A content analysis of smartphone apps for adolescent smoking cessation.
Adolescent cigarette smokers have an increased risk of sustained smoking into adulthood. Smartphone applications (apps) for smoking cessation are a promising treatment resource. However, research on apps for adolescent smoking cessation is limited. This study compared smoking cessation mobile apps targeting an adolescent audience with popular cessation apps for a general audience. Adolescent and general-audience apps were identified by searching the Google Play and Apple App Stores (November 2016). Two coders assessed each app for adherence to clinical practice guidelines for tobacco and adolescent-specific content (2016-2017) and developed a summary score that summed all adherence and adolescent content criteria. Eight adolescent apps were identified and compared with the top 38 general apps (as ranked by Apple and Google). Both general and adolescent apps commonly had adherence content related to developing a quit plan (general: 73.68 per cent; adolescent: 87.50 per cent) and enhancing motivation by describing the rewards of not smoking (general: 76.32 per cent; adolescent: 62.50 per cent). Adolescent-specific content such as peer influence on smoking was common in adolescent apps but not in general apps (general: 5.26 per cent; adolescent: 62.50 per cent). Adolescent apps had a higher general adherence content summary score [t (44) = 2.55, p = .01] and a higher adolescent content summary score [t (7.81) = 2.47, p = .04] than the general apps. On average, adolescent cessation apps included more adherence content and adolescent-specific content than general apps. Future research is needed to determine the extent to which adolescents engage with the adherence content available in these apps.


Analysis of the stimulatory effect of splicing on mRNA production and utilization in mammalian cells.
We have examined how splicing affects the expression of a range of human and nonhuman genes in vertebrate cells. Although our data demonstrate that splicing invariably enhances the level of gene expression, this positive effect is generally moderate. However, in the case of the human beta-globin gene, splicing is essential for significant protein expression. In the absence of introns, 3' end processing is inefficient, and this appears to be causally linked to a significant decrease in the level of both nuclear and cytoplasmic 3' end-processed RNA. In contrast, splicing appears to only modestly enhance nuclear mRNA export. Consistent with this observation, intronless beta-globin gene expression was only partially rescued by the insertion of retroviral nuclear mRNA export elements. Surprisingly, in the case of the highly intron dependent beta-globin gene, the mRNA that did reach the cytoplasm was also only inefficiently translated if it derived from an intronless expression plasmid. Together, these data argue that splicing can increase gene expression by enhancing mRNA 3' end processing, and hence, mRNA production. Moreover, in the case of the highly intron-dependent beta-globin gene, splicing also significantly enhanced the translational utilization of cytoplasmic beta-globin mRNAs.


Desiccation tolerance as a function of age, sex, humidity and temperature in adults of the African malaria vectors Anopheles arabiensis and Anopheles funestus.
Adult mosquito survival is strongly temperature and moisture dependent. Few studies have investigated the interacting effects of these variables on adult survival and how this differs among the sexes and with age, despite the importance of such information for population dynamic models. For these reasons, the desiccation tolerance of Anopheles arabiensis Patton and Anopheles funestus Giles males and females of three different ages was assessed under three combinations of temperature and humidity. Females were more desiccation tolerant than males, surviving for longer periods than males under all experimental conditions. In addition, younger adults were more tolerant of desiccation than older groups. Both species showed reduced water loss rate (WLR) as the primary mechanism by which they tolerate desiccation. Although A. arabiensis is often considered to be the more arid-adapted of the two species, it showed lower survival times and higher WLR than A. funestus. The current information could improve population dynamic models of these vectors, given that adult survival information for such models is relatively sparse.


[The effect of lesion of nucleus ventromedialis hypothalami on neurogenesis in adult ring doves].
In the present study the effects of lesion hypothalami ventromedialis nucleus (VMN) of ring dove (Streptopelia Risoria) on neurogenesis regarding the lesion-induced change of distribution of proliferating cells in the lateral ventricular zone (LVZ) and new neurons in the non-ventricular zone (VZ) were studied by using [3H] thymidine-autoradiographic and immunohistochemistry methods. The results showed that such lesion not only induced significant increase of neurogenesis in telencephalon (up to 1.62 times of that of the intact doves), but also altered distribution patterns of the newborn neurons. Many of the new neurons confined in neostriatum medialis and pars caudalis of telencephalon, where the rate of neurogenesis in intact dove is very low. Such kinds of neurogenesis in the birds with brain lesions may be region-dependent and somewhat underlie brain repair and alteration of endocrine function after brain injury.


Assessment of adherence problems in patients with serious and persistent mental illness: recommendations from the Expert Consensus Guidelines.
Poor adherence to medication treatment can have devastating consequences for patients with serious mental illness. The literature review and recommendations in this article concerning assessment of adherence are reprinted from The Expert Consensus Guideline Series: Adherence Problems in Patients with Serious and Persistent Mental Illness, published in 2009. The expert consensus survey contained 39 questions (521 options) that asked about defining nonadherence, extent of adherence problems in schizophrenia and bipolar disorder, risk factors for nonadherence, assessment methods, and interventions for specific types of adherence problems. The survey was completed by 41 (85%) of the 48 experts to whom it was sent. When evaluating adherence, the experts considered it important to assess both behavior and attitude, although they considered actual behavior most important. They also noted the importance of distinguishing patients who are not willing to take medication from those who are willing but not able to take their medication as prescribed due to forgetfulness, misunderstanding of instructions, or financial or environmental problems, since this will affect the type of intervention needed. Although self- and physician report are most commonly used to clinically assess adherence, they are often inaccurate and may underestimate nonadherence. The experts believe that more accurate information will be obtained by asking about any problems patients are having or anticipate having taking medication rather than if they have been taking their medication; They also recommended speaking with family or caregivers, if the patient gives permission, as well as using more objective measures (e.g., pill counts, pharmacy records, smart pill containers if available, and, when appropriate, medication plasma levels). Use of a validated self-report scale may also help improve accuracy. For patients who appear adherent to medication, the experts recommended monthly assessments for adherence, with additional assessments if there is a noticeable symptomatic change. If there is concern about adherence, they recommended more frequent (e.g., weekly) assessments. The article concludes with suggestions for clinical interview techniques for assessing adherence.


Widespread Distribution of Synaptophysin, a Synaptic Vesicle Glycoprotein, in Growing Neurites and Growth Cones.
Synaptophysin, a 38-kD glycoprotein, is one of the most abundant of the integral membrane proteins of small synaptic vesicles. The protein is widely distributed at synapses throughout the nervous system, where it is believed to be involved in the exocytosis of stored neurotransmitter. We show here that synaptophysin is also widely expressed in growing neurites and growth cones both in vitro and in vivo. In dissociated rat cerebral cortical cultures anti-synaptophysin antiserum (G-95) stains growth cones punctately as soon as they emerge from the cell body. In early cultures all neurites are immunoreactive. Later, synaptophysin is redistributed to become concentrated in axonal varicosities. In developing rat embryos, synaptophysin is expressed in the growing axons of, for instance, the spinal commissural interneurons and the parallel fibres of the cerebellar granule cells long before these neurons have established synaptic connections. These observations suggest that synaptic vesicle proteins like synaptophysin are functionally important in neuronal development.


HIV Infection Is an Independent Predictor of Mortality Among Adults with Reduced Level of Consciousness in Uganda.
The clinical epidemiology of adults admitted with reduced level of consciousness (LOC) in sub-Saharan Africa (SSA) and the impact of HIV infection on the risk of mortality in this population is unknown. We secondarily analyzed data from a cohort study that enrolled 359 consecutive adults with reduced LOC presenting to Mbarara Regional Hospital in Uganda with the aim of comparing the prognostic utility of the Full Outline of Unresponsiveness (FOUR) score to the Glasgow Coma Scale (GCS) Score. For this analysis, we included 336 individuals with known HIV serostatus, obtaining clinical, laboratory, and follow-up data. We recorded investigations and treatments deemed critical by clinicians for patient care but were unavailable. We computed mortality rates and used logistic regression to determine predictors of 30-day mortality. The median GCS was 10. Persons living with HIV infection (PLWH) accounted for 97 of 336 (29%) of the cohort. The 30-day mortality rate in the total cohort was 148 of 329 (45%), and this was significantly higher in PLWH (57% versus 40%, adjusted odds ratio [aOR] 2.39: 95% confidence interval [CI]: 1.31-4.35, P = 0.0046). Other predictors of mortality were presence of any unmet clinical need (aOR 1.72; 95% CIL 1.04-2.84, P = 0.0346), anemia (aOR 1.68; 95% CI: 1.01-2.81, P = 0.047), and admission FOUR score < 12 [aOR 4.26; 95% CI: 2.36-7.7, P < 0.0001). Presentation with reduced LOC in Uganda is associated with high mortality rates, with worse outcomes in PLWH. Improvement of existing acute care services is likely to improve outcomes.


Borrelia burgdorferi sensu lato-infected Ixodes ricinus collected from vegetation near the Arctic Circle.
This is the first study to determine the density of questing Ixodes ricinus in northern Norway. It was performed at two sites in Brønnøy, which has been known for its tick permissive habitats for decades and is one of the northernmost habitats with an abundant I. ricinus population in the world. From April to November 2011, all stages of host-seeking I. ricinus were collected from the two sites. The overall prevalence of nymphs infected with Borrelia burgdorferi sensu lato was 21% and that of adult ticks 46%. The rates of the genospecies Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana were similar to findings in most other studies in Scandinavia, with B. afzelii by far the most prevalent at 76%. The high Borrelia-infection prevalence in ticks from Brønnøy may explain the high incidence rate of reported Lyme borreliosis in the municipality.


Robotic Level III Inferior Vena Cava Tumor Thrombectomy: Initial Series.
Level III inferior vena cava tumor thrombectomy for renal cancer is one of the most challenging open urologic oncology surgeries. We present the initial series of completely intracorporeal robotic level III inferior vena cava tumor thrombectomy. Nine patients underwent robotic level III inferior vena cava thrombectomy and 7 patients underwent level II thrombectomy. The entire operation (high intrahepatic inferior vena cava control, caval exclusion, tumor thrombectomy, inferior vena cava repair, radical nephrectomy, retroperitoneal lymphadenectomy) was performed exclusively robotically. To minimize the chances of intraoperative inferior vena cava thrombus embolization, an "inferior vena cava-first, kidney-last" robotic technique was developed. Data were accrued prospectively. All 16 robotic procedures were successful, without open conversion or mortality. For level III cases (9), median primary kidney (right 6, left 3) cancer size was 8.5 cm (range 5.3 to 10.8) and inferior vena cava thrombus length was 5.7 cm (range 4 to 7). Median operative time was 4.9 hours (range 4.5 to 6.3), estimated blood loss was 375 cc (range 200 to 7,000) and hospital stay was 4.5 days. All surgical margins were negative. There were no intraoperative complications and 1 postoperative complication (Clavien 3b). At a median 7 months of followup (range 1 to 18) all patients are alive. Compared to level II thrombi the level III cohort trended toward greater inferior vena cava thrombus length (3.3 vs 5.7 cm), operative time (4.5 vs 4.9 hours) and blood loss (290 vs 375 cc). With appropriate patient selection, surgical planning and robotic experience, completely intracorporeal robotic level III inferior vena cava thrombectomy is feasible and can be performed efficiently. Larger experience, longer followup and comparison with open surgery are needed to confirm these initial outcomes.


Iso-Seq Allows Genome-Independent Transcriptome Profiling of Grape Berry Development.
Transcriptomics has been widely applied to study grape berry development. With few exceptions, transcriptomic studies in grape are performed using the available genome sequence, PN40024, as reference. However, differences in gene content among grape accessions, which contribute to phenotypic differences among cultivars, suggest that a single reference genome does not represent the species' entire gene space. Though whole genome assembly and annotation can reveal the relatively unique or "private" gene space of any particular cultivar, transcriptome reconstruction is a more rapid, less costly, and less computationally intensive strategy to accomplish the same goal. In this study, we used single molecule-real time sequencing (SMRT) to sequence full-length cDNA (Iso-Seq) and reconstruct the transcriptome of Cabernet Sauvignon berries during berry ripening. In addition, short reads from ripening berries were used to error-correct low-expression isoforms and to profile isoform expression. By comparing the annotated gene space of Cabernet Sauvignon to other grape cultivars, we demonstrate that the transcriptome reference built with Iso-Seq data represents most of the expressed genes in the grape berries and includes 1,501 cultivar-specific genes. Iso-Seq produced transcriptome profiles similar to those obtained after mapping on a complete genome reference. Together, these results justify the application of Iso-Seq to identify cultivar-specific genes and build a comprehensive reference for transcriptional profiling that circumvents the necessity of a genome reference with its associated costs and computational weight.


Framing the elusive concept of sustainability: a sustainability hierarchy.
Usage of the word "sustainability" is widespread and incorporates a plethora of meanings. After reviewing four extant sustainability frameworks, we propose a Sustainability Hierarchy to structure a broad array of issues that have been associated with sustainability. These issues vary widely in their urgency, severity and uncertainty of consequences, and temporal and spatial dimensions. It categorizes actions some view as unsustainable based on their direct or indirect potential to (i) endanger the survival of humans; (ii) impair human health, (iii) cause species extinction or violate human rights; or (iv) reduce quality of life or have consequences that are inconsistent with other values, beliefs, or aesthetic preferences. Effects considered include impediments to the ecosystem functions that support human life, human health, and species viability. This paper argues that for sustainability to become a more meaningful concept, the many worthy issues in the fourth category (values, beliefs, and aesthetic preferences) should not be considered sustainability concerns. Implications for companies, policy makers, and scientists are discussed.


IL-1beta stimulates IL-6 production in cultured skeletal muscle cells through activation of MAP kinase signaling pathway and NF-kappa B.
Recent studies suggest that the skeletal muscle may be a significant site of IL-6 production in various conditions, including exercise, inflammation, hypoperfusion, denervation, and local muscle injury. The mediators and molecular mechanisms regulating muscle IL-6 production are poorly understood. We tested the hypothesis that IL-6 production in muscle cells is regulated by IL-1beta and that mitogen-activated protein (MAP) kinase signaling and NF-kappaB activation are involved in IL-1beta-induced IL-6 production. Cultured C2C12 cells, a mouse skeletal muscle cell line, were treated with different concentrations (0.1-2 ng/ml) of IL-1beta in the absence or presence of the p38 MAP kinase inhibitor SB-208350 or the p42/44 inhibitor PD-98059. Protein and gene expression of IL-6 were determined by ELISA and real-time PCR, respectively. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay and by transfecting myocytes with a luciferase reporter plasmid containing a promoter construct with multiple repeats of NF-kappaB binding site. Treatment of myotubes with IL-1beta resulted in a dose- and time-dependent increase of IL-6 production accompanied by an approximately 25-fold increase in IL-6 mRNA levels. IL-1beta stimulated NF-kappaB DNA binding activity and gene activation. SB-208350 and PD-98059 inhibited the increase in IL-6 production induced by IL-1beta. The present results support the concept that skeletal muscle is an important site of IL-6 production. In addition, the results suggest the IL-1beta regulates muscle IL-6 production at least in part by activating the MAP kinase pathway and NF-kappaB.


Somatostatin immunoreactivity in axon terminals in rat nucleus tractus solitarii arising from central nucleus of amygdala: coexistence with GABA and postsynaptic expression of sst2A receptor.
Axon terminals synapsing on neurones in the nucleus tractus solitarii (NTS) that originate from the central nucleus of the amygdala (CeA) have been shown to contain gamma-aminobutyric acid (GABA) immunoreactivity. Here we investigated whether such terminals also contain somatostatin (SOM), a neuropeptide found in axons distributed throughout the NTS and in somata in the CeA, and known to modulate cardiovascular reflexes when microinjected into the NTS. With fluorescence microscopy, SOM immunoreactivity was seen in the varicosities of some axons throughout the NTS that were anterogradely labelled with biotin dextran amine injected into the CeA. Such varicosities were frequently observed in close proximity to dendrites of NTS neurones that were immunoreactive for the SOM receptor sst(2A) subtype, and in many cases also for catecholamine synthesising enzymes. In the caudal, cardioregulatory zone of NTS, SOM immunoreactivity was localised by electron microscopic pre-embedding gold labelling to boutons containing dense-cored and clear pleomorphic vesicles and forming symmetrical synapses, mostly onto dendrites. Additional post-embedding gold labelling for GABA suggested that a subpopulation (29%) of GABAergic terminals sampled in this area of NTS contained SOM. Almost all boutons anterogradely labelled from the amygdala were GABA-immunoreactive (-IR) and 21% of these were SOM-IR. A similar proportion of these boutons (22%) formed synapses onto dendrites containing immunoreactivity for the SOM receptor sst(2A) subtype. These observations provide evidence that some of the GABAergic projection neurones in the CeA that inhibit baroreceptor reflex responses in the NTS in response to fear or emotional stimuli could release SOM, which might modulate the activity of NTS neurones via an action on sst(2A) receptors.


Countering Zika Virus: The USAMRIID Response.
The United States Army Medical Research Institute of Infectious Diseases (USAMRIID) possesses an array of expertise in diverse capabilities for the characterization of emerging infectious diseases from the pathogen itself to human or animal infection models. The recent Zika virus (ZIKV) outbreak was a challenge and an opportunity to put these capabilities to work as a cohesive unit to quickly respond to a rapidly developing threat. Next-generation sequencing was used to characterize virus stocks and to understand the introduction and spread of ZIKV in the United States. High Content Imaging was used to establish a High Content Screening process to evaluate antiviral therapies. Functional genomics was used to identify critical host factors for ZIKV infection. An animal model using the temporal blockade of IFN-I in immunocompetent laboratory mice was investigated in conjunction with Positron Emission Tomography to study ZIKV. Correlative light and electron microscopy was used to examine ZIKV interaction with host cells in culture and infected animals. A quantitative mass spectrometry approach was used to examine the protein and metabolite type or concentration changes that occur during ZIKV infection in blood, cells, and tissues. Multiplex fluorescence in situ hybridization was used to confirm ZIKV replication in mouse and NHP tissues. The integrated rapid response approach developed at USAMRIID presented in this review was successfully applied and provides a new template pathway to follow if a new biological threat emerges. This streamlined approach will increase the likelihood that novel medical countermeasures could be rapidly developed, evaluated, and translated into the clinic.


Protective Effects of Hydrogen-Rich Saline on Rats with Smoke Inhalation Injury.
To explore the protective effects of hydrogen-rich saline on rats with smoke inhalation injury. 36 healthy male Sprague-Dawley rats were randomly divided into 3 groups (n = 12 per group): sham group (S), inhalation injury plus normal saline treatment group (I+NS), and inhalation injury plus hydrogen-rich saline treatment group (I+HS). 30 min after injury, normal saline and hydrogen-rich saline were injected intraperitoneally (5 mL/kg) in I+NS group and I+HS group, respectively. All rats were euthanized and blood and organ specimens were collected for determination 24 h after inhalation injury. Tumor necrosis factor-alpha (TNF-α) levels, malondialdehyde (MDA) concentrations, nuclear factor kappa B (NF-κB) p65 expression, and apoptosis index (AI) in I+HS group were significantly decreased (P < 0.05), while superoxide dismutase (SOD) activities were increased compared with those in I+NS group; and a marked improvement in alveolar structure was also found after hydrogen-rich saline treatment. Hydrogen-rich saline treatment exerts protective effects in acute lung injury induced by inhalation injury, at least in part through the activation of anti-inflammatory and antioxidant pathways and inhibition of apoptosis.


Fourier domain rotational anisotropy-second harmonic generation.
We describe a novel scheme of detecting rotational anisotropy-second harmonic generation (RA-SHG) signals using a lock-in amplifier referenced to a fast scanning RASHG apparatus. The method directly measures the nth harmonics of the scanning frequency corresponding to SHG signal components of Cn symmetry that appear in a Fourier series expansion of a general RA-SHG signal. GaAs was used as a test sample allowing comparison of point-by-point averaging with the lock-in based method. When divided by the C∞ signal component, the lock-in detected data allowed for both self-referenced determination of ratios of Cn components of up to 1 part in 104 and significantly more sensitive measurement of the relative amount of different Cn components when compared with conventional methods.


Biaxial flexural modulus of antibiotic-impregnated orthopedic bone cement.
Previously reported antibiotic-impregnated cement strengths have been based on uniaxial and fatigue testing methodologies. These methods may not provide an accurate characterization of bone cement's true load-bearing capacity in total joint replacement (TJR). The present study utilized biaxial testing to report on the properties of antibiotic-impregnated cement. Test groups included: PMMA mixed with Vancomycin, Gentamicin, Tobramycin, or no antibiotic (control). In comparison to the control group, PMMA samples mixed with powdered gentamicin resulted in an increase in the mean elastic modulus by 6.50% versus a drop noted with powdered vancomycin and tobramycin by 2.65 and 1.37% respectively. The mean elastic modulus in samples containing liquid gentamicin dropped by 11.6%. This study supports the continued use of powdered antibiotics when clinically indicated, but suggest caution in the use of liquid gentamicin in TJR.


Histone demethylase KDM6B has an anti-tumorigenic function in neuroblastoma by promoting differentiation.
Induction of differentiation is a therapeutic strategy in high-risk neuroblastoma, a childhood cancer of the sympathetic nervous system. Neuroblastoma differentiation requires transcriptional upregulation of neuronal genes. How this process is regulated at epigenetic levels is not well understood. Here we report that the histone H3 lysine 27 demethylase KDM6B is an epigenetic activator of neuroblastoma cell differentiation. KDM6B mRNA expression is downregulated in poorly differentiated high-risk neuroblastomas and upregulated in differentiated tumors, and high KDM6B expression is prognostic for better survival in neuroblastoma patients. In neuroblastoma cell lines, KDM6B depletion promotes cell proliferation, whereas KDM6B overexpression induces neuronal differentiation and inhibits cell proliferation and tumorgenicity. Mechanistically, KDM6B epigenetically activates the transcription of neuronal genes by removing the repressive chromatin marker histone H3 lysine 27 trimethylation. In addition, we show that KDM6B functions downstream of the retinoic acid-HOXC9 axis in inducing neuroblastoma cell differentiation: KDM6B expression is upregulated by retinoic acid via HOXC9, and KDM6B is required for HOXC9-induced neuroblastoma cell differentiation. Finally, we present evidence that KDM6B interacts with HOXC9 to target neuronal genes for epigenetic activation. These findings identify a KDM6B-dependent epigenetic mechanism in the control of neuroblastoma cell differentiation, providing a rationale for reducing histone H3 lysine 27 trimethylation as a strategy for enhancing differentiation-based therapy in high-risk neuroblastoma.


Saccharomyces cerevisiae replication factor C. I. Purification and characterization of its ATPase activity.
Saccharomyces cerevisiae replication factor C (RF-C) was purified 25,000-fold from a protease-deficient strain of yeast. RF-C is a complex of 6 subunits of 130, 86, 41, 40, 37, and 27 kDa. None of the subunits are related through proteolysis or differential phosphorylation. The assay for RF-C used as a substrate single-stranded DNA binding protein-coated singly primed single-stranded mp 18 DNA. This DNA was poorly replicated by yeast DNA polymerase delta with or without its cofactor proliferating cell nuclear antigen (PCNA). In the presence of RF-C, however, replication of the template proceeded efficiently when both ATP and PCNA were present as well. Formation of this replication-proficient complex of DNA polymerase delta required an input of one to two molecules of PCNA per replicated DNA molecule. DNA polymerase epsilon also formed an ATP-dependent complex with PCNA and RF-C. RF-C has a DNA-dependent ATPase activity, equally active on single-stranded and primed single-stranded mp18 DNA. Addition of PCNA stimulated the ATPase of RF-C on primed but not on unprimed DNA, indicating that the increase in ATPase was due to PCNA-enhanced binding of RF-C to the primer terminus. Calf thymus PCNA also stimulated the ATPase activity of yeast RF-C and participated in holoenzyme formation with DNA polymerase delta. These results attest to the structural and functional homology between yeast and mammalian cells for these components of the replication machinery.


Health industry acts to meet security challenge by responding to Joint Commission advisories.
The healthcare industry is advancing in a desirable direction in terms of safety and security--thanks to the success of the JCAHO and the IAHSS--says the author. With the rise in healthcare policies, procedures, and programs, he reports, the incidence and severity of crimes against healthcare facilities continue to fall.


Hypertension: management perspectives.
The increasing worldwide prevalence of hypertension and the related increase in cost due to diagnosis, management and negative outcomes forces public health institutions and clinical researchers to find new strategies to improve blood pressure (BP) control. So what are the possible future perspectives for high BP management? Three main points are briefly discussed in this article: individualized therapy, the known genetic contribution to hypertension development and control, and the improvement of disease management, including perspectives on new antihypertensive drug development. It is likely that the integration of the best available current knowledge with recent diagnostic and therapeutic achievements for the management of hypertension prevention and treatment will lead to the early detection of at-risk conditions, early diagnosis, and individualized and efficacious treatment. The most promising antihypertensive drugs currently in development are innovative renin-angiotensin-aldosterone system modulators. Further drugs have potentially interesting mechanisms of action, but renalase analogs are in the very early phases of development, and available endothelin antagonists have a poor safety profile.


Use of E-Cigarettes and Cigarettes During Late Pregnancy Among Adolescents.
Pregnant adolescents sometimes use cigarettes; however, little is known about e-cigarette use among pregnant adolescents, a population with increased health vulnerability. To examine yearly trends, sociodemographic and pregnancy-related determinants, and the association with small-for-gestational-age (SGA) birth of e-cigarette and/or cigarette use during late pregnancy among adolescents. This cohort study used existing data from the 2016-2021 Pregnancy Risk Assessment Monitoring System on 10 428 US adolescents aged 10 to 19 years who had a singleton birth with complete data on e-cigarette or cigarette use and SGA birth. Adolescents reported e-cigarette and cigarette use during the last 3 months of pregnancy. SGA birth (birth weight below the 10th percentile for the same sex and gestational duration) was determined from birth certificates. Multivariable logistic regression was used to compare the odds of SGA birth across pregnant adolescents who exclusively used e-cigarettes, exclusively used cigarettes, used e-cigarettes and cigarettes, or did not use either. Of the 10 428 pregnant adolescents, 72.7% were aged 18 or 19 years; 58.9% self-identified as White and 23.3% as Black; and 69.8% were non-Hispanic. The weighted prevalence of exclusive e-cigarette use during late pregnancy increased from 0.8% in 2016 to 4.1% in 2021, while the prevalence of exclusive cigarette use decreased from 9.2% in 2017 to 3.2% in 2021. The prevalence of dual use fluctuated, ranging from 0.6% to 1.6%. White pregnant adolescents were more likely than those who self-identified as another race and ethnicity to use e-cigarettes (2.7% vs 1.0% for American Indian or Alaska Native adolescents, 0.8% for Asian or other race adolescents, 0.6% for Black adolescents, and 0.7% for multiracial adolescents). Compared with those who did not use either product, adolescents who exclusively used e-cigarettes (16.8% vs 12.9%; confounder-adjusted odds ratio [AOR], 1.68 [95% CI, 0.89-3.18]) or who used cigarettes and e-cigarettes (17.6% vs 12.9%; AOR, 1.68 [95% CI, 0.79-3.53]) had no statistically significant difference in risk of SGA birth. However, adolescents who exclusively used cigarettes had a more than 2-fold higher risk of SGA birth (24.6% vs 12.9%; AOR, 2.51 [95% CI, 1.79-3.52]). This cohort study suggests that pregnant adolescents increasingly used e-cigarettes, with the highest use among White adolescents. Results from this analysis found that, unlike cigarette use, e-cigarette use during late pregnancy was not statistically significantly associated with an increased risk of SGA birth among adolescents. Due to the uncertainty of this nonsignificant association, future research could benefit from a larger sample size.


High levels of fatty acids inhibit β-casein synthesis through suppression of the JAK2/STAT5 and mTOR signaling pathways in mammary epithelial cells of cows with clinical ketosis.
Ketosis is a metabolic disease of dairy cows often characterized by high concentrations of ketone bodies and fatty acids, but low milk protein and milk production. The Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) and the mechanistic target of rapamycin (mTOR) signaling pathways are central for the regulation of milk protein synthesis. The effect of high levels of fatty acids on these pathways and β-casein synthesis are unknown in dairy cows with clinical ketosis. Mammary gland tissue and blood samples were collected from healthy (n = 15) and clinically-ketotic (n = 15) cows. In addition, bovine mammary epithelial cells (BMEC) were treated with fatty acids, methionine (Met) or prolactin (PRL), respectively. In vivo, the serum concentration of fatty acids was greater (P > 0.05) and the percentage of milk protein (P > 0.05) was lower in cows with clinical ketosis. The JAK2-STAT5 and mTOR signaling pathways were inhibited and the abundance of β-casein was lower in mammary tissue of cows with clinical ketosis (P > 0.05). In vitro, high levels of fatty acids inhibited the JAK2-STAT5 and mTOR signaling pathways (P > 0.05) and further decreased the β-casein synthesis (P > 0.05) in BMEC. Methionine or PRL treatment, as positive regulators, activated the JAK2-STAT5 and mTOR signaling pathways to increase the β-casein synthesis. Importantly, the high concentration of fatty acids attenuated the positive effect of Met or PRL on mTOR, JAK2-STAT5 pathways and the abundance of β-casein (P > 0.05). Overall, these data indicate that the high concentrations of fatty acids that reach the mammary cells during clinical ketosis inhibit mTOR and JAK2-STAT5 signaling pathways, and further suppress β-casein synthesis.


Circulating microRNAs as novel biomarkers for the early diagnosis of acute coronary syndrome.
Small non-coding microRNAs (miRNAs) are important physiological regulators of post-transcriptional gene expression. miRNAs not only reside in the cytoplasm but are also stably present in several extracellular compartments, including the circulation. For that reason, miRNAs are proposed as diagnostic biomarkers for various diseases. Early diagnosis of acute coronary syndrome (ACS), especially non-ST elevated myocardial infarction and unstable angina pectoris, is essential for optimal treatment outcome, and due to the ongoing need for additional identifiers, miRNAs are of special interest as biomarkers for ACS. This review highlights the nature and cellular release mechanisms of circulating miRNAs and therefore their potential role in the diagnosis of myocardial infarction. We will give an update of clinical studies addressing the role of circulating miRNA expression after myocardial infarction and explore the diagnostic value of this potential biomarker.


Adrenocortical function in critically ill patients 24 h after a single dose of etomidate.
We compared the effects of single doses of etomidate and thiopentone on adrenocortical function in a randomised controlled clinical trial involving 35 critically ill patients who needed a general anaesthetic. Just before induction of anaesthesia, a baseline blood cortisol sample was taken. Twenty-four hours later we performed a short adrenocorticotrophic hormone stimulation test. No patient had a low cortisol level (< 160 nmol.l-1) at any time during the study. Baseline, pre-ACTH and post-ACTH cortisol levels were similar in the two groups. However, significantly more patients in the etomidate group had an ACTH-stimulated cortisol increment < 200 nmol.l-1. The clinical significance of these findings is not clear, but we conclude that single doses of etomidate may interfere with cortisol synthesis for at least 24 h in the critically ill.


Horizontal transfer and the evolution of host-pathogen interactions.
Horizontal gene transfer has been long known in viruses and prokaryotes, but its importance in eukaryotes has been only acknowledged recently. Close contact between organisms, as it occurs between pathogens and their hosts, facilitates the occurrence of DNA transfer events. Once inserted in a foreign genome, DNA sequences have sometimes been coopted by pathogens to improve their survival or infectivity, or by hosts to protect themselves against the harm of pathogens. Hence, horizontal transfer constitutes a source of novel sequences that can be adopted to change the host-pathogen interactions. Therefore, horizontal transfer can have an important impact on the coevolution of pathogens and their hosts.


Comparison of fingerstick versus venipuncture for antibody testing of measles and rubella.
The aim of this study was to determine whether the fingerstick method of obtaining blood is an acceptable alternative to venipuncture for measuring antibody levels. Blood specimens for antibody determination were obtained from healthy adult subjects by venipuncture with the serum separated from the clot by standard methodology. Fingerstick samples were also obtained by piercing the second or third finger and collected in Microtainer serum separator tubes. The serum was then separated by centrifugation, and all specimens were immediately stored at -80 degrees C until assayed. There was an excellent correlation between sera collected from fingerstick and venipuncture for both measles and rubella antibody assays. For the measles enzyme immunoassay (EIA), 85% of subjects were immune, and the correlation coefficient between the fingerstick and the venipuncture results was 0.98 using least squares linear regression. For the rubella EIA, 100% of subjects were immune, and the correlation coefficient was 0.83. Both methods showed the same number of immunopositive individuals; furthermore, there were no cases of immunity to either virus that were detected in only 1 fluid source. There was no significant difference in antibody levels from blood obtained by either method.


Structural basis for photo-induced protein cleavage and green-to-red conversion of fluorescent protein EosFP.
Genetically encoded fusion constructs derived from fluorescent proteins (FPs) can be designed to report on a multitude of events and signals in cells, tissues, and entire organs without interfering with the complex machinery of life. EosFP is a novel FP from the scleractinian coral Lobophyllia hemprichii that switches its fluorescence emission from green (516 nm) to red (581 nm) upon irradiation with approximately 400-nm light. This property enables localized tagging of proteins and thus provides a valuable tool for tracking protein movements within live cells. Here, we present the x-ray structures of the green and red forms of WT EosFP. They reveal that formation of the red chromophore is associated with cleavage of the peptide backbone, with surprisingly little change elsewhere in the structure, and provide insights into the mechanism that generates this interesting posttranslational polypeptide modification.


The carbon footprint of dairy production systems through partial life cycle assessment.
Greenhouse gas (GHG) emissions and their potential effect on the environment has become an important national and international issue. Dairy production, along with all other types of animal agriculture, is a recognized source of GHG emissions, but little information exists on the net emissions from dairy farms. Component models for predicting all important sources and sinks of CH(4), N(2)O, and CO(2) from primary and secondary sources in dairy production were integrated in a software tool called the Dairy Greenhouse Gas model, or DairyGHG. This tool calculates the carbon footprint of a dairy production system as the net exchange of all GHG in CO(2) equivalent units per unit of energy-corrected milk produced. Primary emission sources include enteric fermentation, manure, cropland used in feed production, and the combustion of fuel in machinery used to produce feed and handle manure. Secondary emissions are those occurring during the production of resources used on the farm, which can include fuel, electricity, machinery, fertilizer, pesticides, plastic, and purchased replacement animals. A long-term C balance is assumed for the production system, which does not account for potential depletion or sequestration of soil carbon. An evaluation of dairy farms of various sizes and production strategies gave carbon footprints of 0.37 to 0.69kg of CO(2) equivalent units/kg of energy-corrected milk, depending upon milk production level and the feeding and manure handling strategies used. In a comparison with previous studies, DairyGHG predicted C footprints similar to those reported when similar assumptions were made for feeding strategy, milk production, allocation method between milk and animal coproducts, and sources of CO(2) and secondary emissions. DairyGHG provides a relatively simple tool for evaluating management effects on net GHG emissions and the overall carbon footprint of dairy production systems.


Autologous peripheral blood progenitor cells are a potential source of parvovirus B19 infection.
Parvovirus B19 is a cause of delayed red blood cell (RBC) engraftment after marrow transplantation (BMT). The diagnosis of parvovirus infection requires serologic and DNA testing in the context of clinical disease and characteristic marrow morphologic findings; however, the source of infection is often difficult to determine. Investigation of a case of delayed RBC engraftment and pure RBC aplasia (PRCA) occurring 3 months after autologous peripheral blood progenitor cell (PBPC) transplantation in a patient with high-risk diffuse large B-cell lymphoma. DNA testing of serum and of a sample of cryopreserved PBPCs was performed. Marrow morphology showed a maturational arrest of erythroid cells with giant proerythroblasts. Polymerase chain reaction and nucleic acid hybridization confirmed the presence of parvovirus DNA in the serum and in a sample of sequestered PBPCs saved at the time of PBPC harvest. PRCA resolved after the administration of intravenous immune globulin. Autologous PBPCs are a potential source of parvovirus infection, which may cause significant disease after autologous BMT.


[The problem of growing resistance of microorganisms to antibiotic therapy and prospects for Helicobacter pylori eradication].
The problem of growing resistance of microorganisms to antibiotic therapy acquires increasingly greater significance as threatening the loss of endosymbiotic bacteria. The causes, mechanisms, and consequences of this phenomenon are considered. Several groups of modern antibiotic drugs are characterized along with the methods for improving their efficacy and preventing side effects. The schemes for Helicobacter pylori eradication as recommended by the Maastricht consensus are discussed in conjunction with major mistakes accounting for marked reduction of their effectiveness. Terminological issues are briefly considered.


MoCA as a cognitive assessment tool for absence status epilepticus.
De novo absence status is clinically characterized by a confusional syndrome and neurophysiologically by the presence of periodic spike/polyspike-and-wave discharges on EEG. The treatment should be started promptly, and fast recovery is usually seen. However, cognitive symptoms can be very difficult to detect, and no consensus exists on how cognitive improvement can be clinically monitored. We report a patient with absence status epilepticus, whose therapeutic response was monitored neurophysiologically with EEG and clinically with a cognitive test; the Montreal Cognitive Assessment (MoCA). Based on this case report, we describe the use of the MoCA for monitoring cognitive function in a patient with absence status epilepticus. MoCA was evaluated on three occasions, with a total score ranging from 9, before treatment, to 23, when an EEG with no epileptiform discharges was obtained. We suggest that MoCA may be a useful tool to monitor cognitive improvement in absence status epilepticus.


The interaction of radiations of different LET.
Experimental data for mixed radiation of different LET are analysed using an isobologram approach and are shown to be consistent with the special case of 'zero interaction' in a general formulation of the effect of a combination of agents proposed by Berenbaum. This zero interaction is defined in the same sense as interaction between the lesions produced by the same radiation. This makes analysis and predictions of mixed radiation results particularly straightforward. The zero-interaction formula can be mathematically derived from a simple model of mixed radiation called the lesion additivity model using the assumption that different early lesions produced in the radiation mixture can gradually develop into an indistinguishable intermediate state and hence become additive to produce the same end point. The model is shown to be applicable to irradiation under both hypoxic and oxygenated conditions and hence is extended to the use of hypoxic cell sensitisers.


Parametric imaging of cancer with optical coherence tomography.
We present a parametric optical coherence tomography (OCT) technique to improve contrast between malignant and healthy non-neoplastic tissue. The technique incorporates a fully automated method to extract tissue attenuation characteristics. Results are represented visually as a parametric en face image, where the parameter used for contrast is indicative of the relative optical attenuation coefficient of the tissue. We present the first parametric OCT images of human lymph nodes containing malignant cells, and demonstrate improved tissue contrast over en face OCT images.


Stretching and breaking of ultrathin MoS2.
We report on measurements of the stiffness and breaking strength of monolayer MoS(2), a new semiconducting analogue of graphene. Single and bilayer MoS(2) is exfoliated from bulk and transferred to a substrate containing an array of microfabricated circular holes. The resulting suspended, free-standing membranes are deformed and eventually broken using an atomic force microscope. We find that the in-plane stiffness of monolayer MoS(2) is 180 ± 60 Nm(-1), corresponding to an effective Young's modulus of 270 ± 100 GPa, which is comparable to that of steel. Breaking occurs at an effective strain between 6 and 11% with the average breaking strength of 15 ± 3 Nm(-1) (23 GPa). The strength of strongest monolayer membranes is 11% of its Young's modulus, corresponding to the upper theoretical limit which indicates that the material can be highly crystalline and almost defect-free. Our results show that monolayer MoS(2) could be suitable for a variety of applications such as reinforcing elements in composites and for fabrication of flexible electronic devices.


Perinatal death and exposure to dental amalgam fillings during pregnancy in the population-based MoBa cohort.
The aim was to gain knowledge regarding the risk of perinatal death related to exposure to dental amalgam fillings in the mother. Population-based observational cohort study. The Norwegian Mother and Child Cohort Study, a Norwegian birth cohort of children born in 1999-2008 conducted by the Norwegian Institute of Public Health. 72,038 pregnant women with data on the number of teeth filled with dental amalgam. Data on perinatal death (stillbirth ≥ 22 weeks plus early neonatal death 0-7 days after birth) were obtained from the Medical Birth Registry of Norway. The absolute risk of perinatal death ranged from 0.20% in women with no amalgam-filled teeth to 0.67% in women with 13 or more teeth filled with amalgam. Analyses including the number of teeth filled with amalgam as a continuous variable indicated an increased risk of perinatal death by increasing number of teeth filled with dental amalgam (crude OR 1.065, 95% CI 1.034 to 1.098, p<0.001). After adjustment for potential confounders (mothers' age, education, body mass index, parity, smoking during pregnancy, alcohol consumption during pregnancy) included as categorical variables, there was still an increased risk for perinatal death associated with increasing number of teeth filled with amalgam (ORadj 1.041, 95% CI 1.008 to 1.076, p = 0.015). By an increased exposure from 0 to 16 teeth filled with amalgam, the model predicted an almost doubled odds ratio (ORadj 1.915, 95% CI 1.12 to 3.28). In groups with 1 to 12 teeth filled with amalgam the adjusted odds ratios were slightly, but not significantly, increased. The group with the highest exposure (participants with 13 or more teeth filled with amalgam) had an adjusted OR of 2.34 (95% CI 1.27 to 4.32; p = 0.007). The current findings suggest that the risk of perinatal death could increase in a dose-dependent way based on the mother's number of teeth filled with dental amalgam. However, we cannot exclude that the relatively modest odds ratios could be a result of residual confounding. Additional studies on the relationship between exposure to dental amalgam fillings during pregnancy and perinatal death are warranted.


Influence of impact direction on the human head in prediction of subdural hematoma.
The objective of the present study was to analyze the effect of different loading directions following impact, and to evaluate existing global head injury criteria. Detailed and parameterized models of the adult human head were created by using the Finite Element Method (FEM). Loads corresponding to the same impact power were imposed in different directions. Furthermore, the Head Injury Criterion (HIC) and the recently proposed Head Impact Power (HIP) criterion were evaluated with respect to the relative motion between the skull and the brain, as well as the strain in the bridging veins. It was found that the influence of impact direction had a substantial effect on the intracranial response. The largest relative skull-brain motion and strain in the bridging veins occurred with the anterior-posterior (AP) and posterior-anterior (PA) rotational impulses. HIC was unable to predict consequences of a pure rotational impulse while HIP needed individual scaling coefficients for the different terms to account for difference in load direction. When using the proposed scaling procedure, a better prediction of subdural hematoma (SDH) was obtained. It is thus suggested that an evaluation of the synergistic terms is necessary to further improve the injury prediction. These variations should be considered when developing new head injury criteria.


Isolation of transmissible Gastroenteritis virus, pseudorabies virus, and porcine enterovirus from pharyngeal swabs taken from market-weight-swine.
Pharyngeal swab samples were collected at a central Iowa abattoir from 6,010 market-weight slaughter hogs from September 1, 1979 to August 31, 1980. The swab samples were examined for cytopathic viruses by inoculation of monolayer cultures of continuous line of swine testicular cells. Of the 6,010 swab samples tested, transmissible gastroenteritis virus was isolated from 91 (1,51%), pseudorabies virus was isolated from 431 (7.17%), and porcine enterovirus was isolated from 21 (0.35%). Although all 3 viruses were identified throughout the year, transmissible gastroenteritis and pseudorabies viruses were found more frequently during the winter and early spring. In contrast, porcine enterovirus was detected more frequently during the spring and summer.


Tooth loss and associated risk indicators in an adult urban population from south Brazil.
The aim of the present study was to assess the prevalence, extent, and risk indicators of tooth loss in a representative adult, urban population in the Brazilian state of Rio Grande do Sul. A sample of 974 subjects (ages 30 to 103 years, mean 48.7, SD 13.4) representative of the metropolitan area of Porto Alegre, Brazil was selected by a multi-stage probability cluster sampling strategy. In all, 94% of the subjects had experienced tooth loss. The mean tooth loss was 11.2 teeth, and varied between 5.5 and 20.2 teeth in the 30-39 and 60 + years age groups, respectively. The multivariable analysis, adjusted for age, showed that subjects who had lost 7-13 or > or = 14 teeth were more likely to be females (odds ratio (OR) = 1.4, 2.4), of low (OR = 2.8, 5.1) or middle socio-economic status (OR = 2.3, 3.4), and heavy smokers (OR= 2.0, 2.3) than those with 6 or fewer missing teeth. Furthermore, loss of > or = 14 teeth was associated with presence of > 50% teeth with attachment loss > or = 5 mm (OR= 5.7), and loss of 7-13 teeth was associated with presence of > 50% teeth with attachment loss > or = 5 mm (OR = 2.4) and having 15-30% or > 30% decayed-filled teeth (OR = 2.7 and 4.1). In conclusion, tooth loss is highly prevalent in this urban Brazilian population. Gender, socio-economic status, cigarette smoking, caries experience, and attachment loss are important risk indicators. A reduction in the population's tooth loss may be achieved by the implementation of community programs for the prevention and treatment of dental caries and periodontal diseases.


Proteomics by mass spectrometry--go big or go home?
Mass spectrometry is an important technology for mapping composition and flux in whole proteomes. Over the last 5 years in particular, impressive gains in the depth of proteome coverage have been realized, particularly for model organisms. This review will provide an update on advancements in the key analytical techniques, methods and informatics directed towards whole proteome analysis by mass spectrometry. Practical issues involving sample requirements, analysis time and depth of coverage will be addressed, to gauge how useful data-driven approaches are for solving biological problems. Targeted mass spectrometric methods, based on selected reaction monitoring, are presented as a powerful alternative to data-driven methods. They offer robust, transferable protocols for hypothesis-directed monitoring of limited yet biologically significant tracts of any proteome.


[Spontaneous ruptures of allotransplants of human cadaveric kidneys].
On the basis of morphological data it was established that spontaneous ruptures of allotransplanted kidneys of man were connected mainly with juxtamedullar shunting of their blood flow; Impairment of the blood flow was apparently caused both by immune and nonimmune endogenous humoral factors. The pathomorphological picture in spontaneous ruptures of transplants differed from structural changes observed in traumatic damage of the kidney.


Development of an HIV Postexposure Prophylaxis (PEP) Protocol for Trainees Engaging in Academic Global Health Experiences.
Global health (GH) education programs have become increasingly common in U.S. medical schools and graduate medical education programs, with growing numbers of medical students, residents, and fellows participating in clinical experiences in settings with high HIV prevalence and limited resources. However, there are no guidelines for provision of HIV postexposure prophylaxis (PEP) to trainees engaging in these academic GH experiences. Faculty of the Global Health Education Programs (GHEP) at the David Geffen School of Medicine at UCLA and GH partner institutions recognized the need for PEP access for trainees engaged in GH experiences. In 2013-2014, key UCLA faculty collaborated in the development of the UCLA GHEP PEP Protocol, which includes provision of PEP medications to trainees prior to departure, an on-call infectious disease/HIV specialist to advise trainees who have exposures, and a system for following up with exposed trainees while on the GH rotation and after their return. Between February 2014 and September 2016, 112 medical students and 110 residents received education on the PEP protocol during their predeparture orientation. The protocol was used for 28 exposures (27 occupational, 1 nonoccupational), with PEP recommended in 3 occupational cases (all needlesticks) and the single nonoccupational case. There were no reported HIV seroconversions. The authors plan to formally evaluate the PEP protocol, conduct a qualitative assessment with trainees and both UCLA and GH partner faculty, and discuss best practices with institutions across the United States and with GH partners.


Graph rigidity and localization of multi-robot formations.
This paper provides theoretical foundation for the problem of localization in multi-robot formations. Sufficient and necessary conditions for completely localizing a formation of mobile robots/vehicles in SE(2) based on distributed sensor networks and graph rigidity are proposed. A method for estimating the quality of localizations via a linearized weighted least-squares algorithm is presented, which considers incomplete and noisy sensory information. The approach in this paper had been implemented in a multi-robot system of five car-like robots equipped with omni-directional cameras and IEEE 802.11b wireless network.


Early and long-term results of a valve-sparing operation for Marfan syndrome.
We have previously described the experience, rationale, and development of a valve preserving technique, but its role in patients with Marfan syndrome has not previously been defined. Here, we attempt to determine the early and long-term results, timing, and determinants of outcome of this operation in patients with Marfan syndrome. Since 1979, 82 patients (73.2% of all patients with Marfan syndrome undergoing resection of aneurysm of the ascending aorta) were operated on using this technique. Ages ranged from 2 to 69 years (mean, 33.9 years). In all, there were 4 early deaths (4.9%), 2 with acute dissection and 2 with chronic aneurysm operated on as emergencies. There were no early deaths in 67 patients operated on electively. Actuarial survival for patients operated for chronic aneurysm was 94.2%, 94.2%, and 94.2% at 1, 5, and 10 years, respectively; that for acute dissection was 72.7%, 63. 6%, and 63.6%; and that for chronic dissection was 100%, 85.7%, and 75.0%. The probability of needing reoperation was 5.7%, 17.3%, and 17.3% at 1, 5, and 10 years. There were no instances of infective endocarditis or thromboembolic complications except in 2 patients operated on early in the series who had cusp extension. At the end of the follow-up, trivial or no aortic regurgitation was demonstrated in 33.3%, mild in 45.6%, moderate in 21.1%, and severe in 0. Valve-sparing operations are feasible in most patients with Marfan syndrome; they are applicable to patients with both dissection and chronic aneurysm. The early and long-term results are encouraging. Results are better in the absence of dissection, and prophylactic operation is warranted in some cases.


Clinical trial of a new intramuscular iron preparation in iron deficiency anaemia.
A new intramuscular iron preparation (Ferastral) permitting high doses of iron (500 mg) to be given in two simultaneous of 250 mg, was tested in 20 courses given to 11 patients with iron deficiency anaemia. The total iron doses given ranged from 1 000-2 500 mg. The amount injected was calculated from the degree of haemoglobin deficiency. Additional 500-1 000 mg iron were given to fill the depots. Haemoglobin regeneration was satisfactory. Bone marrow aspiration to assess storage iron 2-14 weeks after treatment was carried out in most patients and showed restoration of stainable iron in bone marrow in those cases given Ferastral in doses of 500-1 000 mg greater than calculated to normalize haemoglobin concentrations. In two patients with persistent continued blood loss the bone marrow remained negative for stainable iron. Side-effects were negligible.


Relations between chord and slope conductances and equivalent electromotive forces.
Nonlinear current-voltage relations for ion movement across biological membranes have been observed and significantly complicate the interpretation of electrical measurements on these transport processes. To enable analysis of the electrical measurements two formalisms have evolved, chord and slope, by which equivalent conductances and electromotive forces (emfs) can be obtained. Because, in the presence of nonlinear relations between current and voltage, the chord conductances and emfs are generally not equal to their slope counterparts, it is imperative that they not be intermixed (8). However, when the functional relationship between the current and voltage is known, such as the Goldman-Hodgkin-Katz (GHK) flux equation, it becomes possible to compare the voltage dependencies of these parameters and examine interrelationships between them. In this communication analytical expressions are derived for the chord and slope conductances and emfs for transport of a single ionic species that obeys the GHK flux equation. Using these expressions, it is possible to convert electrical equivalent circuit parameters derived for one formalism to electrical equivalent parameters of the other formalism. Therefore data obtained using either formalism can be used to obtain values for intracellular activity and membrane permeability to the transported ion. Parallel analyses can be applied to other models of ion transport.


Midwives are getting hurt: UK survey of the prevalence and risk factors for developing musculoskeletal symptoms.
To investigate the prevalence, severity and impact of musculoskeletal disorders (MSDs) and to explore individual, work-related and psychosocial risk factors DESIGN: A cross sectional survey SETTING: A self-reported online questionnaire was used to collect data over seven months (May-December 2016). The survey was distributed to midwives across the United Kingdom through the Consultant Midwives Network and the Royal College of Midwives. Prevalence, severity and impact (12-month) of MSDs for nine body parts are presented. The associations between individual, occupational and psychosocial factors and symptoms are examined using Independent samples t-test or Chi-square statistical analyses, with Logistic regression analysis to understand the relative importance of variables. It was found that 92% of the participants reported MSDs, most commonly in the low back (71%), neck (45%) and shoulders (45%). Symptoms impacted on normal activities at work and/or leisure (50%), sick leave (30%) and jobs/duties (45%). Age and time practicing in midwifery were inversely associated with low back symptoms; reported less frequently with increasing age and experience. Longer working hours was a predictor for shoulder symptoms. Over commitment (intrinsic job stress) was associated with neck and more strongly with shoulder symptoms. Those caring for a dependent adult for more than 50 h a week were 4.54 times more likely to have neck discomfort. This first survey of UK Midwives reveals a very high prevalence of low back, neck and shoulder symptoms, resulting in sickness absenteeism, reduction in normal activities and changing roles. Age, years in practice, body mass index, working hours, job satisfaction and job stress are contributory factors. This study highlights the prevalence and impact of musculoskeletal symptoms and the potential harmful impacts on their working life and patient care. The findings will promote risk-awareness and national actions for risk management.


Population pharmacokinetics and pharmacogenetics of tacrolimus in healthy Chinese volunteers.
The aim of this study was to establish population pharmacokinetic models of tacrolimus in healthy Chinese volunteers. A total of 956 tacrolimus whole blood concentrations from 73 healthy volunteers were determined using ultraperformance liquid chromatography mass spectrometry/mass spectrometry. Population pharmacokinetic analyses were performed using NONMEM. The final population pharmacokinetic models were validated with bootstrap and visual predictive check. A number of covariates were analyzed, including CYP3A5 and ABCB1 polymorphism, demographic characteristics and hematological and biological indices. The structural model was a two-compartment model with first-order absorption, and a lag time was fitted to the data. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V(2)/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V(3)/F), absorption rate (ka) and lag time (ALAG) were 27.7 l/h, 37.5 liters, 34.4 l/h, 357 liters, 0.795 h(-1) and 0.226 h, respectively. The interindividual variabilities of these parameters were 63.3, 62.0, 50.8, 52.3, 32.9 and 4.45%, respectively, and the intraindividual variability of observed concentrations was 14.9%. The covariates that were retained in the final models were CYP3A5 genotype on CL/F, and body surface area and red blood count on V(3)/F. Population pharmacokinetic models of tacrolimus were developed in healthy volunteers. These results could provide a reference for individualized tacrolimus therapy in the clinical setting.


Computerized insulin infusion programs are safe and effective in the burn intensive care unit.
Glucose control has repeatedly been shown to influence favorable outcomes in the surgical intensive care unit (ICU). Intensive insulin therapy has recently been associated with reduced infections complications in burn patients. However, traditional protocols are associated with rates of severe hypoglycemia as high as 19%. Two commercial computer glucose control programs have reported rates of severe hypoglycemia (glucose <50 mg/dl) of 0.6 and 0.4%. Recently, the authors' burn ICU adopted an intensive insulin computer-based protocol created at their institution and already successfully in use in their surgical ICU. The authors hypothesized that their protocol can be used effectively in the burn patient population without an increase risk of severe hypoglycemia. All patients admitted to the burn ICU have blood glucose (BG) values checked routinely. With two consecutive hyperglycemic values >200 mg/dl, patients are placed on a computer-based protocol intravenous insulin drip. Once initiated, BGs are tested hourly with adjustments made according to the computer protocol. Values recorded from January to December 2008 were abstracted from the database and analyzed. Thirty-one patients were treated using the computer glucose control protocol and 12,699 measurements were performed. There were eight measurements <50 mg/dl (0.07%). Seventy-six percent of values were within the target range of 90 to 150 mg/dl. Few patients had severe hyperglycemia with BG >300 mg/dl (0.2%). There were no adverse events associated with the hypoglycemic episode. The computer-based protocol is more effective than those previously used at the institution and provides safe, reliable results in the burn patients.


c-Myc programs fatty acid metabolism and dictates acetyl-CoA abundance and fate.
myc(-/-) rat fibroblasts (KO cells) differ from myc(+/+) (WT) cells and KO cells with enforced Myc re-expression (KO-Myc cells) with respect to mitochondrial structure and function, utilization of glucose and glutamine as energy-generating substrates, and ATP levels. Specifically, KO cells demonstrate low levels of glycolysis and oxidative phosphorylation, dysfunctional mitochondria and electron transport chain complexes, and depleted ATP stores. We examined here how these cells adapt to their energy-deficient state and how they differ in their uptake and utilization of long- and medium-chain fatty acids such as palmitate and octanoate, respectively. Metabolic tracing of these molecules showed that KO cells preferentially utilize them as β-oxidation substrates and that, rather than directing them into phospholipids, preferentially store them as neutral lipids. KO cell transcriptional profiling and functional assays revealed a generalized up-regulation of pathways involved in fatty acid transport and catabolism as well as evidence that these cells attempt to direct acetyl-CoA into the tricarboxylic acid (TCA) cycle for ATP production rather than utilizing it for anabolic purposes. Additional evidence to support this idea included the finding that AMP-dependent protein kinase was constitutively activated in KO cells. The complex control of pyruvate dehydrogenase, which links glycolysis to the TCA cycle, was also maximized to ensure the conversion of pyruvate to acetyl-CoA. Despite these efforts to maximize acetyl-CoA for energy-generating purposes, its levels remained chronically low in KO cells. This suggests that tumor cells with Myc deregulation might be susceptible to novel therapies that limit acetyl-CoA availability.


Perioperative factors associated with prolonged mechanical ventilation after complex congenital heart surgery.
To evaluate perioperative factors associated with prolonged mechanical ventilation in children undergoing complex cardiac surgery for congenital heart disease. Retrospective chart review. A tertiary care pediatric cardiac intensive care. None. This retrospective cohort study included all patients undergoing complex cardiac surgical procedures (Risk Adjustment in Congenital Heart Surgery-1 category ≥ 3) at our institution during 2003. We defined prolonged mechanical ventilation as need for mechanical ventilation for ≥ 7 days (90th percentile of duration of mechanical ventilation for the whole cohort). Multivariate logistic regression analyses were used to determine independent relationships between perioperative factors and prolonged mechanical ventilation. A total of 362 patients were admitted to the cardiac intensive care unit after a cardiac surgical procedure of Risk Adjustment in Congenital Heart Surgery-1 ≥ 3 level of complexity and survived to hospital discharge. Median age was 242 days (range, 4 days-14.4 yrs), the median duration of mechanical ventilation was 1.5 days (range, 0-7 days), and 41 patients (11%) were ventilated for ≥ 7 days. Age of <30 days at surgery, higher Pediatric Risk of Mortality III score at the time of cardiac intensive care unit admission, the presence of major noncardiac structural anomalies, healthcare-associated infections, noninfectious pulmonary complications (pleural effusions and pneumothorax), and the need for reintervention were all independently associated with prolonged mechanical ventilation. Younger age, greater severity of illness at postoperative admission, healthcare-associated infections, noninfectious pulmonary complications, and the need for reintervention are associated with prolonged mechanical ventilation after complex cardiac surgery. Future studies and quality improvement initiatives should focus on those risk factors that are modifiable to promote early extubation in children recovering from complex congenital heart surgery.


The association of oestrogen receptor alpha-haplotypes with cardiovascular risk factors in the British Women's Heart and Health Study.
One previous study among women with established coronary heart disease found a gene-treatment interaction between the oestrogen receptor gene (ESR1) and hormone replacement in their association with high density lipoprotein cholesterol (HDL-c). We aimed to replicate these findings in a general population sample. Cross-sectional associations were assessed in a study of 3404 women from 23 towns across Britain who were aged 60-79 at the time of assessment and were described as white by the examining nurse. Women with the T-A haplotype [constructed from two single nucleotide polymorphisms (SNPs) in the first intron of ESR1: c454-397T > C (rs2234693) and c454-351A > G (rs9340799)], which was predicted to be associated with reduced oestrogen response, were more likely to have been past [per haplotype odds ratio 1.16 (95% CI 1.01, 1.33), P = 0.02] or to be current users [per haplotype odds ratio 1.19 (95% CI 0.99, 1.42), P = 0.05] of hormone replacement. However, there was no association between haplotype or either SNP and HDL-c or other cardiovascular disease risk factors and no statistical evidence of an interaction between hormone replacement use and haplotype or either SNP with respect to HDL-c or any other cardiovascular disease risk factors. Women with the T-A haplotype are more likely to use hormone replacement. However, genotyping of ESR1 rs2234693 or rs9340799 in post-menopausal women to tailor hormone replacement is unlikely to markedly improve cardiovascular risk.


Measurement of expressive vocabulary in school-age children: Development and application of the Kilifi Naming Test (KNT).
The dearth of locally developed measures of language makes it difficult to detect language and communication problems among school-age children in sub-Saharan African settings. We sought to describe variability in vocabulary acquisition as an important element of global cognitive functioning. Our primary aims were to establish the psychometric properties of an expressive vocabulary measure, examine sources of variability, and investigate the measure's associations with non-verbal reasoning and educational achievement. The study included 308 boys and girls living in a predominantly rural district in Kenya. The developed measure, the Kilifi Naming Test (KNT), had excellent reliability and acceptable convergent validity. However, concurrent validity was not adequately demonstrated. In the final regression model, significant effects of schooling and area of residence were recorded. Contextual factors should be taken into account in the interpretation of test scores. There is need for future studies to explore the concurrent validity of the KNT further.


Processing of unattended, simple negative pictures resists perceptual load.
As researchers debate whether emotional pictures can be processed irrespective of spatial attention and perceptual load, negative and neutral pictures of simple figure-ground composition were shown at fixation and were surrounded by one, two, or three letters. When participants performed a picture discrimination task, there was evidence for motivated attention; that is, an early posterior negativity (EPN) and late positive potential (LPP) to negative versus neutral pictures. When participants performed a letter discrimination task, the EPN was unaffected whereas the LPP was reduced. Although performance decreased substantially with the number of letters (one to three), the LPP did not decrease further. Therefore, attention to simple, negative pictures at fixation seems to resist manipulations of perceptual load.


Coping in adult patients with severe haemophilia.
An adequate use of coping strategies could help patients to deal with disease-related stress. The study aim was to explore coping behaviour in adult patients with severe haemophilia and its possible determinants. Coping was assessed through three basic dimensions (task-oriented, emotion-oriented and avoidance coping), using the short version of the Coping Inventory for Stressful Situations (CISS-21). Patients' scores were compared with Dutch working men (N = 374), according to three categories: low use (<P25 of normal), average use (P25-P75) and high use (>P75). Determinants were measured using questionnaires on activities (Haemophilia Activities List), participation (Impact on Participation and Autonomy Questionnaire), physical functioning [physical component of the Dutch Arthritis Impact Measurement Scales-2 (D-AIMS2)] and socio-psychological health (psychological component of the D-AIMS2). In total, 86 adults with severe haemophilia (FVIII/IX<1%) were included. The median age was 38 years (range: 18-68) with 85% affected with haemophilia A and 75% using prophylaxis. Patients with haemophilia used task-oriented coping as frequently as the control group (P = 0.13); but used significantly less emotion-oriented coping (57% vs. 25%, P < 0.05) and avoidance coping (P < 0.05). Emotion-oriented coping showed a strong correlation with socio-psychological health (r = 0.67) and weak correlations with participation (r = 0.32) and social interaction (r = 0.29). Other associations of coping strategies with patient characteristics of health status could not be demonstrated. Overall, patients predominantly used the task-oriented approach to deal with their disease; the use of this strategy was comparable to the control group. Having a poor psychological health, less social interaction and/or less participation in daily life was associated with an increased use of emotion-oriented coping.


Contemporary Trends in the Incidence of Metastatic Prostate Cancer Among US Men: Results from Nationwide Analyses.
Studies have noted contrasting findings with regard to the contemporary incidence of metastatic prostate cancer (PCa) in the USA, especially in light of the United States Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA) screening in recent years. We used data from the 18 population- based tumor registries of the Surveillance, Epidemiology and End Results (SEER) 2004-2013 database to study trends in the incidence of metastatic PCa among men stratified by age and race. Joinpoint regression analyses were performed to identify time points associated with any statistically significant change in incidence. Overall, there was a significant increase in incidence between 2009 and 2013 (annual percentage change [APC] 3.10%; p<0.05). In age-stratified analyses, there was a continuous increase in the incidence of metastatic PCa from 2004 to 2013 among men aged 45-54 yr and 55-64 yr (APC 1.77% and 1.43% respectively; both p<0.05). For men aged ≥75 yr there was a significant decline in the incidence of metastatic PCa from 2004 to 2011 (APC -2.07%; p<0.05) and a nonsignificant increase from 2011 onwards (APC 6.09%). Distinct incidence trends were noted for white and black men. While it is too early to presume that the recent decline in PSA screening secondary to the USPSTF statement is causally associated with our findings, our results highlight a concerning trend of increasing metastatic disease. Our results thus warrant validation in future longer-term studies on the contemporary incidence and mortality of metastatic PCa. PATIENT SUMMARY: We noted increasing incidence of metastatic prostate cancer from 2009 onwards among US men (especially those aged 45-74 yr) in a population-based tumor registry. Pending validation in longer-term studies, our results suggest the need for close surveillance of trends for metastatic prostate cancer incidence and mortality.


Novel targetable biomarkers in clear cell carcinoma of the breast uncovered by molecular profiling: A study of nine cases.
We profiled nine pure clear cell carcinomas of the breast using massively parallel DNA and RNA sequencing (NGS), in situ hybridization (ISH), and immunohistochemistry (IHC). All cases were primary mammary clear cell carcinomas that were diagnosed in female patients (mean age: 53.4 years; range: 31-69 years). Based on our findings, we conclude that the majority of clear cell carcinomas are ER/PR positive and consequently amenable to anti-ER treatment modalities. A subset of clear cell carcinomas also harbored alterations in PIK3CA/PTEN/AKT pathway, particularly PTEN, indicating a potential benefit of PI3K/Akt/mTOR inhibitors. The status of I-O biomarkers in clear cell carcinomas indicates a limited therapeutic benefit of immune checkpoint inhibitors (against PD-1/PD-L1).


Hypernatremia in the elderly: relation to infection and mortality.
The records of 23 elderly patients admitted to a county hospital with dehydration and hypernatremia were reviewed. One of these patients had the highest serum sodium level (202 mEq/L) reported in an adult. The overall mortality of 48 percent was not related to the degree of hypernatremia. However, two-thirds of the 17 patients with acute bacteria infections died, whereas all 5 noninfected patients survived. Infection was not always apparent at the time of admission to the hospital. It is proposed that early and appropriate antibiotic therapy may reduce the high mortality associated with hypernatremia in the elderly.


What is career success? A new Asian American psychology of working.
Model minority stereotypes of Asian Americans as high educational and occupational achievers are perpetuated by conceptual and methodological issues in career development research that aggregate across Asian ethnicities and oversample high achievers. These issues render those marginalized, such as working-class immigrants with limited English proficiency, as well as their children, as invisible within research, practice, and policy. A new theoretical framework, entitled the Asian American Intergenerational Model of Psychology of Working (AAIM), questions the mainstream career development assumptions of linearity, stability, and upward mobility that reveal inherent classism. Building on the Psychology of Working Theory (Duffy et al., 2016); the AAIM broadens the scope and definition of work beyond career, and acknowledges the significance of structural and cultural forces on people's work and life. An expanded qualitative analysis of interviews with 17 low-income, working-class, Chinese immigrant parents (Tu et al., 2019) provides an empirical illustration of the intergenerational and coethnic dynamics of vocational experiences central to the AAIM. The working-class immigrants relied on coethnic networks to secure employment within a narrow range of options, many straddling helplessly between arduous manual labor and family demands. Though they had immigrated primarily to provide a better future for their children, many parents struggled to participate meaningfully in their children's development. These findings highlight the need to expand Asian American psychology of working to incorporate systems and social justice perspectives. Research, practice, and policy implications of AAIM advocate for maximal inclusivity and offer directions to address invisibility of the most marginalized and disenfranchised Asian American workers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Multi-Omics Characterization of Circular RNA-Encoded Novel Proteins Associated With Bladder Outlet Obstruction.
Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Totally 3,051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1,414 up-regulated, and 1,637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression levels of five protein-encoding circRNAs were further validated by quantitative RT-PCR and mass spectrometry. The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.


A Case of Adult-Onset Still's Disease Presenting with Urticated Plaques and Acute Myopericarditis.
Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology characterized by spiking fever, evanescent skin rash, arthralgia or arthritis, involvement of various organs, and predominantly neutrophilic leucocytosis. AOSD, although uncommon, has a characteristic constellation of clinical and laboratory features and should be considered in the differential diagnosis of pyrexia of unknown origin associated with a rash and arthralgia. The diagnosis is one of clinical suspicion and it is essential that infections, malignancy, and other rheumatic diseases are excluded. We report a case which illustrates the typical features of AOSD that were treated with steroids and azathioprine.


Racial and Ethnic Differences in Homicides of Adult Women and the Role of Intimate Partner Violence - United States, 2003-2014.
Homicide is one of the leading causes of death for women aged ≤44 years.* In 2015, homicide caused the death of 3,519 girls and women in the United States. Rates of female homicide vary by race/ethnicity (1), and nearly half of victims are killed by a current or former male intimate partner (2). To inform homicide and intimate partner violence (IPV) prevention efforts, CDC analyzed homicide data from the National Violent Death Reporting System (NVDRS) among 10,018 women aged ≥18 years in 18 states during 2003-2014. The frequency of homicide by race/ethnicity and precipitating circumstances of homicides associated with and without IPV were examined. Non-Hispanic black and American Indian/Alaska Native women experienced the highest rates of homicide (4.4 and 4.3 per 100,000 population, respectively). Over half of all homicides (55.3%) were IPV-related; 11.2% of victims of IPV-related homicide experienced some form of violence in the month preceding their deaths, and argument and jealousy were common precipitating circumstances. Targeted IPV prevention programs for populations at disproportionate risk and enhanced access to intervention services for persons experiencing IPV are needed to reduce homicides among women.


Molecular cloning and characterization of triterpene synthases from Medicago truncatula and Lotus japonicus.
Cloning of OSCs required for triterpene synthesis from legume species that are amenable to molecular genetics will provide tools to address the importance of triterpenes and their derivatives during normal plant growth and development and also in interactions with symbionts and pathogens. Here we report the cloning and characterization of a total of three triterpene synthases from the legume species Medicago truncatula and Lotus japonicus. These include a beta-amyrin synthase from M. truncatula (MtAMY1) and a mixed function triterpene synthase from Lotus japonicus (LjAMY2). A partial cDNA predicted to encode a beta-amyrin synthase (LjAMY1) was also isolated from L. japonicus. The expression patterns of MtAMY1, LjAMY1 and LjAMY2 and of additional triterpene synthases previously characterised from M. truncatula and pea differ in different plant tissues and during nodulation, suggesting that these enzymes may have distinct roles in plant physiology and development.


Minimally invasive neuroradiologic model of preclinical transient middle cerebral artery occlusion in canines.
Stroke is currently the third leading cause of death in the United States, with approximately 780,000 Americans affected by a new or recurring stroke each year. Although a variety of therapeutic approaches have shown promise in small-animal models of stroke, the vast majority of clinical trials to test the efficacy of such modalities have failed. To bridge the translational gap between laboratory and clinical research, we developed a preclinical model of acute ischemic stroke in dogs. Using a minimally invasive endovascular approach, a platinum coil was intravascularly guided through the vertebrobasilar system under C-arm fluoroscopy to occlude the M1 segment of the middle cerebral artery (MCA) for 1 h. The approach included femoral artery catheterization to access the MCA and therefore eliminated the occurrence of head trauma associated with other preclinical stroke models relying on transorbital or craniectomy approaches. After 1 h of focal MCA ischemia, the coil was retrieved to cause reperfusion, which was verified by arteriograms. At 24 h, T2-weighted coronal magnetic resonance (MR) images were acquired and processed for three-dimensional reconstruction of the brain and its vasculature. Infarction, limited to the area at risk, was noted. Two independent observers calculated the mean percentage hemispherical lesion volumes as follows: observer 1, 30.9 +/- 2.1%; observer 2, 31.2 +/- 4.3%. Infarct-affected changes in histology were determined by hematoxylin and eosin as well as by Fluoro-Jade staining. This work reports the successful development of a powerful preclinical model of stroke that lends itself to the study of biologic mechanisms as well as to testing experimental therapeutics.


Exploring Technology- and Sensor-Driven Trends in Education: A Natural-Language-Processing-Enhanced Bibliometrics Study.
Over the last decade, there has been a large amount of research on technology-enhanced learning (TEL), including the exploration of sensor-based technologies. This research area has seen significant contributions from various conferences, including the European Conference on Technology-Enhanced Learning (EC-TEL). In this research, we present a comprehensive analysis that aims to identify and understand the evolving topics in the TEL area and their implications in defining the future of education. To achieve this, we use a novel methodology that combines a text-analytics-driven topic analysis and a social network analysis following an open science approach. We collected a comprehensive corpus of 477 papers from the last decade of the EC-TEL conference (including full and short papers), parsed them automatically, and used the extracted text to find the main topics and collaborative networks across papers. Our analysis focused on the following three main objectives: (1) Discovering the main topics of the conference based on paper keywords and topic modeling using the full text of the manuscripts. (2) Discovering the evolution of said topics over the last ten years of the conference. (3) Discovering how papers and authors from the conference have interacted over the years from a network perspective. Specifically, we used Python and PdfToText library to parse and extract the text and author keywords from the corpus. Moreover, we employed Gensim library Latent Dirichlet Allocation (LDA) topic modeling to discover the primary topics from the last decade. Finally, Gephi and Networkx libraries were used to create co-authorship and citation networks. Our findings provide valuable insights into the latest trends and developments in educational technology, underlining the critical role of sensor-driven technologies in leading innovation and shaping the future of this area.


Treatment of the unknown patient: insights from acute stroke.
When an unidentified patient who cannot communicate presents with symptoms and signs suggesting an acute stroke, the decision to thrombolyse is a particular challenge. In a time-pressured environment, clinicians need clear thought processes for diagnosis and treatment. Ethical considerations, diagnosis, identity and previous history, contraindications, time of symptom onset (EDICT) can help decision-making in this situation.


Safety evaluation of two bacterial strains used in Asian probiotic products.
Probiotics, known for their prophylactic and therapeutic properties, are routinely used by the medical community in various regions of the world. In some Asian countries, these products are controlled as pharmaceutical substances and must adhere to strict regulatory guidelines. However, outside of Europe where the European Food Safety Authority has recently adopted a Qualified Presumption of Safety approach for probiotics used in food and feed, current safety requirements do not necessitate screening for the presence of virulence and other risk factors, which may result in the inadvertent use of probiotic strains harboring harmful genes. A safety evaluation was conducted on Enterococcus faecium R0026 and Bacillus subtilis R0179 used in several commercial probiotic products marketed in Asia. Molecular techniques were used to verify the identity of each strain and antibiotic resistance profiles were determined towards clinically relevant antibiotics. Strains were subsequently screened for the presence of enterotoxins and virulence factors and were subjected to 28 days of repeated high-dose oral toxicity testing in rats. No risk factors or aberrant activities were identified using such a detailed approach. Thus, both microbes were deemed to pose low risk to the consumer and, therefore, safe for use as probiotics.


Breastfeeding: breast milk banks and human immunodeficiency virus.
HIV in infants and children in Zimbabwe is virtually limited to vertical transmission. Less than 5 cases of transfusion acquired HIV infections have been documented to date. Zimbabwe was the third country in the world after the United States, to screen transfusion blood and blood products. The controversy of HIV transmission through breast milk is still far from resolved. In developing countries, breast-milk substitutes for formulae are not only prohibitively expensive but dangerous because of unhygienic and economic constraints. The paper argues the case for continued breast-feeding of infants by their HIV seropositive mothers.


Spatial perspective and coordinate systems in autoscopy: a case report of a "fantome de profil" in occipital brain damage.
Autoscopic phenomena refer to complex experiences involving the illusory reduplication of one's own body. Here we report the third long-lasting case of autoscopy in a patient with right occipital lesion. Instead of the commonly reported frontal mirror view (fantôme spéculaire), the patient saw her head and upper trunk laterally in side view (fantôme de profil). We found that the visual appearance and completeness of the autoscopic image could be selectively modulated by active and passive movements, without being influenced by imagining the same movements or by tactile and auditory stimulation. Eyes closure did not disrupt either the perception of the autoscopic body or the effects of the motor stimulation. Moreover, the visual body reduplication was coded neither in purely eye-centered nor in head-centered frames of reference, suggesting the involvement of egocentric coordinate systems (eyes and head centered). A follow-up examination highlighted the stability of the visual characteristics of the body reduplication and its shift induced by displacement of both head and eyes. These findings support the view that autoscopic phenomena have a multisensory motor origin and proprioceptive signals may play an important role in modulating the illusory visual reduplication of the patient's own body, most likely via cross-modal modulation of extrastriate areas involved in body and face perception.


Photochemistry of HgBr(2) in methanol investigated using time-resolved X-ray liquidography.
We investigate the photoinduced dissociation of HgBr(2) in methanol and the ensuring structural dynamics of the photo-products over a time span from 100 ps to 1 μs after photolysis at 267 nm by using time-resolved X-ray liquidography (TRXL). By making use of the atomic-level structural sensitivity of X-ray scattering and the superb 100 ps time resolution of X-ray pulses from a 3rd-generation synchrotron, the structural dynamics of a chemical reaction in solution can be directly monitored. The measured time-dependent X-ray solution scattering signals, analyzed using global-fitting based on DFT calculations and MD simulations, show that photoexcited HgBr(2) dissociates via both two-body (HgBr + Br) and three-body (Hg + Br + Br) dissociation pathways with a ∼2 : 1 branching ratio. Following dissociation, the photoproducts recombine via three reactions involving Br species: (1) Hg + Br, (2) HgBr + Br, and (3) Br + Br. The associated rate constants and branching ratios are determined from the global-fitting analysis. Also, we examine the energy dissipation from reacting solute molecules and relaxation of excited molecules to solvent bath accompanying the temperature rise of 0.54 K. Compared to a previous TRXL study of the photodissociation of HgI(2), the results of this work suggest that the photodissociation pathway of HgBr(2) is different from that of HgI(2), which dissociates predominantly via two-body dissociation, at least to within the currently available time resolution of ∼100 ps. In addition, the error analysis of the fit parameters used in the global-fitting are discussed in detail with a comparison of various error estimation algorithms.


Engaging Patients in Their Care Versus Obscurantism.
Could engaging patients in their care be a means to oppose obscurantism? Obscurantism is defined by Merriam-Webster as "the practice of keeping knowledge or understanding about something from people". This paper discusses the importance of promoting patient engagement and emphasizes that patients and healthcare providers are equally important stakeholders in health care. The discussion occurs in the context of hospital inpatient care as nurses play a critical role in patients' hospitalization experience, including engaging patients in their own care during hospital stays. Paternalism of healthcare providers is recognized as one of the main barriers to integrating the concepts of patient engagement and patient centeredness into every aspect of the care system. Promoting patient engagement is a two-way responsibility, and it requires the cooperation of both patients and healthcare providers. As scientists and healthcare providers, we have the duty to counter obscurantism by promoting understanding of the health of individual citizens and society at large. A culture change in healthcare systems toward being patient-centric and placing value on patient engagement is warranted, and this change must come from healthcare providers. Patient-centered tools that support patient engagement, patient portals, or personal health records are still needed.