurons and their interactions with reticulospinal neurons may be advantageous for investigating the general organization of ascending systems in the vertebrate.


Functional neuroimaging studies of human emotions.
Neuroimaging studies with positron emission tomography and functional magnetic resonance imaging have begun to describe the functional neuroanatomy of human emotion. Taken separately, specific studies vary in task dimensions and in type(s) of emotion studied, and are limited by statistical power and sensitivity. By examining findings across studies in a meta-analysis, we sought to determine if common or segregated patterns of activations exist in different emotions and across various emotional tasks. We surveyed over 55 positron emission tomography and functional magnetic resonance imaging activation studies, which investigated emotion in healthy subjects. This paper will review observations in several regions of interest in limbic (eg, amygdala, anterior cingulate cortex) and paralimbic (eg, medial prefrontal cortex, insula) brain regions in emotional responding.


Maternal perspectives on gestational weight gain: Critical information on developing weight control interventions.
Our aim was to demonstrate what women reported being counselled about weight gain in pregnancy, their perceptions of inappropriate gestational weight gain (GWG), and plans for weight gain in pregnancy. A cross-sectional survey of perceptions of prenatal attendees about inappropriate GWG was conducted at the prenatal clinic of a referral tertiary health facility in south western, Nigeria, between January 1, 2013 and June 30, 2013. Primary outcomes were the perceptions of women about risks involved with inappropriate weight gain and the proportion of women who self-reported being counselled at all on GWG, and had the right knowledge of risk(s) involved with inappropriate weight gain during pregnancy. Of the 348 women who completed the survey, approximately four-fifths (82.8%) reported GWG being discussed at all by health care provider. Fewer women (29.3%) believed there were maternal risks with excess weight gain compared to inadequate weight gain (34.8%). With respect to perception of risks of inappropriate weight gain to infants, 23.65 and 18.4%, respectively, believed there were infant risks with excess and inadequate GWG. Overweight women [OR 0.39 (95% CI 0.16-0.98)] and those who received GWG information from more than one type of health care provider [OR 4.71 (95% CI 1.64-13.78)] had significant increased rate of correct knowledge of risks involved with inappropriate GWG. The lack of awareness of risks involved with inappropriate GWG by over half of respondents underscores the need for improvement in educational intervention on GWG in our environment.


Perirhinal cortex tracks degree of recent as well as cumulative lifetime experience with object concepts.
Evidence from numerous sources indicates that recognition of the prior occurrence of objects requires computations of perirhinal cortex (PrC) in the medial temporal lobe (MTL). Extant research has primarily probed recognition memory based on item exposure in a recent experimental study episode. Outside the laboratory, however, familiarity for objects typically accrues gradually with learning across many different episodic contexts, which can be distributed over a lifetime of experience. It is currently unknown whether PrC also tracks this cumulative lifetime experience with object concepts. To address this issue, we conducted a functional magnetic resonance imaging (fMRI) experiment in healthy individuals in which we compared judgments of the perceived lifetime familiarity with object concepts, a task that has previously been employed in many normative studies on concept knowledge, with frequency judgments for recent laboratory exposure in a study phase. Guided by neurophysiological data showing that neurons in primate PrC signal prior object exposure at multiple time scales, we predicted that PrC responses would track perceived prior experience in both types of judgments. Left PrC and a number of cortical regions that are often co-activated as part of the default-mode network showed an increase in Blood-Oxygen-Level Dependent (BOLD) response in relation to increases in the perceived cumulative lifetime familiarity of object concepts. These regions included the left hippocampus, left mid-lateral temporal cortex, as well as anterior and posterior cortical midline structures. Critically, left PrC was found to be the only region that showed this response in combination with the typically observed decrease in signal for perceived recent exposure in the experimental study phase. These findings provide, to our knowledge, the first evidence that ties signals in human PrC to variations in cumulative lifetime experience with object concepts. They offer a new link between the role of PrC in recognition memory and its broader role in conceptual processing.


The state of affairs in the kingdom of the Red Queen.
One of the most prominent hypotheses to explain the ubiquity of sex and recombination is based on host-parasite interactions. Under the name of the Red Queen hypothesis (RQH), it has had theoretical and empirical support since its conception, but recent theoretical work has shown that the circumstances under which the RQH works remain unclear. Here we review the current status of the theory of the RQH. We argue that recent theoretical work calls for new experimental data and an increased theoretical effort to reveal the driving force of the RQH.


Mastectomy or conservation for early breast cancer: psychological morbidity.
A consecutive series of 197 women under 70 years of age with operable breast cancer, randomised to treatment by a conservation technique in comparison to mastectomy, were assessed using structured interviews. The prevalence of cases of anxiety and depression was high before treatment commenced, there were fewer cases in the conservation group but no significant difference at 3 or 12 months in the number of new cases, social adjustment, or capacity to return to work. Attitudes to treatment showed significant differences between the groups, more women in the conservation group were able to wear their usual clothes and most women rated the cosmetic result highly. Patients were more likely to stop sexual intercourse completely after mastectomy. An effective conservation technique should be an attractive treatment choice available to selected women with early breast cancer.


Luminescent iminophosphorane gold, palladium and platinum complexes as potential anticancer agents.
A series of coordination gold(III), palladium(II), and platinum(II) complexes with a luminescent iminophosphorane ligand derived from 8-aminoquinoline [Ph3P=N-C9H6N] (1), have been synthesized and structurally characterized. The coordination palladium(II) and platinum(II) compounds can evolve further, under appropriate conditions, to give stable cyclometalated endo species [M{κ3-C,N,N-C6H4(PPh2=N-8-C9H6N}Cl] (M = Pd, Pt) by C-H activation of the phenyl group of the PPh 3 fragment. Iminophosphorane 1 and the new metallic complexes are luminescent in DMSO or DMSO:H2O (1:1 mixture) solutions at RT. The compounds have been evaluated for their antiproliferative properties in a human ovarian cancer cell line (A2780S), in human lung cancer cells (A-549) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). Most compounds have been more toxic to the ovarian cancer cell line than to the non-tumorigenic cell line. The new complexes interact with human serum albumin (HSA) faster than cisplatin. Studies of the interactions of the compounds with DNA indicate that, in some cases, they exert anticancer effects in vitro based on different mechanisms of action with respect to cisplatin.


Earring lesions of the parotid tail.
Masses in the parotid tail can be a source of consternation to radiologists and clinicians; inaccurate localization may lead to significant iatrogenic complication. We sought to review the pertinent anatomic localizing features of the parotid tail, relevant facial nerve anatomy, and sources of clinical and radiologic confusion. To conclude, we review imaging features that are helpful in generating a diagnosis in this location. We retrospectively reviewed the imaging and clinical features of 111 parotid tail masses in 103 patients (56 male, 45 female, two of unknown sex; age range, 5 months-81 years). The following imaging findings were noted: size, enhancement, multiplicity of lesions, attenuation on CT scans, signal intensity on MR images, and appearance of the surrounding parotid gland. Diagnosis was confirmed by either surgical resection or biopsy findings or by specific clinical data or characteristic imaging findings. Seventeen types of parotid tail masses were identified. Benign lesions were: pleomorphic adenoma (n = 15), Warthin tumor (n = 14), infectious process (n = 13), venous malformation (n = 9), and Sjögren disease (n = 9), lymphatic malformations (n = 7), lipoma (n = 6), HIV lymphoepithelial lesion (n = 4), first brachial cleft cyst (n = 3), oncocytoma (n = 2), sarcoid (n = 1), and lymph node (n = 1). Malignant lesions were: Non-Hodgkin lymphoma (n = 14), metastatic disease (n = 7), mucoepidermoid carcinoma (n = 4), acinic cell carcinoma (n = 1), and undifferentiated carcinoma (n = 1). Eight patients had two diagnoses. Understanding normal parotid tail anatomy is important to radiologists, because accurate localization has implications for appropriate management of masses in this location, potentially reducing the occurrence of marginal mandibular nerve injury.


Laparoscopic Assessment to Determine the Likelihood of Achieving Optimal Cytoreduction in Patients Undergoing Primary Debulking Surgery for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.
The objective of this study was to evaluate the safety and efficacy of laparoscopic assessment to determine the likelihood of achieving optimal cytoreduction (OC) in patients undergoing primary debulking surgery (PDS) for ovarian cancer. All patients who underwent diagnostic laparoscopy and PDS at our institution from January 2008 to December 2013 were identified. We determined the likelihood of achieving optimal cytoreduction by laparoscopic assessment based on tumor site, pattern of spread, and disease burden. Sensitivity was defined as the number of patients who achieved optimal cytoreduction after laparoscopic assessment divided by the number of patients with disease deemed resectable by laparoscopy. We identified 55 patients during study period. Twenty-one of the 55 patients (38%) were early stage disease. Six (10.9%) patients had disease deemed unresectable and 49 (89.1%) had disease deemed resectable at the time of laparoscopy. OC was achieved in 48 of 49 (97.9%) patients. The sensitivity of laparoscopy in predicting OC was 98% (95% confidence interval, 89.3%-99.9%). The operation was completed laparoscopically in 23 of 49 patients (47%); in 26 of 49 (53%), PDS was performed by laparotomy. There were no port site metastases reported. The rate of postoperative complications was 16%. With a median follow-up of 30 months, the median overall survival was not reached and the 75th percentile for overall survival was 37 months. Laparoscopy was shown to have a high sensitivity in predicting OC and is a feasible tool in triaging patients with ovarian cancer. Laparoscopy is not associated with adverse surgical outcomes.


Endoscopic decompression of acute intestinal distension is associated with reduced mortality in critically ill patients.
Endoscopic placement of intestinal decompression tubes is a feasible technique for treatment of acute intestinal dilation. Given the heterogeneity of the underlying diseases leading to intestinal obstruction data on the significance of endoscopic procedures for treatment of these conditions are sparse. In the study period from 2008 to 2019 all patients receiving a decompression tube were identified by retrospective chart review and analyzed. A total of 59 decompression tubes were placed in 50 patients. Technical success was achieved in 98% (58/59 tubes). As major complication one small bowel perforation occurred (1/59; 1.7%). Causes for impaired intestinal transit comprised tumor stenoses 22% (11/50), infections 18% (9/50), post-operative paralysis 14% (7/50), neurological diseases 8% (4/50), trauma 2% (1/50) and others 36% (18/50). Most patients (74%; 37/50) were critically ill and treated on intensive care unit. Treatment response after tube insertion was documented in 76% of patients (38/50) whereas 24% (12/50) did not fulfill response criteria. Patients with treatment response showed a significantly better outcome compared to non-responders. Responders had a median survival of 113 days (95% CI 41-186) compared to 15 days (95% CI 6-24) in non-responders (p = 0.002). Analysis of laboratory parameters after stratification in responders and non-responders to endoscopic therapy showed that non-responders had significantly higher levels of CRP and lower platelet count at baseline (CRP 262 mg/L (IQR 101-307) vs. 94 mg/L (IQR 26-153): p = 0.027; platelets 69 thsd/μL (IQR 33-161) vs. 199 thsd/μL (IQR 138-289): p = 0.009). Endoscopic decompression is a safe procedure for acute management of impaired intestinal transit even in critically ill patients. Response to therapy is associated with improved outcome and markers of inflammation and organ function such as CRP, platelet count and serum lactate have to be taken into account for therapy monitoring and evaluation of prognosis.


Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.
Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections.


A behavioral intervention promoting physical activity in people with subacute spinal cord injury: secondary effects on health, social participation and quality of life.
To assess, for people with subacute spinal cord injury, if rehabilitation that is reinforced with the addition of a behavioral intervention to promote physical activity leads to a better health, participation and quality of life. Randomized controlled trial. Rehabilitation centers. A total of 39 participants analyzed (45 included), with subacute spinal cord injury in inpatient rehabilitation, dependent on a manual wheelchair (33% tetraplegia, 62% motor complete, 150 ±74 days postinjury). A behavioral intervention promoting physical activity after discharge, involving 13 individual sessions delivered by a coach trained in motivational interviewing, beginning two months before and ending six months after discharge from inpatient rehabilitation. Physical capacity as determined during a maximal exercise test, body mass index, blood pressure, fasting lipid profile, and social participation (IMPACT-S) and quality of life (SF-36) were determined using questionnaires. Measurements were performed two months before discharge, at discharge, and six and 12 months after discharge from inpatient rehabilitation. B represents the between-group difference. Twelve months after discharge, significant intervention effects were found for diastolic blood pressure (B = -11.35 mmHg, 95% CI = -19.98 to -2.71), total cholesterol (B = -0.89 mmol/L, 95% CI = -1.59 to -0.20), low-density lipoprotein cholesterol (B = -0.63 mmol/L, 95% CI = -1.25 to -0.00) and participation (B = 9.91, 95% CI = 3.34 to 16.48). A behavioral intervention promoting physical activity after discharge from inpatient rehabilitation improves social participation and seems to reduce risk factors for cardiovascular disease in people with subacute spinal cord injury.


An additive effect of leading role in the organization between social participation and dementia onset among Japanese older adults: the AGES cohort study.
Several previous studies reported social participation may reduce the incident of dementia; therefore, the type of positions held in the organization may relate to dementia onset. However, this hypothesis remains largely unknown. The purpose of the present study was to examine the additive effect of a leadership position in the organization on dementia onset and social participation among elderly people in a local community, according to data from a Japanese older adults cohort study. Of 29,374 community-dwelling elderly, a total of 15,313 subjects responded to the baseline survey and were followed-up from November 2003 to March 2013. To evaluate the association between dementia onset and social participation as well as the role in the organization, we conducted Cox proportional hazard regression analysis with multiple imputation by age group (aged 75 years older or younger). The dependent variable was dementia onset, which was obtained from long-term care insurance data in Japan; independent variables were social participation and the role in the organization to which they belonged (head, manager, or treasurer). Covariates were sex, age, educational level, marriage status, job status, residence status, alcohol consumption, smoking status, and walking time, instrumental activities of daily living, depression, and medical history. During the follow-up period, 708 young-old elderly people (7.7%) and 1289 old-old elderly people (27.9%) developed dementia. In young-old elderly, relative to social non-participants, adjusted Hazard Ratio (HR) for dementia onset for participants (regular members + leadership positions) was 0.75 (95% confidence interval (CI), 0.64-0.88). Relative to regular members, adjusted HR for dementia onset for non-participants was 1.22 (95% CI, 1.02-1.46), for leadership positions 0.81 (95% CI, 0.65-0.99). The results for old-old elderly participants did not show that any significantly adjusted HR between dementia onset and social participation, the role in the organization. In young-old elderly people, social participation might have a positive effect on dementia onset, and holding leadership positions in organization could lead to a decrease in risk of dementia onset by almost 20% than regular members.


The stability studies and in vitro hepatic microsomal metabolism of some alpha-phenyl-N-substituted nitrones in rats.
Nitrones are a very important class of synthetic chemicals as synthetic intermediates, antioxidant agents, and metabolic oxidation products of secondary amines and imines used drug, food, cosmetic and printing industry. In the present study, the stability experiments and in vitro metabolism studies using rat microsomal preparations fortified with NADPH were carried out using three different alpha-phenyl-N-substituted nitrones ie alpha-phenyl-N-tert-butylnitrone (PTBN), alpha-(2,6-dichlorophenyl)-N-phenylnitrone (DCPPN) and alpha-phenyl-N-adamantanylnitrone (PADN). The separation of these compounds from the potential degradation, isomerization and metabolic products were performed using a reverse phase HPLC system with a diodearray uv detection. Following stability experiments at 37 degrees C using methanolic nitrone solutions, it was observed that PTBN produced trace amounts of benzaldehyde and the corresponding amide. DCPPN also produced trace amounts of amide. After 12 hours, the amount of the amide significantly increased. PADN produced trace amount of benzaldehyde but not any amide. The proposed compounds were incubated with rat microsomal preparations fortified with NADPH, extracted into dichloromethane (DCM) and finally evaporated under nitrogen in the dark conditions. PTBN was metabolized into corresponding amide whereas DCPPN and PADN did not. With all of the substrates, the corresponding aldehydes are observed with both test and control tubes using denaturated microsomes and without co-factors.


A study on ovine pneumonic pasteurellosis: isolation and identification of Pasteurellae and their antibiogram susceptibility pattern in Haramaya District, Eastern Hararghe, Ethiopia.
Sheep constitute the second major component of livestock in Ethiopia. However, efficient utilization of this potential resource is hampered by combination of health problems, poor management and feed shortage. Haramaya district is one of the remote settings in Ethiopia where information about the livestock disease is not well documented. Hence this study was conducted to determine the causative agents and their antimicrobial susceptibility pattern of bacterial Pasteurella isolates among pneumonic ovine in Haramaya district, Eastern Hararghe, Ethiopia. Out of 256 samples examined, Pasteurella was isolated in 64 (25%), of which 38 (59.4%) were from lungs and 26 (40.6%) were from nasal cavities. 87.5% of the isolates were Mannheimia haemolytica and 12.5% were Pasteurella multocida. All of the isolates from the lungs were Mannheimia haemolytica whereas 69% of the isolates from nasals cavities were Mannheimia haemolytica. Age and body temperature were significantly associated with Pasteurella isolates from clinic (P < 0.05). Despite diverse in the site of origins, the isolates exhibited uniformity in sensitivity to a majority of the antibacterial agents. The most effective drug was Cholramphenicol (100%) followed by Sulfamethoxazole (89.1%) and Tetracycline (84.4%). Both species were completely resistant to Gentamycin and Vancomycin. Mannheimia haemolytica is the most common cause of ovine pneumonic pasteurellosis in the study area. The isolates were susceptible to limited antimicrobial agents. Therefore, the antimicrobial susceptibility test should be conducted before treatment, except for critical cases.


Impacts of ocean acidification on carboxylated carbon nanotube effects induced in the clam species Ruditapes philippinarum.
Although the increased production of nanoparticles (NPs) has raised extensive concerns about the potential toxic effects on aquatic organisms, as well as the increasing evidences which documented the impact of ocean acidification (OA) on the physiology and fitness of marine invertebrates, limited number of studies reported their combined toxic effects. For these reasons, in the present study, we investigated the physiological and biochemical responses of one of the most economically important bivalve species in the World, the Manila clam Ruditapes philippinarum, after the exposure to an environmnetally relevant concentration of carboxylated carbon nanotubes and predicted OA conditions. The results showed that the organisms were not only susceptible to NPs but also to seawater acidification. Different responses between low pH and NPs for most tested biomarkers were observed, both in terms of physiological (respiration rate) and biochemical responses (metabolic capacity, oxitative status and neurotoxicity). Acidified pH significantly decreased the respiration rate and metabolism and increased the energy reserves consumption. Moreover, increase of the oxidative damage was also detected under this condition confirming that the mechanism of enhanced toxicity in the organisms should be attributed to lower aggregation state with more suspended NPs in acidified seawater, indicating that seawater acidification significantly influenced the impact of the used NPs in the exposed organisms.


Media-based behavioural treatments for behavioural problems in children.
Many approaches are used to address behavioural problems in childhood including medication or, more usually, psychological treatments either directly with the child and/or his/her family. Behavioural and cognitive-behavioural interventions have been shown to be highly effective but access to these treatments is limited due to factors such as time and expense. Presenting the information parents need in order to manage these behaviour problems in booklet or other media-based format would most likely reduce the cost and increase access to these interventions. To review the effects of media-based cognitive-behavioural therapies for any young person with a behavioural disorder (diagnosed using a recognised instrument) compared to standard care and no-treatment controls. The following electronic databases were systematically searched: CENTRAL (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to August 2005), EMBASE (1980 to August 2005), PsycINFO (1887 to August 2005), CINAHL (1982 to August 2005), Biosis (1985 to August 2005) and Sociofile (1974 to August 2005). References in all selected trials were checked for other trials and experts in the field were contacted for additional information. Randomised and quasi-randomised controlled trials (e.g. trials which used sequential randomisation) of media-based behavioural treatments for behaviour problems in children. Abstracts and titles of studies identified from searches of electronic databases were read to determine whether they met the inclusion criteria. Full copies of those possibly meeting these criteria from electronic or other searches were assessed by the reviewers and queries were resolved by discussion. Data were analysed using RevMan 4.2. Eleven studies including 943 participants were included within this review. In general, media-based therapies for behavioural disorders in children had a moderate, if variable, effect when compared with both no-treatment controls with effects sizes ranging from -0.12 (-1.65, 1.41) to -32.60 (-49.93, -15.27) and as and adjunct to medication with effect sizes ranging from -2.71 (-5.86, -0.44) to -39.55 (-75.01, -4.09). Significant improvements were made with the addition of up to two hours of therapist time. These formats of delivering behavioural interventions for carers of children are worth considering in clinical practice. Media-based interventions may, in some cases, be enough to make clinically significant changes in a child's behaviour, and may reduce the amount of time primary care workers have to devote to each case. They can also be used as the first stage of a stepped care approach. Consequently this would increase the number of families who could possibly benefit from these types of intervention, releasing clinician time that can be reallocated to more complex cases. Media-based therapies would therefore appear to have both clinical and economic implications as regards the treatment of children with behavioural problems.


Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension.
Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited. In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed. A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P = 0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups. Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).


Frequent deregulations in the hedgehog signaling network and cross-talks with the epidermal growth factor receptor pathway involved in cancer progression and targeted therapies.
The hedgehog (Hh)/glioma-associated oncogene (GLI) signaling network is among the most important and fascinating signal transduction systems that provide critical functions in the regulation of many developmental and physiological processes. The coordinated spatiotemporal interplay of the Hh ligands and other growth factors is necessary for the stringent control of the behavior of diverse types of tissue-resident stem/progenitor cells and their progenies. The activation of the Hh cascade might promote the tissue regeneration and repair after severe injury in numerous organs, insulin production in pancreatic beta-cells, and neovascularization. Consequently, the stimulation of the Hh pathway constitutes a potential therapeutic strategy to treat diverse human disorders, including severe tissue injuries; diabetes mellitus; and brain, skin, and cardiovascular disorders. In counterbalance, a deregulation of the Hh signaling network might lead to major tissular disorders and the development of a wide variety of aggressive and metastatic cancers. The target gene products induced through the persistent Hh activation can contribute to the self-renewal, survival, migration, and metastasis of cancer stem/progenitor cells and their progenies. Moreover, the pivotal role mediated through the Hh/GLI cascade during cancer progression also implicates the cooperation with other oncogenic products, such as mutated K-RAS and complex cross-talk with different growth factor pathways, including tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR), Wnt/beta-catenin, and transforming growth factor-beta (TGF-beta)/TGF-beta receptors. Therefore, the molecular targeting of distinct deregulated gene products, including Hh and EGFR signaling components and other signaling elements that are frequently deregulated in highly tumorigenic cancer-initiating cells and their progenies, might constitute a potential therapeutic strategy to eradicate the total cancer cell mass. Of clinical interest is that these multitargeted approaches offer great promise as adjuvant treatments for improving the current antihormonal therapies, radiotherapies, and/or chemotherapies against locally advanced and metastatic cancers, thereby preventing disease relapse and the death of patients with cancer.


The equivalence of information-theoretic and likelihood-based methods for neural dimensionality reduction.
Stimulus dimensionality-reduction methods in neuroscience seek to identify a low-dimensional space of stimulus features that affect a neuron's probability of spiking. One popular method, known as maximally informative dimensions (MID), uses an information-theoretic quantity known as "single-spike information" to identify this space. Here we examine MID from a model-based perspective. We show that MID is a maximum-likelihood estimator for the parameters of a linear-nonlinear-Poisson (LNP) model, and that the empirical single-spike information corresponds to the normalized log-likelihood under a Poisson model. This equivalence implies that MID does not necessarily find maximally informative stimulus dimensions when spiking is not well described as Poisson. We provide several examples to illustrate this shortcoming, and derive a lower bound on the information lost when spiking is Bernoulli in discrete time bins. To overcome this limitation, we introduce model-based dimensionality reduction methods for neurons with non-Poisson firing statistics, and show that they can be framed equivalently in likelihood-based or information-theoretic terms. Finally, we show how to overcome practical limitations on the number of stimulus dimensions that MID can estimate by constraining the form of the non-parametric nonlinearity in an LNP model. We illustrate these methods with simulations and data from primate visual cortex.


Viral and chloroplastic signals essential for initiation and efficiency of translation in Agrobacterium tumefaciens.
The construction of high-level protein expression vectors using the CaMV 35S promoter in concert with highly efficient translation initiation signals for Agrobacterium tumefaciens is a relatively less explored field compared to that of Escherichia coli. In the current study, we experimentally investigated the capacity of the CaMV 35S promoter to direct GFP gene expression in A. tumefaciens in the context of different viral and chloroplastic translation initiation signals. GFP expression and concomitant translational efficiency was monitored by confocal microscopy and Western blot analysis. Among all of the constructs, the highest level of translation was observed for the construct containing the phage T7 translation initiation region followed by the chloroplastic Rubisco Large Subunit (rbcL) 58-nucleotide 5' leader region including its SD-like sequence (GGGAGGG). Replacing the SD-like (GGGAGGG) with non SD-like (TTTATTT) or replacing the remaining 52 nucleotides of rbcL with nonspecific sequence completely abolished translation. In addition, this 58 nucleotide region of rbcL serves as a translational enhancer in plants when located within the 5' UTR of mRNA corresponding to GFP. Other constructs, including those containing sequences upstream of the coat proteins of Alfalfa Mosaic Virus, or the GAGG sequence of T4 phage or the chloroplastic atpI and/or PsbA 5' UTR sequence, supported low levels of GFP expression or none at all. From these studies, we propose that we have created high expression vectors in A. tumefaciens and/or plants which contain the CaMV 35S promoter, followed by the translationally strong T7 SD plus RBS translation initiation region or the rbcL 58-nucleotide 5' leader region upstream of the gene of interest.


A Review of Biological Interventions in Chronic Aphasia.
Aphasia is a common and debilitating condition following stroke. While the gold standard for aphasia treatment is behavioral speech-language therapy, benefits remain modest in chronic stages of recovery. This limitation motivates the pursuit of novel interventions for chronic aphasia. Here, we review biological approaches that have been used (or proposed for use, in the case of regenerative and genetic therapies) to treat chronic aphasia. These techniques aim to ameliorate the deficits of aphasia by directly manipulating brain function, rather than training lost or compensatory functions, although many have been used to augment effects of behavioral therapy. Specifically, we explore the most robust designs of transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and pharmacotherapy that have been applied in chronic (≥6 months) post-stroke aphasia. We also consider less investigated approaches including epidural cortical stimulation and photobiomodulation. All methods are currently in nascent phases and restricted to experimental studies and clinical trials. Although the evidence base remains limited, such interventions may ultimately improve language function and quality of life for those living with chronic aphasia. However, it is crucial that application of these methods consider the effects of concomitant speech-language therapy, as biological interventions combined with behaviorally induced experience-dependent plasticity will likely yield the most beneficial and durable outcomes.


Reactive Molecular Dynamics Simulations of the Silanization of Silica Substrates by Methoxysilanes and Hydroxysilanes.
We perform reactive molecular dynamics simulations of monolayer formation by silanes on hydroxylated silica substrates. Solutions composed of alkylmethoxysilanes or alkylhydroxysilanes in hexane are placed in contact with a hydroxylated silica surface and simulated using a reactive force field (ReaxFF). In particular, we have modeled the deposition of butyl-, octyl-, and dodecyltrimethoxysilane to observe the dependence of alkylsilyl chain length on monolayer formation. We additionally modeled silanization using dodecyltrihydroxysilane, which allows for the comparison of two grafting mechanisms of alkoxysilanes: (1) direct condensation of alkoxysilane with surface-bound silanols and (2) a two-step hydrolysis-condensation mechanism. To emulate an infinite reservoir of reactive solution far away from the substrate, we have developed a method in which new precursor molecules are periodically added to a region of the simulation box located away from the surface. It is determined that the contact angle of alkyl tails bound to the surface is dependent on their grafting density. During the early stages of grafting alkoxy- and hydroxysilanes to the substrate, a preference is shown for silanes to condense with silanols further from the substrate surface and also close to neighboring surface-bound silanols. The kinetics of silica silanization by hydroxysilanes was observed to be much faster than for methoxysilanes. However, the as-deposited hydroxysilane monolayers show similar morphological characteristics to those formed by methoxysilanes.


Potential beneficial uses of coalbed natural gas (CBNG) water.
The CBNG well water is typically managed by discharging into nearby disposal ponds. The CBNG well water could potentially be very useful in the water-limited regions (e.g., arid and semi-arid), but beneficial uses may be hindered by water quality problems. Objectives of this research were to: (1) examine trend analysis of nine years of CBNG well water at discharge (outfall) points and in corresponding disposal ponds, (2) evaluate geochemical processes, (3) identify potential water quality issues, and (4) find potential beneficial uses. The CBNG well water at discharge points and in corresponding disposal ponds was measured on-site for pH and electrical conductivity (EC). These water samples were also analyzed in the laboratory for calcium (Ca), sodium (Na), magnesium (Mg), potassium (K), iron (Fe), aluminum (Al), copper (Cu), arsenic (As), selenium (Se), cadmium (Cd), and barium (Ba). Total dissolved solids (TDS) were calculated from EC measurements. The sodium adsorption ratio (SAR) was calculated from Na, Ca, and Mg concentrations. Trend analyses of outfalls and disposal ponds were conducted separately so that the differences in trends could be compared. Trends in CBNG well water at discharge points are not always the same as trends in CBNG disposal ponds: environmental and geochemical processes play an important role in the water quality of these well waters. Overall trend analyses suggest that CBNG well water at discharge points in all basins of the Powder River Basin meets beneficial use criteria, except for SAR and to some extent EC, for aquatic life, livestock and wildlife watering, and irrigation. The CBNG well water in disposal ponds across all basins meets criteria for all beneficial uses except for As, pH, SAR, and to some extent EC for irrigation, aquatic life, and livestock and wildlife watering.


Household actions can provide a behavioral wedge to rapidly reduce US carbon emissions.
Most climate change policy attention has been addressed to long-term options, such as inducing new, low-carbon energy technologies and creating cap-and-trade regimes for emissions. We use a behavioral approach to examine the reasonably achievable potential for near-term reductions by altered adoption and use of available technologies in US homes and nonbusiness travel. We estimate the plasticity of 17 household action types in 5 behaviorally distinct categories by use of data on the most effective documented interventions that do not involve new regulatory measures. These interventions vary by type of action and typically combine several policy tools and strong social marketing. National implementation could save an estimated 123 million metric tons of carbon per year in year 10, which is 20% of household direct emissions or 7.4% of US national emissions, with little or no reduction in household well-being. The potential of household action deserves increased policy attention. Future analyses of this potential should incorporate behavioral as well as economic and engineering elements.


Frequency and correlates of DSM-5 attenuated psychosis syndrome in a sample of adolescent inpatients with nonpsychotic psychiatric disorders.
DSM-5 conceptualized attenuated psychosis syndrome (APS) as self-contained rather than as a risk syndrome, including it under "Conditions for Further Study," but also as a codable/billable condition in the main section. Since many major mental disorders emerge during adolescence, we assessed the frequency and characteristics of APS in adolescent psychiatric inpatients. Consecutively recruited adolescents hospitalized for nonpsychotic disorders (September 2009-May 2013) were divided into APS youth versus non-APS youth, based on the Structured Interview of Prodromal Syndromes (SIPS) and according to DSM-5 criteria, and compared across multiple characteristics. Of 89 adolescents (mean ± SD age = 15.1 ± 1.6 years), 21 (23.6%) had APS. Compared to non-APS, APS was associated with more comorbid disorders (2.7 ± 1.0 vs 2.2 ± 1.3), major depressive disorder (61.9% vs 27.9%), oppositional defiant disorder/conduct disorder (52.4% vs 25.0%), and personality disorder traits (57.1% vs 7.4%, the only diagnostic category surviving Bonferroni correction). APS youth were more severely ill, having higher SIPS total positive, negative, and general symptoms; Brief Psychiatric Rating Scale total and positive scores; depression and global illness ratings; and lower Global Assessment of Functioning (GAF). Conversely, Young Mania Rating Scale scores, suicidal behavior, prescribed psychotropic medications, and mental disorder awareness were similar between APS and non-APS groups. In multivariable analysis, lowest GAF score in the past year (odds ratio [OR] = 51.15; 95% confidence interval [CI], 2.46-2,439.0) and social isolation (OR = 27.52; 95% CI, 3.36-313.87) were independently associated with APS (r(2) = 0.302, P < .0001). Although psychotic disorders were excluded, 65.2% (APS = 57.1%, non-APS = 67.7%, P = .38) received antipsychotics. One in 4 nonpsychotic adolescent inpatients met DSM-5 criteria for APS. APS youth were more impaired, showing a complex entanglement with a broad range of psychiatric symptoms and disorders, including depression, impulse-control, and, especially, emerging personality disorders. ClinicalTrials.gov identifier: NCT01383915.


Five-Year Eradication of Hepatitis B Infection After an Outreach Immunization Program in the Waorani Population in the Ecuadorian Amazon.
In Waorani communities of the Amazon basin of Ecuador, hepatitis B (HB) surface antigen was found in 14% of asymptomatic persons. The aim of this study was to identify the Waorani population in Ecuador and obtain an epidemiologically adequate coverage of vaccination against hepatitis B virus (HBV) among them. Between February and September 2010, three vaccination campaigns were completed as part of a collaborative activity between the Ecuadorian Ministry of Public Health and the community leaders in the intervention areas. In addition, in 10 of the 22 Waorani communities, during first contact, a questionnaire about risk factors for HBV infection was administered. A total of 16 Waorani communities were registered before the beginning of this intervention, but during the actual process, six additional communities were identified. In total, 1,251 community members were registered, 92.7% of which received all three doses of the vaccine. Among them, 83% of survey respondents reported having been vaccinated, but only 22% were able to show proof. Only 1% of respondents were intravenous drug users, whereas 22% had at least one tattoo. All self-identified as heterosexual, but only 32% reported using condoms during sexual intercourse. By March 2015, no new cases of HB were been reported in any of the Waorani communities. Herein, we report the importance of intersectoral collaboration to strengthen health interventions in an isolated population like the Waorani area.


Bordetella holmesii bacteremia in asplenic children: report of four cases initially misidentified as Acinetobacter lwoffii.
Bordetella holmesii is a fastidious Gram-negative rod that was initially identified in 1995. It causes bacteremia, predominantly among patients with anatomical or functional asplenia. We report four cases of B. holmesii bacteremia in asplenic children occurring within the last 4 years. In all cases, B. holmesii was misidentified by an automated system as Acinetobacter lwoffii.


Impact of fluoride and a static magnetic field on the gene expression that is associated with the antioxidant defense system of human fibroblasts.
Fluoride cytotoxicity has been associated with apoptosis, oxidative stress, general changes in DNA and RNA and protein biosynthesis, whereas the results of studies on the effect of SMF on antioxidant activity of cells are contradictory. Therefore, the aim of our study was to evaluate the simultaneous exposure of human cells to fluoride SMF that are generated by permanent magnets on the expression profile of the genes that are associated with the antioxidant defense system. Control fibroblasts and fibroblasts that had been treated with fluoride were subjected to the influence of SMF with a moderate induction. In order to achieve our aims, we applied modern molecular biology techniques such as the oligonucleotide microarray. Among the antioxidant defense genes, five (SOD1, PLK3, CLN8, XPA, HAO1), whose expression was significantly altered by the action of fluoride ions and the exposure to SMF were normalized their expression was identified. We showed that fluoride ions cause oxidative stress, whereas exposure to SMF with a moderate induction can suppress their effects by normalizing the expression of the genes that are altered by fluoride. Our research may explain the molecular mechanisms of the influence of fluoride and SMF that are generated by permanent magnets on cells.


Best Practices of Blood Cultures in Low- and Middle-Income Countries.
Bloodstream infections (BSI) have a substantial impact on morbidity and mortality worldwide. Despite scarcity of data from many low- and middle-income countries (LMICs), there is increasing awareness of the importance of BSI in these countries. For example, it is estimated that the global mortality of non-typhoidal Salmonella bloodstream infection in children under 5 already exceeds that of malaria. Reliable and accurate diagnosis of these infections is therefore of utmost importance. Blood cultures are the reference method for diagnosis of BSI. LMICs face many challenges when implementing blood cultures, due to financial, logistical, and infrastructure-related constraints. This review aims to provide an overview of the state-of-the-art of sampling and processing of blood cultures, with emphasis on its use in LMICs. Laboratory processing of blood cultures is relatively straightforward and can be done without the need for expensive and complicated equipment. Automates for incubation and growth monitoring have become the standard in high-income countries (HICs), but they are still too expensive and not sufficiently robust for imminent implementation in most LMICs. Therefore, this review focuses on "manual" methods of blood culture, not involving automated equipment. In manual blood cultures, a bottle consisting of a broth medium supporting bacterial growth is incubated in a normal incubator and inspected daily for signs of growth. The collection of blood for blood culture is a crucial step in the process, as the sensitivity of blood cultures depends on the volume sampled; furthermore, contamination of the blood culture (accidental inoculation of environmental and skin bacteria) can be avoided by appropriate antisepsis. In this review, we give recommendations regarding appropriate blood culture sampling and processing in LMICs. We present feasible methods to detect and speed up growth and discuss some challenges in implementing blood cultures in LMICs, such as the biosafety aspects, supply chain and waste management.