Genomic evolution in Barrett's adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome.
A prominent feature of most cancers including Barrett's adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evolving genomic changes and growth of BAC cells. We show that the expression of RAD51 is elevated in BAC cell lines and tissue specimens, relative to normal cells. HR activity is also elevated and significantly correlates with RAD51 expression in BAC cells. The suppression of RAD51 expression, by short hairpin RNA (shRNA) specifically targeting this gene, significantly prevented BAC cells from acquiring genomic changes to either copy number or heterozygosity (P<0.02) in several independent experiments employing single-nucleotide polymorphism arrays. The reduction in copy-number changes, following shRNA treatment, was confirmed by Comparative Genome Hybridization analyses of the same DNA samples. Moreover, the chromosomal distributions of mutations correlated strongly with frequencies and locations of Alu interspersed repetitive elements on individual chromosomes. We conclude that the hsRAD51 protein level is systematically elevated in BAC, contributes significantly to genomic evolution during serial propagation of these cells and correlates with disease progression. Alu sequences may serve as substrates for elevated HR during cell proliferation in vitro, as they have been reported to do during the evolution of species, and thus may provide additional targets for prevention or treatment of this disease.


A recombinant receptor-binding domain in trimeric form generates protective immunity against SARS-CoV-2 infection in nonhuman primates.
A safe and effective vaccine is critical to combat the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with the RBD trimer-induced robust humoral and cellular immune responses, and a high level of neutralizing antibodies was maintained for at least 4.5 months. Moreover, the antibodies that were produced in response to the vaccine effectively cross-neutralized the SARS-CoV-2 501Y.V2 variant (B.1.351). Of note, when the vaccine-induced antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, conferring full protection against a SARS-CoV-2 challenge in rhesus macaques without typical histopathological changes in the lung tissues. These results demonstrated that the SARS-CoV-2 RBD trimer vaccine candidate is highly immunogenic and safe, providing long-lasting, broad, and significant immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.


Ultrasound for the diagnosis of malrotation and volvulus in children and adolescents: a systematic review and meta-analysis.
Despite the advantages of ultrasound (US), upper gastrointestinal contrast series (UGI) remains the first-line diagnostic modality in the diagnosis of midgut malrotation and volvulus in children. Evaluate the diagnostic accuracy of US in the diagnosis of malrotation with or without volvulus in children and adolescents aged 0-21 years, compared with the reference standard (diagnosis by surgery, UGI, CT, MRI, and clinical follow-up individually or as a composite). We searched the electronic databases Ovid-MEDLINE, Embase, Scopus, CINAHL, and the Cochrane library in October 2019 and updated on 18 August 2020. Studies evaluating the diagnostic performance of US for diagnosis of midgut malrotation with or without volvulus in children (0-21 years). The data were extracted independently by two authors and a bivariate model was used for synthesis. Meta-analysis of 17 cohort or cross-sectional studies and 2257 participants estimated a summary sensitivity of 94% (95% CI 89% to 97%) and summary specificity of 100% (95% CI 97% to 100%) (moderate certainty evidence) for the use of US for the diagnosis of malrotation with or without midgut volvulus compared with the reference standard. Subgroup analysis and meta-regression revealed better diagnostic accuracy in malrotation not complicated by volvulus, in the neonatal population and enteric fluid administration before US. Moderate certainty evidence suggests excellent diagnostic accuracy and coupled with the advantages, a strong case exists for the use of abdominal US as the first-line diagnostic test for suspected midgut malrotation with or without volvulus in children and adolescents.


Do people have an ethical obligation to share their health information? Comparing narratives of altruism and health information sharing in a nationally representative sample.
With the emergence of new health information technologies, health information can be shared across networks, with or without patients' awareness and/or their consent. It is often argued that there can be an ethical obligation to participate in biomedical research, motivated by altruism, particularly when risks are low. In this study, we explore whether altruism contributes to the belief that there is an ethical obligation to share information about one's health as well as how other health care experiences, perceptions, and concerns might be related to belief in such an obligation. We conducted an online survey using the National Opinion Research Center's (NORC) probability-based, nationally representative sample of U.S. adults. Our final analytic sample included complete responses from 2069 participants. We used multivariable logistic regression to examine how altruism, together with other knowledge, attitudes, and experiences contribute to the belief in an ethical obligation to allow health information to be used for research. We find in multivariable regression that general altruism is associated with a higher likelihood of belief in an ethical obligation to allow one's health information to be used for research (OR = 1.22, SE = 0.14, p = 0.078). Trust in the health system and in care providers are both associated with a significantly higher likelihood of believing there is an ethical obligation to allow health information to be used (OR = 1.48, SE = 0.76, p<0.001; OR = 1.58, SE = 0.26, p<0.01, respectively). Belief that there is an ethical obligation to allow one's health information to be used for research is shaped by altruism and by one's experience with, and perceptions of, health care and by general concerns about the use of personal information. Altruism cannot be assumed and researchers must recognize the ways encounters with the health care system influence (un)willingness to share one's health information.


Ethical responsibilities in nursing: research findings and issues.
Discussions in the literature assert that nurses are becoming increasingly cognizant of their ethical responsibilities, but that they are often ill prepared to participate in ethical decision making. A review of selected research literature from 1970 to 1987 was undertaken to validate these assertions. A total of 12 studies related to ethical responsibilities was identified in the review; all studies were published between 1980 and 1987. The majority of studies were at the descriptive and exploratory levels and employed Kohlberg's cognitive theory of moral development as their conceptual framework. Significant findings related to educational level and ethical responsibilities were consistent across studies. Findings related to age and clinical experience were mixed; the effects of economic level, religion-religiosity, ethnicity, and other variables on ethical responsibilities were not significant. Issues raised in the light of the existing research include the use of Kohlberg's theory as a conceptual orientation in nursing groups and limited data on the reliability and validity of instruments used in measuring ethical constructs. Recommendations for future research on ethical responsibilities include the validation of Kohlberg's theory for nursing investigations, exploration of other frameworks for developing a multidimensional view of ethical responsibilities, and the use of qualitative research designs.


Current Status of Radiology Education Online: a Comprehensive Update.
The purpose of this study is to evaluate various online resources available for radiology education. An online search was conducted using PubMed (National Library of Medicine, Bethesda, MD) and Google Scholar for publications discussing the applications of online learning in radiology. The search strategy employed a combination of the following terms: radiology, web-based conferencing, radiology education seminars, radiology education online, radiology education programs, online lectures, radiology residency, radiology degree, Radiology-Integrated Training Initiative (R-ITI) e-learning platform, UTAUT, Moodle, active image-based learning, Video conference platforms (VCPs), education, undergraduate, medical students, teaching, virtual learning, blended learning, e-learning, COVID-19, pandemic, OER, open education resources, online learning, course assets, accessibility, 5G Internet, game-based learning, radiology competition, and virtual world. The literature published was reviewed and consolidated. Data from the literature shows that radiology education online and radiology education seminars are undergoing a revolution due to advancements in computers, online software, and 5G Internet speed. The pace of this development has accelerated even further due to the COVID-19 pandemic and thus forced distance online education. Various technologies are available and are being implemented by residency programs across the world to improve radiology education, making it more interactive and safer in this pandemic. Online learning has become an integral part of education in radiology, with new facets being added to it.


Mathematical modeling of the spread of the COVID'19 with optimal control strategies.
In this work, we formulated an SEQIRS mathematical model with four control variables, which describes the spread of the coro-navirus in a community. An optimal control problem was well introduced in order to verify the existence of optimal controls that minimize susceptible, exposed, and infected individuals. Also, we use Pontryagin's Maximum Principle to characterize the optimal control strategies to minimize the spread dynamics of the COVID'19.


Two New Compounds Isolated from the Itea omeiensis and Their Anti-oxidant Activities.
Two new compounds (1-2) together with ten known compounds (3-12) were isolated for the first time from the 95% EtOH extract of aerial parts of Itea omeinesis. Their structures were elucidated based on extensive spectroscopic analyses and comparison with published data. The structure of 1 was further confirmed through single-crystal X-ray diffraction analysis, and circular dichroism (CD) spectrum in combination with acid hydrolysis was employed for the absolute configuration determination of 2. Compound 1 was the first 2-arylbenzo[b]furan with an extra six-membered lactone ring from Itea plants. Anti-oxidant assays indicated that compound 1 possessed significant radical scavenging effects on 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS·+) with IC50 values of 0.14 and 0.06 mg/mL, respectively, which were comparable to the positive control of ascorbic acid. However, no obvious anti-hepatocellular carcinoma activity was observed for compounds 1 and 2.


[Expression of Paenibacillus macerans cyclodextrin glycosyltransferase in Pichia pastoris and Bacillus subtilis].
The cgt gene was isolated from Paenibacillus macerans by PCR amplification and was inserted into vectors of pPIC9K and pMAS. The recombinant vectors were transformed to Pichia pastoris KM71 and Bacillus subtilis WB600, respectively. The results showed that alpha-CGTase activity in the culture media of recombinant P pastoris was only 0.2 U/mL, while it was 1.9 U/mL in recombinant B. subtilis. In addition, we optimized the culture conditions of the recombinant B. subtilis strain. After cultivation at 37 degrees C for 24 h with shake flask, the CGTase forming activity in culture media reached to 4.5 U/mL (hydrolysis activity was 3200 IU/mL), which is 9.8-fold to that of the original strain P. macerans.


Chemoenzymatic preparation of intermediates for the taxol side chain and analogs.
In the present study, optically active cis and trans α-hydroxy-β-lactams were prepared by Baker's yeast reduction of a racemic α-keto-β-lactam and by the hydrolysis of a racemic α-acetoxy β-lactam with the resting cells of Bacillus Subtilis.


Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies.
T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19. Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up. Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19.


Impact of surgically induced weight loss on pelvic floor disorders.
Given the increased prevalence of obesity and pelvic floor disorders (PFDs), we estimated changes in prevalence, bother, and quality of life (QOL) for PFDs in obese women undergoing bariatric surgery. We hypothesized PFDs would improve after surgical weight loss. The prevalence, bother, and QOL impact of PFDs were estimated using validated measures. McNemar's and paired t tests were used to compare pre- and postprocedural outcomes. Power calculations deemed that 90 individuals would achieve at least 80 % power to detect a decrease in prevalence of 12 %. The baseline mean (± standard deviation) age and body mass index (BMI) of the 98 women were 43.3 ± 11.8 years and 39.7 ± 6.2 kg/m.(2) BMI decreased to 34.4 ± 5.8 at 6 months and 34.0 ± 5.6 at 12 months. Whereas the overall prevalence of stress urinary incontinence (SUI) decreased from 22/69 (32 %) at baseline to 10/69 (15 %) at 6 months (p = 0.006) and 14/69 (20 %) at 12 months (p = 0.027), there were no significant decreases in overall prevalence of other PFDs. However, for women with SUI, overactive bladder (OAB), and anal incontinence at baseline, 11/23 (48 %), 8/11 (73 %) and 4/20 (20 %) resolved at 12 months, respectively. Pelvic Floor Impact Questionnaire scores decreased from baseline to 12 months (p < 0.001). Mean visual analog scores for women with SUI, OAB, and anal incontinence decreased at 12 months. Surgical weight loss resulted in resolution of symptoms in nearly half of women with SUI and three quarters of women with OAB and was associated with significant improvement in QOL.


[Interaction of adrenergic and purinergic receptors in the regulation of rat myocardial contractility in postnatal ontogeny].
β-Adrenergic receptor agonist isoproterenol and purinergic receptor agonist 2-methylthio-ATP have a positive effect on the myocardial contractile force and show different efficiencies depending on the age of animals. The maximum inotropic effect of agonists on the ventricular myocardial contractility was observed in 21-day-old rat pups. The study of a combined effect of isoproterenol and 2-methylthio-ATP showed that an increase in the sympathetic regulatory effects on the heart of 21-day-old animals, against the background of a high functional activity of β-adrenergic receptors and P2X receptors of the heart, a combined administration of the agonists led to a mutually complementing effect of an increase in the myocardial contractility.


DNA degradation, UV sensitivity and SOS-mediated mutagenesis in strains of Escherichia coli deficient in single-strand DNA binding protein: effects of mutations and treatments that alter levels of Exonuclease V or recA protein.
Certain strains suppress the temperature-sensitivity caused by ssb-1, which encodes a mutant ssDNA binding protein (SSB). At 42 degrees C, such strains are extremely UV-sensitive, degrade their DNA extensively after UV irradiation, and are deficient in UV mutability and UV induction of recA protein synthesis. We transduced recC22, which eliminates Exonuclease V activity, and recAo281, which causes operator-constitutive synthesis of recA protein, into such an ssb-1 strain. Both double mutants degraded their DNA extensively at 42 degrees C after UV irradiation, and both were even more UV-sensitive than the ssb-1 single mutant. We conclude that one or more nucleases other than Exonuclease V degrades DNA in the ssb recC strain, and that recA protein, even if synthesized copiously, can function efficiently in recombinational DNA repair and in control of post-UV DNA degradation only if normal SSB is also present. Pretreatment with nalidixic acid at 30 degrees C restored normal UV mutability at 42 degrees C, but did not increase UV resistance, in an ssb-1 strain. Another ssb allele, ssb-113, which blocks SOS induction at 30 degrees C, increases spontaneous mutability more than tenfold. The ssb-113 allele was transduced into the SOS-constitutive recA730 strain SC30. This double mutant expressed the same elevated spontaneous and UV-induced mutability at 30 degrees C as the ssb+ recA730 strain, and was three times more UV-resistant than its ssb-113 recA+ parent. We conclude that ssb-1 at 42 degrees C and ssb-113 at 30 degrees C block UV-induced activation of recA protease, but that neither allele interferes with subsequent steps in SOS-mediated mutagenesis.


Passage of duck hepatitis virus in cell cultures derived from avian embryos of different species.
An egg-attenuated strain of duck hepatitis virus was successfully passaged through cell cultures of avian embryos derived from goose, turkey, guinea fowl, Japanese quail, pheasant and chicken. Two field strains of the virus were passaged in a more limited range of species.


Serum lipids and lipoproteins in 157 insulin dependent diabetic children and adolescents in relation to metabolic regulation, obesity and genetic hyperlipoproteinemia.
Serum lipids and lipoproteins were measured in 157 insulin dependent diabetic children and adolescents (IDDM) and in 350 healthy reference individuals. Serum triglyceride values were lower and total cholesterol and high density lipoprotein cholesterol higher in IDDM. Metabolic regulation reflected by glucosuria, postprandial blood glucose, number of hypoglycemic episodes and hemoglobin A1c all correlated strongly with serum triglyceride and very low density lipoprotein cholesterol. Serum lipids and lipoproteins did not correlate with obesity. Three children had genetic hyperlipoproteinemia. In IDDM measurement of serum lipids and lipoproteins can thus be used to further assess metabolic regulation. Measurement of serum lipids and lipoproteins seems warranted for future evaluation of the risk of cardiovascular disease in IDDM.


Mediation of Mothers' Anxiety and Parenting in Children's Behavior Problems during COVID-19.
The outbreak of COVID-19 is affecting the lives of millions of families around the world. The current study was carried out in Israel, following the pandemic's initial outbreak and during the resulting enforced quarantine, confining parents and children to their homes. A sample of 141 Israeli mothers with at least one child between the ages of 3 and 12 (M = 6.92, SD = 2.55) participated as volunteers. About half the sample (50.7%) consisted of girls. Most mothers were cohabiting with a spouse (93%). Mothers completed online questionnaires about their perceptions about the health and economic threats of COVID-19, availability of social support, their anxiety symptoms, hostile/coercive and supportive/engaged parenting behavior, and their children's behavior problems. Results showed expected significant associations between the mothers' reports about having little social support, their anxiety symptoms, hostile/coercive and supportive/engaged parenting behavior, and children's externalizing problems. Likewise, expected significant associations were found between mothers' perceptions about the health and economic threats of COVID-19, their anxiety symptoms, hostile/coercive parenting behavior, and children's internalizing and externalizing problems. Importantly, maternal anxiety and hostile/coercive parenting behavior mediated the associations between lack of support, negative perceptions about the health and economic threats of COVID-19, and children's behavior problems. These findings stress the importance of mothers' mental health and parenting behaviors for children's socioemotional adaptation in the context of COVID-19. Implications of the findings for family interventions intended to help parents and children at this time are suggested.


Globus pallidus internus firing rate modification after motor-imagination in three Parkinson's disease patients.
Motor imagery is thought to involve the same processes of movement preparation as actual movement. Imagination of a simple repetitive movement significantly decreased the firing rate of extracellular micro recording at sensorimotor neurons of globus pallidus internus in three patients with Parkinson's disease, who underwent microelectrode-guided posteroventral pallidotomy. These findings suggest, in agreement with previous clinical and functional neuroimaging studies that the motor corticostriatal circuit could be engaged in mental simulation.


Enriched Environment Attenuates Surgery-Induced Impairment of Learning, Memory, and Neurogenesis Possibly by Preserving BDNF Expression.
Postoperative cognitive dysfunction (POCD) is a significant clinical syndrome. Neurogenesis contributes to cognition. It is known that enriched environment (EE) enhances neurogenesis. We determined whether EE attenuated surgery-induced cognitive impairment and whether growth factors and neurogenesis played a role in the EE effect. Eight-week-old C57BL/6J mice were subjected to carotid artery exposure. Their learning and memory were assessed by Barnes maze, and fear conditioning started 2 weeks after the surgery. Growth factor expression and cell genesis were determined at various times after the surgery. Surgery increased the time for the mice to identify the target hole in the Barnes maze and reduced context-related freezing behavior. Surgery also reduced the expression of brain-derived neurotrophic factor (BDNF) and neurogenesis in the hippocampus. These effects were attenuated by EE. EE also attenuated surgery-induced reduction of phosphorylated/activated tropomyosin-related kinase B (TrkB) and extracellular signal-regulated kinases (ERK), components of BDNF signaling pathway. ANA-12, a selective TrkB antagonist, blocked the effects of EE on cognition, phosphorylation of TrkB and ERK, and neurogenesis. These results provide initial evidence that surgery reduces BDNF expression and neurogenesis in the hippocampus. Our results suggest that EE reduces surgery-induced impairment of learning, memory, and neurogenesis by preserving BDNF expression.


Cavoatrial extension of renal cell cancer: results of operative treatment in Helsinki University Hospital between 1990 and 2000.
To evaluate the technical procedures and the post-operative survival of patients having been operated for renal cell cancer with cavoatrial tumour thrombus (RCC-T). Between 1990 and 2000 the cardiac unit at Helsinki University Central Hospital operated on seven patients for RCC-T. A cardiac surgeon along with a urologist, performed all seven operations using sternolaparotomy (either midline or Chevron incision) with cardiopulmonary bypass. The average duration of the operations was eight hours (range 6-11 hours) and the average perfusion time was 118 minutes (range 35-206). Hypothermic circulatory arrest was used for one patient with an arrest time of 31 minutes. Only with one patient could the cavotomy be closed directly. In four patients a cava resection was performed and closed either with a pericardium patch or a Gore-Tex prosthesis. In two patients the cava was ligated below the renal veins. During the post-operative intensive care, there were two deaths. Of the remaining patients, five were alive after six months, four after 12 months, three after six years and one patient is still alive after 12 years of follow-up. In agreement with previously published results, although peri-operative mortality is relatively high with RCC-T patients, long-term post-operative survival is possible.


The gendered impact of the COVID-19 pandemic on academics working in medical imaging and radiation therapy.
Healthcare workers have been particularly impacted by the COVID-19 pandemic, as have those educating them, albeit differently. Several papers have identified a gendered difference in the impact of the pandemic. This study aims to determine impact of COVID-19 on the health and wellbeing of Medical Imaging and Radiation Therapy (MIRT) academics. An electronic survey was designed in English on Qualtrics and distributed via email and online platforms to MIRT academics. Fifty-one questions were used; demographic (n = 9), work patterns (n = 11), general health (n = 8), mental health (n = 2), physical health (n = 10), and workload (n = 11). Overall, 46 were quantitative and five were qualitative 'open-ended' questions. The survey was open between 3rd March 2021 to 1st May 2021. Quantitative analysis was carried out using MS Excel v 16.61.1ss and SPSS v26. The survey reached 32 countries globally and 412 participants; 23.5% identified as men (n = 97) and 76.5% as women (n = 315). Women reported worse sleep quality than men and overwhelmingly felt they would not like to work remotely again if given a choice. A higher percentage of males, 73% versus 40.5% of females reported getting outdoors less. The CORE-10 validated questionnaire found that 10.3% of males (n = 42) and 2.7% of females (n = 11) experienced severe psychological distress the week immediately before the survey was conducted. While the study has identified some gender-related differences in the impact of COVID-19 on the mental and physical health of MIRT academics, both males and females have experienced significant deterioration in health and wellbeing due to the pandemic. Developing mental health support for MIRT academics and defining optimum methods for raising awareness is recommended.


Type III flagellar protein export and flagellar assembly.
Bacterial flagella, unlike eukaryotic flagella, are largely external to the cell and therefore many of their subunits have to be exported. Export is ATP-driven. In Salmonella, the bacterium on which this chapter largely focuses, the apparatus responsible for flagellar protein export consists of six membrane components, three soluble components and several substrate-specific chaperones. Other flagellated eubacteria have similar systems. The membrane components of the export apparatus are housed within the flagellar basal body and deliver their substrates into a channel or lumen in the nascent structure from which point they diffuse to the far end and assemble. Both on the basis of sequence similarities of several components and structural similarities, the flagellar protein export systems clearly belong to the type III superfamily, whose other members are responsible for secretion of virulence factors by many species of pathogenic bacteria.


[Subgenotype and serotype analysis of hepatitis B virus in Korean chronic hepatitis B patients under treatment].
Hepatitis B virus (HBV) detected in Korean patients almost belongs to genotype C, which is subdivided into subgenotype C1 (or Cs) and C2 (or Ce). It was recently reported that the risk of hepatocellular carcinoma is different between subgenotype C1 and C2. Thus, we studied the distribution of subgenotypes of HBV in Korean chronic hepatitis B (CHB) patients. Specimens of 421 patients, who were diagnosed as CHB and underwent antiviral treatment, were used. After sequence analysis for HBV S gene, subgenotype was identified through phylogenetic analysis. Utilizing the same sequence data, the distribution of serotypes was also investigated. Among 421 patient specimens, genotype C was found in 419 (99.5%) and genotype B in 2 (0.5%). Among the genotype C strains, 417 strains were C2 subgenotype and 2 strains were mixed subgenotypes. However, C2 was evidently found even in the mixed sequences. Serotypes of 419 HBV with genotype C were classified as follows: adr, 385 (91.9%), adw, 22 (5.3%), ayr, 2 (0.4%) and mixed serotype, 10 (2.3%). Serotype of both HBV with genotype B was adw. It was found that HBV detected in Korean CHB patients under treatment almost all belong to the C2 (Ce) genotype.


Ecological ectocrines in experimental epidemiology. A new class, the "pacifarins," is delineated in the nutritional ecology of mouse salmonellosis.
I have attempted to sketch the ideas forged in a long-term investigation of the possible relationship between host nutrition and resistance to infection. Our endeavor had its origins in the now partially forgotten field of experimental epidemiology, once epitomized in somewhat contrasting schools of thought, English and American. The work of Webster, which showed the importance of host genetic constitution, was an early and decisive influence in the work discussed here, and led to formulation of a new laboratory model of infectious disease, which has been fruitful.


Standards of care guidance for sweat testing; phase two of the ECFS quality improvement programme.
More than five decades after the introduction of the quantitative pilocarpine iontophoresis technique, surveys still highlight inconsistencies in the performance and reporting of sweat tests in Europe. The sweat test remains key for the Cystic Fibrosis (CF) diagnostic pathway for all age groups, as it reflects the basic pathophysiological defect in the sweat gland. It is also critical following newborn screening as a confirmatory diagnostic step. Despite its importance, sweat test quality is variable whether performed in the laboratory or as a point of care test. The ECFS DNWG aims to improve sweat test performance, taking into account the barriers and issues identified in the European survey; the previous step in the ECFS sweat test project. This manuscript proposes a grading of sweat test guidance from "acceptable" to "optimal", aiming to pragmatically improve quality while taking into account local situations, especially in resource-limited settings.


Optical coherence tomography for presurgical delineation of basal cell carcinomas on the face-A comparison with histopathology.
To minimize the risk of incomplete excision of basal cell carcinomas (BCC) the macroscopic tumor margins should be adequately defined. Optical coherence tomography (OCT) is a non-invasive imaging tool that can provide structural and vascular information about skin cancer lesions. The study objective was to compare the presurgical delineation of facial BCC by clinical examination, histopathology, and OCT imaging in tumors undergoing full excision. Ten patients with BCC lesions on the face were examined clinically, with OCT and histopathology at 3-mm intervals, from the clinical lesion border and beyond the resection line. The OCT scans were evaluated blinded and a delineation estimate of each BCC lesion was made. The results were compared to the clinical and histopathologic results. OCT evaluations and histopathology were in agreement in 86.6% of the collected data points. In three cases the OCT scans estimated a reduction of the tumor size compared to the clinical tumor border set by the surgeon. The results of this study support the notion that OCT can have a role in the clinical daily practice by aiding clinicians in delineating BCC lesions before surgery.


Morbidity and mortality in the thirty-day period following total hip arthroplasty: risk factors and incidence.
The study sought to ascertain the incidence rates and risk factors for 30-day post-operative complications after primary total hip arthroplasty (THA). Complications were categorized as systemic or local and subcategorized as major or minor. There were 17,640 individuals who received primary THA identified from the 2006-2011 ACS NSQIP. The mortality rate was 0.35% and complications occurred in 4.9%. Age groups ≥ 80 years (P <0.001) and 70-79 years old (P = 0.003), and renal insufficiency (P = 0.02) best predicted mortality. Age ≥80 years (P <0.001) and cardiac disease (P = 0.01) were the strongest predictors of developing any postoperative complication. Morbid obesity (P <0.001) and operative time > 141 minutes (P <0.001) were strongly associated with the development of major local complications.


Toward Real-Time Animal Tracking with Integrated Stimulus Control for Automated Conditioning in Aquatic Eco-Neurotoxicology.
Aquatic eco-neurotoxicology is an emerging field that requires new analytical systems to study the effects of pollutants on animal behaviors. This is especially true if we are to gain insights into one of the least studied aspects: the potential perturbations that neurotoxicants can have on cognitive behaviors. The paucity of experimental data is partly caused by a lack of low-cost technologies for the analysis of higher-level neurological functions (e.g., associative learning) in small aquatic organisms. Here, we present a proof-of-concept prototype that utilizes a new real-time animal tracking software for on-the-fly video analysis and closed-loop, external hardware communications to deliver stimuli based on specific behaviors in aquatic organisms, spanning three animal phyla: chordates (fish, frog), platyhelminthes (flatworm), and arthropods (crustacean). The system's open-source software features an intuitive graphical user interface and advanced adaptive threshold-based image segmentation for precise animal detection. We demonstrate the precision of animal tracking across multiple aquatic species with varying modes of locomotion. The presented technology interfaces easily with low-cost and open-source hardware such as the Arduino microcontroller family for closed-loop stimuli control. The new system has potential future applications in eco-neurotoxicology, where it could enable new opportunities for cognitive research in diverse small aquatic model organisms.


Relationship between personality traits and choosing a medical specialty.
The recent imbalance in the labor market structure of medical specialists can cause problems in access to care, and result in lower quality and increased costs of medical care. The labor market structure of medical specialists requires discussion in relation to specialty selection and personality traits. This study examined the relationship between personality traits and specialist selection among medical students. This study used the Edwards Personal Preference Schedule and a customized questionnaire. The participants were 358 medical students of the College of Medicine at Chang Gung University. Medical students scored the highest in Intraception and the lowest in Deference. Women scored significantly higher compared to men for Intraception, Succorance, and Change, whereas men scored significantly higher than women for Dominance and Heterosexuality. Medical students who have family or friends who are also physicians scored higher in Affiliation and lower in Deference than other medical students. Medical students who did not participate in extracurricular activities scored higher in Aggression than those who did. Fourth-year medical students scored significantly higher in Succorance than 7(th)-year medical students. A significant difference was found among medical students of different specialties regarding Exhibition, Autonomy, Intraception, Succorance, and Nurturance. Surgery students scored significantly higher in Exhibition than general medicine students. Students who chose a specialty scored higher in Autonomy than general medicine students. General medicine students scored higher in Intraception and Succorance than surgery students. The results of this study can be used as a frame of reference in the field of medical education or in the formulation of governmental policies regarding physician human resource management.


Chromosomal evolution in secretory and nonsecretory subline of MOPC 21.
Murine myeloma cell lines are noted for the instability of their immunoglobulin genes and the production of nonsynthesizing variants. In this study, the synthesizing line P3-X63-Ag8 (P3) and its nonsynthesizing subline X63-Ag8-653 (653) were karyotyped and rearrangements of the immunoglobulin carrying chromosomes were investigated. Loss of immunoglobulin synthesis was associated with a reduction in the number of immunoglobulin-carrying chromosomes. When these findings were analyzed in light of published molecular data, it appeared that loss of immunoglobulin synthesis in 653 probably occurred as a result of immunoglobulin gene loss. An unusual finding was the absence of the t(12;15) chromosome in both P3 and 653 cell lines. It was concluded that the t(12;15) chromosome, carried by MOPC 21, has evolved into an unrecognizable form.


MR imaging of hip infection and inflammation.
With its superior anatomical resolution and high sensitivity in depicting pathological processes of the joint, bone marrow and surrounding soft tissue structures, MR imaging is the ideal modality for demonstrating the manifestations and sequelae of the infective and inflammatory conditions common to the hip. Though the imaging features of these conditions may overlap, combining the clinical history and results and other imaging modalities yields a higher degree of specificity, ultimately enhancing the confidence of the radiological interpretation.


Self-rated health and employment status in patients with multiple sclerosis.
The aim is to explore the association between self-rated health and employment status in patients with multiple sclerosis (MS) when controlling for age, gender, functional disability, disease duration, anxiety and depression. One hundred eighty-four people with MS completed a sociodemographic questionnaire that included questions on employment status, the first item of the Short Form-36 Health Survey and the Hospital Anxiety and Depression Scale. Functional disability was assessed using the Expanded Disability Status Scale. The probability of good self-rated health in employed persons was investigated using stepwise logistic regression analyses. Patients with MS who reported good self-rated health were 2.46 times more likely to be employed (95% confidence interval [CI]: 1.08-5.59). Patients without anxiety were 2.64 times more likely to be employed (95%CI: 1.23-5.67). Patients with higher EDSS scores were 0.49 times less likely to be employed (95%CI: 0.33-0.70). Age, gender, disease duration and the presence of depression did not show an increased chance of patient employment. Patients with MS with good self-rated health are more likely to be employed, even after adjusting for age, gender, education, functional disability, disease duration, depression and anxiety. Dependent on the findings of longitudinal studies unravelling the relevant causal pahways, self-rated health might be used as a quick and cheap prognostic marker, which could warn about the possible loss of employment, or changes in functional disability.


Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas.
Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.


Effects of Participation in a Structured Choral Program on the Voice of Older Adults.
To examine the effects of short-term and long-term engagement with structured choral singing on vocal function and quality of life outcomes in older adults. Two groups of older adult singers over 55 years, one with fewer than 4 semesters and one with 4 or more semesters singing in a chorale, were assessed at 3 time points: baseline, after 1 semester of singing, and either after 1 semester of rest or after 1 semester of rest and 1 semester more of singing. Acoustic and aerodynamic measures, voice-related quality of life ratings, and measures of singing accuracy were obtained. Percent change between time points were calculated to determine three outcomes: improvement, lack of change, or worsening of measures across time. Long-term average spectrum (LTAS), difference in first and second harmonics and estimated subglottic pressure were significantly more likely to improve after a semester of singing with less experience singers, and LTAS continued to improve after a semester of rest. Flow was significantly more likely to improve with more singing experience after a semester of singing. Aerodynamic variables consistently changed in more experienced singers and improvement was maintained over the three visits. No significant changes occurred over time for singing accuracy for any singer type. Self-perception of singing voice continued to improve with more singing experience. This study demonstrated that for older adults in good health, regular singing provided a mechanism for maintaining speaking voice over time.


The safety of carotid endarterectomy in diabetic patients: clinical predictors of adverse outcome.
Patients with diabetes mellitus have been shown to have an increased incidence of complications after elective major vascular surgery. The objective of this study was to evaluate a large series of diabetic patients undergoing carotid endarterectomy (CEA) to determine if outcome differed from nondiabetic patients and to examine predisposing factors of poor outcome among diabetic patients. A retrospective review of a prospectively compiled database was performed. From 1992 through 2000, 2151 CEAs were performed at our institution. Of these, 507 were in diabetic patients (23.6%), and the remaining 1644 procedures were in nondiabetic patients (76.4%). Diabetic patients were significantly more likely than nondiabetic patients to have hypertension (70.8% vs 64.5%, P = .01) and cardiac disease (54.6% vs 49.1%, P = .03). They were more likely than nondiabetic patients to be symptomatic before surgery (52.5% vs 47.1%, P = .04) and to have sustained a preoperative stroke (21.3% vs 17.7%, P = .07). No differences were noted in other recorded demographic factors or in intraoperative factors between diabetic and nondiabetic patients. Despite these differences, diabetic patients had similar perioperative outcomes compared with nondiabetic patients, including perioperative myocardial infarction (0.6% vs 0.4%, P = NS), perioperative death (0.8% vs 0.5%, P = NS), and perioperative neurologic events such as transient ischemic attack and stroke (3.2% vs 2.4%, P = NS). Among diabetic patients alone, cigarette smoking, general anesthesia, the use of a shunt, and the lack of clamp tolerance while under regional anesthesia predicted adverse perioperative neurologic outcome, and contralateral occlusion was associated with increased perioperative mortality. Despite an increased prevalence of cardiac disease and preoperative neurologic symptoms among diabetic patients undergoing CEA, the rates of perioperative cardiac morbidity, mortality, and stroke were equal to nondiabetic patients. In contrast to nondiabetic patients, current cigarette smoking appeared to predict increased adverse neurologic outcomes among diabetic patients, and the presence of contralateral occlusion among diabetic patients appeared to predispose them towards increased perioperative mortality. The use of a general anesthetic appeared to increased perioperative neurologic risk among diabetic patients; however, this may be related to surgeon bias in the selection of anesthetic technique. Although diabetic patients may have an increase in complications after other major vascular surgical procedures, the presence of diabetes mellitus does not appear to significantly increase risk.


Glucose and 3-O-methylglucose protection against alloxan poisoning of pancreatic alpha and beta cells.
Alloxan infused into the isolated perfused rat pancreas caused transient insulin secretion release. Alloxan poisoning also prevented subsequent induction of glucose-mediated unsulin release and also prevented the inhibition of glucagon release by glucose. Glucose or 3-O-methylglucose infused simultaneously with alloxan protected the alpha- and beta-cell, allowing subsequent glucose inhibition of glucagon secretion and stimulation of insulin release. The above alloxan effects were dose-related, the alpha-cell being one fourth as sensitive to alloxan as the beta-cell. The data indicate that (1) alloxan and glucose suppression of amino-acid-stimulated glucagon secretion is independent of concomitant insulin secretion; (2) alloxan, like glucose, affects alpha-and beta-cells directly, stimulating the beta-cell and inhibiting the alpha-cell; and (3) alloxan acts on a glucoreceptor system with comparable physicochemical characteristics common to both cell types.


Cobalt amine complexes and Ru265 interact with the DIME region of the mitochondrial calcium uniporter.
We report our investigation into the MCU-inhibitory activity of Co3+ complexes in comparison to Ru265. These compounds reversibly inhibit the MCU with nanomolar potency. Mutagenesis studies and molecular docking simulations suggest that the complexes operate through interactions with the DIME motif of the MCU pore.


Effects of Temporary Clipping as an Expression of Circulatory Individuality: Online Measurement of Temporal Lobe Oxygen Levels During Surgery for Middle Cerebral Artery Aneurysms.
Despite its widespread use, much is left to understand about the repercussions of parent artery temporary clipping in neurosurgery. This study seeks a better comprehension of the subject by aiming at the online measurement of brain tissue oxygen pressure (PbtO2) during such events. This was a prospective observational study. Patients submitted to surgery for middle cerebral artery aneurysms (both ruptured and unruptured) were continuously monitored under Intensive Care Monitoring+ software, in order to obtain temporal (downstream) PbtO2 levels while temporary clips were applied. Separate PbtO2 curve events were identified, extracted, and processed. These were studied for assessing intraindividual and interindividual variability and the potential impact of repeated clipping and previous aneurysmal rupture. Eighty-six temporary clippings (from 20 patients) were recorded with a mean duration of 140.8 (41 - 238) seconds. Temporary arterial occlusion at the M1 segment of the middle cerebral artery produced specifically shaped trajectories, characterized by a preclipping PbtO2 level, rapid downward sigmoid-shaped curve, succession of progressively angled slopes, and lower plateau. The steepest slope of the curve correlated strongly with PbtO2 range (P < 0.001, r = 0.944). These features were highly reproducible only intraindividually and did not vary significantly with repeated clippings. The effects of temporary arterial occlusion on temporal lobe oxygenation demonstrate a high degree of singularity, highlighting the potential benefits of assessing individual available collateral circulation intraoperatively. The "PbtO2 steepest slope" predicted the severity of PbtO2 decrease and was available within the first minute.


Progress in the study of long noncoding RNA in tongue squamous cell carcinoma.
Tongue squamous cell carcinoma (TSCC) is the most common and highly malignant oral squamous cell carcinoma (OSCC) with lymph node metastasis or distant organ metastasis and, thus, low overall survival rates. Studies on the molecular mechanism of the biologic characteristics of TSCC and exploration of targeted therapies have become the frontiers in the research of this disease. Long noncoding RNA (lncRNA), a type of noncoding RNA, plays a key role in the occurrence and development of tumors. In recent years, more and more studies on lncRNA have been focusing on tongue cancer. lncRNA affects the proliferation, invasion, and migration of TSCC cells through a variety of methods and molecular mechanisms. With reference to recent reports, this article provides an overview of the molecular mechanisms of various lncRNAs and their functions in TSCC.


To replicate or not to replicate: achieving selective oncolytic virus replication in cancer cells through translational control.
To ensure that their mRNAs are translated and that the viral proteins necessary for assembling the next generation of infectious progeny are produced, viruses must effectively seize control of the translational machinery within their host cells. In many cases, the ability to productively engage host translational components can determine if a given cell type can support viral replication, illustrating the critical importance of this task in the viral life cycle. Failure to interface properly with the host translational apparatus can compromise the productive growth cycle, resulting in an abortive infection and radically restricting viral replication. Not only have viruses become facile at commandeering this machinery, they are also particularly adept at manipulating cellular translation control pathways for their own ends. In this review, the mechanisms by which numerous viruses manipulate host translational control circuits are discussed. Furthermore, particular attention is devoted to understanding how interfering with the ability of a virus to properly regulate translation in its host can be exploited to generate oncolytic strains that selectively replicate in cancer cells.


Metronomic chemotherapy enhances antitumor effects of cancer vaccine by depleting regulatory T lymphocytes and inhibiting tumor angiogenesis.
Although cancer vaccines are emerging as innovative methods for cancer treatment, these alone have limited potential for treating measurable tumor burden. Thus, the importance of identifying anticancer strategies with greater potency is necessary. The chimeric DNA vaccine CTGF/E7 (connective tissue growth factor linked to the tumor antigen human papillomavirus 16 E7) generates potent E7-specific immunity and antitumor effects. We tested immune-modulating doses of chemotherapy in combination with the CTGF/E7 DNA vaccine to treat existing tumors in mice. Metronomic low doses of paclitaxel, not the maximal tolerable dose, are synergistic with the antigen-specific DNA vaccine. Paclitaxel, given in metronomic sequence with the CTGF/E7 DNA vaccine enhanced the vaccine's potential to delay tumor growth and decreased metastatic tumors in vivo better than the CTGF/E7 DNA vaccine alone. The two possible mechanisms of metronomic paclitaxel chemotherapy are the depletion of regulatory T cells and the inhibition of tumor angiogenesis rather than direct cancer cell cytolytic effects. Results indicate that combination treatment of metronomic chemotherapy and antigen-specific DNA vaccine can induce more potent antigen-specific immune responses and antitumor effects. This provides an immunologic basis for further testing in cancer patients.


Vasoactive intestinal polypeptide (VIP) inhibits rat alveolar macrophage phagocytosis and chemotaxis in vitro.
Vasoactive intestinal polypeptide (VIP) has been shown to inhibit lymphocyte function and is believed to modulate the immune response. We explored the possible immunomodulatory effects of VIP on alveolar macrophage (AM) function by examining its influence on AM phagocytosis and chemotaxis. Rat AMs were collected by bronchoalveolar lavage and incubated for 90 min with polystyrene beads in the presence or absence of VIP in concentrations from 10(-11) M to 10(-5) M. VIP significantly (P less than 0.0001) inhibited AM phagocytosis of polystyrene beads at concentrations of 10(-11) to 10(-6) M, with a maximal inhibition of 35% at 10(-6) M (but no inhibition at 10(-5) M). AMs were also incubated for 90 min in a chemotaxis chamber with endotoxin-activated rat serum (EARS) as a chemoattractant, with or without VIP in concentrations from 10(-9) to 10(-6) M. VIP significantly (P less than 0.0001) inhibited AM chemotaxis by at least 30% at concentrations of 10(-9) to 10(-6) M, with a maximal inhibition of 46% at 10(-7) M. These results indicate that VIP, in concentrations from 10(-11) to 10(-6) M, inhibits rat AM function as assessed by phagocytosis of polystyrene beads and chemotaxis to EARS. The inhibition of alveolar macrophage function is another mechanism by which VIP may modulate the immune response in the lung.


Central insulin enhances sensitivity to cholecystokinin.
Insulin acts in the brain to reduce food intake and body weight. Cholecystokinin (CCK) reduces meal size when administered peripherally. The purpose of these experiments was to examine their interaction. In Experiment 1, Long-Evans rats were infused with vehicle or insulin at doses from 0.5 to 2.0 mU/day into the third cerebral ventricles. Doses of 1.0 mU/day and higher caused reduced body weight. A dose of 0.5 mU/day was therefore taken to be subthreshold. In Experiment 2, rats receiving 0.5 mU/day of insulin intracerebroventricularly had greater suppression of 30-min meal size in response to intraperitoneal CCK-8 at doses from 0.25 to 8 mg/kg than did rats receiving intracerebroventricular saline. By itself, the insulin had no effect on body weight or meal size. However, a change of sensitivity to CCK by control rats over the course of the experiment clouded the interpretation. A third experiment was therefore conducted in which rats received an acute intracerebroventricular injection of insulin (0.1 mU) or saline 1 h prior to a 30-min meal, and IP CCK-8 (4 mg/kg) or saline immediately prior to the meal. As in Experiment 2, insulin, itself, had no effect on meal size but enhanced the anorexic effect of CCK. These results are consistent with the hypothesis that central insulin acts by altering sensitivity to satiety agents.


Silicon facilitation of copper utilization in the rat.
An eight-week, 2 x 4 factorial rat experiment using two levels of dietary copper and four levels of dietary silicon was conducted to further delineate a previously observed silicon-copper interaction in which silicon appears to mimic copper in its effect on the composition of the aorta. Dietary copper concentrations were 1.4 (deficient) and 5.4 (adequate) mg/kg diet, and silicon concentrations were 5, 135, 270, and 540 mg/kg diet. Compared with the lowest level of silicon and copper, weight gains were 15.5% higher for rats fed 540 mg silicon/kg diet and 14.3% higher for those fed 5.4 mg copper/kg diet. The growth-promoting effects of silicon and copper were additive. Evidence that silicon elevated the copper status of copper-deficient rats includes an increase in packed-cell volume by 540 mg silicon/kg diet in the otherwise packed-cell volume-depressed, copper-deficient rats, accompanied by a trend toward higher hemoglobin values and lower relative heart weights. In the copper-adequate rats, evidence that 540 mg silicon/kg diet elevated their copper status includes a two-fold increase in the blood-plasma copper concentration, a three-fold increase in ceruloplasmin activity, and an increase in cardiac, renal, and hepatic copper concentrations. In addition, 540 mg silicon/kg diet resulted in higher aortic dry mass and aortic elastin content in both copper-deficient and copper-adequate rats. While dietary silicon concentrations of 135, 270, and 540 mg/kg diet were all effective in increasing aortic elastin in the copper-adequate rats, only 540 mg silicon/kg diet increased aortic elastin in the copper-deficient rats. These data indicate that some of the metabolic effects attributed to silicon may be manifested through a silicon-facilitated increase in copper utilization.


Ocular kinetics of 8-methoxypsoralen. An experimental study with pigmented and albino rabbits without UVA-stimulation.
Tritiated 8-methoxypsoralen (8-MOP), with radioactivity in the ring system, was injected into both pigmented rabbits and albino rabbits; at 0.5, 1, 2, 4, 6, and 24 h after 8-MOP injection the animals' plasma and ocular radioactivities were determined by liquid scintillation counting. The experiment was done without photostimulation but in incomplete darkness. The plasma radioactivity declined rapidly during the first hour, peak radioactivity occurring in the first samples of vascularized ocular structures taken 0.5 h after the injection. The radioactivity of these tissues generally declined rapidly and similarly in both animal groups. The 1, 2, and 4 h samples of pigmented animals formed an exception; in these the radioactivities in the iris-ciliary body and the retina-choroid of the pigmented animals showed increased activities that were statistically significant, and the plasma radioactivity was exceeded by two to three times. The radioactivities in the internal parts of the eye were lower than in the vascular parts. The radioactivity in the lens reached a peak in the specimens taken 1-2 h after injection and remained at the level of the plasma radioactivity for the rest of the 24 h.


Sensitivity-enhanced double-TROSY experiment for simultaneous measurement of one-bond 15N-1H, 15N-13C' and two-bond 1H-13C' couplings.
A recently published experiment for the measurement of 1JHN, 1JNC', and 2JHC' coupling constants [J. Am. Chem. Soc. 125 (2003) 11504] was modified to yield a double-TROSY experiment which selects 1 of the 16 multiplet components from a 15N-HSQC spectrum recorded of a uniformly 15N/13C-labelled protein. Subspectra containing any 1 of the 16 multiplet components can be generated allowing accurate coupling constant measurements. The experiment is sensitivity enhanced, turning all magnetization components precessing during the evolution time into observable magnetization during the detection time. The experiment is discussed with regard to the previously published alpha/beta-filtered HN(alpha/beta-NC'-J) experiment [J. Magn. Reson. 140 (1999), 32] which measures the same coupling constants.


Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma.
Several groups have reported the significance of circulating microRNA as a biochemical marker of cancer. To our knowledge, however, there are no reports on the significance of circulating microRNA in hepatocellular carcinoma. The aim of this study was to evaluate the significance of plasma microRNA-21 level as a biochemical marker for hepatocellular carcinoma. Plasma microRNA-21 level was measured by qRT-PCR in 10 patients before and after curative resection of hepatocellular carcinoma. Plasma microRNA-21 was also compared in other groups of: 126 patients with hepatocellular carcinoma, 30 patients with chronic hepatitis, and 50 healthy volunteers. The power of microRNA-21 in differentiating hepatocellular carcinoma from chronic hepatitis or from healthy volunteers was compared to that of α-fetoprotein. In the 10-patient group, plasma microRNA-21 levels significantly diminished after surgery compared with the pre-operative values (p=0.0125). Plasma microRNA-21 level in the 126 patients with hepatocellular carcinoma was significantly higher than in patients with chronic hepatitis and healthy volunteers (p<0.0001, p<0.0001, respectively). ROC analysis of plasma microRNA-21 yielded an AUC of 0.773 with 61.1% sensitivity and 83.3% specificity when differentiating hepatocellular carcinoma from chronic hepatitis, and an AUC of 0.953 with 87.3% sensitivity and 92.0% specificity when differentiating hepatocellular carcinoma from healthy volunteers. Both sets of values were superior to α-fetoprotein and improved for the combination of microRNA-21 and α-fetoprotein. Plasma microRNA-21 level is a promising biochemical marker for hepatocellular carcinoma.


Occurrence and distribution of fecal indicators and pathogenic bacteria in seawater and Perna perna mussel in the Gulf of Annaba (Southern Mediterranean).
The identification of fecal contamination in coastal marine ecosystems is one of the main requirements for evaluation of potential risks to human health. The objective of this study was to investigate the occurrence and distribution of fecal indicators and pathogenic bacteria in seawaters and mussels collected monthly during a period of 1 year from four different sites in Northeastern Algeria (sites S1 to S4), through biochemical and molecular analyses. Our research is the first to use molecular analysis to unambiguously identify the potentially pathogenic bacteria present in Algerian Perna perna mussels. The obtained results revealed that the levels of fecal indicator bacteria (FIB) from both P. perna and seawater samples largely exceeded the permissible limits at S2 and S3. This is mainly related to their location close to industrial and coastal activity zones, which contain a mixture of urban, agricultural, and industrial pollutants. Besides, P. perna collected from all sites were severalfold more contaminated by FIB than seawater samples, primarily during the warm season of the study period. Biochemical and molecular analyses showed that isolated bacteria from both seawater and mussels were mainly potentially pathogenic species such as E. coli, Salmonella spp., Staphylococcus spp., Klebsiella spp., Pseudomonas spp., and Proteus spp.


Trends using biological target-based assays for drug detection in complex sample matrices.
In vivo, drug molecules interact with their biological targets (e.g., enzymes, receptors, ion channels, transporters), thereby eliciting therapeutic effects. Assays that measure the interaction between drugs and bio-targets may be used as drug biosensors, which are capable of broadly detecting entire drug classes without prior knowledge of their chemical structure. This Trends article covers recent developments in bio-target-based screening assays for detecting drugs associated with the following areas: illicit products marketed as dietary supplements, food-producing animals, and bodily fluids. General challenges and considerations associated with using bio-target assays are also presented. Finally, future applications of these assays for drug detection are suggested based upon current needs.


Requirement for FBP17 in invadopodia formation by invasive bladder tumor cells.
Invadopodia (protrusions of the plasma membrane formed by invasive tumor cells) have an essential role in bladder tumor invasion. To understand the process of bladder tumor invasion it is crucial to investigate the molecular mechanisms of invadopodia formation. We found that invasive bladder tumor cells express FBP17. In this study we examined the role of FBP17 in bladder tumor cell invadopodia formation and invasion. We used the 3 bladder tumor cell lines YTS-1, T24 and RT4 (ATCC®), and primary culture of bladder tumors from patients. Cells were stained with phalloidin for invadopodia formation. FBP17 knockdown cells were tested for invadopodia formation and subjected to invasion assay using a Transwell® cell culture chamber. We also examined the role of the extended FER-CIP4 homology and Src homology 3 domains of FBP17 in invadopodia formation in FBP17 mutant constructs. Invadopodia formation was observed in invasive bladder tumor cells and FBP17 was localized to invadopodia in invasive cells. FBP17 knockdown decreased invadopodia formation in invasive cells to 13% to 14% (p <0.0005) and decreased their invasive capacity to 14% to 16% (p <0.001). The extended FER-CIP4 homology and Src homology 3 domains of FBP17 were necessary for invadopodia formation and invasion. Invadopodia formation requires membrane deformation activity and recruitment of dynamin-2 mediated by FBP17. FBP17 has a critical role in the process of bladder tumor cell invasion by mediating invadopodia formation.


Dynamic differentiation of F4/80+ tumor-associated macrophage and its role in tumor vascularization in a syngeneic mouse model of colorectal liver metastasis.
Tumor-associated macrophages (TAMs) are highly heterogeneous and play vital roles in tumor progression. Here we adopted a C57BL/6 mouse model imitating the late-stage colorectal liver metastasis (CRLM) by Mc38 colorectal cancer cell injection via the portal vein. With serial sections of CRLM biopsies, we defined 7-9 days post-injection as the critical period for tumor neovascularization, which was initiated from the innate liver vessels via vessel cooption and extended by vascular mimicry and thereof growth of CD34+cells. In samples with increasing-sized liver metastases, the infiltrated Ly6C+ CD11b+ F4/80- monocytes steadily gained the expression of F4/80, a Kupffer cell marker, before transformed into Ly6C- CD11bint F4/80+ cells, which, the same phenotype was also adapted by Ly6C- CD11b- F4/80+ Kupffer cells. F4/80+ TAMs showed proximity to neovascularization and tumor vessels, functionally angiogenic in vivo; and greatly promoted the activation of a few key angiogenic markers such as VEGFA, Ki67, etc. in endothelial cells in vitro. Depletion of macrophages or diversion of macrophage polarization during neovascularization impeded tumor growth and vascularization and resulted in greatly reduced F4/80+ TAMs, yet increased CD11b+ cells due to inhibition of TAM differentiation. In summary, our results showed dynamic and spatial-temporal F4/80+ TAM transformation within the tumor microenvironment and strengthened its role as perivascular and angiogenic TAMs in CRLM.


Allele frequencies of six miniSTR loci (D10S1248, D14S1434, D22S1045, D4S2364, D2S441 and D1S1677) in a Spanish population.
Allele frequencies and forensic parameters for six miniSTR autosomal loci (D10S1248, D14S1434, D22S1045, D4S2364, D2S441 and D1S1677) were obtained from a sample of 264 unrelated individuals from Spain. No significant deviations from Hardy-Weinberg expectations were found. Due to the small PCR products (<125 bp), the use of these non-CODIS (NC) miniSTRs can increase the probability that a degraded sample can be typed. Additionally, these systems can be used in routine paternity analyses where more markers are needed to increase the power of exclusion or in complex paternity cases (e.g. involving closely related individuals).


Instructor comfort level in high-fidelity simulation.
The literature in the use of simulation in nursing education has expanded significantly over the past 5-10 years. What it is like as an instructor who facilitates this experience is largely unexplored. This paper is part of a larger ethnographic study, and represents findings related to the comfort level of instructors facilitating in high-fidelity simulation (HFS). The question of what is it like to engage in simulated clinical experiences as an instructor is presented in this paper. Twenty instructors participated in two separate focus groups and two instructors participated in individual interviews. The average years of nursing experience for this group was over 20 years, whereas the number of years of experience as a clinical instructor was less than five years. Ethical approval was obtained from two academic institutions. A focused ethnography was conducted and included two terms of participant observations, recorded field notes, individual interviews and focus groups. Data was coded and then sorted for themes related to the instructor experience. The primary results focus on the comfort level of instructors in HFS, and what instructors believe this meant to student learning in HFS. What the instructor does during HFS and how they feel about their ability to facilitate HFS has a perceived effect on student learning.


Diffusion biomarkers in chronic myocardial infarction.
Cardiac diffusion tensor magnetic resonance imaging (cDTI) allows estimating the aggregate cardiomyocyte architecture in healthy subjects and its remodeling as a result of cardiac disease. In this study, cDTI was used to quantify microstructural changes occurring in swine (N=7) six to ten weeks after myocardial infarction. Each heart was extracted and imaged ex vivo with 1mm isotropic spatial resolution. Microstructural changes were quantified in the border zone and infarct region by comparing diffusion tensor invariants - fractional anisotropy (FA), mode, and mean diffusivity (MD) - radial diffusivity, and diffusion tensor eigenvalues with the corresponding values in the remote myocardium. MD and radial diffusivity increased in the infarct and border regions with respect to the remote myocardium (p<0.01). In contrast, FA and mode decreased in the infarct and border regions (p<0.01). Diffusion tensor eigenvalues also increased in the infarct and border regions, with a larger increase in the secondary and tertiary eigenvalues.


Effect of selenium deficiency on tissue taurine concentration and urinary taurine excretion in the rat.
The purpose of this study was to determine the effect of selenium deficiency on tissue taurine levels and urinary taurine excretion. Weanling male Sprague-Dawley rats were fed selenium-deficient or selenium-adequate diets for 20 weeks. As selenium deficiency developed, urinary taurine excretion increased in selenium-deficient rats compared to controls. At 12 weeks, the selenium-deficient rats excreted 1.7-fold more taurine than control rats. At the same time plasma glutathione peroxidase was 1.2% of control and plasma glutathione was 226% of control. At 20 weeks, renal taurine was decreased but renal glutathione was increased in selenium-deficient rats compared to controls. Feeding the experimental diet for 6 weeks without methionine supplementation caused a fall in urinary taurine excretion. However, there was no difference between selenium-deficient and control rats. These results indicate that selenium deficiency affects renal handling of taurine in the rat when dietary sulfur amino acids are not restricted.


Dysregulated circulating microRNA-126 in chronic obstructive pulmonary disease: linkage with acute exacerbation risk, severity degree, and inflammatory cytokines.
MicroRNA-126 (miR-126) is engaged in respiratory diseases via regulating airway tissue injury and pulmonary inflammation, while its relation with chronic obstructive pulmonary disease (COPD) is not reported. The study aimed to evaluate the value of miR-126 for estimating COPD acute exacerbation risk and its relation to disease severity and inflammatory cytokines in COPD patients. This study was a case-control study. Seventy acute exacerbation COPD (AECOPD) patients, 70 stable COPD (SCOPD) patients, and 70 healthy controls (HCs) were consecutively recruited. Plasma miR-126 expression was detected by reverse transcription quantitative polymerase chain reaction. Plasma tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) in COPD patients were further determined by enzyme-linked immunosorbent assay. MiR-126 was higher in AECOPD patients compared to SCOPD patients and HCs (both Padj < 0.001). Receiver operating characteristic curves revealed miR-126 distinguished AECOPD patients from SCOPD patients (area under curve (AUC): 0.805, 95%CI: 0.733-0.877) and HCs (AUC: 0.884, 95%CI: 0.829-0.939) and also distinguished SCOPD from HCs (AUC = 0.656, 95%CI: 0.566-0.747). MiR-126 positively related to GOLD stage in both AECOPD patients (p < 0.001) and SCOPD patients (p < 0.001). Furthermore, miR-126 positively linked with TNF-α (p < 0.001), IL-1β (p = 0.002), IL-6 (p = 0.009), and IL-17 (p < 0.001) levels in AECOPD patients; but miR-126 only positively related to TNF-α and IL-17 levels (all p < 0.050), instead of IL-1β or IL-6 level (all p > 0.050) in SCOPD patients and HCs. Dysregulated circulating miR-126 not only relates to COPD susceptibility and its acute exacerbation risk but also links with disease severity and inflammatory cytokines in COPD patients.


The mechanical properties of elastic arteries in Ehlers-Danlos syndrome.
To study whether measurements of wall mechanics can be used as an indicator of disturbed vessel wall integrity and predictor of vessel fragility in Ehlers-Danlos Syndrome (EDS). The wall mechanics of the abdominal aorta (AO) and common carotid artery (CCA) were estimated from the indices Ep (pressure strain elastic modulus) and stiffness (beta) in twelve individuals with EDS of different subtypes and compared with the results of a healthy reference population. Ep and beta were calculated from diameter and pulsatile diameter change determined non-invasively with the aid of an ultrasonic echo-tracking system and blood pressure obtained by the auscultatory method. Compared with normal individuals and their confidence intervals, subjects with EDS had unaltered diameter, Ep and beta in the AO, as well as in the CCA. Analysis of covariance (ANCOVA) also showed unaltered results. AO: diameter (males p = 0.66, females p = 0.27), Ep (males p = 0.81, females p = 0.27) and beta (males p = 0.95, females p = 0.12). CCA: diameter (males p = 0.36, females p = 0.46), Ep (males p = 0.93, females p = 0.48) and beta (males p = 0.86, females p = 0.47). This investigation could not demonstrate any alteration in wall mechanics as a sign of disturbed vessel wall integrity of elastic arteries in EDS. This might indicate that the structural defect in the arterial wall collagen, and thus the tendency to vessel fragility, cannot be revealed under normal physiological pressure conditions.


Hearing loss and microstructural integrity of the brain in a dementia-free older population.
As hearing loss has been identified as an important risk factor for dementia, we aimed to assess the association between hearing loss and microstructural integrity of the brain. A total of 1086 dementia-free participants (mean age = 75.2 [standard deviation: 4.9], 61.4% female) of the population-based Atherosclerosis Risk in Communities (ARIC) study underwent hearing assessment (2016-2017) and magnetic resonance imaging of the brain (2011-2013). Microstructural integrity was determined with diffusion tensor imaging. Multivariable linear regression was used to investigate associations between hearing loss and microstructural integrity of different brain regions and white matter (WM) tracts. Hearing loss was associated with lower WM microstructural integrity in the temporal lobe, lower gray matter integrity of the hippocampus, and with lower WM microstructural integrity of the limbic tracts and the uncinate fasciculus. Our results demonstrate that hearing loss is indepedently associated with lower microstructural integrity in brain regions that are important for different cognitive processes.


Photostatic copying of immunoelectrophoretic patterns with the use of color print filters.
Immunoelectrophoretograms can be replicated inexpensively, rapidly, and to scale by the use of color print filters on a photostatic copy machine. By this method additional copies are readily available for patient charts, permanent record, and any other use.


Isolation and characterization of a gene encoding alpha-tubulin from Candida albicans.
A gene encoding the alpha-tubulin of Candida albicans has been cloned and characterized. Nucleotide sequence analysis reveals the presence of an intron within the structural gene and predicts the synthesis of a polypeptide of 448 amino acid residues. Comparison of nucleotide and amino acid sequences with the Saccharomyces cerevisiae alpha-tubulin encoding genes shows a 75% homology and about 92% similarity respectively. In contrast to S. cerevisiae, C. albicans appears to possess only one gene for alpha-tubulin which is able to functionally complement a S. cerevisiae cold-sensitive tub1 mutant.


Detection of intracranial arterial stenosis using transcranial color-coded duplex sonography, computed tomographic angiography, and digital subtraction angiography.
The aim of this retrospective study was to compare intracranial arterial stenosis in patients with stroke using 3 different methods: transcranial color-coded duplex sonography, computed tomographic (CT) angiography, and digital subtraction angiography in a common clinical practice. Sixty-seven patients (47 male and 20 female; age range, 23-79 years; mean age ± SD, 62.0 ± 9.5 years) were enrolled in this study over 40 months. All patients underwent examinations of the intracranial arteries using transcranial color-coded sonography, CT angiography, and digital subtraction angiography. Findings were divided into 4 groups: normal, mild stenosis (<50%), severe stenosis (50%-99%), and occlusion. Because of technical reasons or an insufficient bone window, 465 of 536 arterial segments in 67 patients were evaluated; 12 stenotic and 15 occluded segments were detected using digital subtraction angiography. The sensitivity, specificity, positive predictive value, and negative predictive value of transcranial color-coded sonography and CT angiography in comparison with digital subtraction angiography as a reference standard were 88.9%, 94.8%, 51.1%, and 99.3% and 81.5%, 98.7%, 78.6%, and 98.6%, respectively. The agreement between transcranial color-coded sonography and CT angiography was 93.8% (κ = 0.559); between transcranial color-coded sonography and digital subtraction angiography, it was 93.9% (κ = 0.588); and between CT angiography and digital subtraction angiography, it was 96.6% (κ = 0.697). Moderate agreement was found between CT angiography, transcranial color-coded sonography, and digital subtraction angiography in the evaluation of intracranial stenosis. Computed tomographic angiography and digital subtraction angiography are sufficient for assessment of the diagnosis.


Cardiovascular sources of systemic embolism: detection and characterization using multidetector CT and MR imaging.
The purpose of this article is to provide a current review of multidetector CT (MDCT) and MRI findings and imaging protocols for the cardiovascular diseases that can precipitate systemic embolism. These conditions include intracardiac thrombus or tumors, paradoxical embolism through right-to-left shunts, and diseases of the thoracic aorta. MDCT and MRI may be helpful for detection of these conditions. Familiarity with the pathogenesis and CT and MRI appearance of these conditions is important as their detection may have a major impact on patient management.


The main and accessory olfactory systems of female mice are activated differentially by dominant versus subordinate male urinary odors.
Previous studies have shown that female preferences for male pheromones depend on the female's reproductive condition and the dominance status of the male. However, it is unknown which olfactory system detects the odors that result in a preference for a dominant male. Therefore, in the present study, we asked whether dominant versus subordinate male urinary odors differentially activate the main and accessory olfactory systems in female (C57Bl/6j) mice by monitoring the induction of the immediate early gene, c-fos. A more robust induction of Fos was observed in female mice which had direct nasal contact with dominant male urinary odors in four specific segments of the accessory olfactory system, i.e., the posteroventral part of the medial amygdala, the bed nucleus of the stria terminalis, the medial part of the preoptic nucleus and the ventrolateral part of the ventromedial hypothalamus, compared to females that were exposed to subordinate male urine. This greater activation of the accessory olfactory pathway by dominant male urine suggests that there are differences in the nonvolatile components of dominant versus subordinate male urine that are detected by the vomeronasal organ. By contrast, subordinate male urinary odors induced a greater activation in the piriform cortex which is part of the main olfactory system, suggesting that female mice discriminate between dominant and subordinate male urine using their main olfactory system as well.


A network simplification approach to ease topological studies about the food-web architecture.
Food webs studies are intrinsically complex and time-consuming. Network data about trophic interaction across different large locations and ecosystems are scarce in comparison with general ecological data, especially if we consider terrestrial habitats. Here we present a complex network strategy to ease the gathering of the information by simplifying the collection of data with a taxonomic key. We test how well the topology of three different food webs retain their structure at the resolution of the nodes across distinct levels of simplification, and we estimate how community detection could be impacted by this strategy. The first level of simplification retains most of the general topological indices; betweenness and trophic levels seem to be consistent and robust even at the higher levels of simplification. This result suggests that generalisation and standardisation, as a good practice in food webs science, could benefit the community, both increasing the amount of open data available and the comparison among them, thus providing support especially for scientists that are new in this field and for exploratory analysis.


Written accounts of living with epilepsy: A thematic analysis.
This study examines the subjective experience of living with epilepsy by thematically analyzing participants' written accounts of their condition. Writing is seen as an individual act allowing for private exploration, reflection and expression of thoughts and feelings. Participants (n=20) were recruited from a United Kingdom hospital and from membership-led organizations for individuals living with seizures. Participants were asked to produce four pieces of writing: 1) about their thoughts and feelings about their condition; 2) a letter to their condition; 3) a letter to their younger self; and 4) about a personal value. All writings were analyzed thematically using a theory- and data-driven approach. Five main-themes and 22 sub-themes emerged from the data. Theme 1: 'seizure onset' demonstrated that the development of seizures and subsequent diagnosis was an important event that could change an individuals' identity. Theme 2: 'seizure symptoms' revealed participants externalized their seizures as an intrusive agent with a constant presence in their lives. Theme 3: 'treatment and outcome' reflected medication as an essential means to controlling seizures with subsequent side effects being perceived as a compromise. Theme 4: 'living with epilepsy' explored the consequences of the condition including restrictions and stigma. Theme 5: 'displays of coping' demonstrated that, for the most part, participants were keen to present themselves as living well with epilepsy. The results add to the growing research applying qualitative methodologies to investigate the phenomenology of epilepsy. Qualitative research can improve our understanding and awareness of the condition, as well as inform clinical practice.


Predicting ketosis during the transition period in Holstein Friesian cows using hematological and serum biochemical parameters on the calving date.
Ketosis often occurs during the postpartum transition period in dairy cows, leading to economic and welfare problems. Previously, ketosis was reported to be associated with hematological and serum biochemical parameters. However, the association between the parameters on the calving date and ketosis during the postpartum transition period remains unclear. This study aimed to investigate this association. Blood samples were collected from the jugular vein of Holstein cows on the calving date and β-hydroxybutyrate was tested once every 3 days (8 times in 21 days). The cows were divided into three groups: non-ketosis, subclinical ketosis, and clinical ketosis. The clinical ketosis group significantly had the highest values of mean corpuscular volume, mean corpuscular hemoglobin, β-hydroxybutyrate, non-esterified fatty acids, and total bilirubin, but the lowest values of red cell distribution width, the counts of white blood cell, monocyte, and eosinophil, albumin, alanine transaminase, lactate dehydrogenase, and amylase. In contrast, the non-ketosis group showed the opposite results (p < 0.05). In conclusion, these parameters are associated with the development and severity of ketosis. Our findings suggest that these parameters on the calving date may be useful indicators to identify dairy Holstein cow susceptible to ketosis during the transition period.


Point-of-Care Ultrasound to Evaluate the Acute Abdomen: A Case of Bowel Perforation After Unknown Single Magnet Ingestion.
We report the case of a 3-year-old boy who presented to the pediatric emergency department in undifferentiated shock with an acute abdomen. Point-of-care ultrasound revealed viscous perforation with a large amount of free fluid. Intraoperatively, a single magnet was discovered as the likely cause of bowel perforation and the resulting state of shock.


Changes in esophageal physiology after paraesophageal hernia repair and Collis gastroplasty.
The surgical approach and technique for paraesophageal hernia (PEH) repair is much debated. The changes in the esophageal physiology after PEH repair with a concomitant Collis gastroplasty (PEH-CG) are not clearly known. The aim of this study was to determine the changes in high resolution esophageal manometry (HREM) and esophageal pH testing after PEH-CG. Retrospective analysis of all patients who underwent PEH-CG at our institution between 2006 and 2013 was performed. Patients had esophageal pH testing, HREM, barium swallow and an upper endoscopy before and after PEH-CG. A total of 182 patients underwent PEH-CG during the study period. Majority of patients had Nissen fundoplication (176, 96.7%) with Toupet in 6 (3.3%). Basal lower esophageal sphincter pressure (LESP) was lower after fundoplication (20.3 mmHg ± 11.3 vs. 25.8 mmHg ± 15.6, p < 0.001), whereas residual LESP was noted to be higher after fundoplication (7.7 mmHg ± 4.9 vs. 6.1 mmHg ± 6.7, p < 0.009). There were no significant changes in the esophageal motility patterns. There was an improvement in total pH and upright pH but not supine pH post PEH-CG. Normalization of total acid exposure after fundoplication was noted in 31 (59.6%) of the 52 patients who had abnormal total acid exposure prior to fundoplication. Objective clinical assessment in patients undergoing PEH-CG demonstrates an effective operation for this complex problem. There was an increase in residual LESP but interestingly, decrease in basal LESP. Additionally, there was an improvement in esophageal acid exposure afterwards. These findings will facilitate future management of PEH.


Psycho-emotional distress in children and adolescents in relation to COVID-19 confinement and pandemic: A systematized review : Author lists.
A stressor such as a pandemic is a trigger to focus on the study of the psycho-emotional impact on children and adolescents from a nursing care perspective. The aim of this systematized review was to know the impact of the lockdown and COVID-19 pandemic on children (from 2 to 12 years) and adolescent (from 13 to 18 years) in relation to daily routines, as well as the most frequent psycho-emotional manifestations. The research was carried out following PRISMA guidelines and was performed using several databases (PubMed, Scopus and Cochrane). The search was focused on children and adolescent population between 2020 and 2021.The literature search was from November to December 2021. Sixteen articles were used to perform the systematized review. A disruption in daily routines and an increase in psycho-emotional manifestations have been observed in young people, which is understood as a worsening of their psycho-emotional integrity. Higher levels of anxiety and depression in adolescents and hyperactivity and dependence disorders in the children have also been reported. In conclusion, children and adolescents have been affected in the psycho-emotional sphere in the same way as adults, therefore, it is necessary to know the presenting characteristics of this group of people in order to be able to establish an effective nursing approach and help preserve the mental integrity, as well as promote resilience.


Improvement of insulin signaling in myoblast cells by an addition of SKIP-binding peptide within Pak1 kinase domain.
Abnormalities in insulin-induced glucose incorporation in skeletal muscle were observed in Type 2 diabetes. Our previous studies revealed that the binding between skeletal muscle and kidney-enriched inositol polyphosphate phosphatase (SKIP) and p21-activated protein kinase (Pak1) at the plasma membrane is induced insulin-dependently and that this binding mediated a rapid and efficient termination of insulin signaling and a subsequent glucose uptake into skeletal muscle cells. Here, we identified 11-amino-acids peptide within kinase domain of Pak1, necessary and sufficient for SKIP binding. Expression of this region in C2C12 cells resulted in an increase in insulin signaling. Supplementation of a synthetic peptide of this sequence increased insulin signaling and insulin-induced glucose uptake into skeletal muscle cell lines. These findings suggest the physiological role of Pak1-SKIP binding in the regulation of insulin signaling in skeletal muscle.


Length of the third stage of labor at term pregnancies is shorter if placenta is located at fundus: prospective study.
To investigate how the location of the placenta at term pregnancies affects the duration of the third stage of labor and to discuss the possible mechanisms affecting the duration of the third stage. We believe that this is the first prospective study comparing the duration of the third stage of labor according to placental location. The placental implantation was determined as anterior (n = 78), posterior (n = 59), or fundal (n = 64) by ultrasound, in 201 women with singleton pregnancies. After delivery of the newborn, oxytocin infusion was routinely given. Duration of the third stage of labor was compared by anova. P < 0.05 was determined as significant. The duration of the third stage of labor was 10.36 +/- 5.94 min, 10.44 +/- 5.35 min, and 8.12 +/- 4.25 min with placentas located anteriorly, posteriorly, and fundal, respectively. The length of the third stage was significantly shorter in the fundal placenta group. In this study, the length of the third stage of labor was approximately 2 min shorter with placentas located at the fundus compared to the other two groups. The mechanism responsible for shorter duration may be the bipolar separation of fundal placentas in contrast to usual unipolar down-up separation of anterior or posterior placentas. Another contributing factor may be the use of oxytocin infusion for the management of the third stage, however this should be investigated by further studies by using real time ultrasonography.


Intracranial hypotension: clinical presentation, imaging findings, and imaging-guided therapy.
To illustrate clinical presentations, imaging findings, and diagnostic and therapeutic approaches associated with various conditions of intracranial hypotension. Intracranial hypotension occurs spontaneously, following (lumbar) dural puncture, accidental dural opening, or excessive surgical cerebrospinal fluid drainage. The typical clinical manifestation - orthostatic headache - may be masqueraded by atypical clinical findings, including coma, frontotemporal dementia, leptomeningeal hemosiderosis-associated symptoms, and others. MRI signs are highly specific, but the imaging strategy to search for spinal cerebrospinal fluid leaks (none, computed tomography myelography, magnetic resonance myelography with gadolinium, digital subtraction myelography) is a matter of debate. The same is true for the mode of treatment (bed rest, blind, fluoroscopy or computed tomography-guided epidural blood patching, fibrin patching, surgery). Clinical presentation as well as diagnostic and therapeutic approaches in intracranial hypotension are very heterogenous.


Notes on the Stenus indubius group with descriptions of four new species from China (Coleoptera, Staphylinidae).
Four new species of the Stenus indubius group from China are described: S. yaoluopingus Hu Tang, sp. n. from Anhui Province, S. lizipingus Hu Tang, sp. n., and S. fuscus Hu Tang, sp. n. from Sichuan Province, and S. absconditus Hu Tang, sp. n. from Guizhou Province. The diagnostic characters of the new species are illustrated and a published key to Chinese species of the group by Puthz, 2017 is modified to include the new species. Additional records of some species of the group are also provided.


Knowledge and practice of complementary medicine amongst public primary care clinic doctors in Kinta district, Perak.
The knowledge and practice of doctors (n=40) towards complementary medicine (CM) in 16 health clinics in the Kinta District were assessed by questionnaire. Thirty-four (85%) responded. More than half felt that acupuncture (73.50), homeopathy (59%) and herbal medicine (59%) were occasionally harmful. Forty-four percent felt manipulative therapy was frequently harmful. Relaxation technique (79%) and nutritional therapy (44%) were considered most frequently useful. 59% used some form of CM. There were no significant differences found in usage rates by gender, age group and exposure to CM during undergraduate training. Sixty-seven percent had encouraged patients to seek CM. Seventy-three percent perceived an increasing demand for CM. Eighty-eight percent were in favour of a hospital based CM referral center. Only 6% were trained in CM.


Assessment of Cost Drivers in Transsphenoidal Approaches for Resection of Pituitary Tumors Using the Value-Driven Outcome Database.
Reducing health care costs while improving quality of care has become imperative in neurosurgical care. The Value-Driven Outcome database at the University of Utah identifies cost drivers and tracks changes over time. Retrospective review was performed for transsphenoidal resections of pituitary adenomas from July 2012 to September 2016. Total cost, subcategory costs, and potential cost drivers were evaluated. There were 272 patients (mean age 51.5 years ± 17.7, 45.6% male) with mean length of stay of 4 days ± 4 evaluated. Total costs included facility utilization (60%), physician professional fees (16%), pharmacy (11%), supplies and implants (7%), laboratory studies (5%), and imaging (1%). Facility costs were driven by neurocritical care unit (30.7%), neurosurgical operating room (16.6%), and neurosurgical floor (11.2%) costs. Multivariable linear regression, after adjusting for length of stay and American Society of Anesthesiologists grade, showed that overall cost was heavily influenced by facility utilization (ρ = 0.98, P = 0.001), pharmacy (ρ = 0.71, P = 0.001), supplies and implants (ρ = 0.51, P = 0.0001), imaging (ρ = 0.51, P = 0.0001), and laboratory (ρ = 0.79, P = 0.001) costs. The top 10 outlier patients accounted for 18.7% of total costs (mean cost for all patients 0.24% ± 0.29). Our results highlight the importance of facility utilization and pharmaceutical, supply/implant, imaging, and laboratory costs as overall cost drivers during transsphenoidal pituitary tumor resection. Facility utilization was a stronger cost driver than any other aspect of care. Strategies to mitigate cost include stratifying low-risk patients to an intermediate care unit and reducing length of stay.


Recognizable rehabilitation movements of multiple unilateral upper limb: An fMRI study of motor execution and motor imagery.
This paper presents a study investigating the recognizability of multiple unilateral upper limb movements in stroke rehabilitation. A functional magnetic experiment is employed to study motor execution (ME) and motor imagery (MI) of four movements for the unilateral upper limb: hand-grasping, hand-handling, arm-reaching, and wrist-twisting. The functional magnetic resonance imaging (fMRI) images of ME and MI tasks are statistically analyzed to delineate the region of interest (ROI). Then parameter estimation associated with ROIs for each ME and MI task are evaluated, where differences in ROIs for different movements are compared using analysis of covariance (ANCOVA). All movements of ME and MI tasks activate motor areas of the brain, and there are significant differences (p < 0.05) in ROIs evoked by different movements. The activation area is larger when executing the hand-grasping task instead of the others. The four movements we propose can be adopted as MI tasks, especially for stroke rehabilitation, since they are highly recognizable and capable of activating more brain areas during MI and ME.