[Risk and prevention of lesions of the lingual nerve in wisdom tooth osteotomy. Analysis of the literature and faculty opinion in maxillofacial surgery in German-speaking countries].
Disturbance of lingual nerve function is one of the relevant complications after surgical removal of lower third molars. In the literature, however, protective measures against this complication are not unanimously recommended. In order to find out the current opinion in terms of the state of the art in this field, a questionnaire was sent to the heads of 39 University Departments for Oral and Maxillofacial Surgery in Germany, Austria, and Switzerland. All of them responded. In 54% of the departments, a periosteal elevator or similar instrument is recommended for the protection of the lingual nerve in every instance, whereas in 8% of the departments this is not recommended. In the remaining departments, the decision about protective measures is made according to the individual anatomical situation. The literature review revealed insufficient data quality for a sound data-based decision on whether and when to use an instrument to protect the lingual nerve. In any case, the statistical risk of a temporary disturbance of the lingual nerve seems to be higher with use of the lingual split (0.5%-19.8%) than with the lateral osteomtomy technique (0%-1.9%). In contrast to widespread opinion, even in anatomically difficult cases, there seems to be no statistical advantage of the standardized use of a protective instrument either in respect to temporary or permanent nerve damage. Yet, a slight increase of temporary lesions seems to be documented when the instrument is used. According to the current literature data, the subperiosteal insertion of an instrument to protect the lingual nerve cannot be considered an essential standard procedure in each case.


Editorial Commentary: Posterior Cruciate Ligament Reconstruction--Do Not Abandon the C-Arm Quite Yet.
Accurate tibial tunnel placement using the arthroscopically-assisted anatomic fovea landmark technique in transtibial posterior cruciate ligament reconstruction is possible without the use of fluoroscopic imaging. However, until a prospective, randomized controlled trial comparing the C-arm and anatomic fovea landmark techniques is completed, abandonment of the C-arm in posterior cruciate ligament reconstruction cannot be recommended.


Management of mild aortic stenosis during coronary artery bypass surgery: an update, 1992-2001.
"Prophylactic" aortic valve replacement (AVR) in patients with asymptomatic, mild-to-moderate aortic stenosis (AS) at the time of CABG is controversial. In 1994, we reported our initial experience involving 44 patients and have now updated our series in an attempt to further evaluate outcomes. Between January 1992 and July 2001, 100 consecutive patients underwent reoperative AVR following previous CABG. Forty patients had their initial surgery at the Brigham & Women's Hospital (BWH) and 60 patients had their coronary surgery elsewhere. None of the 40 BWH patients had a mean valve gradient greater than 25 mmHg at the time of CABG. The mean time interval from CABG to AVR for the entire group was 9.0 years (range: 1.4-21 years). Overall operative mortality (OM) was 7% including 5 deaths (10.2%) among 49 patients requiring additional CABG at the time of AVR and 2 deaths (3.9%) among 51 patients without additional coronary artery intervention. This OM rate was a notable decrease from our earlier report of 18.2% (P = 0.07). Furthermore, operative mortality decreased progressively from 15.4% in 1992-1993 to 0% in 2000-2001 (P = NS). The OM of reoperative AVR following CABG has fallen in recent years. Given the relevance of newer techniques and approaches, it may be reasonable to adopt an expectant management approach in patients with asymptomatic mild-to-moderate AS (i.e., mean systolic gradient less than 25 mmHg) at the time of CABG.


[Contact behavior of elderly females living alone from the social psychologic viewpoint--a preliminary study. III: Social contacts with friends/relatives including contacts with neighbors and former colleagues].
After a theoretical introduction results of a preliminary study on social contacts between elderly women living alone and their friends, neighbours and former colleagues are reported and with regard to further investigations discussed critically.


Indicators of visual scale as predictors of landscape preference; a comparison between groups.
Landscape change alters the visual scale of agricultural landscapes, as production units get larger and strips of taller vegetation are removed between smaller units. Visual scale, defined as the perceptual units reflecting the experience of landscape rooms, visibility and openness, is considered a key factor shaping landscape preference. The visual expression of landscapes affects people in many ways; aesthetic appreciation, health and well being. In order to understand how landscape changes alter the visual scale of landscapes, and hence its effect on human beings, it is important to establish efficient and practical ways of measuring visual scale and its relation to landscape preferences. This paper presents an empirical test of the ability to predict landscape preference of two photo-based indicators of visual scale; percentage open land in the view and size of landscape rooms. A preference survey was conducted with two groups of respondents; a student group from the Norwegian University of Life Sciences (UMB) and a public group. The student group was chosen to represent future landscape professionals. Photos of landscapes varying in the expression of visual scale were shown to survey respondents, who were asked to give scores according to how much they liked the landscapes. Both indicators were found to be predictors of preference for the student group, but not for the public group. The results demonstrate that student preferences do not reflect the landscape preferences of the wider public. The different appreciation of visual scale in the landscape of future landscape professionals and the public implies that experts wanting to reflect preferences of the wider public should be cautious when evaluating the visual impact of landscape change.


Photostability of green and yellow fluorescent proteins with fluorinated chromophores, investigated by fluorescence correlation spectroscopy.
The photostability of the widely used autofluorescent proteins EGFP and EYFP and their fluorinated counterparts were compared by means of fluorescence correlation spectroscopy. We analyzed the reduction of the apparent diffusional time in analogy to fluorescence quenching in which the 'photon concentration' is treated as the quencher concentration. The quantum yields of photobleaching Phi(bl) of EYFP (6.1x10(-)(5)) and EGFP (8.2x10(-)(5)) are in agreement with the previously published values. Among the investigated mutants, EYFP has the highest photostability and there is an enhanced photobleaching in (2-F) Tyr-EYFP. It turns out that the chromophore fluorination has no significant influence on the photostability.


Dry cupping for musculoskeletal pain and range of motion: A systematic review and meta-analysis.
This review evaluated the efficacy and safety of western dry cupping methods for the treatment of musculoskeletal pain and reduced range of motion. A systematic literature search was performed until April 2018 for randomised controlled trials (RCTs) pertaining to musculoskeletal pain or reduced range of motion, treated with dry cupping. Outcomes were pain, functional status, range of motion and adverse events. Risk of bias and quality of evidence was assessed using the modified Downs & Black (D&B) checklist and GRADE. A total of 21 RCTs with 1049 participants were included. Overall, the quality of evidence was fair, with a mean D&B score of 18/28. Low-quality evidence revealed dry cupping had a significant effect on pain reduction for chronic neck pain (MD, -21.67; 95% CI, -36.55, to -6.80) and low back pain (MD, -19.38; 95%CI, -28.09, to -10.66). Moderate-quality evidence suggested that dry cupping improved functional status for chronic neck pain (MD, -4.65; 95%CI, -6.44, to -2.85). For range of motion, low quality evidence revealed a significant difference when compared to no treatment (SMD, -0.75; 95%CI, -0.75, to -0.32). Dry cupping was found to be effective for reducing pain in patients with chronic neck pain and non-specific low back pain. However, definitive conclusions regarding the effectiveness and safety of dry cupping for musculoskeletal pain and range of motion were unable to be made due to the low-moderate quality of evidence. Further high-quality trials with larger sample sizes, long-term follow up, and reporting of adverse events are warranted.


Activation of amino acid transport during steady-state growth of Escherichia coli.
Accumulation of amino acids in exponentially increasing cultures of Escherichia coli was linear, supporting the interpretation that the biphasic response observed when cultures grew without these acids reflects a transient perturbation in accumulation. Rates of accumulation of glutamine, histidine and glycine were compared in steady-state and non-steady-state cultures. Their uptake rates were markedly enhanced in steady-state cultures at low exogenous concentrations, 10 microM or less. The results support the activation of amino acid transport systems by low concentrations of the particular amino acid present during growth. This activation was decreased when exogenous concentrations of the amino acid were markedly increased or when cells were washed free of the amino acid. Upon readdition of the amino acid after washing, recovery of enhanced transport required several generations, supporting a process of recovery other than enzymatic induction. The observation of amino acid enhancement of transport for eight other amino acids examined in steady-state culture suggests that this enhancement is a common process.


COVID-19-related financial strain and adolescent mental health.
The COVID-19 pandemic and associated responses have induced a host of crises worldwide, including an economic recession and a global mental health crisis. The specific effects of recession on youth mental health are understudied. We aimed to examine the mechanisms by which pandemic-related financial strain may affect mental health in a diverse sample of American adolescents. We analyzed data from the Adolescent Brain Cognitive Development Study (ABCD Study®), a large, longitudinal study of diverse US adolescents which collected data before and during the pandemic (N = 9,720, mean age 12.9 years, 18.2% Black). Linear mixed-effects models tested associations of financial strain (parent-reported household wage loss and youth-reported financial stress) with depressive symptomatology over time, covarying for multiple confounders including pre-pandemic socioeconomic status and psychopathology, and pandemic-related environmental factors. Longitudinal mediation analyses examined potential mechanisms leading from wage loss to youth mental health. Financial strain was highly prevalent, especially among low-income participants, with >70% of the total sample reporting lost wages. Both wage loss and subjective financial stress were associated with depressive symptomatology over time (Estimate = 0.04, P = 0.014; Estimate = 0.17, P < 0.001; respectively). The association between financial stress and depressive symptomatology was robust to the addition of multiple environmental confounders (Estimate = 0.16, P < 0.001). Both family-level (family conflict) and individual-level (financial stress) factors mediated the relationship between wage loss and depressive symptomatology. The financial effects of COVID-19 (and worldwide responses to it) have taken a significant toll on youth mental health. In families that lost wages, youth-reported financial stress and familial factors mediated the relationship between wage loss and mental health over time. Findings highlight financial stress as a key driver of youth mental health burden and identify familial factors as critical targets for intervention to mitigate mental health risks in periods of economic crises. This study was supported by the National Institute of Mental Health [grant numbers K23MH120437 (RB), R01MH117014 (TMM)]; the Lifespan Brain Institute of Children's Hospital of Philadelphia and Penn Medicine, University of Pennsylvania.


A dataset of plant and microbial community structure after long-term grazing and mowing in a semiarid steppe.
Grazing and mowing are two dominant management regimes used in grasslands. Although many studies have focused on the effects of grazing intensity on plant community structure, far fewer test how grazing impacts the soil microbial community. Furthermore, the effects of long-term grazing and mowing on plant and microbial community structure are poorly understood. To elucidate how these management regimes affect plant and microbial communities, we collected data from 280 quadrats in a semiarid steppe after 12-year of grazing and mowing treatments. We measured plant species abundance, height, coverage, plant species diversity, microbial biomass, and microbial community composition (G+ and G- bacteria; arbuscular mycorrhizal and saprotrophic fungi; G+/G- and Fungi/Bacteria). In addition, we determined the soil's physical and chemical properties, including soil hardness, moisture, pH, organic carbon, total nitrogen, and total phosphorus. This is a long-term and multifactorial dataset with plant, soil, and microbial attributes which can be used to answer questions regarding the mechanisms of sustainable grassland management in terms of plant and microbial community structure.


P53 suppresses cell proliferation, metastasis, and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway.
To investigate the role of P53 in the pathogenesis of osteosarcoma and the possible mechanism involved in it. The anti-proliferative effect of P53 was assessed using the cell counting Kit-8 assay. The migration and invasion potential were analyzed using wound-healing and transwell assays, respectively. The Matrigel capillary tube formation assay was performed to mimic in-vivo angiogenesis. Immunoblotting and immunofluorescence were used to observe protein levels and distribution of actin fibers. Finally, S2448p-mammalian target of rapamycin (mTOR) expression was detected on osteosarcoma tissues using immunohistochemistry. Firstly, P53 potently inhibited cell proliferation in osteosarcoma cell line (MG63) and in human normal osteoblasts (hFOB1.19) in vitro at the IC50 ranged from 50 to 500 nmol/l. Then, an inhibitory effect of P53 on metastasis was observed in osteosarcoma cell line MG63, along with the cytoskeletal rearrangements and suppression of the phosphorylation of PI3K downstream factors including AKT and mTOR. These results show that P53 suppresses cell proliferation and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway, which might be an effective novel therapeutic candidate against osteosarcoma in the future.


Upregulation of SNHG14 suppresses cell proliferation and metastasis of colorectal cancer by targeting miR-92b-3p.
Ample evidence have demonstrated that long noncoding RNAs small nucleolus RNA host gene 14 (SNHG14) serves as a master regulator in various cancers. However, the exact mechanism of SNHG14 in colorectal cancer (CRC) remains unknown. In the present study, we concentrate on the potential function of SNHG14 in the pathogenesis of CRC. From the quantitative reverse transcription-polymerase chain reaction results, SNHG14 was found to be downregulated in CRC tissues compared with the normal mucous samples, and its low expression was significantly correlated with poor clinical outcomes. Overexpression of SNHG14 inhibited cell growth, induced cell apoptosis, suppressed migration and invasion by inhibiting epithelial-mesenchymal transition process. Furthermore, mechanistic studies revealed that miR-92b-3p could rescue the CRC progress induced by SNHG14. Consequently, SNHG14 exhibited low expression in CRC tissues and involved in CRC progression and metastasis by competing for miR-92b-3p, and SNHG14 could be used as a valuable biomarker and therapeutic target for CRC.


Community Leadership through Conversations and Coordination: the Role of Local Surveys in Community Foundation Run Community Indicators Projects.
Community indicators (CI) projects rely on a variety of sources for the data that they make available to measure community well-being. While statistics collected and distributed by national and local governments are perhaps the most prevalent, some communities in both Canada and the United States have found great advantages to commissioning or administering their own surveys of local community members in order to enhance the insights that government-curated data can provide. In this paper we examine two organizations engaged with indicator projects that have opted to do so from the perspectives of their primary CI project supporters: the Vancouver Foundation in Canada and the Central New York Community Foundation in the United States. Among the advantages explored are increased capacity in key community leadership elements of: engaging residents, working across sectors, commissioning and disseminating local data and research, shaping public policy, and marshaling resources. We conclude by reflecting on the many synergies between the CI and community foundation (CF) movements, paying attention to their shared interests in community well-being through better conversations and coordination among the organizations in the communities they serve.


Beta-adrenergic blockade by nadolol in control of ventricular tachyarrhythmias.
The antiarrhythmic effect of nadolol, a long-acting, nonselective beta antagonist without intrinsic sympathomimetic or membrane-stabilizing properties, was evaluated in 36 patients with ventricular dysrhythmias as determined by three baseline 24-hour Holter recordings at a time when subjects were receiving placebo. Nadolol was administered once daily at a dose of 40 to 80 mg and increased at weekly intervals to a maximum daily dose of 640 mg. Thereafter the drug was stopped gradually and placebo was given again for a period of 2 weeks. Nadolol was effective in reducing premature ventricular contractions (PVCs) in 17 of 36 patients (48%), in reducing ventricular couplets in 24 of 27 patients (89%), and in reducing nonsustained runs of ventricular tachycardia in all 13 subjects. Serum nadolol levels obtained at dosages resulting in a 75% reduction in PVCs varied from 58 to 853 ng/ml. In the majority of the subjects studied, a nadolol dosage of 160 mg/day or less was effective for arrhythmia suppression.


Group II metabotropic glutamate receptors inhibit cAMP-dependent protein kinase-mediated enhancemednt of tetrodotoxin-resistant sodium currents in mouse dorsal root ganglion neurons.
Tetrodotoxin (TTX)-resistant sodium currents are important in nociception and nociceptive sensitization, which is partially due to their cAMP/protein kinase A (PKA)-mediated enhancement. Here we studied the effects of group II mGluR activation on TTX-resistant sodium currents in cultured mouse dorsal root ganglion (DRG) neurons. Activation of adenylyl cyclase with forskolin caused an increase in the amplitude of TTX-R currents and a leftward shift of the activation curve. When neurons were treated with ammonium pyrrolidinedithiocarbamate (APDC), a selective group II mGluR agonist, both the forskolin-induced increase in current amplitude and the shift of activation curve were blocked. LY341495, a group II mGluR antagonist, prevented these inhibitory effects of APDC. Our results suggest that group II mGluRs can negatively regulate TTX-R sodium currents in mouse DRG neurons.


ABE8e adenine base editor precisely and efficiently corrects a recurrent COL7A1 nonsense mutation.
Base editing introduces precise single-nucleotide edits in genomic DNA and has the potential to treat genetic diseases such as the blistering skin disease recessive dystrophic epidermolysis bullosa (RDEB), which is characterized by mutations in the COL7A1 gene and type VII collagen (C7) deficiency. Adenine base editors (ABEs) convert A-T base pairs to G-C base pairs without requiring double-stranded DNA breaks or donor DNA templates. Here, we use ABE8e, a recently evolved ABE, to correct primary RDEB patient fibroblasts harboring the recurrent RDEB nonsense mutation c.5047 C > T (p.Arg1683Ter) in exon 54 of COL7A1 and use a next generation sequencing workflow to interrogate post-treatment outcomes. Electroporation of ABE8e mRNA into a bulk population of RDEB patient fibroblasts resulted in remarkably efficient (94.6%) correction of the pathogenic allele, restoring COL7A1 mRNA and expression of C7 protein in western blots and in 3D skin constructs. Off-target DNA analysis did not detect off-target editing in treated patient-derived fibroblasts and there was no detectable increase in A-to-I changes in the RNA. Taken together, we have established a highly efficient pipeline for gene correction in primary fibroblasts with a favorable safety profile. This work lays a foundation for developing therapies for RDEB patients using ex vivo or in vivo base editing strategies.


[Description of the case of adverse pasteurellosis in a cirrhosis patient. Case report].
The article describes a clinical case of an unfavorable course of pasteurellosis in a patient with liver cirrhosis. Possible variants of the clinical course, clinical and epidemiological data, on the basis of which pasteurellosis can be suspected, modern recommendations for antibiotic therapy are considered.


Nutritional vitamin B12 deficiency-associated Infantile epileptic spasms syndrome: Clinico-neurophysiological presentation, response to treatment, and neurodevelopmental outcome.
Nutritional vitamin B12 deficiency has been shown to cause Infantile epileptic spasms syndrome (IESS) in infants in anecdotal studies. In this retrospective cohort study, we intended to study the clinical presentation, neurophysiological, laboratory abnormalities, treatment, and neurodevelopmental outcome at 6-months in infants presenting with IESS secondary to nutritional vitamin B12 deficiency (NVBD) and to compare these variables from the rest of the infants with IESS without vitamin B12 deficiency. We included only spasm-free cases or those who showed at least a 50% reduction in spasm frequency on D7 after starting oral/parenteral vitamin B12. We used well-validated measurement tools like the Developmental Assessment Scale for Indian Infants (DASII), Child Feeding Index (CFI), Burden of amplitudes and epileptiform discharges (BASED) score, countable Hypsarrhythmia paroxysm index (cHPI), durational Hypsarrhythmia paroxysm index (dHPI), and Early childhood epilepsy severity scale (E-CHESS) score for documenting these variables. Data from 162 infants with IESS (21 caused by NVBD) were included in our study. The NVBD group had more patients residing in the rural region, with lower socioeconomic status, vegetarian mothers and poor complementary feeding index (p<0.001 for all). The NVBD group also had less number of patients requiring antiseizure medications (ASMs) and hormonal therapy(p<0.001), remained seizure free at six months (p=0.008), lower number of clusters per day (p=0.02) and the number of spasms per clusters at presentation (p=0.03), lower BASED score (p=0.03) and cHPI, dHPI at presentation (p<0.001). All of them remained spasm-free, with normal electroencephalogram at 6-months. Development quotient at baseline, at 6-months, and improvement in development quotient between these two-time points were more in the vitamin B12 deficiency group (p<0.001). All of them had clinical features of pre-ITS (infantile tremor syndrome) or ITS and it was found to be the only independent predictor of NVBD in infants with IESS. Mothers of all these infants had low serum vitamin B12 levels (<200 pg/ml). Nutritional vitamin B12 deficiency may cause IESS in infants. Hence, vitamin B12 deficiency needs to be ruled out in patients with IESS without any definite etiology.


Association of Pioneer Accountable Care Organizations vs traditional Medicare fee for service with spending, utilization, and patient experience.
The Pioneer Accountable Care Organization (ACO) Model aims to drive health care organizations to reduce expenditures while improving quality for fee-for-service (FFS) Medicare beneficiaries. To determine whether FFS beneficiaries aligned with Pioneer ACOs had smaller increases in spending and utilization than other FFS beneficiaries while retaining similar levels of care satisfaction in the first 2 years of the Pioneer ACO Model. Participants were FFS Medicare beneficiaries aligned with 32 ACOs (n = 675,712 in 2012; n = 806,258 in 2013) and a comparison group of alignment-eligible beneficiaries in the same markets (n = 13,203,694 in 2012; n = 12,134,154 in 2013). Analyses comprised difference-in-differences multivariable regression with Oaxaca-Blinder reweighting to model expenditure and utilization outcomes over a 2-year performance period (2012-2013) and 2-year baseline period (2010-2011) as well as adjusted analyses of Consumer Assessment of Healthcare Providers & Systems (CAHPS) survey responses among random samples of beneficiaries in Pioneer ACOs (n = 13,097), FFS (n = 116,255), or Medicare Advantage (n = 203,736) for 2012 care. Beneficiary alignment with a Pioneer ACO in 2012 or 2013. Medicare spending, utilization, and CAHPS domain scores. Total spending for beneficiaries aligned with Pioneer ACOs in 2012 or 2013 increased from baseline to a lesser degree relative to comparison populations. Differential changes in spending were approximately -$35.62 (95% CI, -$40.12 to -$31.12) per-beneficiary-per-month (PBPM) in 2012 and -$11.18 (95% CI, -$15.84 to -$6.51) PBPM in 2013, which amounted to aggregate reductions in increases of approximately -$280 (95% CI, -$315 to -$244) million in 2012 and -$105 (95% CI, -$148 to -$61) million in 2013. Inpatient spending showed the largest differential change of any spending category (-$14.40 [95% CI, -$17.31 to -$11.49] PBPM in 2012; -$6.46 [95% CI, -$9.26 to -$3.66] PBPM in 2013). Changes in utilization of physician services, emergency department, and postacute care followed a similar pattern. Compared with other Medicare beneficiaries, ACO-aligned beneficiaries reported higher mean scores for timely care (77.2 [ACO] vs 71.2 [FFS] vs 72.7 [MA]) and for clinician communication (91.9 [ACO] vs 88.3 [FFS] vs 88.7 [MA]). In the first 2 years of the Pioneer ACO Model, beneficiaries aligned with Pioneer ACOs, as compared with general Medicare FFS beneficiaries, exhibited smaller increases in total Medicare expenditures and differential reductions in utilization of different health services, with little difference in patient experience.


Selective digestion of mouse metaphase chromosomes.
Metaphase chromosomes prepared from colcemid-treated mouse L929 cells by non-ionic detergent lysis exhibit distinct heterochromatic centromere regions and associated kinetochores when viewed by whole mount electron microscopy. Deoxyribonuclease I treatment of these chromosomes results in the preferential digestion of the chromosomal arms leaving the centromeric heterochromatin and kinetochores apparently intact. Enrichment in centromere material after DNase I digestion was quantitated by examining the increase in 10,000 X g pellets of the 1.691 g/cc satellite DNA relative to main band DNA. This satellite species has been localized at the centromeres of mouse chromosomes by in situ hybridization. From our analysis it was determined that DNase I digestion results in a five to six-fold increase in centromeric material. In contrast to the effect of DNase I, micrococcal nuclease was found to be less selective in its action. Digestion with this enzyme solubilized both chromosome arms and centromeres leaving only a small amount of chromatin and intact kinetochores.


Identification of biomarkers related to glycolysis with weighted gene co-expression network analysis in oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) is the most common tumor in the oral cavity and maxillofacial region. Increasing evidence suggests that aerobic glycolysis plays an important role in the occurrence, development, and prognosis of OSCC. Therefore, the identification of biomarkers related to glycolysis in OSCC represents considerable potential for improving its treatment. In the present study, a single-sample gene-set enrichment analysis (ssGSEA) algorithm with weighted gene co-expression network analysis (WGCNA) were used to quantify the degree of glycolysis and identify key modules with the greatest correlation with glycolysis. Glycolytic scores significantly correlated with prognosis. In the key module 5 HUB genes were finally selected, which displayed a robust predictive effect. The expressions of key genes were associated with glycolysis. The research comprehensively analyzed the glycolysis of OSCC and identified several biomarkers related to glycolysis. These biomarkers may represent potential therapeutic targets for future OSCC therapy.


Altering access to autobiographical episodes with prior semantic knowledge.
Within autobiographical knowledge, semantic and episodic memory are traditionally considered separate, but newer models place them along a continuum, which raises the possibility of an intermediate form of knowledge - personal semantics. This study tested how different types of semantics - general semantics and two forms of personal semantics - impact access to personal episodic memories. In two experiments, participants made a series of true/false judgments about a prime statement, which reflected a general semantic fact, a context-dependent (e.g., repeated event) or context-independent (e.g., trait), personal semantic fact and then retrieved a specific past episodic memory. There was a significantly stronger priming effect for accessing specific episodic memories after judging personal semantic facts versus general facts. We also found that context-dependent and -independent personal semantic facts had separable priming effects on episodic memory. These findings support a continuum model of memory and verifies that there are multiple forms of personal knowledge.


Resisting abortion stigma in situ: South African womxn's and healthcare providers' accounts of the pre-abortion counselling healthcare encounter.
Abortion providers and pregnant people who undergo abortion potentially face significant stigma. Researchers have started to explore how womxn respond to abortion stigma, usually focusing on individual strategies in managing or reducing stigma effects. Drawing on narrative data from research conducted on womxn's and healthcare providers' experiences of the pre-abortion healthcare encounter in the South African public health sector, we highlight how stigma may be resisted in social ways within this context. Everyday chatter and informal social support amongst womxn in the waiting room provided a counterpoint for health service providers' ascription of shame to the womxn, and a sense of solidarity amongst the womxn. Health service providers narrated their decision to do abortion work through the socially affirming hero canonical narrative, and womxn described their counselling as helpful. These social and discursive practices resist the awfulisation of abortion and provide relief for the womxn and the healthcare providers in particular contexts.


Acetylation and oxidation phenotypes in malignant lymphoma.
101 white British adults with Hodgkin's disease or non-Hodgkin's lymphoma were phenotyped for acetylation status using dapsone and for oxidation status with debrisoquine prior to treatment. The frequencies of acetylation and oxidation phenotypes in these patients were compared with reference populations of normal subjects. No significant difference in phenotype frequency was found in the lymphoma patients. This suggests that neither of these metabolic polymorphisms for exogenous compounds is strongly associated with these malignancies. Owing to the small size of the study, however, an effect of these phenotypes could not be excluded.


Transfer of measles, mumps, and rubella antibodies from mother to infant. Its effect on measles, mumps, and rubella immunization.
Sera from 42 mother-infant pairs were examined to determine the effect of passively acquired enhanced neutralizing (ENt) antibody on immunization. The ENt antibodies to measles, mumps, and rubella were greater in term newborns than in their mothers, with mean ratio of 1.8:1, 1.3:1, and 1.2:1, respectively. In 21% to 25% of the children, these antibodies persisted until 12 months of age. When immunized with trivalent measles-mumps-rubella vaccine, children who had persisting ENt measles and rubella titers had significantly lower mean antibody responses than children without detectable antibodies to the two viruses. Persisting ENt mumps antibodies did not affect the postimmunization titers. Seroconversion rates to any of the three viruses were not different in children with or without preexisting ENt antibody.


[Split skin and full-thickness skin grafts].
Skin grafting is one of the earliest described surgical procedures. In the age of microsurgery and free-tissue transfer, it remains a utilitarian means of achieving soft tissue reconstruction. Free skin grafts can be classified into three types: full-thickness skin grafts, split-thickness skin grafts, and composite grafts. The indications, techniques, donor site considerations, postoperative complications, and results of each type are reviewed. The full-thickness skin graft for facial and cervical reconstruction is usually harvested from the upper arm or postauricular region and is applied under a tie-over dressing. When comparing the functional and aesthetic results of full-thickness skin grafts and split-thickness skin grafts in terms of morbidity, skin elasticity, skin sensitivity, matching, and scar recurrence, full-thickness skin grafting seems to be the most adequate technique.


Magnetite fine particle and nanoparticle environmental contamination from industrial uses of coal.
Recently it has been shown that there are two types of magnetite particles in the human brain, some, which occur naturally and are jagged in appearance, and others that arise from industrial sources, such as coal fired power plants, and are spherical. In order to confirm the latter, the magnetic component of coal ash is first purified and characterized by XRD, showing that it is magnetite with an average particle size of 211 nm. Studies confirm the coal ash magnetic behavior, and that the magnetite is not bound to the other components of coal ash but exist as an isolatable component. SEM studies confirm that in the process of burning coal at very high temperatures for industrial uses, the magnetite formed is spherically shaped, as recent studies of brain tissues of highly exposed urban residents have found. As such, the use of coal for industrial applications such as coking in the production of steel and in power plants is indicated to be a major source of the spherical magnetic combustion-associated magnetite fine particle and nanoparticle environmental pollution. The capacity of these magnetic particles to penetrate and damage the blood-brain-barrier and the early development of Alzheimer's disease hallmarks in exposed populations calls for detail analysis of magnetic fine and nanoparticle distribution across the world. Summation: Industrial coal usage produces spherical magnetic particles and nanoparticles, identical to those associated with neurological disorders.


Identifying Intraoperative Behaviors Associated With Surgical Resident Teachability.
The resident-attending dyad influences the intraoperative training of surgery residents. To better understand the role of trainees within the dyad, we hypothesized there is a measurable concept of "teachability," a combination of the trainee's observed skills and behaviors with their performance. This study aims to define teachability and identify discrete intraoperative behaviors that contribute to this concept. We posit that residents who are active learners as demonstrated by asking questions, proposing next steps, and initiating purposeful actions have higher teachability. Previously recorded videos from 26 laparoscopic inguinal hernia repairs performed by two PGY-5 general surgery residents at a Midwest tertiary care center were qualitatively reviewed for intraoperative behaviors. A summative content analysis identified behaviors associated with increased teachability and improved operative performance assessment scores. Average frequencies of intraoperative behaviors for resident 1 and 2 (R1 and R2) were not significantly different, although R2 asked more medical knowledge and technical questions. While the rate of attending feedback was similar for both residents (x=3.82 vs 3.40, p=0.646), R1 consistently incorporated feedback (x=2.27 vs 0.40, p=0.001) whereas R2 needed frequent prompting (x=2.45 vs 1.55, p=0.239). R1 scored higher in all but one operative performance assessment category, including overall performance (x=4.17 vs 2.93, p=0.007), but R2 had a larger magnitude of overall improvement (+1 vs +2). Teachability is a dynamic component of the resident-attending dyad. While intraoperative active learning behaviors do not appear to be associated with teachability, asking questions may increase the magnitude of improvement in performance. Most importantly, the ability to incorporate intraoperative feedback in real time seems to be a critical aspect of teachability and warrants further research.


Diagnostic value of bronchoalveolar lavage fluid galactomannan assay for invasive pulmonary aspergillosis in adults: A meta-analysis.
To analyse the diagnostic accuracy of bronchoalveolar lavage fluid galactomannan (BALF-GM) assay for invasive pulmonary aspergillosis (IPA) in adults to determine the optimal diagnostic cut-off by meta-analysis. PubMed, Embase, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI), and China Wanfang databases were searched to collect relevant studies on the diagnostic value of BALF-GM for IPA from inception to March 2022. The summary receiver operating characteristic (SROC) curve was drawn to determine the optimal diagnostic cut-off. Nineteen articles (56 data sets) were included. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.79 (95% CI: 0.72-0.84), 0.92 (95% CI: 0.88-0.94), 9.25 (95% CI: 6.84-12.52), 0.23 (95% CI: 0.18-0.30), 39.44 (95% CI: 29.55-52.65), and 0.92 (95% CI: 0.90-0.94), respectively. The area under the curves (AUCs) were 0.92, 0.86, 0.93, 0.89, 0.88, and 0.94 when the cut-off values were 0.5, 0.8, 1.0, 1.5, 2.0, and 3.0, respectively. Sixteen studies were included in the combined analysis when the cut-off value was 0.5. The results showed that the pooled sensitivity, specificity, PLR, NLR and DOR of BALF-GM (cut-off 0.5) for the diagnosis of IPA were 0.89 (95% CI: 0.83-0.93), 0.79 (95% CI: 0.71-0.86), 4.33 (95% CI: 3.04-6.16), 0.14 (95% CI: 0.09-0.22), and 31.51 (95% CI: 17.43-56.98). The AUC was 0.92 (95% CI: 0.89-0.94). BALF-GM has excellent diagnostic accuracy for adult IPA, which can be diagnosed early and treated early to reduce the mortality rate. Considering the sensitivity, specificity, PLR and NLR, the recommended diagnostic cut-off of BALF-GM for adult IPA is 0.5.


Multi-year field trials provide a massive repository of trait data on a highly diverse population of tomato and uncover novel determinants of tomato productivity.
Tomato (Solanum lycopersicum) is a prominent fruit with rich genetic resources for crop improvement. By using a phenotype-guided screen of over 7900 tomato accessions from around the world, we identified new associations for complex traits such as fruit weight and total soluble solids (Brix). Here, we present the phenotypic data from several years of trials. To illustrate the power of this dataset we use two case studies. First, evaluation of color revealed allelic variation in phytoene synthase 1 that resulted in differently colored or even bicolored fruit. Secondly, in view of the negative relationship between fruit weight and Brix, we pre-selected a subset of the collection that includes high and low Brix values in each category of fruit size. Genome-wide association analysis allowed us to detect novel loci associated with total soluble solid content and fruit weight. In addition, we developed eight F2 biparental intraspecific populations. Furthermore, by taking a phenotype-guided approach we were able to isolate individuals with high Brix values that were not compromised in terms of yield. In addition, the demonstration of novel results despite the high number of previous genome-wide association studies of these traits in tomato suggests that adoption of a phenotype-guided pre-selection of germplasm may represent a useful strategy for finding target genes for breeding.


Isolation of an antiidiotypic antibody with acetylcholine-receptor-like binding properties from myasthenia gravis patients.
The network theory predicts that a subpopulation within the antiidiotypic (anti-Id) antibody response will be the internal image of the priming stimulus. In myasthenia gravis, a portion of the anti-acetylcholine-receptor (anti-AChR) antibody repertoire is directed against the ligand-binding site. These antibodies would be expected to elicit an "anti-idiotype" which is the internal image of the receptor-binding site and hence may also bind cholinergic ligands. We have utilized this theoretical specificity to isolate anti-Id antibodies with AChR-like ligand-binding properties from the serum of 4 myasthenia gravis patients using a choline affinity column. Affinity-purified antibodies from one patient were characterized and found to exhibit binding properties similar to the AChR for various cholinergic ligands.


Being at risk for cardiovascular disease: perceptions and preventive behavior in people with and without a known genetic predisposition.
This study compares and explains differences in perceptions of cardiovascular disease (CVD) risk and preventive behaviors in people with and without a known genetic predisposition to CVD. A cross-sectional study using two samples was performed. The first sample (genetic predisposition; n = 51) consisted of individuals recently diagnosed with familial hypercholesterolemia (FH) through DNA testing. The second sample (no genetic predisposition; n = 49) was recruited among patients with CVD-risk profiles based on family history of CVD, cholesterol levels, and blood pressure, registered at general practices. Participants filled out a postal questionnaire asking about their perceived risk, causal attributions (i.e. genetic and lifestyle), and about perceived efficacy and adoption of preventive behavior (i.e. medication adherence and adoption of a healthy diet and being sufficiently active). Perceived comparative risk, genetic attributions of CVD, and perceived efficacy of medication were higher in the "genetic predisposition" sample than in the "no genetic predisposition" sample. The samples did not differ on lifestyle attributions, efficacy of a healthy lifestyle, or preventive behavior. Individual differences in perceived risk, genetic attributions, perceived efficacy of medication, and adoption of a healthy lifestyle were best explained by family history of CVD. Our findings suggest that in people diagnosed with a single gene disorder characterized by a family disease history such as FH, family disease history may be more important than DNA information in explaining perceptions of and responses to risk.


Quality improvement and reconciliation process for automated dispensing cabinet medication overrides.
To describe a pharmacist-led reconciliation process for automated dispensing cabinet (ADC) medication override setting maintenance at an academic medical center. ADC override management requires alignment of people, processes, and technology. This evaluation describes system-wide improvements to enhance institutional medication override policy compliance by establishing a formalized evaluation and defined roles to streamline ADC dispense setting management. A pharmacist-led quality improvement initiative revised the institutional medication override list to improve medication dispensing practices across an academic medical center campus with a pediatric hospital and 2 adult hospitals. This initiative included removal of patient care unit designations from the medication override list, revision of institutional override policy, creation of an online submission form, and selection of ADC override metrics for surveillance. A conceptual framework guided decisions for unique dosage forms and interdisciplinary engagement. Employing this framework revised workflows for stakeholders in the medication-use process through clinical pharmacist evaluation, existing shared governance structure communication, and pharmacy automation support.The revised policy increased the number of medications available for override from 80 to 106 (33% increase) and unique dosage forms from 166 to 191 (15% increase). The total number of medication dispense settings was reduced from 5,600 to 541 (90% decrease). The proportion of override dispenses compliant with policy increased from 59% to 98% (P < 0.001). Median monthly ADC overrides remained unchanged following policy revision (P = 0.995). ADC override rate reduction was observed across the institution, with the rate decreasing from 1.4% to 1.2% (P < 0.001). Similar ADC override rate reductions were observed for adult, pediatric, and emergency department ADCs. This initiative highlights pharmacists' role in leading institutional policy changes that influence the medication-use process through ADC dispensing practices. A pharmacist-led reconciliation process that removed practice area designations from our medication override policy streamlined ADC setting maintenance, increased the compliance rate of ADC override transactions, and provided a formalized process for future evaluation of medication overrides.


Targeting inflammatory diseases via apoptotic mechanisms.
Induction of apoptosis in immune cells is a crucial mechanism used by the body to produce immune resolution. The homeostatic mechanisms employed are currently being identified and, to date, studies have highlighted some of the signals that regulate the immune response. The exposure of phosphatidylserine on the surface of an apoptotic neutrophil is sufficient to limit the immune response in acute inflammation, whereas apoptosis of key effector cells can limit the response in chronic inflammation. Other therapeutic approaches that are being investigated include the inhibition of apoptosis by blocking the caspase cascade. This approach will be of particular relevance for the treatment of inflammatory central nervous system diseases and sepsis. An alternative approach being examined is forced resolution, whereby apoptosis is induced in effector cells, principally T cells, through activation-induced cell death mediated by Fas receptors. Inhibitors of this mechanism have been identified and targeted in several studies.


Ripasudil Eyedrops Ameliorated Bullous Keratopathy Complicated with Cytomegalovirus Corneal Endotheliitis: A Case Report.
We describe a case of bullous keratopathy complicated with cytomegalovirus (CMV) corneal endotheliitis that was successfully treated with ripasudil eye drops. A retrospective case report. A 65-year-old female patient diagnosed with CMV-associated anterior uveitis in the right eye was referred to us when anterior uveitis recurred with bullous keratopathy. Initial best-corrected visual acuity (BCVA) was 0.4 (decimal visual acuity). Her condition did not improve with anti-CMV treatment, and BCVA decreased to 0.07. At this point, intraocular pressure (IOP) was 20 mmHg, and ripasudil eye drops were started for IOP control. After 1 month, not only had IOP decreased to 14 mm Hg but the condition of the corneal edema had also improved. The central corneal thickness decreased to a normal level, and the BCVA recovered to 0.8. Ripasudil eye drops not only lower IOP in patients with CMV corneal endotheliitis but may also have the potential to treat bullous keratopathy.


Two distinct secretory vesicle-priming steps in adrenal chromaffin cells.
Priming of large dense-core vesicles (LDCVs) is a Ca(2+)-dependent step by which LDCVs enter a release-ready pool, involving the formation of the soluble N-ethyl-maleimide sensitive fusion protein attachment protein (SNAP) receptor complex consisting of syntaxin, SNAP-25, and synaptobrevin. Using mice lacking both isoforms of the calcium-dependent activator protein for secretion (CAPS), we show that LDCV priming in adrenal chromaffin cells entails two distinct steps. CAPS is required for priming of the readily releasable LDCV pool and sustained secretion in the continued presence of high Ca(2+) concentrations. Either CAPS1 or CAPS2 can rescue secretion in cells lacking both CAPS isoforms. Furthermore, the deficit in the readily releasable LDCV pool resulting from CAPS deletion is reversed by a constitutively open form of syntaxin but not by Munc13-1, a priming protein that facilitates the conversion of syntaxin to the open conformation. Our data indicate that CAPS functions downstream of Munc13s but also interacts functionally with Munc13s in the LDCV-priming process.


Ionothermal synthesis of Fe3O4 magnetic nanoparticles as efficient heterogeneous Fenton-like catalysts for degradation of organic pollutants with H2O2.
Fe3O4 magnetic nanoparticles (MNPs) are attractive heterogeneous Fenton-like catalysts for oxidative degradation of organic pollutants with H2O2. Herein highly efficient and stable Fe3O4 MNPs (Fe3O4-op-DES, ca. 10nm) were successfully prepared via a novel oxidative precipitation-combined ionothermal synthesis, which comprised oxidative precipitation of FeSO4·7H2O in choline chloride:2urea deep eutectic solvent. Among five different Fe3O4 particles tested, Fe3O4-op-DES MNPs exhibited the highest catalytic activity with the activation energy of 47.6kJmol-1 for degradation of Rhodamine B (RhB) with H2O2 under the same conditions (Fe3O4 dosage of 0.50gL-1, H2O2 concentration of 40mmolL-1, pH 6.4, 55°C, 2h). Fe3O4-op-DES MNPs were magnetically recoverable, and had good catalytic stability and recyclability without the need of regeneration (>98% degradation efficiency of RhB in 2h and pseudo-first-order rate constant of 0.0376min-1 after having been continuously running for 12h). The superior catalytic performance of Fe3O4-op-DES MNPs was attributed to the combination of multiple technologically important features, including the nanometer size, high Fe2+ content, large surface area, high density of surface active sites and stable crystal structure (no phase transformation, negligible iron leaching and particle aggregation after reaction). The wide applicability of Fe3O4-op-DES MNPs was also demonstrated by the degradation of four other organic pollutants.


Determination of ivabradine and its N-demethylated metabolite in human plasma and urine, and in rat and dog plasma by a validated high-performance liquid chromatographic method with fluorescence detection.
A sensitive and selective high-performance liquid chromatographic method with native detection of fluorescence was developed and validated for the quantitation of ivabradine and its N-demethylated metabolite in plasma (rat, dog, human) and human urine. The procedure involves the use of an analogue as internal standard, solid-phase extraction on cyano cartridges, separation on a Nova-Pak C8 column and fluorescence detection. Calibration curves are linear in the concentration ranges from 0.5 to 100 ng/ml in plasma and 2.0 to 500 ng/ml in urine with a limit of quantitation set at 0.5 and 2.0 ng/ml in plasma and urine, respectively. The analysis of plasma and urine samples (spiked with the analytes at low, medium and high concentrations of the calibration range) demonstrates that both analytes can be measured with precision and accuracy within acceptable limits. Quality controls spiked with analyte concentrations up to 10000 ng/ml can also be analysed with excellent precision and accuracy after dilution of the samples. The parent drug and its metabolite are stable in plasma and urine after short-term storage (24 h at room temperature and after three freeze-thaw cycles) as well as after long-term storage at -20 degrees C (at least 6 months in animal plasma and 12 months in human plasma and urine). The method has been used to quantify both compounds in plasma and urine samples from clinical and non-clinical studies with ivabradine.


Comprehensive identification of high-frequency and co-occurring Mafa-B, Mafa-DQB1, and Mafa-DRB alleles in cynomolgus macaques of Vietnamese origin.
High-frequency alleles and/or co-occurring human leukocyte antigen (HLA) alleles across loci appear to be more important than individual alleles, because they might be markers of disease risk that have clinical value as biomarkers for targeted screening or the development of new therapies. To better elucidate the major histocompatibility complex background and to facilitate the experimental use of cynomolgus macaques, Mafa-B, Mafa-DQB1, and Mafa-DRB alleles were characterized and their combinations were investigated from 30 macaques of Vietnamese origin by cloning and sequencing. A total of 48 Mafa-B, 22 Mafa-DQB1, and 42 Mafa-DRB alleles, were detected in this study, respectively. In addition, two Mafa-DQB1 and eight Mafa-DRB alleles represented novel sequences that had not been documented in earlier studies. Our results also showed that the macaque from Vietnam might be valuable because >30% of the test animals possessed Mafa-DRB*w304 (30%) and -DQB1*0616 (30%). We report that the combination of major histocompatibility complex (MHC) class I and II alleles, including the combination of DRB3*0403-DRB*w304, DRB1*1013-DRB*w304, and Mafa-B*007:01:01-DRB*w304, which was in 17%, 13%, and 13% of the animals, respectively. Interesting, more than two Mafa-DQB1 alleles detected in one animal in this study suggest that Mafa-DQB1, like Mafa-DRB, might be a duplication in the chromosome, which have ever been documented in cynomolgus monkeys but has not yet been observed in rhesus macaques or other primates. Our results for the high frequency of commonly co-occurring MHC alleles across loci in a cohort of the Vietnamese cynomolgus macaque emphasized the value of this species as a model for biomedical research.


Predictors of long-term survival after out-of-hospital cardiac arrest: the impact of Activities of Daily Living and Cerebral Performance Category scores.
Current focus on immediate survival from out-of-hospital cardiac arrest (OHCA) has diverted attention away from the variables potentially affecting long-term survival. To determine the relationship between neurological and functional status at hospital discharge and long-term survival after OHCA. Prospective data collection for all OHCA patients aged >18 years in the Jerusalem district (n=1043, 2008-2009). Length of survival after OHCA. Potential predictors: Activities of Daily Living (ADL) and Cerebral Performance Category (CPC) scores at hospital discharge, age and sex. There were 52/279 (18.6%) survivors to hospital discharge. Fourteen were discharged on mechanical ventilation (27%). Interviews with survivors and/or their legal guardians were sought 2.8±0.6 years post-arrest. Eighteen died before long-term follow-up (median survival 126 days, IQR 94-740). Six improved their ADL and CPC scores between discharge and follow-up. Long-term survival was positively related with lower CPC scores (p=0.002) and less deterioration in ADL from before the arrest to hospital discharge (p=0.001). For each point increment in ADL at hospital discharge, the hazard ratio of death was 1.31 (95%CI 1.12, 1.53, p=0.001); this remained unchanged after adjustment for age and sex (HR 1.26, 95%CI 0.07, 1.48, p=0.005). One-third of the patients discharged from hospital after OHCA died within 30 months of the event. Long-term survival was associated both with better neurological and functional level at hospital discharge and a smaller decrease in functional limitation from before to after the arrest, yet some patients with a poor neurological outcome survived prolonged periods after hospital discharge.


Fluid shear stress stimulates big mitogen-activated protein kinase 1 (BMK1) activity in endothelial cells. Dependence on tyrosine kinases and intracellular calcium.
Mitogen-activated protein (MAP) kinases including ERK1/2 and JNK play an important role in shear stress-mediated gene expression in endothelial cells (EC). A new MAP kinase termed big MAP kinase 1 (BMK1/ERK5) has been shown to phosphorylate and activate the transcription factor MEF2C, which is highly expressed in EC. To determine the effects of shear stress on BMK1, bovine aortic EC were exposed to steady laminar flow (shear stress = 12 dynes/cm2). Flow activated BMK1 within 10 min with peak activation at 60 min (7.1 +/- 0.6-fold) in a force-dependent manner. Flow was the most powerful activator of BMK1, significantly greater than H2O2 or sorbitol. An important role for non-Src tyrosine kinases in flow-mediated BMK1 activation was demonstrated by inhibition with herbimycin A, but not with the Src inhibitor PP1 or overexpression of kinase-inactive c-Src. BMK1 activation was calcium-dependent as shown by inhibition with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester or thapsigargin. As shown by specific inhibitors or activators, flow-mediated BMK1 activation was not regulated by the following: intracellular redox state; intracellular NO; protein kinase A, C, or G; calcium/calmodulin-dependent kinase; phosphatidylinositol 3-kinase; or arachidonic acid metabolism. In summary, flow potently stimulates BMK1 in EC by a mechanism dependent on a tyrosine kinase(s) and calcium mobilization, but not on c-Src, redox state, or NO production.


Acetylsalicylic acid/esomeprazole fixed-dose combination.
The fixed-dose acetylsalicylic acid (ASA)/esomeprazole capsule combines the cardiovascular (CV) protective effects of low-dose ASA with the gastroprotective effects of the proton pump inhibitor esomeprazole. It is approved for use as a convenient once-daily regimen in the prevention of CV and cerebrovascular events in patients requiring continuous low-dose ASA who are at risk of developing gastric and/or duodenal (peptic) ulcers. In two large, 26-week, randomized, double-blind, multinational, phase III trials (ASTERIX and OBERON) in patients who were receiving low-dose ASA for the prevention of CV events and who had an increased risk of ulcer development, the incidence of endoscopy-proven peptic ulcers (primary endpoint) was significantly lower with the addition of esomeprazole 20 mg/day versus placebo. Moreover, patient-reported dyspeptic symptoms (epigastric pain and epigastric burning) were reported in significantly fewer patients in the low-dose ASA plus esomeprazole group than in the low-dose ASA plus placebo group. Low-dose ASA plus esomeprazole treatment was generally well tolerated, with a similar adverse event profile to that seen with low-dose ASA plus placebo.


Topical inhibition of oral carcinoma cell with polymer delivered celecoxib.
Celecoxib has a potential role for oral cancer chemoprevention but its systemic side effects are a concern. Topical chemoprevention is a promising way to reduce the toxicity. This study was designed to determine whether topical application of polymer delivered celecoxib would have an inhibitory effect on human oral carcinoma cells. Seventeen nude mice were intradermally inoculated with the carcinoma cells, and then were divided into control and treatment groups. Tumor growth was measured for 15 days, at which significant difference was found between two groups (P<0.001). This study indicates a potential role of polymer film delivered celecoxib for topical inhibition of oral cancer.


CD44--a molecule involved in leukocyte adherence and T-cell activation.
The study of cell surface molecules that are involved in interactions between immune and non-hematopoietic cells in various microenvironments is currently an area of great interest. One molecule that appears to be involved in multiple steps of normal immune cell function is now called CD44 and has been known previously as Pgp-1, In(Lu)-related p80, Hermes, ECM-III and HUTCH-I. Within the past year, the co-identity of all of these independently discovered molecules has become apparent, and the role of the CD44 molecule in T-cell activation has been discovered. In this review, Barton Haynes and his colleagues bring together numerous divergent lines of investigation on the CD44 molecule, review the many functional roles attributed to it, and present a unifying view of how, with numerous ligands, it may participate in several areas of normal immune cell function.


Dimerization of BTas is required for the transactivational activity of bovine foamy virus.
The BTas protein of bovine foamy virus (BFV) is a 249-amino-acid nuclear regulatory protein which transactivates viral gene expression directed by the long terminal repeat promoter (LTR) and the internal promoter (IP). Here, we demonstrate the BTas protein forms a dimeric complex in mammalian cells by using mammalian two hybrid systems and cross-linking assay. Functional analyses with deletion mutants reveal that the region of 46-62aa is essential for dimer formation. Furthermore, our results show that deleting the dimerization region of BTas did not affect the localization of BTas, but that it did result in the loss of its transactivational activity on the LTR and IP. Furthermore, BTas (Delta46-62aa) retained binding ability to the LTR and IP similar to that of the wild-type BTas. These data suggest the dimerization region is necessary for the transactivational function of BTas and is crucial to the replication of BFV.


Shorter telomeres correlate with an increase in the number of uniparental disomies in patients with chronic lymphocytic leukemia.
This study investigated the correlation of the extent of chromosomal aberrations including uniparental disomies (UPDs) by SNP-chip analysis and FISH to telomere length in 46 patients with CLL. CLL harboring high risk aberrations, i.e. deletions of 11q22-23 or 17p13, had significantly shorter telomeres (higher ΔTL) compared to patients with CLL without such abnormalities. Patients with high chromosomal aberration rates had a worse overall survival compared to cases with lower aberration rates. Interestingly, however, an increase was found in the number of UPDs with shorter telomeres. These findings support the idea that telomeres in CLL cells play a role in the overall chromosome stability and could be involved in the occurrence of UPDs.


pN0(i+) and pN1mi Breast Cancer: Treatment and Outcomes in Comparison With pN0 and pN1a in the Modern Era.
Locoregional recurrence risk and the role of locoregional radiation therapy (LRRT) in pN0(i+) and pN1mi breast cancer are unclear. This study compares locoregional relapse-free survival (LRRFS) in patients with pN0(i+) and pN1mi relative to pN0 and pN1a disease and evaluates LRRFS according to locoregional treatment. We studied 10,271 patients referred between 2006 and 2011 with newly diagnosed pT1-T2, pN0, pN0(i+), pN1mi, or pN1a, M0 breast cancer. Outcomes were 10-year Kaplan-Meier LRRFS, relapse-free survival (RFS), distant relapse-free survival, and breast cancer-specific survival. Multivariable analysis of LRRFS and RFS was performed in pN0(i+) and pN1mi cohorts. Median follow-up was 9.3 years. In patients with pN0 (n = 7492), pN0(i+) (n = 305), pN1mi (n = 619), and pN1a (n = 1855) disease, LRRT was used in 1.1%, 24.3%, 45.7%, and 71.1%, respectively. Ten-year outcomes were LRRFS 96%, 92%, 97%, and 96% (P < .001), distant RFS 94%, 91%, 90%, and 84% (P < .001), and breast cancer-specific survival 95%, 90%, 93%, and 87% (P < .001), respectively. Ten-year LRRFS for patients treated with breast-conserving surgery alone, with breast RT, and with LRRT were 81%, 93%, and 91% for patients with pN0(i+) (P = .16) and 94%, 96%, and 100% for patients with pN1mi (P = .02), respectively. Among patients treated with mastectomy, 10-year LRRFS with surgery alone and with LRRT were 93% and 100% for patients with pN0(i+) (P = .12) and 95% and 99% for patients with pN1mi (P = .09). On multivariable analysis of patients with pN0(i+) and pN1mi, systemic therapy was associated with improved LRRFS in patients with pN0(i+) (hazard ratio [HR], 0.2; [0.06-0.6]; P = .005) and patients with pN1mi (HR, 0.1; [0.03-0.5]; P = .006). In patients with pN1mi, LRRT was associated with a trend toward increased LRRFS (HR, 0.2; [0.03-1.1]; P = .07). LRRT was not significantly associated with improved RFS in pN0(i+) or pN1mi disease. In the era of sentinel node staging and modern systemic therapy, patients with pN0(i+) and PN1mi treated with LRRT experienced 10-year LRR risks ≤10% after breast-conserving surgery or mastectomy and RT. LRRT was associated with a trend toward increased LRRFS in pN1mi but not pN0(i+) disease.


Effect of pretreatment diclofenac sodium on postendodontic pain: A randomised controlled trial.
Effective management of endodontic pain represents a continuing challenge. Many of the dental professionals are facing significant problems associated with postendodontic pain. Hence, the postendodontic pain has to be prevented at its primary stage without waiting for its occurrence. This trial was carried out to evaluate the use of a preoperative, single oral dose of diclofenac sodium for the prevention and control of postendodontic pain. Fifty patients were randomly assigned to two groups, placebo and diclofenac sodium (100 mg). The medications were administered 30 min before the start of standard endodontic treatment. Postoperative pain was assessed after 6, 12, and 24 h by using a visual analog scale. Postendodontic pain showed a statistically significant difference between both groups at 6 and 12 h (P < 0.05) and there was no significant difference at 24 h. Postendodontic pain was substantially reduced by preoperative administration of single oral dose of diclofenac sodium. It is thus possible to conclude that these favorable results might help to prevent postendodontic pain, especially in patients with a low pain threshold.


Lead, nickel and vanadium in seafood: an exposure assessment for Kuwaiti consumers.
Human exposure to lead (Pb), nickel (Ni) and vanadium (V) through the ingestion of six species of fish and two species of shrimp in Kuwait are determined. The study on seafood consumed by the Kuwaiti residents was analyzed by conducting a survey in five districts of the country, namely, Kuwait city (Capital), Farwaniya, Jahra, Hawaly and Ahmedi. Samples consisting of fish and shrimp were purchased from the local fish market during November 1995 and June 1996. Based on the survey, three major factors were investigated: (i) Pb, Ni and V concentration in the fish of locally consumed fish and shrimp; (ii) daily dietary intake of these elements in humans through consumption of seafood; and (iii) characterizing potential health risks associated with the estimated daily intakes. The risk associated with Pb, Ni and V in seafood was estimated based on a Hazard Index (HI). Although the highest HI (using the 95th percentiles of the daily intake of the element as the dose of concern) was observed for zobaidy, hamoor and shrimp, it is always < 1. This indicated that no serious health threats are associated with oil-related elements in fish and shrimp.


The Association Between Urinary Benzophenone Concentrations and Personal Care Product Use in Korean Adults.
Benzophenone (BP) derivatives are widely used in personal care products (PCPs) for protection from ultraviolet radiation. Because of their broad applications, BP derivatives have been found in various human bodily fluids. In the present study, we investigated the relationship between urinary concentrations of BP derivatives and PCP use in Korean adults. A urinary BP biomonitoring survey was conducted in Korea by the Ministry of Food and Drug Safety in 2014. BP derivatives (BP-1, BP-3, and 4-OH-BP) were measured in urine samples from 168 Korean adults (mean age, 43.2 ± 15.4 years) by high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Information about the use of PCPs in the past 7 days was obtained by direct interviews. The mean levels of BP-1, BP-3, and 4-OH-BP were 0.87, 5.87, and 0.13 ng/g creatinine, respectively. The geometric mean levels of BP-1, BP-3, and 4-OH-BP were significantly higher in female than those in male. The medians of the urinary concentration of BP derivatives were significantly higher among users of the following PCPs than those in non-users; the PCPs included sunscreen, skin care products, functional cosmetics, makeup base, makeup, lip cosmetics, eye cosmetics, color cosmetics, perfume products, and nail products. A regression analysis revealed a significant linear association between urinary BP-3 concentrations and the number of additional cosmetic products used. These findings provide evidence of a positive association between exposure to PCPs and urinary BP derivative concentrations in Korean adults.


Acute and long-term in vitro effects of zinc oxide nanoparticles.
Since most of the toxic studies of zinc oxide nanoparticles (ZnO NPs) focused on acute and high-dose exposure conditions, the aim of the present study was to fill the existing knowledge gap of long-term effects of ZnO NPs at sub-toxic doses. To overcome this point, we have evaluated the toxic, genotoxic, and carcinogenic effects of ZnO NPs under long-term treatments (12 weeks), using a sub-toxic dose (1 µg/mL) according to acute 48-h exposure. Preliminarily, oxidative stress and genotoxic/oxidative DNA damage were determined under acute exposure and high-dose conditions. To determine the role of oxidative DNA damage, a wild-type mouse embryonic fibroblast (MEF Ogg1 (+/+)) and its isogenic 8-oxo-guanine DNA glycosylase 1 (Ogg1) knockout partner (MEF Ogg1 (-/-)) cell lines were used. Although short-term exposure (24-h) experiments demonstrated that ZnO NPs were able to induce ROS, genotoxicity, and oxidative DNA damage in both cell lines, no effects were obtained under long-term exposure scenario. Thus, 1 µg/mL exposure over 12 weeks was unable to induce genotoxicity as well as cellular transformation in both cell types, as indicated by the lack of observed morphological cell changes, variations in the secretion of matrix metalloproteinases, and anchorage-independent cell growth ability, regarded as cancer-like phenotypic hallmarks. Our results indicate that short-term effects of ZnO NP exposure are not replicated under long-term and sub-toxic dose conditions. All together, the lack of genotoxic/carcinogenic effects after chronic treatments seem to indicate a reduced risk associated with ZnO NP exposure.


Complication Avoidance in Endoscopic Skull Base Surgery.
Endoscopic endonasal approaches to the skull base pathology have developed and evolved dramatically over the past 2 decades, particularly with collaboration between neurosurgery and otolaryngology physicians. These advances have increased significantly the use of such approaches beyond just resection of pituitary adenomas, including a variety of skull base pathologies. As the field has evolved, so has our understanding of the complications accompanying endoscopic skull base surgery, as well as techniques to both avoid and manage these complications. These are discussed here.


Long-term results in maxillary deficiency using intraoral devices.
Cleft lip and palate patients often present maxillary retrusion and class III malocclusion after cleft repair. Maxillary distraction is a technique that can provide simultaneous skeletal advancement and expansion of soft tissue. Twelve patients with cleft maxillary deficiency due to cleft lip and palate were treated by Le Fort I osteotomy and two intraoral distraction devices that were activated after 4 days of latency period, 1mm per day on both sides. Long-term clinical and cephalometric evaluation of one and two years demonstrate stable results concerning the skeletal, dental and soft tissue relations. In this paper we discuss the advantages of distraction osteogenesis as a method for treatment of maxillary deficiency in cleft patients in terms of stability and relapse. The indications for maxillary distraction: (1) Moderate and severe retrusion that needs large advancement as in cleft lip and palate patients. (2) Forward and downward lengthening of the maxilla with no need for intermediate bone graft. (3) Growing patients. In conclusion, maxillary distraction in moderate or severe retrusion, as in cleft patients offers marked maxillary advancement with long-term stability.


Effect of Tumor Location on Outcome After Laparoscopic Low Rectal Cancer Surgery: A Propensity Score Matching Analysis.
Dissection of the distal anterolateral aspect of the mesorectum remains a surgical challenge for low rectal cancer, posing a higher risk of residual mesorectum, which might lead to the increased incidence of local recurrence for patients with anterior wall involvement. This study aimed to assess the effect of tumor location on outcome after laparoscopic low rectal cancer surgery. This is a single-center, retrospective study. The study was conducted at West China Hospital in China. Patients with low rectal cancer who underwent laparoscopic total mesorectal excision from 2011 to 2016 were enrolled. Patients were divided into anterior and nonanterior groups according to tumor location. Propensity score matching analysis was used to reduce the selection bias. The primary end point was local recurrence. The secondary end points included overall survival, disease-free survival, and the positive rate of circumferential resection margin. A total of 404 patients were included, and 176 pairs were generated by propensity score matching analysis. Multivariate analysis showed that anterior location was an independent risk factor of local recurrence (HR, 12.6; p = 0.006), overall survival (HR, 3.0; p < 0.001), and disease-free survival (HR, 2.3; p = 0.001). For patients with clinical stage II/III or T3/4, anterior location remained a prognostic factor for higher local recurrence and poorer survival. Local recurrence was rare in patients with clinical stage II/III (1.4%) or T3/4 (1.5%) tumors that were not located anteriorly. This study was limited by its retrospective nature. Anterior location is an independent risk factor of local recurrence, overall survival, and disease-free survival for low rectal cancer. More strict and selective use of neoadjuvant therapy should be considered for patients who have clinical stage II/III or T3/4 tumors that are not located anteriorly. A larger cohort study is warranted to validate the prognostic role of anterior location for low rectal cancer. See Video Abstract at http://links.lww.com/DCR/B622. ANTECEDENTES:La disección de la cara anterolateral distal del mesorrecto sigue siendo un desafío quirúrgico en el cáncer de recto inferior, constituyendo un alto riesgo de mesorrecto residual, que podría ocasionar una mayor incidencia de recurrencia local en pacientes con compromiso de la pared anterior.OBJETIVO:El objetivo del estudio fue evaluar el efecto de la localización del tumor en el resultado posterior a la cirugía laparoscópica de cáncer de recto inferior.DISEÑO:Estudio restrospectivo de un único centro.ÁMBITO:El estudio se realizó en el West China Hospital en China.PACIENTES:Pacientes con cáncer de recto inferior que se sometieron a excisión mesorrectal total laparoscópica entre 2011 y 2016. Los pacientes se dividieron en grupos, anterior y no anterior, según la localización del tumor. Se utilizó un puntaje de propensión por análisis de concordancia para reducir el sesgo de selección.PRINCIPALES VARIABLES EVALUADAS:El objetivo principal fue la recurrencia local. Los objetivos secundarios incluyeron la sobrevida global, la sobrevida libre de enfermedad y la tasa de positividad del margen de resección circunferencial.RESULTADOS:Se incluyeron un total de 404 pacientes y se generaron 176 pares mediante un puntaje de propensión por análisis de concordancia. El análisis multivariado mostró que la localización anterior era un factor de riesgo independiente de recidiva local (HR = 12,6, p = 0,006), sobrevida global (HR = 3,0, p <0,001) y sobrevida libre de enfermedad (HR = 2,3, p = 0,001). En pacientes con estadio clínico II /III o T3/4, la ubicación anterior continuó como un factor pronóstico para una mayor recurrencia local y una menor sobrevida. La recidiva local fue excepcional en pacientes con tumores en estadio clínico II / III (1,4%) o T3 / 4 (1,5%) que no estaban localizados hacia anterior.LIMITACIONES:Este estudio estuvo limitado por su carácter retrospectivo.CONCLUSIONES:La localización anterior es un factor de riesgo independiente de recidiva local, sobrevida global y sobrevida libre de enfermedad para el cáncer de recto inferior. Se debe considerar un uso más estricto y selectivo de la terapia neoadyuvante para pacientes en estadio clínico II / III o T3 /4 de tumores que no se localizan hacia anterior. Se justifica un estudio de cohorte más grande para validar el impacto pronóstico de una ubicación anterior del cáncer de recto inferior. Consulte Video Resumen en http://links.lww.com/DCR/B622. (Traducción-Dr. Lisbeth Alarcon-Bernes).


Compensatory plasticity and cross-modal reorganization following early visual deprivation.
For human and non-human primates, vision is one of the most privileged sensory channels used to interact with the environment. The importance of vision is strongly embedded in the organization of the primate brain as about one third of its cortical surface is involved in visual functions. It is therefore not surprising that the absence of vision from birth, or the loss of vision later in life, has huge consequences, both anatomically and functionally. Studies in animals and humans, conducted over the past few decades, have demonstrated that the absence of vision causes massive structural changes that take place not only in the visually deprived cortex but also in other brain areas. These studies have further shown that the visually deprived cortex becomes responsive to a wide variety of non-visual sensory inputs. Recent studies even showed a role of the visually deprived cortex in cognitive processes. At the behavioral level, increases in acuity for auditory and tactile processes have been reported. The study of the congenitally blind brain also offers a unique model to gain better insights into the functioning of the normal sighted brain and to understand to what extent visual experience is necessary for the brain to develop its functional architecture. Finally, the study of the blind brain allows us to investigate how consciousness develops in the absence of vision. How does the brain of someone who has never had any visual perception form an image of the external world? In this paper, we discuss recent findings from animal studies as well as from behavioural and functional brain imaging studies in sighted and blind individuals that address these questions.


Is handedness exogenously determined? Counterevidence from South Korea.
Establishing whether handedness is exogenously determined can help explain the relationship between handedness and various health and economic outcomes. It can also ensure the use of handedness as an instrument in empirical applications. Using data from the Korean National Health and Nutrition Examination Survey and the National Health and Nutrition Examination Survey in the United States, I investigate the exogeneity of children's handedness by examining the determinants of mixed-handedness. In the analysis using Korean data, parents' age, parents' non-right-handedness, and family income influence the likelihood of children's mixed-handedness. In the U.S. data analysis, however, none of the child and family characteristics, except being Asian, predict the likelihood of mixed-handedness. These results suggest that mixed-handedness, further handedness cannot be generalized as exogenous and is a race-specific characteristic.


Orthodromic activation of hippocampal CA1 region of the rat.
(1) The posterior alveus (PA), the anterior alveus (AA) and the Schaffer collaterals (SCH) evoked field potential components which were organized as parasagittal strips of various widths. Spatially continuous and interactive lamellae are suggested. (2) By correlation with unit activities, the early postsynaptic components evoked by PA, AA and SCH were inferred to be extracellular excitatory postsynaptic potentials (EPSPs) and the late, long-duration components, the inhibitory postsynaptic potentials (IPSPs). The hypothesis that interneurons as well as pyramidal cells generate the field is proposed and discussed. (3) One- and two-dimensional profiles of deep evoked potentials and current source-sink analysis revealed excitatory synapses in stratum oriens for the PA and AA inputs and in stratum radiatum for the SCH input. The late dipole field evoked by PA and AA possessed current sources in strata radiatum and pyramidale, the sites of the inhibitory synapses. The late dipole field evoked by SCH had another component possibly generated by recurrent activity, afterpotentials or relayed activity through CA3.


Cyclic changes in the human fallopian tube isthmus and their functional importance.
Morphologic studies in rabbits have indicated that a column of tenacious mucus occupies the isthmic lumen in estrus. This secretion disappears after ovulation, and cilia are prominent at the time of ovum transport through the isthmus. This study was designed to seek evidence of similar mucus in the human fallopian tube isthmus. Isthmic segments were taken from 18 normally ovulating women throughout the menstrual cycle. Specimens were also obtained from 10 other women further to elucidate endocrine dependence of observed morphologic variations. Appearances consistent with luminal isthmic mucus were obtained in two women in the late follicular phase and in one woman immediately after ovulation. Observable mucus was absent and cilia were prominent in women in the early follicular phase, in the luteal phase, postmenopausally, in late pregnancy, and in the puerperium. The results described are consistent with the hypothesis that differential sperm and ovum transport in the human fallopian tube isthmus is at least partially determined by the presence or absence of estrogen-dependent luminal mucus.


Movement characteristics of the inclined surface flow of the open channel on the nanoscale surface.
This study investigates the water flow characteristics on a solid surface with nanoscale compared to a normal solid surface. The experiment uses a high-speed video system and Fiber-optic Laser Doppler Velocimetry to measure the flow condition of the droplet and velocity distribution profile in the inclined surface flow of the open channel, respectively. The results showed that the movement speed of water droplets on the nanoscale surface was about 2 times faster than on the normal surface. The mean error of each velocity profile was 0.6%. The results reveal that the velocity profile is not significantly influenced by whether the flume bottom is coated with nanoscale material or not in the inclined surface flow of the open channel.


[Biomechanical compensatory mechanisms of hips and spine : The essentials for spine and hip surgeons].
Spinal alignment changes with age and degeneration. Different compensatory mechanisms of the spine are necessary to preserve spinal balance. The capacity of compensation of the spine decreases with age. Thus, the pelvis and the lower limbs become involved in the compensatory mechanism. Concomitant osteoarthritis of the hip could impair this capacity. The biomechanical principles of compensation are described with respect to planning reconstructive hip and spine surgery.


The use of splenic artery embolization to maintain adequate hepatic arterial inflow after hepatic artery thrombosis in a split liver transplant recipient.
Split liver transplant is gaining increasing use in the current environment of growing organ shortage. It is associated with a higher risk of complications, owing to its complexity and technical challenges. Splenic artery steal syndrome, is a complication that can occur following liver transplant and cause inadequate hepatic arterial inflow, hepatic artery thrombosis and graft loss. We report a successful management of hepatic artery thrombosis and splenic artery steal syndrome after a split liver transplant by surgical thrombectomy followed by angiography and splenic artery embolization. 60-year old female, with liver cirrhosis, who underwent a deceased donor right lobe orthotopic liver transplant. The procedure was complicated by hepatic artery thrombosis, requiring re-exploration. However, despite anastomotic revision the patient had poor hepatic arterial inflow. Both angiography and ultrasonography demonstrated splenic artery steal syndrome. This was successfully managed by splenic artery embolization with improved hepatic artery flow on ultrasonography and angiography. Splenic artery steal syndrome is a rare complication that can occur after a liver transplant. Experience with this phenomenon is limited in split liver transplantation.We demonstrated successful early management of splenic artery steal syndrome with coil embolization in a split liver transplant preventing further morbidity and graft loss.


The effect of the type of colloid on the efficacy of hypertonic saline colloid mixtures in hemorrhagic shock: dextran versus hydroxyethyl starch.
Colloids increase and prolong the efficacy of hypertonic saline solutions in hemorrhagic shock. We compared the efficacy of dextran 60 and hydroxyethyl starch (HES) 200,000/0.5 at iso-oncotic concentrations of 6.5 or 6% in a 7.5% NaCI solution. Thirty-two rabbits were bled to maintain a mean arterial pressure at 35 mmHg. Twenty-five percent of the shed blood volume was replaced after 40 min by bolus infusion either with hypertonic dextran (HS-DEX) (n = 16) or with hypertonic hydroxyethyl starch (HS-HES) (n = 16). The animals were then observed for a 120-min period. In both groups immediate and complete restoration of cardiovascular function was achieved in up to 30 min and adequate restoration maintained for 60 min after infusion. During the subsequent 60 min signs of insufficient oxygen supply indicated the recurrence of near shock levels. Greater stability of hemodynamic efficacy was observed when dextran was added to hypertonic saline. The decrease in mean arterial pressure was lower in the dextran group (P < 0.05). The subsequent increase in avDO2 (v. cava sup.) was approximately 50% lower with dextran (1 ml/dl compared to 1.8 ml/dl); (P < 0.05). These differences occurred primarily within the initial 15 min although the differences in mean arterial pressure were recorded only after 30-60 min. A 50% reduction in lactate levels (1.1 compared to 2.0 mmol; P < 0.05) in immediate response to reinfusion indicates an increased lactate absorption and thus improved perfusion of poorly perfused tissue in the dextran group. A further, important difference may be due to the different effects on the microcirculation. As evidenced by a decline in the end-expiratory arterial CO2 gradient, dextran effected a significant (P < 0.01) improvement in decreased pulmonary CO2 emission during shock. This indicates a greater rise of blood flow in poorly perfused, ventilated pulmonary areas. In summary, in our model dextran appeared to be the superior colloid compared to HES, particularly during the first hour after initiation of treatment, although direct proof of an improved long term outcome has not been demonstrated.


Acetyl-CoA regulates lipid metabolism and histone acetylation modification in cancer.
Acetyl-CoA, as an important molecule, not only participates in multiple intracellular metabolic reactions, but also affects the post-translational modification of proteins, playing a key role in the metabolic activity and epigenetic inheritance of cells. Cancer cells require extensive lipid metabolism to fuel for their growth, while also require histone acetylation modifications to increase the expression of cancer-promoting genes. As a raw material for de novo lipid synthesis and histone acetylation, acetyl-CoA has a major impact on lipid metabolism and histone acetylation in cancer. More importantly, in cancer, acetyl-CoA connects lipid metabolism with histone acetylation, forming a more complex regulatory mechanism that influences cancer growth, proliferation, metastasis.


Functional analysis of drought and salt tolerance mechanisms of mulberry RACK1 gene.
The receptor for activated C kinase 1 (RACK1) protein acts as a central hub for the integration of many physiological processes in eukaryotic organisms. Plant RACK1 is implicated in abiotic stress responses, but the underlying molecular mechanisms of stress adaptation remain largely unknown. Here, the overexpression of the mulberry (Morus alba L.) RACK1 gene in Arabidopsis decreased tolerance to drought and salt stresses and MaRACK1 overexpression changed expression levels of genes in response to stress and stimuli. We developed a simple and efficient transient transformation system in mulberry, and the mulberry seedlings transiently expressing MaRACK1 were hypersensitive to drought and salt stresses. The expression levels of guanine nucleotide-binding protein (G-protein) encoding genes in mulberry and Arabidopsis were not affected by MaRACK1 overexpression. The interactions between RACK1 and G-proteins were confirmed, and the RACK1 proteins from mulberry and Arabidopsis could not interact with their respective G-proteins, which indicated that RACK1 may regulate stress responses independently of G-proteins. Additionally, MaRACK1 may regulate drought and salt stress tolerances by interacting with a fructose 1, 6-bisphosphate aldolase. Our findings provide new insights into the mechanisms underlying RACK1 functions in abiotic stress responses and important information for their further characterization.


Effect of storage time of transfused plasma on early and late mortality after coronary artery bypass grafting.
Because some concern has been raised about the storage time of red blood cells and outcomes after cardiac surgery, we investigated whether longer storage time of transfused plasma increases the risk for early or late mortality among patients who have undergone coronary artery bypass grafting. We retrospectively analyzed the data of all 10,626 patients who underwent isolated coronary artery bypass grafting in Catharina Hospital, Eindhoven, The Netherlands, between January 1998 and December 2007. All patients who received at least 1 unit of plasma intraoperatively or during the first 5 postoperative days were studied. They were divided into 3 groups (only younger plasma, only older plasma, and any older plasma groups) according to the storage time of the plasma (cutoff point, 323 days). After we had excluded 122 patients who were unavailable for follow-up, we found that 375 of the remaining patients (n = 745) received only younger plasma 370 patients received any older plasma, and 200 patients received only older plasma (mean follow-up, 1565 ± 1137 days; median follow-up, 1629 days). The storage time of plasma, when entered as either a continuous variable or a dichotomous variable, was a risk factor for early but not late mortality. Log-rank testing revealed no statistical difference in long-term survival among the groups. Longer storage time of plasma is a risk factor for early but not late mortality among patients who have undergone coronary artery bypass grafting.


Hepatitis C virus infection in injection drug users in Bavaria: risk factors for seropositivity.
Hepatitis C Virus (HCV) infection is the most common disease among intravenous drug users (IDUs). All patients admitted to the detoxification unit 1991-1997 and meeting ICD-10 diagnosis of opioid dependency were tested for anti-HCV serology. Thousand and forty nine patients were included in the study. About 61.3% of the IDUs were anti-HCV positive. Increasing age (PR: 1.46; 95% CI: 1.34-1.60), living with a significant other drug user (PR: 1.17; 95% CI: 1.05-1.31), history of therapy (PR: 1.62; 95% CI: 1.50-1.74), history of imprisonment (PR: 1.48; 95% CI: 1.36-1.61), history of emergency treatment (PR: 1.23; 95% CI: 1.12-1.35), additional daily consumption of benzodiazepines (PR: 1.10; 95% CI: 1.00-2.21) or alcohol (PR: 1.26; 95% CI: 1.14-1.38), frequency of injecting heroin (daily: PR: 0.86; 95% CI: 0.78-0.96; previously: PR: 1.14; 95% CI: 1.03-1.26) and type of opioid dependency (methadone: PR: 1.26; 95% CI: 1.13-1.41) were significant factors, considered as individual factors, for positive anti-HCV serology. Using multiple logistic regression we found that older age (OR: 3.54, 95% CI: 1.30-9.67), longer duration of opioid use (OR: 5.74; 95% CI: 1.82-18.13), living with a significant other drug user (OR: 1.47; 95% CI: 1.01-2.16), history of therapy (OR: 4.87; 95% CI: 1.67-14.20), history of imprisonment (OR: 1.92; 95% CI: 1.12-3.28), history of emergency treatment (OR: 1.45; 95% CI: 1.06-1.99) and additional daily consumption of alcohol (OR: 1.49; 95% CI: 1.04-2.13) remained independently associated with positive anti-HCV serology. These data support the need for early prevention strategies, namely, education of teachers in schools and further training of counsellors informing IDUs of what they can do to minimise the risk of becoming infected or of transmitting infectious agents to others.


Synergistic Effect of Allium-like Ni9 S8 & Cu7 S4 Electrodeposited on Nickel Foam for Enhanced Water Splitting Activity.
This study explores a water-splitting activity using a biphasic electrodeposited electrode on nickel foam (NF). The *Ni9 S8 /Cu7 S4 /NF electrode with citric acid reduction exhibits superior OER (oxygen evolution reaction) and HER (hydrogen evolution reaction) performance with reduced overpotential and a steeper Tafel slope. The *Ni9 S8 /Cu7 S4 /NF electrode displays the ultra-low overpotential value of 212 mV for OER and 109 mV for HER at the current density of 10 mA cm-2 . The Tafel slope of 25.4 mV dec-1 for OER and 108 mV dec-1 for HER was found from that electrode. The maximum electrochemical surface area (ECSA), lowest series resistance and lowest charge transfer resistance are found in citric acid reduced electrode, showing increased electrical conductivity and quick charge transfer kinetics. Remarkably, the *Ni9 S8 /Cu7 S4 /NF electrode demonstrated excellent stability for 80 hours in pure water splitting and 20 hours in seawater splitting. The synergistic effect of using bimetallic (Cu&Ni) sulfide and enhanced electrical conductivity of the electrode are caused by reduction of metal sulfide into metallic species resulting in improved water splitting performance.


A label-free quantification method by MS/MS TIC compared to SILAC and spectral counting in a proteomics screen.
In order to assess the biological function of proteins and their modifications for understanding signaling mechanisms within cells as well as specific biomarkers to disease, it is important that quantitative information be obtained under different experimental conditions. Stable isotope labeling is a powerful method for accurately determining changes in the levels of proteins and PTMs; however, isotope labeling experiments suffer from limited dynamic range resulting in signal change ratios of less than approximately 20:1 using most commercial mass spectrometers. Label-free approaches to relative quantification in proteomics such as spectral counting have gained popularity since no additional chemistries are needed. Here, we show a label-free method for relative quantification based on the TIC from peptide MS/MS spectra collected from data-dependent runs can be used effectively as a quantitative measure and expands the dynamic range over isotope labeling experiments allowing for abundance differences up to approximately 60:1 in a screen for proteins that bind to phosphotyrosine residues.


ADAMTS13 activity, high VWF and FVIII levels in the pathogenesis of deep vein thrombosis.
Deep vein thrombosis (DVT) is a common multi-factorial disease with a partially understood aetiology. Although the roles of high factor (F)VIII and von Willebrand factor (VWF) levels are recognized, that of ADAMTS13 is still unclear. To assess the association between ADAMTS13 activity levels, VWF antigen (VWF:Ag) and FVIII coagulant activity (FVIII:C) levels and DVT. 365 Italian DVT patients and 292 age- and sex-matched controls were considered. Plasma ADAMTS13 activity was measured using FRETS-VWF73 assay. VWF:Ag and FVIII:C were measured using immunoassay and one-stage clotting assay (ACL TOP analyzer), respectively. Quartile analyses were performed to evaluate the individual association between ADAMTS13 activity, VWF:Ag, FVIII:C and DVT. The combined effect of high VWF levels (> 4th quartile) and low ADAMTS13 levels (< 1st quartile) was evaluated using binary variables. All models were age- and sex-adjusted. Estimated risks were reported as Odds ratio (OR) with 95% confidence intervals (CI). ADAMTS13 activity was lower in DVT patients (94% vs. 98% of controls). Patients with an ADAMTS13 activity <1st quartile (86%) showed a 1.6-fold increased risk of DVT (95%CI, 1.05-2.55). The combination of low ADAMTS13 activity and high VWF:Ag levels was associated with a 15-fold increased risk (95%CI, 7.80-33.80). VWF:Ag and FVIII:C were associated to DVT with a dose-response relationship. ADAMTS13 activity < 86% was associated with a moderate risk of DVT. The co-presence of low ADAMTS13 activity and high VWF levels resulted in a strong synergistic effect on DVT risk. The association of VWF:Ag and FVIII:C with DVT was confirmed.