Gene products specifying adhesion of uropathogenic Escherichia coli are minor components of pili.
The papE, papF, and papG genes of uropathogenic Escherichia coli are dispensable for the synthesis and assembly of pili associated with pyelonephritis, called Pap pili. Phenotypically, papF and papG mediate digalactoside [alpha-D-Galp-(1----4)-beta-D-Galp)-specific adhesion. Although whole bacterial cells of a papE mutant bind to this receptor, purified pili from such a mutant do not. This is in contrast to pili purified from the wild type, which bind specifically. The DNA sequences of the papE and papF genes are presented, together with the deduced primary structure of the gene products. Both proteins have most of the features characteristic of Escherichia coli type 1 and Pap pilins. The PapE protein can be detected in the purified wild-type pilus by NaDodSO4/polyacrylamide gel electrophoresis followed by silver staining or by autoradiography of gels to which radioiodinated pili have been applied. In rabbits immunized with purified Pap pili, antibodies specific for both PapE and PapF are produced. We propose that PapE and PapF are minor pilins in the Pap pilus.


An information model for computable cancer phenotypes.
Standards, methods, and tools supporting the integration of clinical data and genomic information are an area of significant need and rapid growth in biomedical informatics. Integration of cancer clinical data and cancer genomic information poses unique challenges, because of the high volume and complexity of clinical data, as well as the heterogeneity and instability of cancer genome data when compared with germline data. Current information models of clinical and genomic data are not sufficiently expressive to represent individual observations and to aggregate those observations into longitudinal summaries over the course of cancer care. These models are acutely needed to support the development of systems and tools for generating the so called clinical "deep phenotype" of individual cancer patients, a process which remains almost entirely manual in cancer research and precision medicine. Reviews of existing ontologies and interviews with cancer researchers were used to inform iterative development of a cancer phenotype information model. We translated a subset of the Fast Healthcare Interoperability Resources (FHIR) models into the OWL 2 Description Logic (DL) representation, and added extensions as needed for modeling cancer phenotypes with terms derived from the NCI Thesaurus. Models were validated with domain experts and evaluated against competency questions. The DeepPhe Information model represents cancer phenotype data at increasing levels of abstraction from mention level in clinical documents to summaries of key events and findings. We describe the model using breast cancer as an example, depicting methods to represent phenotypic features of cancers, tumors, treatment regimens, and specific biologic behaviors that span the entire course of a patient's disease. We present a multi-scale information model for representing individual document mentions, document level classifications, episodes along a disease course, and phenotype summarization, linking individual observations to high-level summaries in support of subsequent integration and analysis.


Phenotypic Consequence of Rearranging the N Gene of RABV HEP-Flury.
Nucleoprotein (N) is a key element in rabies virus (RABV) replication. To further investigate the effect of N on RABV, we manipulated an infectious cDNA clone of the RABV HEP-Flury to rearrange the N gene from its wild-type position of 1 (N-P-M-G-L) to 2 (P-N-M-G-L), 3 (P-M-N-G-L), or 4 (P-M-G-N-L), using an approach that left the viral nucleotide sequence unaltered. Subsequently, viable viruses were recovered from each of the rearranged cDNA and examined for their gene expression levels, growth kinetics in cell culture, pathogenicity in suckling mice and protection in mice. The results showed that gene rearrangement decreased N mRNA transcription and vRNA replication. As a result, all viruses with rearranged genomes showed worse replication than that of rHEP-Flury in NA cells at a MOI of 0.01, but equivalent or slightly better replication levels at a MOI of 3. Consequently, the lethality in suckling mice infected with N4 was clearly attenuated compared with rHEP-Flury. However, the protection to mice was not enhanced. This study not only gives us insight into the understanding of the phenotype of RABV N gene rearrangement, but also helps with rabies vaccine candidate construction.


Overestimation of flow velocity through leaks in mechanical valve prostheses and through small orifices by continuous-wave Doppler.
The reliability of continuous-wave Doppler flow velocity measurements through small regurgitant lesions, such as in prosthetic leakage, has not been systematically analyzed. To evaluate the accuracy of continuous-wave Doppler in prosthetic valve leakage and small orifices in an in vitro, steady-flow model-flow velocities through the leaks of twelve intact mechanical prostheses and through six circular nozzles (area 0.5 to 20 mm2) were measured at pressure drops between 30 and 105 mm Hg. These results were compared with those predicted by the modified Bernoulli equation. Laser Doppler anemometry of flow velocities through the nozzles was also performed. Despite high correlation, there was substantial overestimation of Bernoulli predicted velocities by echo Doppler in the prosthetic leaks (mean +12.3% +/- 9.4%; range 90.3% to 143.4%). In the nozzles < or = 10 mm2, but not in the largest (20 mm2) nozzle, there was also overestimation of the Bernoulli predicted velocities (mean +6.2% +/- 2%). Laser Doppler anemometry of flow velocities through the nozzles showed slightly lower values than predicted by the Bernoulli equation. Thus, continuous-wave echo Doppler overestimates flow velocities through small orifices. This apparently is, at least in part, due to transit time effects and should be taken into account when using echo Doppler in small (< 10 mm2) orifices, such as in mild to moderate regurgitant lesions and prosthetic valve leakage.


[Possibilities of using proteins from unicellular algae in biological life support systems].
The concentration, amino acid composition and biological value of proteins of unicellular algae belonging to various taxonomic groups (Chlorella, Chlamydomonas, Spirulina, Euglena) were investigated. With respect to their characteristics, these algae hold promise as components of biological life-support systems (BLSS). Indices characterizing the protein and biomass quality and biological value were calculated. Such indices as A/E (where A is an essential amino acid and E is the sum total of amino acids), E/T (where E is nitrogen of essential amino acids and T is its sum total), amino acid number, factor of digestibility in vitro were high enough and close to the respective parameters of the reference protein. Animal experiments showed high biological value of the algal biomass and the lack of its toxic or other adverse effects. The data on the quantity and quality of protein from the unicellular algae are indicative of its high biological value and applicability to BLSS. It is suggested that the differences in the protein composition associated with various algal forms and cultivation conditions can be used to produce balanced diets by varying the portion of each form of the photoautotrophic component of BLSS.


Process-symptom-bridges in psychotherapy: An idiographic network approach.
real-time monitoring of psychotherapeutic processes was recently described as a promising, new way of tracking periods of change in ongoing treatments. This approach generates complex, multivariate datasets that have to be presented in an intuitive way for clinicians to aid their clinical decision-making. Using network modeling and new approaches in centrality analyses, we examine "bridge nodes" between symptom stress and aspects of the psychotherapeutic process between therapy session (intersession processes, ISP). Method:we recorded intersession processes as well as depressive and anxiety symptoms using daily questionnaires in ten cases. Regularized, thresholded intraindividual dynamic networks were estimated. We applied bridge centrality analysis to identify individual bridges between psychotherapeutic processes and symptoms in the resulting models. Case-wise interpretations of bridge centrality values are offered. bridge centrality analysis revealed individual bridge nodes between intersession processes and symptom severity. Strength and direction of bridges varied substantially across individuals. given current methodological challenges, idiographic network studies are feasible and offer important insights for psychotherapy process research. In this case, we demonstrated how patients deal with periods of increased symptom stress. In this case we have described how patients deal with their therapy under increased symptom load. Bridges between psychotherapeutic processes and symptom stress are a promising target for monitoring systems based on ISP. Future studies should examine the clinical utility of network-based monitoring and feedback in ongoing therapies. In the near future, process feedback systems based on idiographic models could serve clinicians to improve treatments.


Collaborative consultation in natural environments: strategies to enhance family-centered supports and services.
This article presents current information on recommended practices related to the delivery of early intervention (EI) supports and services to infants and toddlers with, or at risk for, communication deficits and their families. The focus is on presenting the changing paradigm for speech-language pathologists (SLPs) working in EI based on the best available research evidence and expert opinion. The article includes a brief review of the recommended and promising practices for early communication intervention and applies the content to the role of the SLP as a consultant to caregivers. It provides strategies for "how to" join into the everyday activities/routines and places with the caregiver and child in order to facilitate caregiver-implemented intervention that will enhance caregiver-child interactions and promote the child's participation and learning. The importance of, and strategies for, collaborative consultation with diverse caregivers within a family-centered approach is presented. This article provides important and timely information for professionals and families related to family-centered EI practices, caregiver-implemented interventions, adult teaching strategies, and collaborative consultation with families of infants and toddlers with, or at risk for, communication deficits. SLPs can use the information presented to inform their practices when working with these young children and their families.


Automated Microsurgical Tool Categorization using a Surface-Based EMG System.
The selection of micro-surgical tools and their usage form a critical component in today's surgical outcome. The success or failure of the surgery depends on how effectively the surgeon has applied the tools on the operating patient. Popular surgical tools, including forceps, clamp applicators, micro-scissors, and needle holders, are typically used in operating procedures, and characterising the same set of tools in conjunction with the surgeon's implementation remains a topic of continued interest. There have been several computer vision-based approaches to segment and detect the tools used in the surgery, where the microscopic recordings are evaluated, however surgeon's haptic feedback and the subtle variation drawn is not evidently reported. The video-based detection system also suffers from the problem of masking or shadowing critical information while in use. Hence, efforts to extract localised information during the surgery are very valuable in addition to the video-acquired outcome. The surface-based electromyography (sEMG) system offers electro-muscular signals at the skin that characterise the actions performed. The work attempts to evaluate the adoption of sEMG signals for the detection of micro-surgical tools. In this work, a pilot study of handling micro-surgical tools and classifying the same using two-channel sEMG signals from the machine learning (ML) model is performed. A two-channel sEMG acquisition system connected to the electrodes was designed and used to build a staged and supervised data set consisting of operating surgical tools. Five hand-crafted features, each from an individual channel, were employed and utilised to design an accurate model. An accuracy of 97.43% was achieved for running the ANN model on sEMG signals to classify five surgical tools based on their press-and-release action. The use of sEMG signals for tool detection is a step towards the development of tool characterisation and the assessment of surgeons' skills.Clinical relevance- A two-channel sEMG signal acquisition system to detect micro-surgical tool usage was developed. Mapping the surgery outcome with the tool handling characteristics will be a valuable addition to the existing video-based assessment of the surgery. The subtle tool handling characteristics of the surgeon are effective in improving the overall outcome of the surgery, and it is possible to extract this information only from the proposed approach.


Seminal glucose levels: a prognostic factor of sperm survival to cryopreservation?
Considering that glucose is an important component of seminal plasma and is a cryoprotectant at high concentrations, the aim of this study was to investigate the possible association of glucose levels in fresh semen with the sperm survival and motility rates following cryopreservation. This was a prospective study including 149 men undergoing semen analysis due to male and/or female infertility. The seminal samples were analyzed according to the World Health Organization standards and glucose concentrations were measured using a dipstick glucometer. Samples were cryopreserved with Test Yolk Buffer-Gentamicine freezing medium under liquid nitrogen for an average of 120 days. The frozen aliquots were thawed at 37°C for 10 minutes and analyzed using the same methods and protocols used pre-freezing. Glucose levels ranged from 14 to 99 mg/dL and were similar in individuals with normal (n=100) vs. abnormal (n=49) semen analysis. The rates of sperm recovery (total, alive or motile sperm) in the cryopreserved samples did not change among samples with different glucose levels (p>0.05, Kruskal-Wallis ANOVA and Spearman's correlation coefficient). There appears to be no association between glucose levels in human semen samples and their resistance to cryopreservation.


Influence of cimetidine, sulfinpyrazone, and cigarette smoking on theobromine metabolism in man.
Theobromine metabolism and clearance were investigated at steady-state under chronic oral dosing conditions in eight healthy volunteers, four of whom were cigarette smokers. The subjects were studied before and after separate 1 week pretreatments with cimetidine (1 g/day) and sulfinpyrazone (800 mg/day). Theobromine plasma clearance (ClTB) was 33% higher in smokers than in non-smokers due to induction of all metabolic pathways (3-demethylation, 7-demethylation, and formation of 6-amino-5-(N-methylformylamino)-1-methyluracil (AMMU]. 7-Demethylation was induced by cigarette smoking to a greater extent than the other pathways. Cimetidine pretreatment inhibited theobromine 3-demethylation and AMMU formation resulting in a 27% decrease in ClTB in the combined smoker/nonsmoker group. The 7-demethylation pathway was unaffected by cimetidine. In contrast, sulfinpyrazone pretreatment increased ClTB by 50% in the whole group by approximately equal induction of each metabolic pathway. The extent of induction due to sulfinpyrazone was 2.4-fold greater in nonsmokers than in smokers. When compared with previous data relating to theophylline, the results suggest that theobromine 3-demethylation is mediated by the same form(s) of cytochrome P-450 involved in theophylline demethylation, while a second form(s) of cytochrome P-450 is involved in theobromine 7-demethylation and theophylline 8-hydroxylation. In addition, since AMMU formation was inhibited by cimetidine and induced by cigarette smoking and sulfinpyrazone, it would appear that the conversion of theobromine to AMMU is also mediated by cytochrome P-450.


[Immunoglobulins and nonspecific immunity factors in leukemias].
The authors report the data on immunoglobulins G, A, M content and their relationship with other factors of natural immunity in 55 patients with acute myeloblastic leukemia and in 43 patients with chronic lymphatic leukemia. The results have evidenced the impaired synthesis of immunoglobulins in acute in acute leukemia and the reduction of IgA and IgM already in the initial stage of chronic lymphatic leukemia. A correlation between mean values of immunoglobulins content and other factors of immunological resistance allowed a statement to be made that in the absence of impaired immunoglobulins synthesis there is a distinct coincidence of immunoglobulin content curves and titres of agglutinating and bacteriolytic antibodies.


Atomic model of an infectious rotavirus particle.
Non-enveloped viruses of different types have evolved distinct mechanisms for penetrating a cellular membrane during infection. Rotavirus penetration appears to occur by a process resembling enveloped-virus fusion: membrane distortion linked to conformational changes in a viral protein. Evidence for such a mechanism comes from crystallographic analyses of fragments of VP4, the rotavirus-penetration protein, and infectivity analyses of structure-based VP4 mutants. We describe here the structure of an infectious rotavirus particle determined by electron cryomicroscopy (cryoEM) and single-particle analysis at about 4.3 Å resolution. The cryoEM image reconstruction permits a nearly complete trace of the VP4 polypeptide chain, including the positions of most side chains. It shows how the two subfragments of VP4 (VP8(*) and VP5(*)) retain their association after proteolytic cleavage, reveals multiple structural roles for the β-barrel domain of VP5(*), and specifies interactions of VP4 with other capsid proteins. The virion model allows us to integrate structural and functional information into a coherent mechanism for rotavirus entry.


Radiographic, computed tomographic and arthroscopic findings in 23 dogs with osteochondrosis of the tarsocrural joint.
Twenty-three dogs with osteochondrosis of the tarsocrural joint were evaluated by radiography, computed tomography (CT) and arthroscopy. The radiographic examination included an extended and flexed mediolateral, a plantarodorsal, a flexed dorsoplantar skyline view, and a plantaromedial-dorsolateral and a plantarolateral-dorsomedial view (two oblique views). The CT examination was carried out in ventral recumbency and 1 mm slices were taken with a bone window setting; 31 lesions were identified in the 46 joints examined. The arthroscopic exploration used either a plantar or a dorsal puncture, depending on the site of the lesion. In six cases the lateral, and in 17 cases the medial trochlear ridge was involved. Although the survey radiographs were sufficient to make a diagnosis, the CT examination helped to determine the exact site, and the number and size of the fragments of bone. A four-stage classification system comparable to the one used in man was established. Arthroscopy provided information about synovial inflammation and damage to the joint cartilage, and made it possible to remove fragments of bone from one-third of the cases.


Operator Product Expansion for Form Factors.
We propose an operator product expansion for planar form factors of local operators in N=4 SYM theory. This expansion is based on the dual conformal symmetry of these objects or, equivalently, the conformal symmetry of their dual description in terms of periodic Wilson loops. A form factor is decomposed into a sequence of known pentagon transitions and a new universal object that we call the "form factor transition." This transition is subject to a set of nontrivial bootstrap constraints, which are sufficient to fully determine it. We evaluate the form factor transition for maximally helicity-violating form factors of the chiral half of the stress tensor supermultiplet at leading order in perturbation theory and use it to produce operator product expansion predictions at any loop order. We match the one-loop and two-loop predictions with data available in the literature.


Use of Tigecycline for Diabetic Foot Infections
The aim of this study is to evaluate tigecycline for diabetic foot infections (DFIs). In this prospective observational study, the investigators included patients who had consultation with the Diabetic Foot Council of Ege University Faculty of Medicine (Izmir, Turkey) between March 2013 and July 2015 and who used tigecycline during their treatment. Treatment success was assessed by design-specific criteria for each evaluation. The study included 105 cases. Of those, 37 (35.2%) were women (mean [± standard deviation] age, 61.9 ± 11.9 years). The success rate of tigecycline treatment was 93.3% in mild infections, 56.2% in moderate, 57.7% in severe, and 61.9% in all cases. The authors found a 9-fold decrease (P = .046) in the success of tigecycline treatment among those who developed moderate or severe DFIs and a 6.4-fold decrease (P < .0001) among those who had arterial stenosis. For 33 (71.7%) of 46 (43.8%) patients who experienced a side effect, tigecycline treatment was continued as it could be tolerated. If tigecycline is to be the treatment choice, extra attention must be paid to patients with arterial stenosis, severe DFIs, and side effects. The common disadvantage is the high side effect rate, especially nausea. However, it is generally not necessary to discontinue the medication in cases with nausea. Therefore, tigecycline may be used as a choice of therapy in mild DFIs.


Epigenetic modifications in pediatric acute lymphoblastic leukemia.
Aberrant epigenetic modifications are well-recognized drivers for oncogenesis. Pediatric acute lymphoblastic leukemia (ALL) is no exception and serves as a model toward the significant impact these heritable alterations can have in leukemogenesis. In this brief review, we will focus on the main aspects of epigenetics, which control leukemogenesis in pediatric ALL, mainly DNA methylation, histone modification, and microRNA alterations. As we continue to gain better understanding of the driving mechanisms for pediatric ALL at both diagnosis and relapse, therapeutic interventions directed toward these pathways and mechanisms can be harnessed and introduced into clinical trials for pediatric ALL.


Computational color prediction versus least-dissimilar matching.
The performance of color prediction methods CIECAM02, KSM2, Waypoint, Best Linear, Metamer Mismatch Volume Center, and Relit color signal are compared in terms of how well they explain Logvinenko and Tokunaga's asymmetric color matching results [Seeing Perceiving24, 407 (2011)]. In their experiment, four observers were asked to determine (three repeats) for a given Munsell paper under a test illuminant which of 22 other Munsell papers was the least-dissimilar under a match illuminant. Their use of "least-dissimilar" as opposed to "matching" is an important aspect of their experiment. Their results raise several questions. Question 1: Are observers choosing the original Munsell paper under the match illuminant? If they are, then the average (over 12 matches) color signal (i.e., cone LMS or CIE XYZ) made under a given illuminant condition should correspond to that of the test paper's color signal under the match illuminant. Computation shows that the mean color signal of the matched papers is close to the color signal of the physically identical paper under the match illuminant. Question 2: Which color prediction method most closely predicts the observers' average least-dissimilar match? Question 3: Given the variability between observers, how do individual observers compare to the computational methods in predicting the average observer matches? A leave-one-observer-out comparison shows that individual observers, somewhat surprisingly, predict the average matches of the remaining observers better than any of the above color prediction methods.


PE_PGRS antigens of Mycobacterium tuberculosis induce maturation and activation of human dendritic cells.
Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis, infects one-third of the world's population. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). DCs are sentinels of the immune system and are important for eliciting both primary and secondary immune responses to pathogens. In this context, to understand the molecular pathogenesis of tuberculosis and host response to mycobacteria and to conceive prospective vaccine candidates, it is important to understand how cell wall Ags of M. tuberculosis and, in particular, the proline-glutamic acid_polymorphic guanine-cytosine-rich sequence (PE_PGRS) family of proteins modulate DC maturation and function. In this study, we demonstrate that two cell wall-associated/secretory PE_PGRS proteins, PE_PGRS 17 (Rv0978c) and PE_PGRS 11 (Rv0754), recognize TLR2, induce maturation and activation of human DCs, and enhance the ability of DCs to stimulate CD4(+) T cells. We further found that PE_PGRS protein-mediated activation of DCs involves participation of ERK1/2, p38 MAPK, and NF-kappaB signaling pathways. Priming of human DCs with IFN-gamma further augmented PE_PGRS 17 or PE_PGRS 11 Ag-induced DC maturation and secretion of key proinflammatory cytokines. Our results suggest that by activating DCs, PE_PGRS proteins, important mycobacterial cell wall Ags, could potentially contribute in the initiation of innate immune responses during tuberculosis infection and hence regulate the clinical course of tuberculosis.


Woman's position during second stage of labour.
For centuries, there has been controversy around whether being upright (sitting, birthing stools, chairs, squatting) or lying down have advantages for women delivering their babies. The objective of this review was to assess the benefits and risks of the use of different positions during the second stage of labour (i. e. from full dilatation of the cervix). Relevant trials are identified from the register of trials maintained by the Cochrane Pregnancy and Childbirth Group, and from the Cochrane Controlled Trials Register. Trials were included which compared various positions assumed by pregnant women during the second stage of labour. Randomised and quasi-randomised trials with appropriate follow-up were included. Trials were independently assessed for inclusion, and data extracted, by the two authors. Disagreements would have been resolved by consensus with an editor. Meta-analysis of data is performed using the RevMan software. Results should be interpreted with caution as the methodological quality of the 18 trials was variable. Use of any upright or lateral position, compared with supine or lithotomy positions, was associated with: 1. Reduced duration of second stage of labour (12 trials - mean 5.4 minutes, 95% confidence interval (CI) 3.9 - 6.9 minutes). This was largely due to a considerable reduction in women allocated to use of the birth cushion. 2. A small reduction in assisted deliveries (17 trials - odds ratio (OR) 0.82, 95% CI 0.69 - 0.98). 3. A reduction in episiotomies (11 trials - OR 0.73, 95% CI 0.64 - 0.84). 4. A smaller increase in second degree perineal tears (10 trials - OR 1.30, 95% CI 1.09 - 1.54). 5. Increased estimated risk of blood loss > 500ml (10 trials - OR 1.76, 95% CI 1.34 - 3.32). 6. Reduced reporting of severe pain during second stage of labour (1 trial - OR 0.59, 95% CI 0.41 - 0.83). 7. Fewer abnormal fetal heart rate patterns (1 trial - OR 0.31, 95% CI 0.11 - 0.91). The tentative findings of this review suggest several possible benefits for upright posture, with the possibility of increased risk of blood loss > 500ml. Women should be encouraged to give birth in the position they find most comfortable. Until such time the benefits and risks of various delivery positions are estimated with greater certainty when methodologically stringent trials data are available, then women should be allowed to make informed choices about the birth positions in which they might wish to assume for delivery of their babies.


Insights Into Onchocerca volvulus Population Biology Through Multilocus Immunophenotyping.
We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides derived from 8 of 10 proteins tested: OVOC1192(1-15), OVOC9988(28-42), OVOC9225(320-334), OVOC7453(22-36), OVOC11517(14-28), OVOC3177(283-297), OVOC7911(594-608), and OVOC12628(174-188). Our data show that differences in immunoreactivity to variant antigenic peptides may be used to characterize Ov populations, thereby elucidating features of Ov population biology previously inaccessible because of the limited availability of parasite material.


Retinal burns from laser pointers: a risk in children with behavioural problems.
To explore self-inflicted retinal burns from laser pointers in children. Literature review of laser pointer retinal injuries in childhood and online survey of UK Consultant Ophthalmologists. A cohort of local children with self-inflicted injury is described. The matter is topical. We review progress in recent legislation and policy change in the UK. Four of 77 case reports of laser burns in childhood analysed reported psychological or behavioural issues. Three of four children in our cohort had such issues. Delay in diagnosis occurred in two of our patients. Structural retinal damage persisted for over 12 months in all four children (seven eyes). Our survey of UK ophthalmologists found 159 cases of injury (85% male), 80% under 20 years of age. The majority of the laser pointers were purchased online. Many patients (36%) suffered moderate vision loss (6/18 to 6/60 Snellen), while 17% (at least 11 patients) suffered severe vision loss (<6/60 Snellen). We highlight the risk of macular damage and vision loss from handheld lasers specifically in children with behavioural, learning or mental health issues. The diagnosis may be difficult or delayed in such children. In children with uncertain macular changes, ophthalmologists should explore the history for possible instances of exposure to handheld lasers pointers. Regulatory authorities and manufacturers of handheld lasers need to be aware of the risk to children. Furthermore, there is a need to better inform parents, carers and teachers of the risk of ocular self-injury from such lasers pointers.


A national e-Delphi towards the measurement of safe medication practices in Portuguese hospitals.
To determine the face and content validity of items for measuring safe medication practices in Portuguese hospitals. 128 items were drafted from content analysis of existing questionnaires and the literature, employing preferred terms of the WHO International Classification for Patient Safety (Portuguese version). A two-round e-Delphi was convened, using a purposive multidisciplinary panel. Hospital-based experts were asked to rate the relevance of items on a 7-point Likert scale and to comment on their clarity and completeness. The response rate was similar in both rounds (70.3% and 73.4%, respectively). In the first round 91/128 (71.1%) items reached the predefined level of positive consensus. In the second round 23 additional items reached positive consensus, as well as seven items newly derived by the panel. Most items have face and content validity, indicating relevance and clarity, and can be included in a future questionnaire for measuring safe medication practices in Portuguese hospitals.


Promoting data harmonization to evaluate vaccine hesitancy in LMICs: approach and applications.
Factors influencing the health of populations are subjects of interdisciplinary study. However, datasets relevant to public health often lack interdisciplinary breath. It is difficult to combine data on health outcomes with datasets on potentially important contextual factors, like political violence or development, due to incompatible levels of geographic support; differing data formats and structures; differences in sampling procedures and wording; and the stability of temporal trends. We present a computational package to combine spatially misaligned datasets, and provide an illustrative analysis of multi-dimensional factors in health outcomes. We rely on a new software toolkit, Sub-National Geospatial Data Archive (SUNGEO), to combine data across disciplinary domains and demonstrate a use case on vaccine hesitancy in Low and Middle-Income Countries (LMICs). We use data from the World Bank's High Frequency Phone Surveys (HFPS) from Kenya, Indonesia, and Malawi. We curate and combine these surveys with data on political violence, elections, economic development, and other contextual factors, using SUNGEO. We then develop a stochastic model to analyze the integrated data and evaluate 1) the stability of vaccination preferences in all three countries over time, and 2) the association between local contextual factors and vaccination preferences. In all three countries, vaccine-acceptance is more persistent than vaccine-hesitancy from round to round: the long-run probability of staying vaccine-acceptant (hesitant) was 0.96 (0.65) in Indonesia, 0.89 (0.21) in Kenya, and 0.76 (0.40) in Malawi. However, vaccine acceptance was significantly less durable in areas exposed to political violence, with percentage point differences (ppd) in vaccine acceptance of -10 (Indonesia), -5 (Kenya), and -64 (Malawi). In Indonesia and Kenya, although not Malawi, vaccine acceptance was also significantly less durable in locations without competitive elections (-19 and -6 ppd, respectively) and in locations with more limited transportation infrastructure (-11 and -8 ppd). With SUNGEO, researchers can combine spatially misaligned and incompatible datasets. As an illustrative example, we find that vaccination hesitancy is correlated with political violence, electoral uncompetitiveness and limited access to public goods, consistent with past results that vaccination hesitancy is associated with government distrust.


Association of drinking pattern with risk of coronary heart disease incidence in the middle-aged and older Chinese men: Results from the Dongfeng-Tongji cohort.
Epidemiologic studies have found that moderate alcohol consumption was associated with a decreased risk of coronary heart disease (CHD) incidence. Nevertheless, whether the drinking pattern is associated with CHD incidence still remains inconclusive. We included 8,469 Chinese men aged 45-81 years, who were free of CHD, stroke, or cancer at baseline from Dongfeng-Tongji cohort. A semi-structured questionnaire was used to collect information on alcohol consumption and other covariates. Cox proportional hazard regression model was applied to estimate the multivariable-adjusted hazard rations (HRs) and 95% confidence intervals (95% CIs). During an average of 4.36 years of follow-up, we identified 959 incident CHD events. Compared with non-drinkers, the multivariable-adjusted HR (95% CI) of CHD incidence was 0.84 (0.71-0.98) in current drinkers. With respect to drinking pattern, men who consumed 20.01-40 grams ethanol once a time had a 24% lower risk of incident CHD (HR = 0.76, 95% CI = 0.62, 0.94) compared with non-drinkers. The adjusted HRs (95% CI) of CHD incidence were 0.80 (0.65, 0.99), 1.02 (0.84, 1.22), and 0.75 (0.59-0.96) in subjects who consumed 0.01-10, 10.01-30, and > 30 grams ethanol per day, respectively. Participants who consumed 20.01-40 grams ethanol per time with less than 5 times per week had the lowest risk of CHD incidence (HR = 0.73, 95% CI = 0.52, 0.96). No significant associations were observed between type or frequency of alcohol consumption and CHD incidence. Drinking was associated with a lower risk of CHD incidence in middle-aged and older Chinese men and moderate quantity of ethanol amounts once a time with lower frequency could been considered as a healthy drinking pattern, which might modify the relationship between alcohol consumption and incident CHD.


[IMMUNE SYSTEM DATA IN PATIENTS WITH PERSISTENT RECURENT HERPES VIRUS INFECTIONS IN DYNAMICS OF COMPLEX THERAPY].
The positive clinical, serolgical and immunological effects of Glutamyl-Triptophan in patients on persistent herpes virus infections are shown. Treatment resulted in the increase of avidity on HSV 1, HSV 2, CMV, EBV antibody, the levels of CD3+-, ICD8+-, CD16+-, CD3+HLA-DR+- (%, abs) and.CD3+CD25t-cells (%), that indicates the optimization of the immune systemdata. The data received allow to recommend Bestim for patients with persistent herpes virus infections.


Pulmonary vascular endothelial injury and acute pulmonary hypertension caused by COVID-19: the fundamental cause of refractory hypoxemia?
Coronavirus disease (COVID-19) is a severe infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to the cells; angiotensin converting enzyme 2 (ACE2) receptor. In the first severe case of COVID-19 in Shenzhen city, we found that in addition to the typical clinical manifestations, our patient presented hemoptysis, refractory hypoxemia and pulmonary fibrosis-like changes on computed tomography (CT) involving alveoli and pulmonary interstitium in the early stage and acute pulmonary hypertension and right heart failure in the later stage, which were not completely justified by myocarditis, acute respiratory distress syndrome (ARDS), pulmonary fibrosis and high PEEP level. The lung compliance deterioration of this patient was not as serious as we expected, indicating classic ARDS was not existed. Simultaneously, the first autopsy report of COVID-19 in China showed normal-structured alveoli and massive thick excretion in the airway. Then, we speculated that the virus not only attacked alveolar epithelial cells, but also affected pulmonary vascular endothelial cells. Imbalance in the ACE2-RAAS- bradykinin axis and the cytokine storm could be an important mechanism leading to pathophysiological changes in pulmonary vascular and secondary refractory hypoxemia. Pulmonary vasculitis or capillaritis associated to immune damage and an inflammatory storm could exist in COVID-19 because of ground-glass opacities in the subpleural area, which are similar to connective tissue disease associated interstitial lung disease (CTD-ILD). Thus, this case elucidates new treatment measures for COVID-19.


On the accuracy of bulk synthetic CT for MR-guided online adaptive radiotherapy.
MR-guided radiotherapy (MRgRT) relies on the daily assignment of a relative electron density (RED) map to allow the fraction specific dose calculation. One approach to assign the RED map consists of segmenting the daily magnetic resonance image into five different density levels and assigning a RED bulk value to each level to generate a synthetic CT (sCT). The aim of this study is to evaluate the dose calculation accuracy of this approach for applications in MRgRT. A planning CT (pCT) was acquired for 26 patients with abdominal and pelvic lesions and segmented in five levels similar to an online approach: air, lung, fat, soft tissue and bone. For each patient, the median RED value was calculated for fat, soft tissue and bone. Two sCTs were generated assigning different bulk values to the segmented levels on pCT: The sCTICRU uses the RED values recommended by ICRU46, and the sCTtailor uses the median patient-specific RED values. The same treatment plan was calculated on two the sCTs and the pCT. The dose calculation accuracy was investigated in terms of gamma analysis and dose volume histogram parameters. Good agreement was found between dose calculated on sCTs and pCT (gamma passing rate 1%/1 mm equal to 91.2% ± 6.9% for sCTICRU and 93.7% ± 5.3% b or sCTtailor). The mean difference in estimating V95 (PTV) was equal to 0.2% using sCTtailor and 1.2% using sCTICRU, respect to pCT values CONCLUSIONS: The bulk sCT guarantees a high level of dose calculation accuracy also in presence of magnetic field, making this approach suitable to MRgRT. This accuracy can be improved by using patient-specific RED values.


MetaGlyph: Automatic Generation of Metaphoric Glyph-based Visualization.
Glyph-based visualization achieves an impressive graphic design when associated with comprehensive visual metaphors, which help audiences effectively grasp the conveyed information through revealing data semantics. However, creating such metaphoric glyph-based visualization (MGV) is not an easy task, as it requires not only a deep understanding of data but also professional design skills. This paper proposes MetaGlyph, an automatic system for generating MGVs from a spreadsheet. To develop MetaGlyph, we first conduct a qualitative analysis to understand the design of current MGVs from the perspectives of metaphor embodiment and glyph design. Based on the results, we introduce a novel framework for generating MGVs by metaphoric image selection and an MGV construction. Specifically, MetaGlyph automatically selects metaphors with corresponding images from online resources based on the input data semantics. We then integrate a Monte Carlo tree search algorithm that explores the design of an MGV by associating visual elements with data dimensions given the data importance, semantic relevance, and glyph non-overlap. The system also provides editing feedback that allows users to customize the MGVs according to their design preferences. We demonstrate the use of MetaGlyph through a set of examples, one usage scenario, and validate its effectiveness through a series of expert interviews.


Molecular bases of combined subtotal deficiencies of C6 and C7: their effects in combination with other C6 and C7 deficiencies.
Combined subtotal deficiency of C6 and C7, in which both proteins are expressed at very low levels, has been observed in homozygous form in two families. A defect at the 5' splice donor site of intron 15 of the C6 gene explains the low molecular weight of the C6 protein and is probably responsible for its low expressed concentration. The C7 defect is more enigmatic: the protein is of normal molecular weight, low circulating concentration, and altered isoelectric point. An Arg > Ser codon substitution in exon 11 is the only molecular alteration within the mature C7 protein. These defects are associated with a characteristic set of polymorphic DNA markers in the C6/C7 region, forming a distinct haplotype. The haplotype has been found in combination with a number of other haplotypes containing defective genes that lead either to C6 or C7 deficiency, but with different consequences. Where it is combined with a C6-deficient gene, the serum C7 levels can be surprisingly high, possibly because there is no C6 generating C56 to consume the C7. In contrast, where the C7 genes are both defective (but still partially functional), there may be a profound deficit of circulating C7 because there is ample C6 to produce C56 and consume the already small amount of C7. Each molecular defect has also been found in isolation and has the expected effect.


Quantification of left ventricular dimensions on line with biplane transesophageal echocardiography and lateral gain compensation.
To determine the feasibility and accuracy of biplane transesophageal echocardiography (TEE) with automatic boundary detection (ABD) for the estimation of left ventricular areas, we examined 19 consecutive patients with the use of this technique. In addition, we evaluated the utility of lateral gain compensation (LGC) to improve the online tracking of the ABD algorithm on the lateral endocardial-blood boundary of the echocardiographic image. The transverse plane short-axis TEE view and the longitudinal plane two chamber TEE view were used for the analysis. A semiquantitative estimate (in degrees) of the endocardial circumference, in which the boundary was correctly identified and tracked on line, improved from a mean of 198 degrees to 360 degrees with LGC (P less than 0.001). Results of comparisons of offline and online biplane TEE cavity areas revealed excellent correlations of values for the 16 patients (84%) in whom adequate transverse plane short-axis images were obtained (r values greater than 0.9 at systole and diastole). The correlation was also excellent (r values greater than 0.9) in the nine patients in whom longitudinal plane two-chamber views adequate for ABD analysis were obtained at systole and diastole. LGC significantly improved the accuracy of endocardial detection and tracking, which otherwise would be limited due to the anisotropic properties of the myocardium. Thus, ABD during biplane TEE may be feasible in a significant number of patients and accurately reflects left ventricular areas when compared with offline methods.


Systematic review and evidence based recommendations on texture modified foods and thickened liquids for adults (above 17 years) with oropharyngeal dysphagia - An updated clinical guideline.
Oropharyngeal dysphagia (OD) has significant consequences for both the person with dysphagia and the society. An often-used treatment for OD is the recommendation of the texture of food and liquids. This recommendation seems to be based more on best practice than on evidence from a systematic review of existing scientific evidence. The aim of this paper was to report the result of an up-date of an original national guideline focussing on whether thickened liquids (review question 1) and modified foods (review question 2) are beneficial for adults above 17 years with OD in relation to three critical outcomes (aspiration, pneumonia and death) and seven important outcomes (dehydration, weight loss, mealtime performance, patient preferences, intervention adherence and quality of life). Three steps were used. First: An updated systematic literature search. Second: An assessment of the quality of the evidence for each review question by means of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Third: Development of clinical recommendations based on the evidence, assessment of the risk benefit ratio, and perceived patient preferences. The body of evidence consisted of two RCTs for review question 1 both using nectar thickened liquids or honey-thickened liquids. No evidence was found for two important outcomes, mealtime performance and quality of life. With regard to risk of pneumonia, death, aspiration, dehydration, weight loss and intervention adherence no significant differences were found. The outcome addressing patient preferences, found a non-significant increased dissatisfaction with nectar thickened liquids (RR 1.11; 95% CI 0.95-1.30) and a significant increased dissatisfaction with honey thickened liquids compared to thin liquids/chin down (RR 1.18; 95% CI 1.01-1.37). No evidence was identified for review question 2. Based on the quality of the evidence, assessment of the risk benefit ratio, and perceived patient preferences a weak recommendation against the use of texture modified liquids and good clinical practice pointing for the use of texture modified foods in patients with OD were made.


Burkitt's lymphoma in a young Brazilian boy.
Burkitt's lymphoma is not an uncommon malignancy in the paediatric population. It is a high-grade non-Hodgkin B-cell lymphoma which may present as endemic, sporadic and human immunodeficiency-associated subtypes. The African, or endemic, variant usually involves the maxilla and other facial bones while head and neck manifestations in sporadic Burkitt's lymphoma are rare. We described a case of oral Burkitt's lymphoma involving the right jaw in a 4-year-old boy. The patient presented with a rapidly-enlarging swelling of one month duration, toothache-like pain and radiographical appearance of 'floating teeth' in the right mandible. Incisional biopsy revealed small round tumour cells with scarce cytoplasm and multiple small nuclei interspersed by phagocytic macrophages. The tumour cells were immunopositivity for CD20 and CD10, expressed weak positivity for CD3, negative for CD5 and showed > 90% positivity for Ki-67. Tumour remission was achieved with six cycles of chemotherapy with the CHOP regime.


[Acute confusional syndrome as first manifestation of primary hyperparathyroidism].
Hyperparathyroid crisis is an uncommon clinical state characterized by severe hypercalcemia which can produce an acute confusional syndrome (ACS) or delirium. We are reporting the case of a 58-year male with calcemias greater than 14 mg/dl, that were due to a parathyroid adenoma (primary hyperparathyroidism), and caused his admission in UCI with change in the conscience level, global afectation of the cognitive functions, letargia and disorentiation among other clinical symptoms. The patient was operated by our Service on lower left parathyroidectomy with PTH rapid or turbo assay and decreasing such hormone levels about 75%. After the surgery his evolution was satisfactory obtaining the normocalcemia.


Are US populations appropriate for trials of human immunodeficiency virus vaccine? The HIVNET Vaccine Preparedness Study.
Questions exist about whether testing of preventive human immunodeficiency virus (HIV)-1 vaccines, which will require rapid recruitment and retention of cohorts with high HIV-1 seroincidence, is feasible in the United States. A prospective cohort study was conducted in 1995-1997 among 4,892 persons at high risk for HIV infection in nine US cities. At 18 months, with an 88% retention rate, 90 incident HIV-1 infections were observed (1.31/100 person-years (PY), 95% confidence interval (CI): 1.06, 1.61). HIV-1 seroincidence rates varied significantly by baseline eligibility criteria--1.55/100 PY among men who had sex with men, 0.38/100 PY among male intravenous drug users, 1.24/100 PY among female intravenous drug users, and 1.13/100 PY among women at heterosexual risk-and by enrollment site, from 0.48/100 PY to 2.18/100 PY. HIV-1 incidence was highest among those men who had sex with men who reported unprotected anal intercourse (2.01/100 PY, 95% CI: 1.54, 2.63), participants who were definitely willing to enroll in an HIV vaccine trial (1.96/100 PY, 95% CI: 1.41, 2.73), and women who used crack cocaine (1.62/100 PY, 95% CI: 0.92, 2.85). Therefore, cohorts with HIV-1 seroincidence rates appropriate for HIV-1 vaccine trials can be recruited, enrolled, and retained.


Bounds of parameter estimation for interference signals.
Parameter estimation, especially frequency estimation, from noisy observations of interference is essential in optical interferometric sensing and metrology. The Cramer-Rao bound (CRB) of such estimation determines measurement sensitivity limit. Unlike the well-studied complex sinusoids in communication theory, an optical interference signal is distinctly different in its model parameters and noise statistics. The connection between these parameters and their estimation bounds has not been well understood. Here we propose a complete, realistic multiparameter interference model corrupted by a combination of shot noise, dark noise, and readout noise. We derive the Fisher information matrix and the CRBs for all model parameters, including intensity, visibility, optical path length (frequency), and initial phase. We show that the CRBs of frequency and phase are coupled but not affected by the knowledge of intensity and visibility. Knowing the initial phase offers significant sensitivity advantage, which is verified by both theoretical derivations and numerical simulations. In addition to the complete model, a shot noise-limited case is studied, permitting the calculation of the CRBs directly from measured data.


Metabolism of omega-6 polyunsaturated fatty acids in women with dysmenorrhea.
Menstrual pain (dysmenorrhea) is one of the main complaints in clinics for women. The pain is often accompanied by other symptoms such as headache, nausea, constipation or diarrhea, urinary frequency, and vomiting which often leave the patients incapacitated for work or school for a few days. Dietary supplementation with polyunsaturated fatty acids (PUFA) has been shown to alleviate the menstrual pain. The purpose of the present study was to compare the effect of dietary supplementation with PUFA (sunflower seed oil, borage oil and fish oil concentrate) for three months on RBC membrane fatty acid composition in healthy and dysmenorrheica young women. Conversion of linoleic acid, via gamma-linolenic acid, to dihomo-gamma-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) in dysmenorrheic subjects as compared to the controls was slower whereas the level of arachidonic acid (a precursor of pro-inflammatory PGE2) was not affected by the supplementation. Since there are no known side-effects associated with supplementation of these nutrients, management of dysmenorrhea through nutrition modulation should be an acceptable alternative to drug treatments.


Awareness of Diabetic Retinopathy: Insight From the National Health and Nutrition Examination Survey.
This study determines the prevalence and associated correlates of people unaware of their diabetic retinopathy diagnosis in the U.S. Participants unaware of diabetic retinopathy from the National Health and Nutrition Examination Survey from 2005 to 2008 were identified. The prevalence of those unaware of their diabetic retinopathy diagnosis was determined. Descriptive statistics and logistic regression were used to determine correlates associated with being unaware of one's diabetic retinopathy diagnosis (completed in 2018‒2020). Among 5,563 participants aged ≥40 years who underwent fundus photography, the prevalence of those unaware of their diabetic retinopathy diagnosis was 10.6% (9.8 million). This included 23.1% of those with self-reported diabetes (2.9 million) and 6.8% of those who reported not having diabetes (6.9 million). Among participants reporting diabetes with photographic evidence of retinopathy, 70.1% were unaware. Among individuals with self-reported diabetes, correlates of being unaware of one's diabetic retinopathy diagnosis included diabetes diaganosis for ≥10 years (OR=3.15, 95% CI=1.78, 5.56), HbA1c ≥6.5% (OR=2.92, 95% CI=1.65, 5.18), and treatment with insulin only (OR=4.04, 95% CI=1.43, 11.39). Self-reported hypertension was associated with decreased odds of undiagnosed diabetic retinopathy (OR=0.48, 95% CI=0.28, 0.82). Among those without self-reported diabetes, correlates of being unaware of diabetic retinopathy included older age (OR=1.02, 95% CI=1.01, 1.04), male sex (OR=1.83, 95% CI=1.31, 2.56), Black race (OR=1.81, 95% CI=1.12, 2.92), Hispanic race/ethnicity (OR=1.60, 95% CI=1.14, 2.25), elevated blood pressure (OR=1.54, 95% CI=1.23, 1.93), current smoking (OR=1.74, 95% CI=1.21, 2.51), and history of stroke (OR=2.20, 95% CI=1.06, 4.58). A substantial proportion of individuals with diabetic retinopathy are unaware of the diagnosis. These data provide a path toward refining efforts to diagnose and treat diabetic retinopathy to decrease the burden of preventable blindness.


Long-Term Effects of Bariatric Surgery on Gut Microbiota Composition and Faecal Metabolome Related to Obesity Remission.
Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.


Point-of-care ultrasound-guided cannulation versus standard cannulation in hemodialysis vascular access: A controlled random order crossover pilot feasibility study.
Standard cannulation practice for hemodialysis consists of inserting needles "blindly" through skin into an arteriovenous fistula (AVF), which is more likely to cause damage. Point-of-care ultrasound (POCUS) guided cannulation has potential for less damage; however, efficacy of this technique has not been explored. Our purpose was to test the feasibility and effectiveness of POCUS guidance for cannulation of AVFs in hemodialysis patients. A random-order crossover research design was used; patients and nurses acted as their own control. Sample included 13 patients with functioning AVFs and 9 nurses, recruited from a single hemodialysis center. All nurses cannulated all patients using standard and POCUS-guided cannulation. Data were collected at each cannulation (time taken, nurse position, probe direction, pressures, patient satisfaction, pain scores). Ultrasound images of needle position were collected from which needle tip locations inside vessels were measured. Nurses were surveyed at three timepoints and were interviewed at conclusion of data collection. Analysis involved linear mixed-models for clinical data, descriptive statistics for binary and feasibility data, and content analysis for interview data. Eleven patients and seven nurses completed. Protocol adherence was 94.4%. Two miscannulations occurred, both during standard cannulation. Cannulation time using POCUS guidance was significantly higher than standard cannulation (p = 0.008, 95% CI 39-166). All other variables showed no statistically significant difference. Content analysis of interview data showed cultural shift toward use of POCUS; nurses gained confidence and become more proficient in their POCUS technique. Random-order crossover is a feasible design to measure differences in POCUS-guided and standard cannulation. It is also feasible to implement POCUS into hemodialysis centers and whilst POCUS guidance takes longer, nurses become more proficient, and confident with persistent use.


Determining the relative salience of recognised push variables on health professional decisions to leave the UK National Health Service (NHS) using the method of paired comparisons.
The primary and secondary impacts from the COVID-19 pandemic are claimed to have had a detrimental impact on health professional retention within the UK National Health Service (NHS). This study set out to identify priorities for intervention by scaling the relative importance of widely cited push (leave) influences. During Summer/Autumn 2021, a UK-wide opportunity sample (n=1958) of NHS health professionals completed an online paired-comparisons exercise to determine the relative salience of work-related stress, workload intensity, time pressure, staffing levels, working hours, work-homelife balance, recognition of effort and pay as reasons why health professionals leave NHS employment. The study is believed to be the first large-scale systematic assessment of factors driving staff exits from the NHS since the COVID-19 pandemic. All professions gave primacy to work-related stress, workload intensity and staffing levels. Pay was typically located around the midpoint of the respective scales; recognition of effort and working hours were ranked lowest. However, differences were apparent in the rank order and relative weighting of push variables between health professions and care delivery functions. Ambulance paramedics present as an outlier, notably with respect to staffing level (F-stat 4.47, p=0.004) and the primacy of work-homelife balance. Relative to staffing level, other push variables exert a stronger influence on paramedics than nurses or doctors (f 4.29, p=0.006). Findings are relevant to future NHS health professional retention intervention strategy. Excepting paramedics/ambulance services, rankings of leave variables across the different health professional families and organisation types exhibit strong alignment at the ordinal level. However, demographic differences in the weightings and rankings, ascribed to push factors by professional family and organisation type, suggests that, in addition to signposting universal (all-staff) priorities for intervention, bespoke solutions for different professions and functions may be needed.


Sesame effects on testicular damage in streptozotocin-induced diabetes rats.
Reproductive dysfunction is a consequence of diabetes. Diabetes is associated with changes in testicular tissue. Sesame oil contains large amounts of polyunsaturated fatty acids and lignin with antioxidant activity, vitamin E, and monounsaturated fatty acid (MUFA). The present study investigated the effects of sesame on testis histology and male reproductive parameters in streptozotocin-induced diabetic rats. Thirty mature male Wistar rats were randomly divided into three groups, i.e., control (C), diabetic-control (DC), and sesame-treated diabetic rats (SD). Diabetes was induced by a single dose of streptozotocin (65 mg/kg; i.p). The animals were treated by a single intraperitoneal sesame extract injection (100 mg/kg b.w.) once daily for 6 weeks. The biochemical analysis revealed that the diabetes resulted in significant (p<0.05) reduction in spermiogenesis, testosterone, LH, and FSH levels. Light microscopic analysis showed remarkable (p<0.05) reduction in STD (seminiferous tubules diameter), SPI (spermatogenesis index) thickness of the epithelium, and significant increase in thickness of the interstitial tissue in the diabetic group compared with the control group. Simultaneous administration of the sesame could fairly up-regulate testosterone, LH, and FSH of the animals in this group. However, some differences were manifested with improved histological features as thickness of the epithelium, seminiferous tubules diameter, and spermatogenesis index. These data demonstrated that sesame significantly improved diabetes complication in rat testis. This study suggested that sesame might have a protective effect against oxidative stress-induced impaired testicular functions in diabetic rats.


Effect of nosocomial infections due to antibiotic-resistant organisms on length of stay and mortality in the pediatric intensive care unit.
To determine the prevalence, risk factors, and outcomes of nosocomial infection due to antimicrobial resistant bacteria in patients treated in the pediatric intensive care unit (PICU). Nested case-cohort study. Patient data were collected prospectively, and antimicrobial susceptibility data were abstracted retrospectively. A large pediatric teaching hospital. All PICU patients admitted from September 1, 1999, to September 1, 2001, unless they died within 24 hours after PICU admission, were 18 years old or older, or were neonatal intensive care unit patients receiving extracorporeal membrane oxygenation. A total of 135 patients with more than 1 nosocomial bacterial infection were analyzed; 52% were male, 75% were white, the mean Pediatric Risk of Mortality score was 10.5, and the mean age was 3.5 years. Of these patients, 37 (27%) had nosocomial infections due to antibiotic-resistant organisms. In univariate analysis, transplantation (odds ratio [OR], 2.83 [95% confidence interval (CI), 1.05-7.66]) and preexisting lung disease (OR, 2.63 [95% CI, 1.18-5.88]) were associated with nosocomial infections due to antibiotic-resistant organisms. Age, Pediatric Risk of Mortality score at admission, length of hospital stay before infection, and other underlying conditions were not associated with infections due to antibiotic-resistant organisms. Patients infected with antibiotic-resistant organisms had greater mean PICU lengths of stay after infection, compared with patients infected with antibiotic-susceptible organisms (22.9 vs 12.8 days; P=.004), and higher crude mortality rates (OR, 2.40 [95% CI, 1.03-5.61]). Identifiable risk factors exist for nosocomial infections due to antibiotic-resistant organisms. In univariate analysis, infections due to antibiotic-resistant bacteria are associated with increased length of stay in the PICU after onset of infection and increased mortality.


Recombinant IFN-alpha in lymphomas.
The effectiveness of interferon (IFN) therapy in malignant lymphoma is analyzed in this review. Although various treatment regimens including IFN at various dose levels have so far not proved to have curative potential, a substantial palliative effect has been noted in hairy-cell leukemia and in some non-Hodgkin lymphomas of low-grade malignancy. Early stages of lymphoma disease are more responsive to IFN therapy, and this holds true also for chronic lymphocytic leukemia, in which IFN treatment is usually not effective in progressed disease after chemotherapy. Concepts of early-phase treatment and of remission maintenance by using IFN therapy are discussed on the basis of the data from several studies.


Early captopril treatment prevents hypertrophydependent gene expression in hearts of SHR.
Treatment of spontaneously hypertensive rats (SHR) with captopril (100 mg . kg-1 . day-1) throughout development and during the first 16 wk of life leads to a reduction in blood pressure and left ventricular hypertrophy. Blood pressures and hypertrophy are reduced in these animals (vs. untreated SHR) for up to 24 wk after discontinuation of the drug. We used conventional blot hybridization and Western analysis to examine hypertrophy-dependent gene expression during this period. Ventricular expression of the atrial natriuretic peptide gene was reduced by >90% at 16 wk of age in the captopril-treated SHR. Expression increased in the 24 wk after discontinuation of treatment, but remained well below that of the untreated SHR. A similar reduction in ventricular c-myc gene expression was seen with captopril treatment. Neither renal expression of the atrial natriuretic peptide gene nor ventricular expression of the c-fos gene was affected by captopril. This study demonstrates that captopril treatment during a critical period of development in the SHR leads to a sustained reduction in hypertrophy-dependent myocardial gene expression, which does not revert to levels seen in the untreated SHR after discontinuation of the drug.


Intramyocellular lipid content is increased after exercise in nonexercising human skeletal muscle.
Intramyocellular lipid (IMCL) content has been reported to decrease after prolonged submaximal exercise in active muscle and, therefore, seems to form an important local substrate source. Because exercise leads to a substantial increase in plasma free fatty acid (FFA) availability with a concomitant increase in FFA uptake by muscle tissue, we aimed to investigate potential differences in the net changes in IMCL content between contracting and noncontracting skeletal muscle after prolonged endurance exercise. IMCL content was quantified by magnetic resonance spectroscopy in eight trained cyclists before and after a 3-h cycling protocol (55% maximal energy output) in the exercising vastus lateralis and the nonexercising biceps brachii muscle. Blood samples were taken before and after exercise to determine plasma FFA, glycerol, and triglyceride concentrations, and substrate oxidation was measured with indirect calorimetry. Prolonged endurance exercise resulted in a 20.4 +/- 2.8% (P < 0.001) decrease in IMCL content in the vastus lateralis muscle. In contrast, we observed a substantial (37.9 +/- 9.7%; P < 0.01) increase in IMCL content in the less active biceps brachii muscle. Plasma FFA and glycerol concentrations were substantially increased after exercise (from 85 +/- 6 to 1450 +/- 55 and 57 +/- 11 to 474 +/- 54 microM, respectively; P < 0.001), whereas plasma triglyceride concentrations were decreased (from 1498 +/- 39 to 703 +/- 7 microM; P < 0.001). IMCL is an important substrate source during prolonged moderate-intensity exercise and is substantially decreased in the active vastus lateralis muscle. However, prolonged endurance exercise with its concomitant increase in plasma FFA concentration results in a net increase in IMCL content in less active muscle.


Subsurface phenomena and the splashing of drops on shallow liquids.
High-speed movies have been taken of the formation of the sub-surface cavity and of the Rayleigh jet formed during the splash of a drop on a shallow liquid. They show that the initial increase and subsequent decrease in the rate of rise of the jet and the maximum jet height with decreasing depth of liquid are the result of the interaction of the subsurface cavity with the solid boundary beneath the liquid. This interaction modifies considerably the pressure gradients in the liquid during the formation and collapse of the cavity.


ASTRA: Atomic Surface Transformations for Radiotherapy Quality Assurance.
Treatment for glioblastoma, an aggressive brain tumour usually relies on radiotherapy. This involves planning how to achieve the desired radiation dose distribution, which is known as treatment planning. Treatment planning is impacted by human errors, inter-expert variability in segmenting (or outlining) the tumor target and organs-at-risk, and differences in segmentation protocols. Erroneous segmentations translate to erroneous dose distributions, and hence sub-optimal clinical outcomes. Reviewing segmentations is time-intensive, significantly reduces the efficiency of radiation oncology teams, and hence restricts timely radiotherapy interventions to limit tumor growth. Moreover, to date, radiation oncologists review and correct segmentations without information on how potential corrections might affect radiation dose distributions, leading to an ineffective and suboptimal segmentation correction workflow. In this paper, we introduce an automated deep-learning based method: atomic surface transformations for radiotherapy quality assurance (ASTRA), that predicts the potential impact of local segmentation variations on radiotherapy dose predictions, thereby serving as an effective dose-aware sensitivity map of segmentation variations. On a dataset of 100 glioblastoma patients, we show how the proposed approach enables assessment and visualization of areas of organs-at-risk being most susceptible to dose changes, providing clinicians with a dose-informed mechanism to review and correct segmentations for radiation therapy planning. These initial results suggest strong potential for employing such methods within a broader automated quality assurance system in the radiotherapy planning workflow. Code to reproduce this is available at https://github.com/amithjkamath/astraClinical Relevance: ASTRA shows promise in indicating what regions of the OARs are more likely to impact the distribution of radiation dose.


High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells' stemness properties in vitro and in vivo. The authors' data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo. CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient's clinical outcomes in the future.


Behavior characteristics of the attention network of military personnel with high and low trait anxiety.
Converging evidence reveals significant increase in both state anxiety and trait anxiety during the past 2 decades among military servicemen and servicewomen in China. In the present study, we employed the Chinese version of the State-trait Anxiety Inventory (STAI) to examine trait and state anxiety in Chinese military servicemen and servicewomen. We further evaluated orienting, alerting and execution inhibition using the attention network test.Healthy military servicemen and servicewomen were recruited for the present study. The STAI was used to measure both state and trait anxiety and the attention network test was done to determine reaction time and accuracy rate.Fifty-seven subjects were eligible for the study. Their mean STAI score was 3.2 ± 2.8 (range, 1-17) and 29 (50.9%) subjects were categorized into the high trait anxiety group and 28 (49.1%) subjects into the low trait anxiety group. The reaction time of the high trait anxiety group to incongruent, congruent, and neutral target was significantly longer than that of the low trait anxiety group (P < .05). Moreover, the accurate rate of the high trait anxiety group for incongruent, congruent, and neutral target was significantly higher than that of the low trait anxiety group (P < .05). Repeated analysis of variance showed marked effect of trait anxiety, cue types, and target types on reaction time. There was significant interaction among trait anxiety, target types, and cue types. Trait anxiety and target types also had marked effect on the accurate rate. Multivariate analysis showed no marked effect of trait anxiety on the alerting, orienting, and execution inhibition subnetwork.The present study has demonstrated that military service personnel with high trait anxiety requires more time for cognitive processing of external information but exhibits enhanced reaction accuracy rate compared to those with low trait anxiety. Our findings indicate that interventional strategies to improve the psychological wellbeing of military service personnel should be implemented to improve combat mission performance.


Experimental improvement of cow milk fatty acid composition in organic winter diets.
Organic milk is seen as more healthy in terms of its fatty acid (FA) profile. In three on-farm crossover trials with 10-12 cows in each group, different forages were compared for their potential to improve the FA composition. Different hay qualities (hay of pasture vs. hay of leys), additional energy sources (fodder beets vs. wheat) and roughage qualities (hay of pasture vs. grass silage) were compared for their effect on the FA composition of the milk. Rumenic acid (CLA cis-9, trans-11) and α-linolenic acid (ALA) were selected as principal markers to evaluate effects. The overall CLA cis-9, trans-11 was low (3.6-6.3 g kg⁻¹ fat), whereas ALA levels were intermediate (6.8-9.4 g kg⁻¹ fat). Differences between the forages were explained by the fat metabolism of the ruminants. Organic winter milk is low in several desirable FAs. Diets rich in mature fodder and sugar were a poor choice for an improved FA composition.


Impact of an Intervention on Healthy Offerings and Allergenic Food Management in Restaurants: A Parallel Randomized Controlled Study.
The consumption of out-of-home meals is increasing. This study is aimed at assessing the effect of an intervention on healthy offerings and the management of food allergies and intolerances. Ten (control group) and eight restaurants (intervention group) were randomized in a 12-month parallel controlled trial. The outcomes were changes regarding adherence to the Mediterranean diet (AMed) and gluten management (SMAP) criteria, the traffic light rating category, nutrients, and gluten- and allergen-free content of dishes. After 12 months, and compared with baseline, there was an improvement of ≥25% in four items of the AMed criteria in the intervention group, whereas an increase in the offer of dairy desserts without added sugar, and a decrease in the first course offerings of vegetables and/or legumes were observed in the control group (p < 0.05). Also, after 12 months, there was an improvement of ≥50% in four SMAP criteria (p < 0.05) and in the mean average of all SMAP criteria (p = 0.021) compared with baseline in the intervention group, in which intra- and inter-group improvements for desserts in traffic light ratings, nutrients, and allergens were observed (p < 0.05). Therefore, the intervention showed beneficial effects, improving the quality of menus toward the Mediterranean diet pattern and gluten and food allergy/intolerance management.


Differential determinants of cancer cell insensitivity to antimitotic drugs discriminated by a one-step cell imaging assay.
Cancer cells can be drug resistant due to genetic variation at multiple steps in the drug response pathway, including drug efflux pumping, target mutation, and blunted apoptotic response. These are not discriminated by conventional cell survival assays. Here, we report a rapid and convenient high-content cell-imaging assay that measures multiple physiological changes in cells responding to antimitotic small-molecule drugs. Our one-step, no-wash assay uses three dyes to stain living cells and is much more accurate for scoring weakly adherent mitotic and apoptotic cells than conventional antibody-based assays. We profiled responses of 33 cell lines to 8 antimitotic drugs at multiple concentrations and time points using this assay and deposited our data and assay protocols into a public database (http://lincs.hms.harvard.edu/). Our data discriminated between alternative mechanisms that compromise drug sensitivity to paclitaxel and revealed an unexpected bell-shaped dose-response curve for BI2536, a highly selective inhibitor of Polo-like kinases. Our approach can be generalized, is scalable, and should therefore facilitate identification of molecular biomarkers for mechanisms of drug insensitivity in high-throughput screens and other assays.


Assessing oral health literacy of university nursing students: A cross-sectional exploratory study.
Research has proven a link between oral health and numerous chronic systemic diseases. To achieve better health outcomes, there is a need to involve interprofessional primary health care providers, such as nurses to raise awareness and promote oral health. Nurses have regular contact with patients which provides a unique opportunity to impart disease-specific information and technical skills for patients to self-manage their oral health conditions. However, the baseline oral health literacy of undergraduate nursing students at the University of Sydney is not known. Before creating a targeted curriculum to improve oral health literacy amongst nursing students, it is essential to assess the baseline oral health knowledge of these students. This study aimed to assess the oral health literacy level among undergraduate nursing students of the University of Sydney, Australia. An exploratory research approach was used. A cross-sectional survey study was conducted using the validated Comprehensive Measure of Oral Health Knowledge (CMOHK) instrument. A univariate general linear model was used to explore the association of CMOHK total score with demographic and educational variables. A total number of 197 nursing students participated in the survey, with a mean CMOHK score of 15.48, SD 3.27. 72% were categorized as having good, 16% fair and 12% poor oral health knowledge. The analysis from the six individual knowledge domains of the CMOHK revealed lower percentages of correct responses in the periodontal disease and oral cancer knowledge domains. Students with English as their second language, on average, scored 2 fewer correct responses (p <.001) than students whose first language was English. Low socioeconomic status was not associated with a low level of oral health literacy. The baseline results show a good level of general oral health knowledge as measured by the CMOHK. However, periodontal disease and oral cancer were identified as the particular domains where a knowledge gap exists. These findings may help to map and design an oral health education intervention to improve oral health literacy amongst nursing students. Culturally responsive pedagogy may need to be considered for students with English as their second language. This baseline survey data may potentially facilitate integrating oral health in nursing education and practice.


Adverse drug events among hospitalized Medicare patients: epidemiology and national estimates from a new approach to surveillance.
Although adverse drug events (ADEs) are a well-recognized problem among hospitalized patients, there is no system for monitoring them. Six high-alert medications and associated adverse events were selected for inclusion in the Medicare Patient Safety Monitoring System (MPSMS), a national surveillance system designed to identify and track over time inpatient adverse events within the hospitalized fee-for-service Medicare population. Explicit chart review algorithms were used to identify medication exposures and associated adverse events from the the 2004 MPSMS sample's medical records. The associations of ADEs with patient characteristics, length of stay, mortality, and 30-day readmission were assessed with bivariate analyses and hierarchical linear regression modeling (HGLM) approaches. National ADE rates and numbers of adverse events were estimated using weighted HGLM. On the basis of 25,145 hospital visits in the 2004 MPSMS sample, an estimated 8.2% of patients exposed to warfarin experienced associated ADEs, as did 13.6% exposed to heparin, 10.7% exposed to insulin/hypoglycemic agents, and 0.5% exposed to digoxin. Some 0.6% of patients exposed to antibiotics experienced antibiotic-associated Clostridium difficile infection (CDI). Patients with ADEs had increased length of stay and in-hospital and 30-day mortality, except that patients with antibiotic-associated CDI did not have increased in-hospital mortality, and patients with ADEs associated with heparin did not have increased 30-day mortality. An estimated 888,000 ADEs occurred in hospitalized Medicare patients from these medications alone. This new approach to detecting ADEs and estimating the national burden of ADEs from selected medications may be adapted for other types of ADEs in the Medicare population and may offer guidance to policymakers on appropriate areas of focus for patient safety.


[Cathepsin L cysteine protease from Taenia solium: its biological role in the infection and potential use for the immunodiagnosis of neurocysticercosis].
Taenia solium is a plane helminth responsible for taeniasis and human cysticercosis, the latter being the result of the consumption of infective eggs. Cysticerci can develop in different human tissues, often in the central nervous system, causing neurocysticercosis (NCC). For the diagnosis of NCC, an adequate interpretation of clinical data, neuroimaging results and serological tests are required. However, serological tests could be improved by developing candidate antigens able to increase their sensibility and specificity. In the last years, a series of surface and secretory proteins of T. solium essential for the parasite-host interaction have been described. One of these families is cathepsin L cysteine proteases, which have a predominant role in the development and survival of the parasite. They take part in the tissue invasion, immune response evasion, excystation and encystment of cysticercus. They are considered potential antigens for the immunodiagnosis of neurocysticercosis.


Antitrichomonad action, mutagenicity, and reduction of metronidazole and other nitroimidazoles.
Twelve 4- and 5-nitroimidazole derivatives, including metronidazole and two of its metabolites, tinidazole, dimetridazole, and nimorazole, were tested for antitrichomonad action on Tritrichomonas foetus (KV(1)) and Trichomonas vaginalis (ATCC 30001) for mutagenicity on a nitroreductase-positive (TA 100) and a nitroreductase-deficient (TA 100-FR(1)) strain of Salmonella typhimurium, as well as for the reducibility of the nitro group by T. foetus homogenates. Compounds with activity <1% of that of metronidazole are regarded as inactive. All antitrichomonad compounds induce mutations and can be reduced. S. typhimurium TA 100 gave mutations under both aerobiosis and anaerobiosis; TA 100-FR(1), however, gave mutations only under anaerobiosis. Certain compounds that are reducible, and the nonreducible derivatives, were inactive. Metronidazole and its inactive 4-nitro analogue were reduced in a four-electron process in ferredoxin- or methyl viologen-mediated reactions with the same velocity. The results underscore the role of the reduction of the nitro group in the antitrichomonad and in the mutagenic activity of nitroimidazoles.


Surface modifications of Nitinol for biomedical applications.
Cathodic electrophoretic deposition (EPD) has been utilized for the fabrication of composite films for the surface modification of NiTi shape memory alloys (Nitinol). In the proposed method, chitosan (CH) was used as a matrix for the incorporation of other functional materials, such as heparin, hydroxyapatite and bioglass. Chitosan-heparin films were deposited from solutions of non-stoichiometric chitosan-heparin complexes. It was found that the addition of anionic heparin to the solutions of cationic chitosan resulted in a significant increase in the cathodic deposition rate. The thickness of the films prepared by this method varied in the range of 0.1-3 microm. The ability of the chitosan-heparin films to bind antithrombin, as measured by binding of (125)I-radiolabeled antithrombin, was much greater than that of pure chitosan films. Composite chitosan-hydroxyapatite films, with thickness of 1-30 microm, were obtained as monolayers or laminates, containing chitosan-hydroxyapatite layers, separated by layers of pure chitosan. The hydroxyapatite nanoparticles showed preferred orientation in the chitosan matrix with the c-axis parallel to the substrate surface. The films showed corrosion protection of the Nitinol substrates in Ringer's physiological solutions. The feasibility of the fabrication of composite films containing hydroxyapatite and bioglass in the chitosan matrix has been demonstrated. The method offers the advantages of room temperature processing. The deposition mechanisms and possible applications of the films are discussed.


Study of liquid chromatography/electrospray ionization mass spectrometry matrix effect on the example of glyphosate analysis from cereals.
Glyphosate is one of the most common pesticides used in the pre-harvest treatment of cereals. This paper examines the matrix effect of glyphosate liquid chromatography/electrospray ionization mass spectrometric (LC/ESI-MS) analysis in wheat and rye. The matrix effect (ionization suppression) was found to be dependent on sample particle size taken for the extraction. If samples are ground to very small particles severe ionization suppression occurs. For lower glyphosate contents (<1 mg/kg) the signal may even be suppressed by more than 90%. The matrix effect was found to be dependent on the matrix - rye showed significantly stronger ionization suppression than wheat, although these matrices are not very different. The matrix effect also depends on the concentration of glyphosate in the post-extraction spiked samples. It is demonstrated that the isotope-labelled standard (13)C(2)-glyphosate undergoes different ionization suppression than glyphosate and is therefore not efficient in compensating for matrix effect. At the same time the extrapolative dilution approach allows to efficiently compensate for matrix effect.


Sequences learned without awareness can orient attention during the perception of human activity.
Human activity contains sequential dependencies that observers may use to structure a task environment (e.g., the ordering of steps when tying shoes or getting into a car). Two experiments investigated how people take advantage of sequential structure to understand activity and respond to behaviorally relevant events. Participants monitored animations of simplified human movement to identify target hand gestures. In the first experiment, participants were able to use predictive sequential dependencies to more quickly identify targets. In addition, performance was best at the point in time that followed the sequence. However, the second experiment revealed that how sequential structure affects detection depends on whether the sequence predicts the timing of target events. In all cases, sequence learning was observed without participants' awareness of the sequential dependencies. These results suggest that human activity sequences can be learned without awareness and can be used to adaptively guide behavior.


Normobaric oxygen therapy strategies in the treatment of postcraniotomy pneumocephalus.
Postsurgical pneumocephalus is an unavoidable sequela of craniotomy. Sufficiently large volumes of intracranial air can cause headaches, lethargy, and neurological deficits. Supplemental O(2) to increase the rate of absorption of intracranial air is a common but unsubstantiated neurosurgical practice. To the authors' knowledge, this is the first prospective study to examine the efficacy of this therapy and its effect on the rate of pneumocephalus absorption. Thirteen patients with postoperative pneumocephalus that was estimated to be > or = 30 ml were alternately assigned to breathe 100% O(2) using a nonrebreather mask (treatment group) or to breathe room air (control group) for 24 hours. Head computed tomography (CT) scans without contrast enhancement were obtained at the beginning and end of treatment or control therapy. A neuroradiologist blinded to the type of treatment used software to calculate the 3D volume of the pneumocephalus from the CT scans. The percentage of pneumocephalus absorption was calculated for each study participant. There was no statistically significant difference between the treatment and control groups regarding the mean initial pneumocephalus volume or time interval between CT scans. There was a significant difference (p = 0.009) between the mean rate of pneumocephalus volume reduction in the treatment (65%) and control groups (31%) per 24 hours. No patient suffered adverse effects related to treatment. Administration of postsurgical supplemental O(2) through a nonrebreather mask significantly increases the absorption rate of postcraniotomy pneumocephalus as compared with breathing room air.


Thyroid hormone receptor alpha1 directly controls transcription of the beta-catenin gene in intestinal epithelial cells.
Thyroid hormones, T3 and T4, are known regulators of intestine development. The best characterized example is the remodeling of the gastrointestinal tract during amphibian metamorphosis. Thyroid hormones act via nuclear receptors, the TRs, which are T3-dependent transcription factors. We previously showed that intestinal epithelial cell proliferation is controlled by thyroid hormones and the TRalpha gene. To analyze the mechanisms responsible, we studied the expression of genes belonging to and/or activated by the Wnt/beta-catenin pathway, a major actor in the control of physiological and pathological epithelial proliferation in the intestine. We show that T3-TRalpha1 controls the transcription of the beta-catenin gene in an epithelial cell-autonomous way. This is parallel to positive regulation of proliferation-controlling genes such as type D cyclins and c-myc, known targets of the Wnt/beta-catenin. In addition, we show that the regulation of the beta-catenin gene is direct, as TR binds in vitro and in chromatin in vivo to a specific thyroid hormone-responsive element present in intron 1 of this gene. This is the first report concerning in vivo transcriptional control of the beta-catenin gene. As Wnt/beta-catenin plays a crucial role in intestinal tumorigenesis, our observations open a new perspective on the study of TRs as potential tumor inducers.


Implications of the invariant gamma-chain on the intracellular transport of class II histocompatibility antigens.
We have examined the role of the invariant gamma-chain on the intracellular transport of human class II histocompatibility antigens. mRNA was selected by hybridization to cDNA corresponding to class II alpha-, beta-, and gamma-chains, and the obtained mRNA fractions were injected individually and in various combinations into X. laevis oocytes. Translation products were isolated after various periods of chase, and their carbohydrate moieties were analyzed to monitor the subcellular localization of polypeptide chains. A mixture of alpha-, beta-, and gamma-chains, or gamma-chains alone, were transported and glycosylated to the same extent as in a B lymphoblastoid cell line. However, although alpha- and beta-chains formed a complex in the absence of the gamma-chain, the transport of this complex was slowed down. Furthermore, the glycosylation of alpha- and beta-chains appeared incomplete. Thus, the invariant gamma-chain seems to play a crucial role for the rate of transport and glycosylation of class II alpha- and beta-chains.


Contact Dermatitis in Trivandrum.
One hundred patients (63 males and 37 females) were patch tested. Maidmum number (32) of cases were skilled labourers, housewives (19) and manual labourers (10) Cement (24), metals (22) and foot-wear (14) constituted the major causes for dermatitis Fifty one patients showed positive patch tests with potassium dichromate. The source of chromate sensitivity in 47.03% was cement and in 33.32% metals in the wearing apparel.


Perception of environmental hazards in Hong Kong Chinese.
A public sample of Hong Kong Chinese (N = 167) rated the levels of threat of 25 environmental hazards and gave quantitative judgments to six risk characteristics for each hazard. It was found that women, older participants, and less educated individuals found the hazards to be more threatening to the environment than did men, younger participants, and more educated individuals, respectively. A new spatial model emerged from a principal component analysis carried out on responses to six risk characteristics. Instead of replicating the well-documented factors of unknown risk versus dread risk, we found a structure defined by a known and dread risk factor and a controllable risk factor. Findings were discussed in light of potential influences of the Confucian heritage on the perception of risks among Hong Kong Chinese.


Antimicrobial resistance in Neisseria gonorrhoeae: history, molecular mechanisms and epidemiological aspects of an emerging global threat.
Neisseria gonorrhoeae is the agent of gonorrhea, a sexually transmitted infection with an estimate from The World Health Organization of 78 million new cases in people aged 15-49 worldwide during 2012. If left untreated, complications may include pelvic inflammatory disease and infertility. Antimicrobial treatment is usually effective; however, resistance has emerged successively through various molecular mechanisms for all the regularly used therapeutic agents throughout decades. Detection of antimicrobial susceptibility is currently the most critical aspect for N. gonorrhoeae surveillance, however poorly structured health systems pose difficulties. In this review, we compiled data from worldwide reports regarding epidemiology and antimicrobial resistance in N. gonorrhoeae, and highlight the relevance of the implementation of surveillance networks to establish policies for gonorrhea treatment.