Temperature-dependent development and demography of Scymnus subvillosus (Coleoptera: Coccinellidae) reared on Hyalopterus pruni (Homoptera: Aphididae).
The development, survival, and fecundity of Scymnus subvillosus (Goeze) (Coleoptera: Coccinellidae) were studied at 20, 25, 30, and 35 degrees C, 60 +/- 5% RH, and a photoperiod of 16:8 (L:D) h (5,000 lux) under laboratory conditions. The total developmental time from egg hatch to adult eclosion ranged from 22.6 d at 20 degrees C to 10.6 d at 35 degrees C. The developmental rates of the egg stage, the larval stage, and total preadult stage at different temperatures increased linearly with increasing temperature. The thermal summation of the egg stage, the larval stage, and the total preadult stage was 77.5, 145.8 and 300 degree-days (DD), respectively. The developmental threshold of the egg stage, the larval stage, and the total preadult stage was 7.4, 4.1, and 7.1 degrees C, respectively. The life history raw data were analyzed using the age-stage, two-sex life table. The intrinsic rate of increase was 0.0845, 0.1138, 0.1395, and 0.0668 d(-1) at 20, 25, 30, and 35 degrees C, respectively. The net reproductive rate was highest at 25 degrees C (R0 = 78.7), and lowest at 35 degrees C (R0 = 4.7). The mean generation time was shortest at 35 degrees C (T = 23.9 d). The life table data can be used for the projection of population growth and designing mass rearing programs.


Epstein-Barr virus infection is predictive of CNS involvement in systemic AIDS-related non-Hodgkin's lymphomas.
This study aimed at correlating Epstein-Barr virus (EBV) infection of systemic AIDS-related non-Hodgkin lymphomas (AIDS-NHL) with the development of a CNS localization of the tumor. Demographic, epidemiologic, clinical, histologic, and virologic features were collected for all systemic AIDS-NHL patients included in the study (n = 50). Pathologic specimens were classified according to the working formulation for NHL and the Revised European-American Lymphoma classification. EBV infection in tumor tissue samples was studied by EBV small encoded RNA in situ hybridization; EBV-DNA detection in CSF was carried out by nested polymerase chain reaction using Epstein-Barr nuclear antigen-1-specific primers. In addition, selected EBV-positive lymphomas were subjected to a detailed characterization of EBV molecular heterogeneity. Eleven patients had a CNS involvement at some point during their clinical history (four at diagnosis and seven at relapse). Thirty patients (11 with CNS involvement and 19 without) harbored EBV infection of the tumor. Sensitivity, specificity, and positive and negative predictive values of EBV-DNA detection in CSF for CNS involvement by lymphoma were 90%, 100%, 100%, and 97.6%, respectively. Factors significantly predictive of CNS involvement were EBV infection of the tumor (P=.003), an extranodal disease at diagnosis other than CNS (P=.006), and a non-CNS relapse (P=.01). In four cases of CNS involvement, EBV-DNA in CSF preceded any other sign of disease by a mean of 35 days. These results show that EBV infection of the tumor clone significantly increases the risk of CNS involvement by systemic AIDS-NHL, without regard of specific molecular features. The detection of EBV-DNA in the CSF of AIDS-NHL patients may select cases with higher risk of CNS involvement and, therefore, may prove useful in the therapeutic stratification of these tumors.


Inappropriate antibiotic prescribing and demand for antibiotics in patients with upper respiratory tract infections is hardly different in female versus male patients as seen in primary care.
Unnecessary prescribing of antibiotics is a major public health concern. General practitioners (GPs) prescribe most antibiotics, often for upper respiratory tract infections (URTIs), and have in general been shown to prescribe antibiotics more often to women. No studies have examined the influence of patient gender on unnecessary antibiotic prescribing. To study a possible gender difference in unnecessary antibiotic prescriptions for URTIs in general practice; to assess whether a possible difference is explained by patient demand for antibiotics. Post-hoc analysis of a cross-sectional study including 15,022 patients with URTI (acute rhinitis, acute otitis media, acute sinusitis, acute pharyngotonsillitis) from Argentina, Denmark, Lithuania, Russia, Spain and Sweden (HAPPY AUDIT Project). The association between gender and unnecessary antibiotic prescriptions, unadjusted and adjusted for treatment demand, was analysed using logistic regression models. A total of 25% of patients with URTI received antibiotics; in 45% of the cases, antibiotics were unnecessary. Overall, no gender difference for unnecessary prescribing of antibiotics for URTIs was found. Women with acute otitis media received an unnecessary antibiotic twice as often as men (14.4% versus 7.1%). In Danish patients with acute pharyngotonsillitis, there was a gender difference in unnecessary prescriptions for antibiotics (women 29.1% versus men 48.6%). Some 14% of patients receiving unnecessary antibiotics demonstrated a demand for antibiotics, but no gender difference was found in this group. This study indicated a high rate of unnecessary antibiotic prescribing for URTIs in general practice, but overall found no gender differences in receiving unnecessary antibiotic prescriptions.


Self-organization in a simple model of adaptive agents playing 2 x 2 games with arbitrary payoff matrices.
We analyze, both analytically and numerically, the self-organization of a system of "selfish" adaptive agents playing an arbitrary iterated pairwise game (defined by a 2 x 2 payoff matrix). Examples of possible games to play are the prisoner's dilemma (PD) game, the chicken game, the hero game, etc. The agents have no memory, use strategies not based on direct reciprocity nor "tags" and are chosen at random, i.e., geographical vicinity is neglected. They can play two possible strategies: cooperate (C) or defect (D). The players measure their success by comparing their utilities with an estimate for the expected benefits and update their strategy following a simple rule. Two versions of the model are studied: (1) the deterministic version (the agents are either in definite states C or D) and (2) the stochastic version (the agents have a probability c of playing C). Using a general master equation we compute the equilibrium states into which the system self-organizes, characterized by their average probability of cooperation c(eq). Depending on the payoff matrix, we show that c(eq) can take five different values. We also consider the mixing of agents using two different payoff matrices and show that any value of c(eq) can be reached by tuning the proportions of agents using each payoff matrix. In particular, this can be used as a way to simulate the effect of a fraction d of "antisocial" individuals--incapable of realizing any value to cooperation--on the cooperative regime hold by a population of neutral or "normal" agents.


Characterization of PfPuf2, member of the Puf family RNA-binding proteins from the malaria parasite Plasmodium falciparum.
Puf proteins are a family of evolutionarily conserved translational regulators in eukaryotes. The malaria parasite has two Puf proteins (PfPuf1 and PfPuf2) that share 25% homology in the RNA binding domain. Here we confirmed the preferential expression of PfPuf2 in gametocyte stages using Northern analysis. The transcriptional initiation site of this gene, mapped using RNA ligase-mediated rapid amplification of cDNA end and primer extension, is located approximately 300 bp upstream from the translational start codon. The 3' end of PfPuf2 is located approximately 250 bp downstream from the stop codon. The total length of the RNA is approximately 2.1 kb, consistent with the mRNA size determined by Northern analysis. Recombinant PfPuf2 proteins expressed in bacteria were purified and used to produce polyclonal antibodies. Western blot further established the preferential synthesis of PfPuf2 in gametocyte stages. Using the Nanos-responsive elements (NRE) in the Hunchback mRNA of Drosophila melanogaster as an artificial target sequence, we tested the binding of PfPuf2 Puf domain to this sequence using the yeast three-hybrid system. The results showed that PfPuf2 Puf domain bound specifically to NRE, suggesting that PfPuf2 may be involved in translational regulation of target genes using a conserved mechanism of the Puf family proteins.


The combined effects of salinity and pH on shell biomineralization of the edible mussel Mytilus chilensis.
Coastal ecosystems influenced by river discharges are subjected to important environmental changes. Understanding how marine biota cope with its environment is relevant in predicting the responses to future conditions imposed by climate change. To date, a large number of studies have addressed the role of pH on shell and biomineralization properties on multiple calcifying species; however the role of salinity in combination with other stressors has been poorly studied. In particular, the edible mussel Mytilus chilensis, an important marine resource of the Chilean coasts, inhabits estuarine areas which show high natural variability in terms of pH and salinity. Here, we studied how M. chilensis shell periostracum, shell organic matrix and crystal orientation are affected by different pH (8.1 and 7.7) and salinity conditions (30, 25 and 20 psu), isolated and in combination, at different time intervals. Our results show differences in the plasticity of the different biomineralogical properties studied during the experiment under the different pH and salinity treatments. While the periostracum thickness and the total shell organic matter were not affected by pH and salinity, the periostracum organic composition did. Higher amounts of polysaccharides were observed under low pH conditions after 20 days of experiment, while after 60 days, low salinity was responsible for the decrease of the polysaccharides and proteins in the periostracum. Low salinity also produced a major disorder in crystal organization at the outer shell surface. Finally, total shell weight was only affected by low pH conditions under lower salinity conditions (20 psu). From the results, in the majority of the shell properties observed we did not observe any combined effect of pH and salinity. Also, we detected that the magnitude of the impacts of salinity and pH are variable and time-dependent. This would be suggesting some level of acclimatization of M. chilensis to lower pH and salinity conditions.


Human natural killer cells exposed to IL-2, IL-12, IL-18, or IL-4 differently modulate priming of naive T cells by monocyte-derived dendritic cells.
Dendritic cells (DCs) play a crucial role in naive T-cell priming. Recent data suggested that natural killer (NK) cells can influence the capability of DCs to promote Th1 polarization. This regulatory function is primarily mediated by cytokines released in the microenvironment during inflammatory responses involving NK cells. In this study, we show that human NK cells exposed for short time to interleukin (IL)-12, IL-2, or IL-18, promote distinct pathways of Th1 priming. IL-12- or IL-2-conditioned NK cells induce maturation of DCs capable of priming IFN-gamma-producing Th1 cells. On the other hand, IL-18-conditioned NK cells induce Th1 polarization only when cocultured with both DCs and T cells. In this case, IL-2 released by T cells and IL-12 derived from DCs during the priming process promote interferon (IFN)-gamma production. In contrast, when NK cells are exposed to IL-4, nonpolarized T cells releasing only low levels of IL-2 are generated. Thus, the prevalence of IL-12, IL-2, IL-18, or IL-4 at inflammatory sites may differentially modulate the NK-cell interaction with DCs, leading to different outcomes in naive T-cell polarization.


Development and external validation of dual online tools for prognostic assessment in elderly patients with high-grade glioma: a comprehensive study using SEER and Chinese cohorts.
Elderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict overall survival (OS) and cancer-specific survival (CSS), assisting clinical decision-making. We scrutinized data from the SEER database on 5,245 elderly patients diagnosed with high-grade glioma between 2000-2020, segmenting them into training (3,672) and validation (1,573) subsets. An additional external validation cohort was obtained from our institution. Prognostic determinants were pinpointed using Cox regression analyses, which facilitated the construction of the nomogram. The nomogram's predictive precision for OS and CSS was gauged using calibration and ROC curves, the C-index, and decision curve analysis (DCA). Based on risk scores, patients were stratified into high or low-risk categories, and survival disparities were explored. Using multivariate Cox regression, we identified several prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with high-grade gliomas, including age, tumor location, size, surgical technique, and therapies. Two digital nomograms were formulated anchored on these determinants. For OS, the C-index values in the training, internal, and external validation cohorts were 0.734, 0.729, and 0.701, respectively. We also derived AUC values for 3-, 6-, and 12-month periods. For CSS, the C-index values for the training and validation groups were 0.733 and 0.727, with analogous AUC metrics. The efficacy and clinical relevance of the nomograms were corroborated via ROC curves, calibration plots, and DCA for both cohorts. Our investigation pinpointed pivotal risk factors in elderly glioma patients, leading to the development of an instrumental prognostic nomogram for OS and CSS. This instrument offers invaluable insights to optimize treatment strategies.


Effect of a major quantitative trait locus for porcine reproductive and respiratory syndrome (PRRS) resistance on response to coinfection with PRRS virus and porcine circovirus type 2b (PCV2b) in commercial pigs, with or without prior vaccination for PRRS.
A major QTL for host response to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infection was identified in a previous study. Single nucleotide polymorphism WUR10000125 (WUR), which is in complete linkage disequilibrium with the putative causative mutation, can be used as a tag SNP for the QTL. However, the effect of WUR following PRRS vaccination and/or coinfection with other pathogens is not known. Therefore, objectives of this study were to estimate the effect of WUR on host response following PRRS vaccination and coinfection of PRRSV with porcine circovirus type 2b (PCV2b), to estimate genetic parameters for host response to vaccination and coinfection, and to estimate the effect of previously identified candidate SNP under PRRSV-only or PCV2b-only infection on host response to coinfection. Data from 2 trials, comprising a total of 396 commercial crossbred nursery pigs from a single genetic source, were used for all analyses. Pigs were preselected based on WUR genotype: approximately half AA and half AB, where B is the favorable and dominant allele. At weaning, pigs were shipped to Kansas State University, where half of the pigs were vaccinated with a PRRS modified live virus vaccine. Four weeks later, all pigs were coinfected with field strains of PRRSV and PCV2b and followed for 42 d. Body weight and serum viremia measurements were collected following vaccination and coinfection to calculate ADG and viral load (VL), respectively. Average heritability estimates for PRRS VL, PCV2b VL, and ADG were 0.29, 0.09, and 0.40, respectively. After vaccination, AB pigs had lower vaccination VL ( = 0.03) and faster gain ( = 0.004) than AA pigs, as expected. After coinfection, AB pigs had lower PRRSV VL ( < 0.001) but did not significantly differ from AA pigs in growth rate ( = 0.86). For PCV2b VL, suggestive evidence of an interaction between vaccination and WUR genotype ( = 0.11) was detected, where AB pigs had significantly lower PCV2b VL when vaccinated ( = 0.007) but not when they were not vaccinated ( = 0.87). In addition to WUR, several PRRS-associated SNP and a PCV2b-associated SNP had significant effects on host response to coinfection. In conclusion, marker-assisted selection based on WUR genotype alone, or along with other candidate SNP for PRRSV and PCV2b infection, is a promising strategy to select for improved host response to not just PRRS but also coinfection of PRRSV with PCV2b and perhaps other pathogens.


Evaluation of microcirculation in elderly patients with venous trophic ulcers.
Altogether 112 patients over 50 years of age suffering from varicosity and chronic trophic ulcers of the distal limb segments were examined. The work was based on an analysis of the microcirculatory flow in lower limb tissues (laser Doppler flowmetry, BLF 21 system, Transonic Systems Inc., USA) and on the evaluation of tissue metabolism by measuring partial oxygen and carbon dioxide tension (percutaneous polarography; TCM-3 system, Radiometry Company, Denmark). The postischemic and orthostatic tests were used to assess the functional microcirculatory reserve. The data obtained indicate local tissue hypoxia in elderly patients with venous trophic ulcers associated with an increase of the basal flow only in the lower third of the leg. Venous trophic ulcers are marked by a significant reduction of partial oxygen tension in the tissues adjacent to the area of trophic ulcers to 4.3+/-0.5 mm Hg on the average in the presence of the low functional microcirculatory reserve. Local tissue hypoxia in the area of trophic ulcers, which develops despite an increase of blood inflow to the microcirculatory bed evidences inhibition of tissue flow and activation of the arterio-venular bypasses. The results obtained in the course of the study allow to optimize the treatment policy in elderly patients suffering from venous trophic ulcers. In addition to the measures lowering venous hypertension, the treatment should include correction of microcirculatory disorders, which is to be carried out in the pre- and postoperative periods.


Acute febrile respiratory reaction after praziquantel treatment during asymptomatic late form of acute schistosomiasis.
Paradoxical reactions (Jarish Herxheimer-like reactions) have been described in patients treated with praziquantel (PZQ) during acute schistosomiasis (infected≤ 3 mo), while PZQ treatment of chronic schistosomiasis is generally considered to be safe. We report an acute febrile reaction with respiratory decompensation following PZQ treatment in a 17-year-old male patient who had no potential (re)exposure to infection for at least 5 months and was therefore considered to have reached the chronic stage of disease. We speculate that the clinical manifestations in our patient constitute a very late paradoxical reaction in an unusually long acute phase of infection.


Prevalence of Extended-Spectrum Beta-Lactamase Resistance and CTX-M-Group 1 Gene in Escherichia coli from the Water and Sediment of Urbanized Mangrove Ecosystems of Kerala.
The study aimed to determine the prevalence of extended-spectrum β-lactamase resistance and CTX-M-group 1 gene in Escherichia coli from the water and sediment of three urbanized mangrove ecosystems of Kerala. A total of 119 E. coli isolates were screened for antibiotic susceptibility to 16 antibiotics. According to the phylogenetic analysis of E. coli isolates, nonpathogenic group A and pathogenic group D (29.4% and 23.5%) were the predominant phylotypes found in water samples. The most frequent phylotypes found in sediment samples were nonpathogenic groups A and B1 (27.9% and 26.4%). The highest incidence of antibiotic resistance in E. coli was against cefotaxime and colistin (100%). A significant difference in the prevalence of CTX-M-group 1 gene was observed among E. coli isolates in water samples (p < 0.05). The results indicate a high prevalence of β-lactamase harboring E. coli in the mangrove ecosystems that can hamper mangrove-dependent aquaculture practices and human health.


Preparation and mechanical properties of edible rapeseed protein films.
Edible films were manufactured from rapeseed oil extraction residues. To prepare rapeseed protein (RP) films, various concentrations of plasticizers and emulsifiers were incorporated into the preparation of a film-forming solution. The optimal conditions for the preparation of the RP film were 2% sorbitol/0.5% sucrose as plasticizer and 1.5% polysorbate 20 as an emulsifier. In addition, RP blend films were prepared. Gelidium corneum or gelatin was added to improve the physical properties of the RP film, and the highest tensile strength value of the films was 53.45 MPa for the 3% RP/4% gelatin film. Our results suggest that the RP-gelatin blend film is suitable for applications in food packaging. Edible RP films prepared in the present investigation can be applied in food packaging.


Immunoexpression of P16INK4a, Rb and TP53 proteins in bronchiolar columnar cell dysplasia (BCCD) in lungs resected due to primary non-small cell lung cancer.
Lung cancer is the leading cause of death worldwide. High mortality comes out mainly of the fact that majority of the cases are diagnosed in advanced stadium. An expanded diagnostics of precancerous conditions would certainly contribute to lowering the mortality rate. Many of the molecular changes accompanying the multistep cancer development could be observed using the immunohistochemistry method. In this paper we describe the morphology and cell cycle proteins immunoexpression of the novel probable preinvasive lesion - bronchiolar columnar cell dysplasia (BCCD). Thirty cases of BCCD selected out of 193 patients population, treated for primary non-small cell lung cancer were investigated. Loss of P16INK4a protein was observed in 70% of all cases and was statistically significant in patients with adenocarcinoma. Two cases show abnormal cytoplasmic localization of this protein. TP53 protein accumulates in 26.7% of all BCCD. Rb protein was active in 48.3% of the BCCD cases. In two cases we observed differentiation of the cells composing BCCD into multilayer epithelium of the squamous type, which occurs with formation of desmosomes. We suppose that BCCD may be preneoplastic lesion leading to adenocarcinoma as well as to peripheral squamous cell lung cancer.


From Embryotomy to Cesarean: Changes in Obstetric Operatory Techniques in Nineteenth- and Twentieth-Century Urban Brazil.
This article traces the historical processes by which Brazil became a world leader in cesarean sections. It demonstrates that physicians changed their position toward and use of different obstetric surgeries, in particular embryotomies and cesarean sections, over the course of the nineteenth and twentieth centuries. The authors demonstrate that Catholic obstetricians, building upon both advancements in cesarean section techniques and new civil legislation that gave some personhood to fetuses, began arguing that fetal life was on par with its maternal counterpart in the early twentieth century, a shift that had a lasting impact on obstetric practice for decades to come. In the second half of the twentieth century, cesarean sections proliferated in clinical practice, but abortions remained illegal. Most importantly, women remained patients to be worked on rather than active participants in their reproductive lives.


Cognitive behavioral treatment groups for people with chronic depression in Hong Kong: a randomized wait-list control design.
This study examined the effectiveness of a cognitive-behavioral treatment (CBT) group for Chinese people with depression in Hong Kong. Ninety-six subjects with depression were randomly assigned to CBT and control groups. After 10 weeks of treatment, participants in the CBT group had significantly fewer symptoms of depression, dysfunctional rules, and negative emotions, and significantly more adaptive coping skills when compared to the participants in the control group. Effect size statistics showed medium to large differences in symptoms of depression, coping skills, dysfunctional rules, and assumptions and negative emotions between the participants of the two groups (Cohen's d, between 0.50 and 0.88, except for positive emotions). Forty percent of the participants in the experimental group achieved a clinically significant level [reliable change index (RC)>1.96] of improvement. Lastly, the results of a multiple regression analysis provided some evidence of a linkage between cognition and depression among the participants in the experimental group. The design and content of the CBT groups, which aimed at facilitating the understanding and modification of automatic thoughts and dysfunctional rules, and of negative and positive coping skills among the participants, might have contributed to the initial positive results.


Sexual sadism in the context of rape and sexual homicide: an examination of crime scene indicators.
This study investigates the convergent and predictive validity of behavioral crime scene indicators of sexual sadism in the context of rape and sexual homicide. The study is based on a sample of 268 adult males sentenced to a federal penitentiary in Canada. Information regarding crime scene behaviors was gathered from police records, a clinical interview with a psychologist, and a semistructured interview with the offender. A series of logistic regressions were performed to determine whether behavioral crime scene indicators of sexual sadism were associated with an official diagnosis of sexual sadism and were able to distinguish between sexual aggressors against women and sexual murderers. Findings suggest that several crime scene behaviors overlap with an official diagnosis of sexual sadism as well as being able to distinguish between sexual aggressors of women and sexual murderers. Importantly, the majority of crime scene behaviors associated with a clinical diagnosis of sexual sadism are not the same as those associated with sexual homicide.


Network Types and Functional Health in Old Age: It is Not Just the Size of the Network That Matters.
Findings on the effect of network size and support on functional health are mixed. We examine whether network types, that simultaneously incorporate multiple network characteristics, are associated with functional health in late life. Data are from the National Social Life, Health, and Aging Project (N = 3005). We estimated the longitudinal effect of membership in five multidimensional network types on disability in six activities of daily living using negative binomial regression, and on mobility (assessed using a timed walk test) using a generalized linear mixed model. Compared to those in the large without strain network, older adults in the small, restricted, high contact network had fewer disabilities but worse mobility, while those in the large network with strain also had worse mobility. Care plans focusing on function and mobility should consider multiple aspects of older adults' social networks including network size, diversity, and relationship strain.


Laboratory diagnostics in dog-mediated rabies: an overview of performance and a proposed strategy for various settings.
The diagnosis of dog-mediated rabies in humans and animals has greatly benefited from technical advances in the laboratory setting. Approaches to diagnosis now include the detection of rabies virus (RABV), RABV RNA, or RABV antigens. These assays are important tools in the current efforts aimed at the global elimination of dog-mediated rabies. The assays available for use in laboratories are reviewed herein, as well as their strengths and weaknesses, which vary with the types of sample analyzed. Depending on the setting, however, the public health objectives and use of RABV diagnosis in the field will also vary. In non-endemic settings, the detection of all introduced or emergent animal or human cases justifies exhaustive testing. In dog RABV-endemic settings, such as rural areas of developing countries where most cases occur, the availability of or access to testing may be severely constrained. Thus, these issues are also discussed along with a proposed strategy to prioritize testing while access to rabies testing in the resource-poor, highly endemic setting is improved. As the epidemiological situation of rabies in a country evolves, the strategy should shift from that of an endemic setting to one more suitable for a decreased rabies incidence following the implementation of efficient control measures and when nearing the target of dog-mediated rabies elimination.


Hemp ( Cannabis sativa L.) seed oil: analytical and phytochemical characterization of the unsaponifiable fraction.
Non-drug varieties of Cannabis sativa L., collectively namely as "hemp", have been an interesting source of food, fiber, and medicine for thousands of years. The ever-increasing demand for vegetables oils has made it essential to characterize additional vegetable oil through innovative uses of its components. The lipid profile showed that linoleic (55%), α-linolenic (16%), and oleic (11%) were the most abundant fatty acids. A yield (1.84-1.92%) of unsaponifiable matter was obtained, and the most interesting compounds were β-sitosterol (1905.00 ± 59.27 mg/kg of oil), campesterol (505.69 ± 32.04 mg/kg of oil), phytol (167.59 ± 1.81 mg/kg of oil), cycloartenol (90.55 ± 3.44 mg/kg of oil), and γ-tocopherol (73.38 ± 2.86 mg/100 g of oil). This study is an interesting contribution for C. sativa L. consideration as a source of bioactive compounds contributing to novel research applications for hemp seed oil in the pharmaceutical, cosmetic food, and other non-food industries.


Diagnosis of mastocytosis subsets using a morphometric point counting technique.
Mastocytosis, a disease that varies in its clinical presentation, is usually documented by histologic examination of lesional skin. However, no universally accepted histopathologic criteria exist for establishing the diagnosis of this disease. We have combined the method of morphometric point counting with the mast cell-specific stain, conjugated avidin, to accurately quantify mast cells in cutaneous tissue sections of mastocytosis. Using this histologic approach, we found that macules, papules, and nodules of mast cell disease had from ninefold to nearly a 160-fold greater mast cell content than was observed in normal skin and in several other cutaneous disorders. This technique also permitted the objective histologic stratification of mastocytosis skin lesions according to their mast cell density. Morphometric point counting in conjunction with conjugated avidin offers a simple and accurate method for establishing the diagnosis of mastocytosis.


Hereditary spastic paraplegia: More than an upper motor neuron disease.
Hereditary spastic paraplegias (HSPs) are a group of rare inherited neurological diseases characterized by extreme heterogeneity in both their clinical manifestations and genetic backgrounds. Based on symptoms, HSPs can be divided into pure forms, presenting with pyramidal signs leading to lower-limb spasticity, and complex forms, when additional neurological or extraneurological symptoms are detected. The clinical diversity of HSPs partially reflects their underlying genetic backgrounds. To date, 76 loci and 58 corresponding genes [spastic paraplegia genes (SPGs)] have been linked to HSPs. The genetic diagnosis is further complicated by the fact that causative mutations of HSP can be inherited through all possible modes of transmission (autosomal-dominant and -recessive, X-linked, maternal), with some genes showing multiple inheritance patterns. The pathogenic mutations of SPGs primarily lead to progressive degeneration of the upper motor neurons (UMNs) comprising corticospinal tracts. However, it is possible to observe lower-limb muscle atrophy and fasciculations on clinical examination that are clear signs of lower motor neuron (LMN) involvement. The purpose of this review is to classify HSPs based on their degree of motor neuron involvement, distinguishing forms in which only UMNs are affected from those involving both UMN and LMN degeneration, and to describe their differential diagnosis from diseases such as amyotrophic lateral sclerosis.


[State of the osteoarticular apparatus of the craniovertebral region following restorative-reconstructive surgery].
Clinico-radiological examination of patients with a history of various types of operative treatment conducted on the craniovertebral region and cervical segment of the spine located below it established more precisely that in many cases neither decompression nor stabilization could completely arrest and eliminate the pathological process and the appearance of secondary deformities and neurological disorders in this region. That is why many operative methods for the management of lesions in this region require further study and elaboration.


Predicting the semantic category of internally generated words from neuromagnetic recordings.
In this study, we explore the possibility to predict the semantic category of words from brain signals in a free word generation task. Participants produced single words from different semantic categories in a modified semantic fluency task. A Bayesian logistic regression classifier was trained to predict the semantic category of words from single-trial MEG data. Significant classification accuracies were achieved using sensor-level MEG time series at the time interval of conceptual preparation. Semantic category prediction was also possible using source-reconstructed time series, based on minimum norm estimates of cortical activity. Brain regions that contributed most to classification on the source level were identified. These were the left inferior frontal gyrus, left middle frontal gyrus, and left posterior middle temporal gyrus. Additionally, the temporal dynamics of brain activity underlying the semantic preparation during word generation was explored. These results provide important insights about central aspects of language production.


Race Differences in Interventions and Survival After Out-of-Hospital Cardiac Arrest in North Carolina, 2010 to 2014.
Background Following the implementation of the HeartRescue project, with interventions in the community, emergency medical services, and hospitals to improve care and outcomes for out-of-hospital cardiac arrests (OHCA) in North Carolina, improved bystander and first responder treatments as well as survival were observed. This study aimed to determine whether these improvements were consistent across Black versus White individuals. Methods and Results Using the Cardiac Arrest Registry to Enhance Survival (CARES), we identified OHCA from 16 counties in North Carolina (population 3 million) from 2010 to 2014. Temporal changes in interventions and outcomes were assessed using multilevel multivariable logistic regression, adjusted for patient and socioeconomic neighborhood-level factors. Of 7091 patients with OHCA, 36.5% were Black and 63.5% were White. Black patients were younger, more females, had more unwitnessed arrests and non-shockable rhythm (Black: 81.0%; White: 75.4%). From 2010 to 2014, the adjusted probabilities of bystander cardiopulmonary resuscitation (CPR) went from 38.5% to 51.2% in White, P<0.001; and 36.9% to 45.6% in Black, P=0.002, and first-responder defibrillation went from 13.2% to 17.2% in White, P=0.002; and 14.7% to 17.3% in Black, P=0.16. From 2010 to 2014, survival to discharge only increased in White (8.0% to 11.4%, P=0.004; Black 8.9% to 9.5%, P=0.60), though, in shockable patients the probability of survival to discharge went from 24.8% to 34.6% in White, P=0.02; and 21.7% to 29.0% in Black, P=0. 10. Conclusions After the HeartRescue program, bystander CPR and first-responder defibrillation increased in both patient groups; however, survival only increased significantly for White patients.


Biosynthesis and transport of lysosomal alpha-glucosidase in the human colon carcinoma cell line Caco-2: secretion from the apical surface.
The human adenocarcinoma cell line Caco-2 was used for studies on the biosynthesis and transport of lysosomal acid alpha-glucosidase in polarized epithelial cells. Metabolic labelling revealed that in Caco-2 cells alpha-glucosidase is synthesized as a precursor form of 110 x 10(3) Mr. This form is converted into a precursor of slightly higher Mr (112 x 10(3)) by the addition of complex oligosaccharide chains. Via an intermediate form of 95 x 10(3) Mr, this precursor is processed into a mature form of 76 x 10(3) Mr. Combination of metabolic labelling with subcellular fractionation showed that the 112 x 10(3) Mr precursor of alpha-glucosidase is transported to the lysosomes. However, the same form is secreted into the culture medium (20% of newly synthesized enzyme after 4 h of chase). Immunoprecipitation of alpha-glucosidase from culture medium derived from either the apical or basolateral site of radiolabelled Caco-2 cells, showed that 70-80% of the total amount of precursor form present in the medium is secreted from the apical membrane. Measurement of enzyme activities also showed that alpha-glucosidase, unlike other lysosomal enzymes, is mainly secreted via the apical pathway. Furthermore, immunocytochemistry showed the presence of a precursor form of alpha-glucosidase on the apical, but not the basolateral, membrane of the Caco-2 cells. We conclude that alpha-glucosidase is, unlike all other secretory proteins studied so far, secreted preferentially from the apical membrane of Caco-2 cells.


Cochlear Implantation in Patients with Keratitis-Ichthyosis-Deafness Syndrome: A Report of Two Cases.
Keratitis-ichthyosis-deafness (KID) syndrome is a syndrome which presents with hearing loss and visual and keratinization disorders. In such patients, hearing aids cannot be effectively used in the rehabilitation of hearing loss because of the frequent blockage of the external ear canal with epithelial debris and due to dry and tense skin of the external ear canal. Moreover, severe or profound hearing loss also limits the benefits gained from the conventional hearing aids. On the other hand, cochlear implantation is a method that has been used in limited cases in the literature. This study presents the results of cochlear implantation applied in our clinic to two children who had been diagnosed with KID. Audiological assessments before and after the cochlear implant operation were performed using pure-tone audiometry, immittance audiometry, and auditory brainstem response (ABR), and the postoperative follow-up was conducted using pure-tone audiometry. Skin problems, visual disturbances, and other additional problems complicate the short-term and long-term rehabilitation after implantation in individuals with KID syndrome. Close monitoring should be exercised due to possible skin complications that may develop during the postoperative period. The families and rehabilitation teams should be warned about the possible visual disturbances and skin complications.


Urban and rural differences in characteristics of ovarian cancer patients.
The aim of the study was evaluation of the urban and rural differences in ovarian cancer patients' characteristics at the moment of diagnosis. The study comprised women with ovarian cancer diagnosed and treated in the Division of Gynecological Surgery of Poznan University of Medical Sciences between 2004-2011. The patients were divided into 3 groups based on their place of residence: 1) patients residing in large cities (over 50,000 people), 2) inhabitants of small towns (below 50,000 people), 3) women from rural areas. Among the studied groups of patients no differences were found in the FIGO stage at diagnosis (p=0.453), histological grade of the tumour (p=0.916), histopathological types of ovarian neoplasms (p=0.431), median tumour volume (p=0.855), presence of fluid in the pouch of Douglas (p=0.872). Women with ovarian cancer residing in large cities had lower median parity (p=0.0005), higher education level status (p=0.0001), and experienced menarche at an earlier age (p=0.039). There were no differences in the use of oral contraception (p=0.93) and body mass index (p=0.23) between the women included in the study. There were no differences in advancement of ovarian cancer at the moment of diagnosis or in tumour type and size between women residing large cities, small towns and rural areas. Several ovarian cancer risk factors were more common among ovarian cancer patients living in urbanized areas.


Dehydratase mediated 1-propanol production in metabolically engineered Escherichia coli.
With the increasing consumption of fossil fuels, the question of meeting the global energy demand is of great importance in the near future. As an effective solution, production of higher alcohols from renewable sources by microorganisms has been proposed to address both energy crisis and environmental concerns. Higher alcohols contain more than two carbon atoms and have better physiochemical properties than ethanol as fuel substitutes. We designed a novel 1-propanol metabolic pathway by expanding the well-known 1,2-propanediol pathway with two more enzymatic steps catalyzed by a 1,2-propanediol dehydratase and an alcohol dehydrogenase. In order to engineer the pathway into E. coli, we evaluated the activities of eight different methylglyoxal synthases which play crucial roles in shunting carbon flux from glycolysis towards 1-propanol biosynthesis, as well as two secondary alcohol dehydrogenases of different origins that reduce both methylglyoxal and hydroxyacetone. It is evident from our results that the most active enzymes are the methylglyoxal synthase from Bacillus subtilis and the secondary alcohol dehydrogenase from Klebsiella pneumoniae, encoded by mgsA and budC respectively. With the expression of these two genes and the E. coli ydjG encoding methylglyoxal reductase, we achieved the production of 1,2-propanediol at 0.8 g/L in shake flask experiments. We then characterized the catalytic efficiency of three different diol dehydratases on 1,2-propanediol and identified the optimal one as the 1,2-propanediol dehydratase from Klebsiella oxytoca, encoded by the operon ppdABC. Co-expressing this enzyme with the above 1,2-propanediol pathway in wild type E. coli resulted in the production of 1-propanol at a titer of 0.25 g/L. We have successfully established a new pathway for 1-propanol production by shunting the carbon flux from glycolysis. To our knowledge, it is the first time that this pathway has been utilized to produce 1-propanol in E. coli. The work presented here forms a basis for further improvement in production. We speculate that dragging more carbon flux towards methylglyoxal by manipulating glycolytic pathway and eliminating competing pathways such as lactate generation can further enhance the production of 1-propanol.


The Chronic Graft-versus-Host Disease Failure-Free Survival (cGVHD-FFS) Index.
In clinical trials of chronic graft-versus-host disease (cGVHD), the need to start a new systemic treatment is considered a treatment failure. A composite endpoint called "failure-free survival" (FFS), where events are initiation of a new systemic cGVHD treatment, recurrent malignancy, and death, has been suggested as a possible long-term indicator of success. The goal of the current study was to identify changes in cGVHD manifestations from baseline to 6 months that could accurately predict subsequent longer-term FFS, thereby making it possible to assess outcomes earlier than would otherwise be possible. We used data from 2 prospective, multicenter, observational studies to develop the cGVHD-FFS index. The cGVHD-FFS index was calculated at 6 months, a typical timepoint for assessment of the primary endpoint of phase II cGVHD trials. Subsequent FFS was only 45% within the next 2 years. We found that changes in the scores for the eyes, joint/fascia, and mouth ulcers from baseline to 6 months were associated with subsequent FFS, but the prognostic accuracy of these changes was not adequate for use in trials. Biomarker studies might help to identify criteria that improve prediction of long-term clinical outcomes in patients with cGVHD.


Efficacy and safety of tofacitinib in rheumatoid arthritis-associated interstitial lung disease: TReasure real-life data.
Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is a major concern in RA. These patients have been included in clinical trials and in the post-marketing setting of RA patients using tofacitinib. We aimed to assess the real-life efficacy and safety of tofacitinib in patients with RA-ILD. RA patients with ILD diagnosis based on the HRCT images of the lungs from eight different centres recruited to study. As a control group, RA patients without ILD under tofacitinib were included. Demographic data, patients' characteristics, available pulmonary function tests regarding RA and RA-ILD at the visit in which tofacitinib was initiated and for the last follow-up visit under tofacitinib were recorded. Reasons for tofacitinib discontinuation were also recorded. Drug retention rates were compared by log-rank test. p-value <0.05 was considered statistically significant. A total of 47(42.6% male) RA patients with RA-ILD and a control group of 387 (17.8% male) patients without RA-ILD were included in analysis. After the median of 12 (9-19) months follow-up, mean FEV1%; 82.1 vs. 82.8 (pre/post-treatment, respectively, p=0.08), mean FVC%; 79.8 vs. 82.8 (pre/post-treatment, respectively, p=0.014) were stable and worsening was observed in 2/18 (11.1%) patients. Retention rates were similar (p=0.21, log-rank). In RA-ILD group, most common cause of drug discontinuation was infections (6.3 vs. 2.4 per 100 patient-years). Treatment strategy of RA-ILD patients is still based on small observational studies. A high rate of discontinuation due to infections was observed in RA-ILD patients under tofacitinib; however, RA-ILD patients were older than RA patients without ILD.


Ottowia oryzae sp. nov., isolated from Andong sikhye, a Korean traditional rice beverage.
A Gram-stain-negative, non-spore-forming, non-motile, short-rod-shaped bacterial strain, designated KADR8-3T, isolated from Andong sikhye in Andong-si, Gyeongsangbuk-do, Republic of Korea, was characterized using a polyphasic approach. On the basis of morphological, genetic and chemotaxonomic characteristics, it was determined to belong to the genus Ottowia. The phylogenetic similarity based on the 16S rRNA gene sequences indicated the strain formed a clade with Ottowia beijingensis GCS-AN-3T, Ottowia thiooxydans DSM 14619T, Ottowia pentelensis RB3-7T and 'Ottowia shaoguanensis' J5-66T, showing the highest similarity to O. beijingensis GCS-AN-3T (96.3 %). The major fatty acids were C16 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c). The predominant respiratory quinone was Q-8. The polar lipids present were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, two unidentified aminolipids and two unidentified lipids. The genomic DNA G+C content was 66.80 mol%. These results supported that strain KADR8-3T was clearly distinguishable from its closely related species and represents a novel species of the genus Ottowia, for which the name Ottowia oryzae is proposed. The type strain is KADR8-3T (=KACC 19325T=NBRC 113109T).


Regulation of cytochrome P-450b and P-450e mRNA expression in the developing rat. Hybridization to synthetic oligodeoxyribonucleotide probes.
We conducted solution hybridization and Northern blot experiments utilizing synthetic 18'-mer oligodeoxyribonucleotides complementary to two major rat hepatic phenobarbital-inducible cytochrome P-450s, P-450b and P-450e, to assess their mRNA expression during rat development. At all ages studied, with one exception (i.e. in day 22 neonates), P-450b mRNA was not detected in control animals. However, traces of P-450e message were observed in control animals on day 22 and persisted to adulthood. Phenobarbital pretreatment caused marked increases in hepatic mRNA for both P-450s as early as 22 days after conception. No increases were observed in RNA isolated from phenobarbital-pretreated day 10 or 19 rats. In general, the inducible levels of P-450b and P-450e mRNA increased as a function of age. The age-dependent increase in responsiveness to phenobarbital was associated with an age-dependent decrease in the ratio of P-450b to P-450e mRNA levels. The levels of P-450b/P-450e varied from a ratio of 19 at day 22 of development to a ratio of 5 at day 62 of development. Maximal levels of phenobarbital-induced hepatic RNA for both isozymes occurred 24 days after birth (day 46 of development), at which time P-450b and P-450e mRNAs accumulated to levels 2.4- and 1.8-fold greater, respectively, than levels found in comparably induced adult rat liver. Northern blot analyses indicated that the major mRNA species hybridizing to either the P-450b or P-450e oligomers in all age groups studied was approximately 1.8 kilobases.


Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor.
1. This study examined whether Paeoniflorin (PF), the major active components of Chinese herb Paeoniae alba Radix, has neuroprotective effect in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). 2. Subcutaneous administration of PF (2.5 and 5 mg kg(-1)) for 11 days could protect tyrosine hydroxylase (TH)-positive substantia nigra neurons and striatal nerve fibers from death and bradykinesia induced by four-dose injection of MPTP (20 mg kg(-1)) on day 8. 3. When given at 1 h after the last dose of MPTP, and then administered once a day for the following 3 days, PF (2.5 and 5 mg kg(-1)) also significantly attenuated the dopaminergic neurodegeneration in a dose-dependent manner. Post-treatment with PF (5 mg kg(-1)) significantly attenuated MPTP-induced proinflammatory gene upregulation and microglial and astrocytic activation. 4. Pretreatment with 0.3 mg kg(-1) 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor (A1AR) antagonist, 15 min before each dose of PF, reversed the neuroprotective and antineuroinflammatory effects of PF. 5. In conclusion, this study demonstrated that PF could reduce the MPTP-induced toxicity by inhibition of neuroinflammation by activation of the A1AR, and suggested that PF might be a valuable neuroprotective agent for the treatment of PD.


An in vitro study of microleakage of occlusal composite restorations polymerized by a conventional curing light and a PAC curing light.
With the increase in usage of bonded dentistry procedures, so comes the development of advanced technology to polymerize it. The purpose of this in vitro study was to evaluate the microleakage of sealants and resin restorations utilizing two different curing lights. The conventional Ortholux curing light (OCL) and the Plasma Arc Curing (PAC) light attached to the KCP air abrasion unit of American Dental Technologies were utilized to polymerize sealants and resin restorations on extracted third molars and premolars. Forty-eight caries-free teeth were divided into 4 groups of 12 specimens. Occlusal sealants were polymerized on groups 1 and 3. Class I composite resin restorations were polymerized on groups 2 and 4. The PAC light polymerized group 2 and the OCL was used for groups 3 and 4. Therefore a comparison between the two light sources' polymerization could be measured by evaluating the microleakage of the two sets of specimens. The PAC light polymerized the Z100 adhesive for 5 seconds and the OCL polymerized it for 10 seconds. The Z100 A-1 composite placed in two 1 mm increments was polymerized with the PAC light for 10 seconds and the OCL for 40 seconds. The teeth were thermocycled 200 times between 5 degrees C and 55 degrees C. The teeth, coated with fingernail polish excluding the occlusal surface, were soaked in 5% methylene blue for 4 hours, removed, and rinsed with water. The teeth were invested in clear resin (Castin Craft) and sectioned longitudinally using an Isomet diamond saw. Microleakage was scored "0" if no leakage was present. Scored "1" if the leakage was present to 1/2 the preparation depth. Scored "2" if the leakage was present past the 1/2 way point but not to the pulpal floor of the preparation. A score of "3" was used if the leakage reached the pulpal floor. Unpaired t-Tests were used to statistically analyze the data. A significant difference (p < 0.05) was found between groups 1 and 3. The PAC light used to polymerize the sealants in group 1 produced no microleakage. A significant difference (p < .005) was found between groups 2 and 4. The OCL produced less microleakage (16 and 20 out of 24 sections) than the resin restorations polymerized with the PAC (only 8 of 24 sections with no microleakage. The 10-second cure by the PAC light appears to be insufficient in polymerizing a class I composite resin restoration. Possibly longer exposures with the PAC would produce less microleakage. Further research needs to be performed to evaluate if the PAC light, with an intensity of 1196 mW/cm2, may be producing high levels of strain within the setting composite. This strain may be responsible for the statistically significant increase in microleakage of the restorations polymerized with the PAC light.). It appears the PAC light would be best utilized to cure sealants and/or possibly polymerize orthodontic brackets. The conventional curing light appears to remain the best choice for polymerizing class I composite restorations.


Small intestinal bacterial overgrowth: histopathologic features and clinical correlates in an underrecognized entity.
Small intestinal bacterial overgrowth (SIBO) is a common cause of chronic diarrhea and malabsorption. Morphologic changes associated with this condition have not, to our knowledge, been studied in detail. To better characterize the histopathologic changes associated with SIBO by comparing the clinicopathologic features of patients with SIBO (duodenal aspirate cultures with > or =10(5) colony-forming units [CFUs]/mL) to controls with cultures found to be negative (<10(5) CFUs/mL). We included 67 consecutive patients with SIBO and 55 controls in the series. Each duodenal biopsy was assessed for the following features: villous to crypt ratio, intraepithelial lymphocytosis, crypt apoptoses, basal plasmacytosis, cryptitis/villitis, peptic duodenitis, erosions/ulcers, eosinophilia, and absence of goblet and Paneth cells; and correlated with clinical features and culture results. Decreased villous to crypt ratio (<3ratio1) was more frequent in SIBO than controls (24% versus 7%; P = .01). Duodenal biopsies from patients with SIBO were slightly less likely to be judged within reference range than were controls (52% versus 64%; P = .27). There were no significant differences in any of the other histologic features. Clinically, patients in the SIBO group were older than the age of controls (mean, 60 years versus 52 years; P = .02), and they were more likely to have one of the known predisposing factors for bacterial overgrowth (66% versus 36%; P = .002). Other clinical features, including presenting symptoms, were similar. Villous blunting is the only feature more common to SIBO than to controls. More than half of biopsies from SIBO patients are histologically unremarkable. Therefore, SIBO needs to be considered as a potential etiology for gastrointestinal symptoms even when duodenal biopsies are found to be normal.


Search for new fermions ("quirks") at the Fermilab Tevatron collider.
We report results of a search for particles with anomalously high ionization in events with a high transverse energy jet and large missing transverse energy in 2.4 fb⁻¹ of integrated luminosity collected by the D0 experiment at the Fermilab Tevatron pp collider. Production of such particles (quirks) is expected in scenarios with extra QCD-like SU(N) sectors, and this study is the first dedicated search for such signatures. We find no evidence of a signal and set a lower mass limit of 107, 119, and 133 GeV for the mass of a charged quirk with strong dynamics scale Λ in the range from 10 keV to 1 MeV and N=2, 3, and 5, respectively.


Preemptive kidney transplantation is associated with survival benefits among pediatric patients with end-stage renal disease.
Kidney transplantation is the preferred treatment for pediatric end-stage renal disease (ESRD). Preemptive transplantation avoids the increased morbidity and mortality of dialysis. Yet, previous studies have not demonstrated significant graft or patient survival benefits for children undergoing transplantation preemptively versus nonpreemptively. These previous studies were limited by small samples sizes and low rates of adverse events. Here we compared graft failure and mortality rates using Kaplan-Meier methods and Cox regression among a large national cohort of children with ESRD undergoing preemptive versus nonpreemptive kidney transplantation between 2000 and 2012. Among 7527 pediatric kidney transplant recipients in the United States Renal Data System, 1668 underwent preemptive transplantation. Over a median 4.8 years follow-up, 1314 experienced graft failure, and over a median 5.2 years of follow-up, 334 died. Dialysis exposure versus preemptive transplantation conferred a higher risk of graft failure (hazard ratio 1.32; 95% confidence interval: 1.10-1.56) and a higher risk of death (hazard ratio 1.69; 95% confidence interval: 1.22-2.33) in multivariable analysis. Compared with children undergoing preemptive transplantation, children on dialysis for >1 year had a 52% higher risk of graft failure and those on dialysis >18 months had an 89% higher risk of death, regardless of donor source. Thus, preemptive transplantation is associated with substantial benefits in allograft and patient survival among children with ESRD, particularly when compared with children who receive dialysis for >1 year. These findings support policies to promote early access to transplantation and avoidance of dialysis for children with ESRD whenever feasible.


The reduced osteogenic potential of Nf1-deficient osteoprogenitors is EGFR-independent.
Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by mutations in the NF1 gene. Recalcitrant bone healing following fracture (i.e. pseudarthrosis) is one of the most problematic skeletal complications associated with NF1. The etiology of this condition is still unclear; thus, pharmacological options for clinical management are limited. Multiple studies have shown the reduced osteogenic potential of Nf1-deficient osteoprogenitors. A recent transcriptome profiling investigation revealed that EREG and EGFR, encoding epiregulin and its receptor Epidermal Growth Factor Receptor 1, respectively, were among the top over-expressed genes in cells of the NF1 pseudarthrosis site. Because EGFR stimulation is known to inhibit osteogenic differentiation, we hypothesized that increased EREG and EGFR expression in NF1-deficient skeletal progenitors may contribute to their reduced osteogenic differentiation potential. In this study, we first confirmed via single-cell mRNA sequencing that EREG over-expression was associated with NF1 second hit somatic mutations in human bone cells, whereas Transforming Growth Factor beta 1 (TGFβ1) expression was unchanged. Second, using ex-vivo recombined Nf1-deficient mouse bone marrow stromal cells (mBMSCs), we show that this molecular signature is conserved between mice and humans, and that epiregulin generated by these cells is overexpressed and active, whereas soluble TGFβ1 expression and activity are not affected. However, blocking either epiregulin function or EGFR signaling by EGFR1 or pan EGFR inhibition (using AG-1478 and Poziotinib respectively) did not correct the differentiation defect of Nf1-deficient mBMSCs, as measured by the expression of Alpl, Ibsp and alkaline phosphatase activity. These results suggest that clinically available drugs aimed at inhibiting EGFR signaling are unlikely to have a significant benefit for the management of bone non-union in children with NF1 PA.


Estrogen and brain: synthesis, function and diseases.
This review summaries recent evidence from clinical and basic science studies on estrogen central nervous system. For decades, estrogen was thought of only as a "sex hormone" and plays a fundamental role in regulating behavioral and physiological events. In recent years, accumulated evidence shows that estrogen also plays very important roles in the brain. Recent basic science studies show that estrogen treatment decreases the neuronal response to various forms of insult through the regulation of both estrogen synthesis and estrogen receptor expression in the brain. Some clinical evidence also suggests that estrogen deprivation might be implicated as a risk factor in various neurodegenerative diseases. Estrogen may play a neuroprotective role through estrogen dependent alterations in cell survival, enhancement of synaptic transmission and neurogenesis. Some of the mechanisms underlying these effects are independent of the classical nuclear estrogen receptors and involve direct modulation of neurotransmitter receptor function, or anti-oxidant activities of estrogen. It is controversial whether estrogen is indicated in the prevention or treatment of various brain disorders such as Alzheimer's disease. The conflicting findings suggest that several variables, including age, estrogen dose and formulation, the length of treatment, may determine whether the potential benefits of estrogen treatment would outweigh the associated risks.


Interplay between HIV-1 infection and host microRNAs.
Using microRNA array analyses of in vitro HIV-1-infected CD4(+) cells, we find that several host microRNAs are significantly up- or downregulated around the time HIV-1 infection peaks in vitro. While microRNA-223 levels were significantly enriched in HIV-1-infected CD4(+)CD8(-) PBMCs, microRNA-29a/b, microRNA-155 and microRNA-21 levels were significantly reduced. Based on the potential for microRNA binding sites in a conserved sequence of the Nef-3'-LTR, several host microRNAs potentially could affect HIV-1 gene expression. Among those microRNAs, the microRNA-29 family has seed complementarity in the HIV-1 3'-UTR, but the potential suppressive effect of microRNA-29 on HIV-1 is severely blocked by the secondary structure of the target region. Our data support a possible regulatory circuit at the peak of HIV-1 replication which involves downregulation of microRNA-29, expression of Nef, the apoptosis of host CD4 cells and upregulation of microRNA-223.


[Investigations on the fatty acid composition of lipids from Salmonella minnesota S and R forms (author's transl)].
Non-covalently bound lipids were extracted from 2 Salmonella minnesota S forms and 5 R mutants (chemotype Ra-Re) isolated from these strains. The lipids were subsequently analysed with regard to fatty acid composition. The extracts were free of lipid A, as determined by absence of beta-hydroxymyristic acid. The fatty acid distribution in the lipids of the two S forms, cultivated at 37 degrees C to the beginning of the stationary phase of growth, agreed very closely, and the values corresponded to those reported in the literature for S. typhimurium. In contrast, there was a progressive reduction in the content of C17- and C19-cyclopropane fatty acids, going from Ra-Rc mutants. The total cyclopropane fatty acids decreased from approximately 30% (Ra) to approximately 7% (Rc). The lipids from the Rd1 and the Re mutants had a fatty acid composition identical to that of the Rc mutant. The decrease in cyclopropane fatty acid content was compensated for in all strains by an increase in the corresponding unsaturated fatty acids (16:1; 18:1). Variations in the incubation temperature (30, 37, 41 degrees C) affected the ratio of the single fatty acids as determined for the Ra, Rc and Re mutants. The content of unsaturated fatty acids increased with the reduction in temperature, while the proportion of cyclopropane fatty acids decreased (stationary growth phase). These changes were much more pronounced with the Ra mutant than with the Rc and the Re mutants. The differences among the mutants with regard to fatty acid distribution were apparent at all temperature levels. In addition, the fatty acid composition of the lipids varied with the phase of growth, as already reported for E. coli and other gram-negative organisms. The content of cyclopropane fatty acids increased from the exponential to the stationary phases, with simultaneous reduction in the proportion of corresponding unsaturated fatty acids. Again, the lipid composition of the Ra mutant varied to a greater extent than did that of the Rc and the Re mutants. Similar changes appeared in the phosphatidyl ethanolamine fractions of the three mutants. There were also changes in the neutral lipids that agreed in part with those of the total lipids. The cause of the reduced cyclopropane fatty acid synthesis in S. minnesota R mutants possessing an incomplete LPS-core structure (Rb2-Re) is at present unknown. The physiological significance of these findings as well remains for the moment speculative, as the functional role of cyclopropane fatty acids in biological membranes has not yet been elucidated. Possible relations to membrane permeability and to transfer of antibiotics are discussed.


A highly infectious 'mycoplasma' that inhibits meiosis in the fungus Coprinus.
We have discovered a cytoplasmically inherited infectious agent that inhibits meiosis in a species of Coprinus, a basidiomycetous fungus. From infectivity, filtration, centrifugation and ultrastructural studies we believe the agent to be a mycoplasma. The agent is highly infectious to several strains of the host species and is capable of spreading rapidly through infected hosts. No pathological effect has been seen on any aspect of growth or differentiation of the fungus except for the inability of infected strains or undergo meiosis. The failure of meiosis results in mushrooms that do not produce the normal black spores and are therefore pale in colour. The paleness represents a simple assay for the presence and activity of the infectious agent. Infected hosts do not display any ultrastructural abnormalities in the vegetative stages, only in the cells in which meiosis should occur. In the meiotic cells, at the time when normal cells are undergoing synapsis and synaptinemal complexes are forming, the vacuoles of the infected cells become occupied with vesicular, membrane-bound bodies resembling in shape and form mycoplasmas. Extracts from infected clones may be filtered through 0.2-mum filters and retain full infectivity. The infectious material may be pelleted from such extracts at only 10 000g. Migration experiments, as well as the filtration studies, rule out involvement directly of nuclei. The high rate of infection and spread of the mycoplasma through the host, combined with the anatomical simplicity of the host, make this an ideal system in which to study the basis of infection. The singularity of the pathological effect make this host-parasite association useful in studying both the underlying mechanisms of mycoplasma pathogenicity and to investigate the regulation of meiosis. This is only the second report of mycoplasmas in fungi.


Tailored thrombolytic therapy. A perspective.
In contrast with current standard regimens, it seems more appropriate to tailor thrombolytic therapy to individual patient characteristics. A proposed model for such tailored therapy is based on individual assessment of benefits and risks of thrombolytic therapy, taking into account the response of individual patients to the therapy given. Potential benefits of thrombolysis in individual patients can be predicted by use of demographic patient characteristics (age, sex, history of previous infarction) together with indicators of the ischemic area at risk (total ST segment deviation) and treatment delay. Using these parameters, the number of "lives saved" by thrombolytic therapy for specific patient characteristics can be estimated. Similarly, the risk of intracranial hemorrhage during thrombolytic therapy can be estimated from the patient's age, blood pressure at admission, and body weight. Depending on benefit/risk estimates, a choice can be made between regimens with high, medium, or modest thrombolytic efficacy. Continuous multilead ECG ischemia monitoring and rapid assays of myocardial proteins in serum can be used to assess the occurrence or absence of reperfusion and to detect signs of reocclusion. Such data help to decide whether thrombolytic therapy should be continued or intensified or might be discontinued in individual patients before the total standard dose has been administered. Such tailored reduction of the total thrombolytic dose will reduce the risk for bleeding complications in some of the patients. The concept of tailoring thrombolytic therapy and the models presented for benefit/risk assessment should be tested in clinical studies and may subsequently help the physician to select the optimal approach in individual patients.


Safety of early carotid artery stenting after systemic thrombolysis: a single center experience.
Background. Patients with acute ischemic stroke due to internal carotid artery (ICA) disease are at high risk of early stroke recurrence. A combination of IV thrombolysis and early carotid artery stenting (CAS) may result in more effective secondary stroke prevention. Objective. We tested safety and durability of early CAS following IV thrombolysis in stroke patients with residual stenosis in the symptomatic ICA. Methods. Of consecutive patients treated with IV rtPA, those with residual ICA stenosis ≥70% or <70% with an ulcerated plaque underwent early CAS (>24 hours). The protocol included pre-rtPA MRI and MR angiography, and post-rtPA carotid ultrasound and CT angiography. Stroke severity was assessed by the NIH Stroke Scale (NIHSS). Three- and twelve-month stent patency was assessed by ultrasound. Twelve-month functional outcome was assessed by the modified Rankin Scale (mRS). Results. Of 145 consecutive IV rtPA-treated patients, 6 (4%) underwent early CAS. Median age was 76 (range 67-78) years, median NIHSS at stroke onset was 12 (range 9-16) and 7 (range 7-8) before CAS. Median onset-to-CAS time was 48 (range 30-94) hours. A single self-expandable stent was implanted to cover the entire lesion in all patients. The procedure was uneventful in all patients. After 12 months, all patients had stent patency, and the functional outcome was favourable (mRS ≤ 2) in all but 1 patient experiencing a recurrent stroke for new-onset atrial fibrillation. Conclusion. This small case series of a single centre suggests that early CAS may be considered a safe alternative to CEA after IV rtPA administration in selected patients at high risk of stroke recurrence.


A comparative study of two third-generation anti-hepatitis C virus ELISAs.
The sensitivity and specificity of two third-generation screening tests for the detection of antibody to hepatitis C virus (anti-HCV) was evaluated in a side-by-side study (Abbott HCV EIA 3.0/Ortho HCV ELISA 3.0). Specimens that were reactive in either ELISA were then retested by the other ELISA, and confirmed by RIBA-3. The screening of 15,540 serum samples from healthy blood donors showed a significantly lower number of reactive cases tested by Ortho (21 out of 8,805, 0.24%), than tested by Abbott (35 out of 6,735, 0.52%). In the side-by-side comparison, we found that significantly (p = 0.005) more Ortho-positive samples were also reactive in Abbott (14/21, 66.6%), than in Abbott followed by Ortho (7/35, 20%). Moreover, the RIBA analysis revealed a significantly (p = 0.014) higher number of RIBA-positive specimens among those reactive in Ortho 10/21 (47.6%), than among those reactive in Abbott 6/35 (17.2%), thus the former provides a greater positive predictive value. However, we did not observed differences in the sensitivity between Abbott and Ortho, because all RIBA-positive samples demonstrated reactivity in both ELISAs.


[Strategies for the Treatment of Community-Acquired Pneumonia in HIV-Positive Patients].
Study purpose According to the Robert Koch Institute, 84,700 people in Germany suffer from HIV infection. One-third of the affected persons is over 50 years old. In Germany, community-acquired pneumonia (CAP) is a widespread disease with more than 250,000 cases per year. Incidence and mortality increase with the age of the affected individuals. For this reason, diagnostic and therapeutic strategies are needed to guide medical care of HIV-infected patients presenting with CAP. Methodology HIV therapists were interviewed about their diagnostic approach, risk stratification strategy and therapeutic approach to HIV-associated community-acquired pneumonia (HIV +/CAP) using a questionnaire. 56 completed questionnaires were analysed. Results Half of the respondents reported that CAP occurred in 1 to 5 % of HIV-infected individuals per year. This indicates an estimated number of up to 4200 HIV +/CAP cases per year in Germany - a much higher number than expected from the literature. 58.9 % of respondents considered that the pathogenic spectrum did not differ in HIV +/CAP from non-HIV/CAP. 80.3 % of respondents applied the same antibiotic regimens in HIV +/CAP as used in patients with non-HIV/CAP. Conclusion Even though over 40 % of HIV therapists agree that the pathogenic spectrum of HIV +/CAP differs from that of non-HIV/CAP, over 80 % of therapists managed these patients in accordance with the S3-guidelines for non-immunocompromised CAP-patients, because specific guidelines for the treatment of HIV +/CAP are lacking. Since specific data on the aetiology and the clinical course of HIV +/CAP depending, for instance, on CD4-count and antiretroviral therapy are missing, we feel that the clinical course of HIV +/CAP should be further analysed in the context of prospective cohort studies.


Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study.
Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited. To assess the treatment and renal/bone safety outcomes following the switch to TAF. We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF. We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019). At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.


Tritium metabolism in man.
Tritium metabolism in human beings was studied in volunteers who had exposure to tritiated water accidentally, by measuring the organically bound tritium with liquid scintillation counter, in sperms and plasma proteins. 2% of the initial urinary tritium specific activity was incorporated as bound tritium in sperms. In plasma proteins, on the 20th day of exposure, tritium bound in globulin was 3 times higher than that of albumin, tritium bound in globulin was 3 times higher than that of albumin.


Does self-focused attention in social anxiety depend on self-construal? Evidence from a probe detection paradigm.
Cognitive models of social anxiety disorder propose self-focused attention as a key maintenance factor of the disorder. However, whether this holds true for different cultural contexts has not been investigated. The present experiment investigated the influence of self-construal (interdependent versus independent) on self-focused attention in high and low socially anxious individuals. Eighty-seven participants, divided into high versus low socially anxious and interdependent versus independent self-construal, performed a self-focused attention probe detection paradigm. A reaction time metric relating to attention deployment on the self versus the other served as an index of self-focused attention. In individuals with an interdependent self-construal those who are highly socially anxious showed decreased self-focused attention compared to those who are low socially anxious. In individuals with an independent self-construal the effect of social anxiety was less strong and in the opposite direction (but congruent with cognitive models). These results indicate that self-focused attention in social anxiety depends on self-construal. These findings implicate different therapies for people with social anxiety disorder, depending on their self-construal.


Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor.
Transient receptor potential vanilloid 6 (TRPV6) is a calcium channel implicated in multifactorial diseases and overexpressed in numerous cancers. We recently reported the phenyl-cyclohexyl-piperazine cis-22a as the first submicromolar TRPV6 inhibitor. This inhibitor showed a seven-fold selectivity against the closely related calcium channel TRPV5 and no activity on store-operated calcium channels (SOC), but very significant off-target effects and low microsomal stability. Here, we surveyed analogues incorporating structural features of the natural product capsaicin and identified 3OG, a new oxygenated analog with similar potency against TRPV6 (IC50 = 0.082 ± 0.004 μM) and ion channel selectivity, but with high microsomal stability and very low off-target effects. This natural product-inspired inhibitor does not exhibit any non-specific toxicity effects on various cell lines and is proposed as a new tool compound to test pharmacological inhibition of TRPV6 mediated calcium flux in disease models.


The effect of stinging nettle (Urtica dioica) seed oil on experimental colitis in rats.
This study investigated the effect of Urtica dioica, known as stinging nettle, seed oil (UDO) treatment on colonic tissue and blood parameters of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced with 1 mL of TNBS in 40% ethanol by intracolonic administration with a 8-cm-long cannula with rats under ether anesthesia, assigned to a colitis group and a colitis+UDO group. Rats in the control group were given saline at the same volume by intracolonic administration. UDO (2.5 mL/kg) was given to the colitis+UDO group by oral administration throughout a 3-day interval, 5 minutes later than colitis induction. Saline (2.5 mL/kg) was given to the control and colitis groups at the same volume by oral administration. At the end of the experiment macroscopic lesions were scored, and the degree of oxidant damage was evaluated by colonic total protein, sialic acid, malondialdehyde (MDA), and glutathione levels, collagen content, tissue factor activity, and superoxide dismutase and myeloperoxidase activities. Colonic tissues were also examined by histological and cytological analysis. Pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), lactate dehydrogenase activity, and triglyceride and cholesterol levels were analyzed in blood samples. We found that UDO decreased levels of pro-inflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol, which were increased in colitis. UDO administration ameliorated the TNBS-induced disturbances in colonic tissue except for MDA. In conclusion, UDO, through its anti-inflammatory and antioxidant actions, merits consideration as a potential agent in ameliorating colonic inflammation.


Narratives of Survivorship: A Study of Breast Cancer Pathographies and Their Place in Cancer Rehabilitation.
The focus on cancer rehabilitation has increased, but breast cancer patients still report unmet rehabilitation needs. Since many women today will live long beyond their diagnosis, there are multiple challenges for the healthcare system in supporting these women in their new life situation. A more individualized approach is seen as necessary to optimize the rehabilitation for survivors. Pathographies, i.e., autobiographical or biographical accounts of experiences of illness, expose us to personal accounts of the journey through illness and treatment, offering us details, emotions, phrasings, and imagery from an individual perspective. In this literary study, we have analyzed two contemporary Swedish-speaking pathographies about breast cancer. In our analysis, we have presented perspectives on survivorship, and the authors' ways of conveying their breast cancer experiences through narrative. The pathographies envision the prominent impact the breast cancer has on the authors' lives. Narratives of survivorship have the potential to complement the more general medical knowledge with their nuanced and multifaceted stories of breast cancer. Learning from this type of material may improve the understanding of the complexity of breast cancer survivorship issues. This may be a way to become more attuned to identifying individual needs and preferences of breast cancer patients.


Associations and interactions between bare lymphocyte syndrome factors.
The bare lymphocyte syndrome, a severe combined immunodeficiency due to loss of major histocompatibility complex (MHC) class II gene expression, is caused by inherited mutations in the genes encoding the heterotrimeric transcription factor RFX (RFX-B, RFX5, and RFXAP) and the class II transactivator CIITA. Mutagenesis of the RFX genes was performed, and the properties of the proteins were analyzed with regard to transactivation, DNA binding, and protein-protein interactions. The results identified specific domains within each of the three RFX subunits that were necessary for RFX complex formation, including the ankyrin repeats of RFX-B. DNA binding was dependent on RFX complex formation, and transactivation was dependent on a region of RFX5. RFX5 was found to interact with CIITA, and this interaction was dependent on a proline-rich domain within RFX5. Thus, these studies have defined the protein domains required for the functional regulation of MHC class II genes.


Normal mode analysis of a relaxation process with Bayesian inference.
Measurements of relaxation processes are essential in many fields, including nonlinear optics. Relaxation processes provide many insights into atomic/molecular structures and the kinetics and mechanisms of chemical reactions. For the analysis of these processes, the extraction of modes that are specific to the phenomenon of interest (normal modes) is unavoidable. In this study we propose a framework to systematically extract normal modes from the viewpoint of model selection with Bayesian inference. Our approach consists of a well-known method called sparsity-promoting dynamic mode decomposition, which decomposes a mixture of damped oscillations, and the Bayesian model selection framework. We numerically verify the performance of our proposed method by using coherent phonon signals of a bismuth polycrystal and virtual data as typical examples of relaxation processes. Our method succeeds in extracting the normal modes even from experimental data with strong backgrounds. Moreover, the selected set of modes is robust to observation noise, and our method can estimate the level of observation noise. From these observations, our method is applicable to normal mode analysis, especially for data with strong backgrounds.


Protective effect of Macleaya cordata isoquinoline alkaloids on lipopolysaccharide-induced liver injury in broilers.
This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the TLR4/MyD88/NF-κB pathway. Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers.


Supercentenarians: slower ageing individuals or senile elderly?
Although the increase in the number of centenarians is well documented today, at least in some countries, this is still not the case for people having reached the age of 110 years or more: the supercentenarians. The supercentenarians emerged in the mid-1960s. Their numbers have regularly increased since the mid-1970s. The current prevalence of known supercentenarians in countries involved in the database is approximately five to six times more than in the mid-1970s. In roughly 20 years the maximum age observed has increased by about 10 years from 112 to 122 years. The annual probability of death at age 110 is as low as 0.52 with the validated data (n=106) or with the exhaustive and validated data (n=73). The probabilities of death stagnate between 110 and 115 years, and all the computed probabilities fall below the ceiling of 0.6. Our results are compatible with the last extrapolations of mortality trajectories using a logistic or a quadratic model.


A novel method to assess intraarticular screw penetration into the joint space.
This study aims to propose a novel method to detect articular penetration of screws by relying on their electrical conductivity properties and control the validity of this method. In this ex vivo study, conducted between June 2017 and August 2017, we used five fresh sheep shoulder joints. First, the shoulder joint space was filled with saline solution. An insulated cannula was placed in the joint capsule, and a conductive wire was introduced into the joint via this cannula. A single titanium screw was inserted from the tuberculum majus into the posteroinferior quadrant of the humeral head under fluoroscopic observation. Conductivity was continuously measured using a digital multimeter. When a sudden decrease in conduction resistance was detected, fluoroscopic images were obtained in the anteroposterior (AP) and lateral directions. These images were assessed for penetration by a blinded surgeon. Penetration was confirmed by dissection of the joint. There was a significant decrease in electrical resistance when screw penetration occurred (p<0.001). All penetration events were confirmed using our novel method. For all five of the specimens, either AP or lateral images could not be used to confirm penetration. For two of these specimens, penetration was undetectable in both AP and lateral fluoroscopic images, but a decrease in resistance was recorded. The described method exhibits greater sensitivity and accuracy for metal penetration to joint, and it is effective in detecting screws in the joints. The novel method described in this paper was applied in a prototype setting, and we believe that this concept can continue to be developed.


Effects of dietary nitrate on inflammation and immune function, and implications for cardiovascular health.
Inorganic dietary nitrate, found abundantly in green leafy and some root vegetables, elicits several beneficial physiological effects, including a reduction in blood pressure and improvements in blood flow through nitrate-nitrite-nitric oxide signaling. Recent animal and human studies have shown that dietary nitrate and nitrite also modulate inflammatory processes and immune cell function and phenotypes. Chronic low-grade inflammation and immune dysfunction play a critical role in cardiovascular disease. This review outlines the current evidence on the efficacy of nitrate-rich plant foods and other sources of dietary nitrate and nitrite to counteract inflammation and promote homeostasis of the immune and vascular systems. The data from these studies suggest that immune cells and immune-vasculature interactions are important targets for dietary interventions aimed at improving, preserving, or restoring cardiovascular health.


Transcriptional regulation of the channel catfish virus genome direct repeat region.
Channel catfish virus (CCV), a member of the herpesvirus family, causes a severe haemorrhagic disease in juvenile channel catfish. In this report, we confirm that CCV gene expression is temporally regulated into immediate-early (IE), early and late phases, similar to that of other herpesviruses. The transcriptional regulation of the 14 genes within the direct repeat region of the CCV genome was determined by Northern hybridization analysis of RNA isolated from infected cells in the presence or absence of metabolic inhibitors. Two CCV genes within the direct repeat, ORFs 1 and 3, expressed IE transcripts. Early RNAs were encoded by ORFs 2-9 and 11-14. ORFs 4, 7 and 10-13 expressed late transcripts after the onset of viral DNA replication. A time-course study conducted without metabolic inhibitors confirmed that CCV direct repeat transcription is temporally regulated. The characterization of CCV transcription during cytolytic infection in vitro will provide a foundation for the analysis of CCV gene expression in tissues of acutely and latently infected catfish.


Real social analytics: A contribution towards a phenomenology of a digital world.
This article argues against the assumption that agency and reflexivity disappear in an age of 'algorithmic power' (Lash 2007). Following the suggestions of Beer (2009), it proposes that, far from disappearing, new forms of agency and reflexivity around the embedding in everyday practice of not only algorithms but also analytics more broadly are emerging, as social actors continue to pursue their social ends but mediated through digital interfaces: this is the consequence of many social actors now needing their digital presence, regardless of whether they want this, to be measured and counted. The article proposes 'social analytics' as a new topic for sociology: the sociological study of social actors' uses of analytics not for the sake of measurement itself (or to make profit from measurement) but in order to fulfil better their social ends through an enhancement of their digital presence. The article places social analytics in the context of earlier debates about categorization, algorithmic power, and self-presentation online, and describes in detail a case study with a UK community organization which generated the social analytics approach. The article concludes with reflections on the implications of this approach for further sociological fieldwork in a digital world.


HIV infection and incidence of ischemic stroke.
To determine the association of HIV infection and immunodeficiency with incidence of ischemic stroke. Cohort study of HIV-positive and matched HIV-negative adult Kaiser Permanente Northern and Southern California (KPNC and KPSC, respectively) members during 1996-2011 (KPNC) or 2000-2011 (KPSC). We used Poisson models to obtain rate ratios for incident ischemic stroke associated with HIV infection, both overall and stratified by CD4 cell counts (cells/μl) and HIV RNA copies (copies/ml), with HIV-negative individuals as the reference group. We also obtained rate ratios for risk factors in the HIV-positive subset. Among 24,768 HIV-positive and 257,600 HIV-negative individuals, the ischemic stroke rate per 100,000 person-years was 125 (n = 151 events) for HIV-positive and 74 (n = 1128 events) for HIV-negative individuals, with an adjusted rate ratio of 1.4 [95% confidence interval (CI) 1.2-1.7). Compared with HIV-negative individuals, HIV-positive individuals with recent CD4 cell counts of 500 cells/μl at least (rate ratio 1.0, 95% CI 0.8-1.4) or recent HIV RNA less than 500 copies/ml (rate ratio 1.1, 95% CI 0.9-1.4) had no excess risk of ischemic stroke, with similar results for HIV-positive individuals with nadir CD4 cell counts of 500 cells/μl at least (rate ratio 1.4, 95% CI 0.8-2.2) or 200-499 cells/μl (rate ratio 1.2, 95% CI 0.9-1.5). Among HIV-positive individuals only, recent CD4 cell count less than 200 cells/μl (rate ratio 2.5, 95% CI 1.3-4.6) was associated with an increased risk of ischemic stroke after adjustment for recent HIV RNA and nadir CD4 cell count, whereas recent HIV RNA and nadir CD4 were not independent risk factors. Ischemic stroke incidence in HIV-positive individuals with high CD4 cell count or low HIV RNA is similar to that of HIV-negative individuals.


Daily L-leucine supplementation in novice trainees during a 12-week weight training program.
To investigate the effects of daily oral L-leucine ingestion on strength, bone mineral-free lean tissue mass (LTM) and fat mass (FM) of free living humans during a 12-wk resistance-training program. Twenty-six initially untrained men (n = 13 per group) ingested either 4 g/d of L-leucine (leucine group: age 28.5 ± 8.2 y, body mass index 24.9 ± 4.2 kg/m2) or a corresponding amount of lactose (placebo group: age 28.2 ± 7.3 y, body mass index 24.9 ± 4.2 kg/m2). All participants trained under supervision twice per week following a prescribed resistance training program using eight standard exercise machines. Testing took place at baseline and at the end of the supplementation period. Strength on each exercise was assessed by five repetition maximum (5-RM), and body composition was assessed by dual energy X-ray absorptiometry (DXA). The leucine group demonstrated significantly higher gains in total 5-RM strength (sum of 5-RM in eight exercises) and 5-RM strength in five out of the eight exercises (P < .05). The percentage total 5-RM strength gains were 40.8% (± 7.8) and 31.0% (± 4.6) for the leucine and placebo groups respectively. Significant differences did not exist between groups in either total percentage LTM gains or total percentage FM losses (LTM: 2.9% ± 2.5 vs 2.0% ± 2.1, FM: 1.6% ± 15.6 vs 1.1% ± 7.6). These results suggest that 4 g/d of L-leucine supplementation may be used as a nutritional supplement to enhance strength performance during a 12-week resistance training program of initially untrained male participants.


The radiological approach to precocious puberty.
Precocious puberty is caused by a heterogeneous group of disorders, which range from idiopathic to malignant tumours. The radiologist's role is to help: (1) differentiate precocious puberty from pubertal variants; (2) identify the underlying cause of precocity if present; and (3) assess for effectiveness of treatment. This pictorial review discusses the types of precocious puberty and their underlying aetiologies, differentiates precocious puberty from pubertal variants and illustrates the appropriate imaging evaluation for the patient diagnosed with precocious puberty.


Electrospun PCL/Gel-aligned scaffolds enhance the biomechanical strength in tendon repair.
Tendons can transmit mechanical force from muscles to bones for movement. However, the mechanical strength of tendons is compromised after surgery, thus causing a high rate of tendon retear. Hence, the design and preparation of biodegradable materials with excellent mechanical properties have become an urgent demand for sports medicine. In this study, biomimetic polycaprolactone (PCL)/gelatin (Gel)-aligned scaffolds were fabricated for the mechanical restoration of the injured tendon in a rabbit model. The diameter of nanofibers was about 427.82 ± 56.99 nm, which was approximate to that of the native collagen fibrils; the directional consistency of the nanofibers in PCL/Gel-aligned scaffolds reached 77.33 ± 3.22%, which were ultrastructurally biomimetic. Compared to the observations for the control group, the in vitro mechanical results showed that the PCL/Gel-aligned scaffolds (P/G-A) were anisotropic in terms of failure load, tensile strength, and Young's modulus. After verifying their good cytocompatibility, the scaffolds were implanted into the rabbit patellar tendon in situ. The biomechanical properties of the repaired tendon in P/G-A reached 343.97 ± 65.30 N in failure load, 85.99 ± 16.33 MPa in tensile strength, 590.84 ± 201.87 MPa in Young's modulus, and 171.29 ± 61.50 N mm-1 in stiffness in vivo at 8 weeks post operation. In a word, our results demonstrated that P/G-A could support the regenerated tissue of injured patellar tendons to restore the biomechanical strength in a rabbit model. This suggested that the PCL/Gel-aligned scaffolds can pave a promising way to improve the healing of injured tendons in the clinic in the future.