Environmental DNA metabarcoding reveals winners and losers of global change in coastal waters.
Studies of the ecological effects of global change often focus on one or a few species at a time. Consequently, we know relatively little about the changes underway at real-world scales of biological communities, which typically have hundreds or thousands of interacting species. Here, we use COI mtDNA amplicons from monthly samples of environmental DNA to survey 221 planktonic taxa along a gradient of temperature, salinity, dissolved oxygen and carbonate chemistry in nearshore marine habitat. The result is a high-resolution picture of changes in ecological communities using a technique replicable across a wide variety of ecosystems. We estimate community-level differences associated with time, space and environmental variables, and use these results to forecast near-term community changes due to warming and ocean acidification. We find distinct communities in warmer and more acidified conditions, with overall reduced richness in diatom assemblages and increased richness in dinoflagellates. Individual taxa finding more suitable habitat in near-future waters are more taxonomically varied and include the ubiquitous coccolithophore Emiliania huxleyi and the harmful dinoflagellate Alexandrium sp. These results suggest foundational changes for nearshore food webs under near-future conditions.


Beta-catenin non-canonical pathway: A potential target for inflammatory and hyperproliferative state via expression of transglutaminase 2 in psoriatic skin keratinocyte.
Psoriasis is a chronic, local as well as a systemic, inflammatory skin condition. Psoriasis influences the quality of life up to 3.8% of the population and occurs often between 15 and 30 years of age. Specific causes are linked to psoriasis, including the interleukin IL-23/IL-17 Axis, human antigen leucocyte (HLA), and tumor necrosis factor-α (TNF-α). Secukinumab is a monoclonal antibody that specifically binds and neutralizes IL-17A required in the treatment of Psoriasis. The signaling pathways of Wnt govern multiple functions of cell-like fate specification, proliferation, polarity, migration, differentiation with their signaling controlled rigorously, given that dysregulation caused by various stimuli, can lead to alterations in cell proliferation, apoptosis, and human inflammatory disease. Current data has supported non-canonical Wnt signaling pathways in psoriasis development, particularly Wnt5a activated signaling cascades. These interconnected factors are significant in interactions between immune cells, keratinocytes, and inflammatory factors due to a higher degree of transglutaminase 2, mediated by activation of the keratinocyte hyperproliferation of the psoriatic patient's epidermis. This study discusses the pathology of Wnt5a signaling and its involvement in the epidermal inflammatory effects of psoriasis with other related pathways.


Motivation for health information seeking and processing about clinical trial enrollment.
Low patient accrual in clinical trials poses serious concerns for the advancement of medical science in the United States. Past research has identified health communication as a crucial step in overcoming barriers to enrollment. However, few communication scholars have studied this problem from a sociopsychological perspective to understand what motivates people to look for or pay attention to information about clinical trial enrollment. This study applies the model of Risk Information Seeking and Processing (RISP) to this context of health decision making. By recognizing the uncertainties embedded in clinical trials, we view clinical trial enrollment as a case study of risk. With data from a random-digit-dial telephone survey of 500 adults living in the United States, we used structural equation modeling to test the central part of the RISP model. In particular, we examined the role of optimistic feelings, as a type of positive affect, in motivating information seeking and processing. Our results indicated that rather than exerting an indirect influence on information seeking through motivating a psychological need for more information, optimistic feelings have more direct relationships with information seeking and processing. Similarly, informational subjective norms also exhibit a more direct relationship with information seeking and processing. These results suggest merit in applying the RISP model to study health decision making related to clinical trial enrollment. Our findings also render practical implications on how to improve communication about clinical trial enrollment.


Environmental impacts of shifts in energy, emissions, and urban heat island during the COVID-19 lockdown across Pakistan.
Restrictions on human and industrial activities due to the coronavirus (COVID-19) pandemic have resulted in an unprecedented reduction in energy consumption and air pollution around the world. Quantifying these changes in environmental conditions due to government-enforced containment measures provides a unique opportunity to understand the patterns, origins and impacts of air pollutants. During the lockdown in Pakistan, a significant reduction in energy demands and a decline of ∼1786 GWh (gigawatt hours) in electricity generation is reported. We used satellite observational data for nitrogen dioxide (NO2), carbon monoxide (CO), sulphur dioxide (SO2), aerosol optical depth (AOD) and land surface temperature (LST) to explore the associated environmental impacts of shifts in energy demands and emissions across Pakistan. During the strict lockdown period (March 23 to April 15, 2020), we observed a reduction in NO2 emissions by 40% from coal-based power plants followed by 30% in major urban areas compared to the same period in 2019. Also, around 25% decrease in AOD (at 550 nm) thickness in industrial and energy sectors was observed although no major decrease was evident in urban areas. Most of the industrial regions resumed emissions during the 3rd quarter of April 2020 while the urban regions maintained reduced emissions for a longer period. Nonetheless, a gradual increase has been observed since April 16 due to relaxations in lockdown implementations. Restrictions on transportation in the cities resulted in an evident drop in the surface urban heat island (SUHI) effect, particularly in megacities. The changes reported as well as the analytical framework provides a baseline benchmark to assess the sectoral pollution contributions to air quality, especially in the scarcity of ground-based monitoring systems across the country.


Carotid Artery Injury in Anterior Cervical Spine Surgery: Multicenter Cohort Study and Literature Review.
Retrospective study and literature review. To provide more comprehensive data about carotid artery injury (CAI) or cerebrovascular accident (CVA) related to anterior cervical spine surgery. We conducted a retrospective, multicenter, case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network. Medical records of 17 625 patients who went through cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were analyzed. Also, we performed a literature review using Medline and PubMed databases. The following terms were used alone, and in combination, to search for relevant articles: cervical, spine, surgery, complication, iatrogenic, carotid artery, injury, cerebrovascular accident, CVA, and carotid stenosis. Among 17 625 patients that were analyzed, no cases were reported to experienced CAI or CVA after cervical spine surgery. Nevertheless, in our PubMed search we found 157 articles, but only 5 articles matched our study objective criteria; 2 cases were reported to present CAI and 3 cases presented CVA. CAI and CVA related to anterior cervical spine surgeries are extremely rare. We were not able to find neither in our retrospective study nor in our literature research a correlation between the type or length of anterior cervical spine procedure with CVA or CAI complications. However, surgeons should be aware of the possibility of vascular complications and minimize intraoperative direct vascular manipulations or retraction. Preoperative screening for underlying vascular pathology and risk factors is also important.


Smart multisensor kernel.
We describe in this paper a smart multisensor kernel, given the shape of a wriststrap and able to characterise a current physiological state among a number of ones resulting from a previous analysis, and to transmit those results using a radio link. The main advantage of this product is its adaptability. As examples, we describe two applications which are the remote monitoring of elderly people and the sleep staging.


Association of the Skn7 and Yap1 transcription factors in the Saccharomyces cerevisiae oxidative stress response.
Saccharomyces cerevisiae Skn7p is a stress response transcription factor that undergoes aspartyl phosphorylation by the Sln1p histidine kinase. Aspartyl phosphorylation of Skn7p is required for activation of genes required in response to wall stress, but Skn7p also activates oxidative stress response genes in an aspartyl phosphorylation-independent manner. The presence of binding sites for the Yap1p and Skn7p transcription factors in oxidative stress response promoters and the oxidative stress-sensitive phenotypes of SKN7 and YAP1 mutants suggest that these two factors work together. We present here evidence for a DNA-independent interaction between the Skn7 and Yap1 proteins that involves the receiver domain of Skn7p and the cysteine-rich domains of Yap1p. The interaction with Yap1p may help partition the Skn7 protein to oxidative stress response promoters when the Yap1 protein accumulates in the nucleus.


Structural analysis of repetitive DNA sequences in the bovine corticotropin-beta-lipotropin precursor gene region.
Repetitive DNA sequences in the bovine corticotropin-beta-lipotropin precursor gene region have been mapped and subjected to nucleotide sequence analysis. Two of the four repetitive DNA segments found are located in the 5'-flanking region, and one each within the intervening sequences. Each repetitive DNA segment contains one to three highly homologous unit sequences with an approximate length of 120 base pairs. All the unit sequences are flanked on the 3' side by tandem repeats. There are about 10(5) copies of the repetitive DNA in the bovine genome. Comparison of the bovine repetitive sequences with those of other mammalian species reveals the presence of a homologous segment of approximately 40 base pairs. This segment and the region preceding it in the bovine repetitive DNA exhibit sequence homology with the region encompassing the origin of DNA replication in papovaviruses.


Comparative genomic analysis of Staphylococcus lugdunensis shows a closed pan-genome and multiple barriers to horizontal gene transfer.
Coagulase negative staphylococci (CoNS) are commensal bacteria on human skin. Staphylococcus lugdunensis is a unique CoNS which produces various virulence factors and may, like S. aureus, cause severe infections, particularly in hospital settings. Unlike other staphylococci, it remains highly susceptible to antimicrobials, and genome-based phylogenetic studies have evidenced a highly conserved genome that distinguishes it from all other staphylococci. We demonstrate that S. lugdunensis possesses a closed pan-genome with a very limited number of new genes, in contrast to other staphylococci that have an open pan-genome. Whole-genome nucleotide and amino acid identity levels are also higher than in other staphylococci. We identified numerous genetic barriers to horizontal gene transfer that might explain this result. The S. lugdunensis genome has multiple operons encoding for restriction-modification, CRISPR/Cas and toxin/antitoxin systems. We also identified a new PIN-like domain-associated protein that might belong to a larger operon, comprising a metalloprotease, that could function as a new toxin/antitoxin or detoxification system. We show that S. lugdunensis has a unique genome profile within staphylococci, with a closed pan-genome and several systems to prevent horizontal gene transfer. Its virulence in clinical settings does not rely on its ability to acquire and exchange antibiotic resistance genes or other virulence factors as shown for other staphylococci.


Cell shape changes induced by cationic anesthetics.
The effects of local anesthetics on cultivated macrophages were studied in living preparations and recorded in still pictures and time-lapse cine-micrographs. Exposure to 12mM lidocaine or 1.5 mM tetracaine resulted in rounding in 10-15 min. Rounding was characterized by cell contraction, marked increase in retraction fibrils, withdrawal of cell processes, and, in late stages, pulsation-like activity and zeiosis. Cells showed appreciable membrane activity as they rounded. Respreading was complete within 15 min of perfusion in drug-free medium and entailed a marked increase in surface motility over control periods. As many as eight successive cycles of rounding and spreading were obtained with lidocaine without evidence of cell damage. The effects of anesthetics were similar to those observed with EDTA, but ethylene-glycol-bis(beta-aminoethylether)-N, N'-tetraacetic acid-Mg was ineffective. Rounding was also induced by benzocaine, an anesthetic nearly uncharged at pH 7.0. Quaternary (nondischargeable) compounds were of low activity, presumably because they are slow permeants. Lidocaine induced rounding at 10 degrees C and above but was less effective at 5 degrees C and ineffective at 0 degrees C. Rounding by the anesthetic was also obtained in media depleted or Na or enriched with 10 mM Ca or Mg. The latter finding, together with the failure of tetrodotoxin to induce rounding, suggests that the anesthetic effect is unrelated to inhibition of sodium conductance. It is possible that the drugs influence divalent ion fluxes or some component of the contractile cells' machinery, but a metabolic target of action cannot yet be excluded.


Researching the Experiences of Children with Cancer: Considerations for Practice.
Children and adolescents with cancer often participate in medical and psychosocial research throughout their diagnosis and treatment. Furthermore, this involvement frequently extends into the survivorship period. Sometimes referred to as "doubly vulnerable" research participants, children and adolescents with cancer are not only minors, but also minors facing significant medical, developmental, and psychosocial stressors associated with chronic illness. Thus, it is important to exercise care in designing and conducting research with this population; however, these considerations have not been adequately addressed in pediatric healthcare literature. Therefore, the purpose of this review is to describe the research preferences and experiences of children and adolescents with cancer to identify techniques for supporting this population as research participants. By incorporating developmentally appropriate, context-specific, and child-centered adjustments, researchers can help children and adolescents with cancer effectively and meaningfully describe their illness experiences while also developing a positive outlook on future research participation.


Efficient methodology to correlate structural with optical properties of GaAs nanowires based on scanning electron microscopy.
Twin boundaries and boundaries between zincblende (ZB) and wurtzite (WZ) segments of GaAs-related nanowires (NWs) form intrinsic heterointerfaces with essential consequences for the application of such nanomaterials in optoelectronic devices. We show that for GaAs and GaAs/(Al, Ga)As core/shell NWs, crystal twinning along the NW axis can be imaged with a spatial resolution of 10 nm using secondary electrons in a scanning electron microscope (SEM). Changes of the crystal structure from the ZB to the WZ phase have been investigated by electron backscatter diffraction. In addition to these methods, we employ spectrally and spatially resolved cathodoluminescence measurements in the same SEM to study the correlation between the structural and optical properties in single NWs. Two GaAs/AlAs/GaAs core/shell/shell NWs differing significantly in the crystal structure along their axis have been investigated combining these three techniques in order to demonstrate the strength of the employed methodology. Our experiments show that based on commonly available SEM methods, an overview of the structural properties along an entire NW and their impact on the spectral and spatial luminescence distribution can be efficiently obtained providing a quick feedback for the optimization of growth conditions.


Benzo[a]pyrene activates interleukin-6 induction and suppresses nitric oxide-induced apoptosis in rat vascular smooth muscle cells.
Benzo[a]pyrene, a ubiquitous environmental pollutant, has been suggested to be capable of initiating and/or accelerating atherosclerosis. Accumulation of vascular smooth muscle cells (VSMCs) in vessel intima is a hallmark of atherosclerosis. Nitric oxide (NO) can suppress VSMCs proliferation and induce VSMCs apoptosis. NO plays a compensatory role in the vascular lesions to reduce proliferation and/or accelerate apoptosis of VSMCs. The aim of this study was to investigate whether benzo[a]pyrene can affect VSMCs growth and apoptosis induced by NO. Benzo[a]pyrene (1-30 μmol/L) did not affect the cell number and cell cycle distribution in VSMCs under serum deprivation condition. Sodium nitroprusside (SNP), a NO donor, decreased cell viability and induced apoptosis in VSMCs. Benzo[a]pyrene significantly suppressed SNP-induced cell viability reduction and apoptosis. VSMCs cultured in conditioned medium from cells treated with benzo[a]pyrene could also prevent SNP-induced apoptosis. Benzo[a]pyrene was capable of inducing the activation of nuclear factor (NF)-κB and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in VSMCs. Both NF-κB inhibitor and p38 MAPK inhibitor significantly reversed the anti-apoptotic effect of benzo[a]pyrene on SNP-treated VSMCs. Incubation of VSMCs with benzo[a]pyrene significantly and dose-dependently increased interleukin (IL)-6 production. A neutralizing antibody to IL-6 effectively reversed the anti-apoptotic effect of benzo[a]pyrene on SNP-treated VSMCs. Taken together, these results demonstrate for the first time that benzo[a]pyrene activates IL-6 induction and protects VSMCs from NO-induced apoptosis. These findings propose a new mechanism for the atherogenic effect of benzo[a]pyrene.


Algal-bacterial processes for the treatment of hazardous contaminants: a review.
Microalgae enhance the removal of nutrients, organic contaminants, heavy metals, and pathogens from domestic wastewater and furnish an interesting raw material for the production of high-value chemicals (algae metabolites) or biogas. Photosynthetic oxygen production also reduces the need for external aeration, which is especially advantageous for the treatment of hazardous pollutants that must be biodegraded aerobically but might volatilize during mechanical aeration. Recent studies have therefore shown that when proper methods for algal selection and cultivation are used, it is possible to use microalgae to produce the O(2) required by acclimatized bacteria to biodegrade hazardous pollutants such as polycyclic aromatic hydrocarbons, phenolics, and organic solvents. Well-mixed photobioreactors with algal biomass recirculation are recommended to protect the microalgae from effluent toxicity and optimize light utilization efficiency. The optimum biomass concentration to maintain in the system depends mainly on the light intensity and the reactor configuration: At low light intensity, the biomass concentration should be optimized to avoid mutual shading and dark respiration whereas at high light intensity, a high biomass concentration can be useful to protect microalgae from light inhibition and optimize the light/dark cycle frequency. Photobioreactors can be designed as open (stabilization ponds or high rate algal ponds) or enclosed (tubular, flat plate) systems. The latter are generally costly to construct and operate but more efficient than open systems. The best configuration to select will depend on factors such as process safety, land cost, and biomass use. Biomass harvest remains a limitation but recent progresses have been made in the selection of flocculating strains, the application of bioflocculants, or the use of immobilized biomass systems.


The impact of past pregnancy experience on subsequent perinatal outcomes.
In perinatal epidemiology, the basic unit of analysis has traditionally been the individual pregnancy. In this study, we sought to explore the idea of a 'reproductive life'-based approach to modelling the effects of reproductive exposures and outcomes, where the basic unit of analysis is a woman's entire reproductive experience. Our objective was to explore whether a first pregnancy risk factor, excess gestational weight gain, has a direct effect on the birthweight outcomes of a subsequent pregnancy, independent of the weight gain and other risk factors of the second pregnancy. A study population was created by linking the obstetric records of 1220 women who delivered their first and second offspring at a McGill University teaching hospital in Montreal, Canada. Multivariable linear and logistic regression analyses were used to model the effects of gestational weight gain above recommendation on the birthweight Z-score and risk of large-for-gestational age (LGA) subsequent offspring. After adjusting for the risk factors of the second pregnancy, an independent effect from the first pregnancy was seen on the birthweight Z-score, (effect size OR 0.17 [95% CI 0.05, 0.28] but not risk of LGA of the second pregnancy 1.30 [95% CI 0.89, 1.89]). We concluded that a pregnancy-centred approach to research that conceptualizes pregnancies as self-contained and interchangeable events may not always be appropriate, and propose that analytical methods for some perinatal research questions may need to consider a given pregnancy in the context of a woman's past reproductive experiences.


Evaluation of White Matter Injury Patterns Underlying Neuropsychiatric Symptoms after Mild Traumatic Brain Injury.
To determine if a central axonal injury underlies neuropsychiatric symptoms after mild traumatic brain injury (mTBI) by using tract-based spatial statistics analysis of diffusion-tensor images. The institutional review board approved this study, with waiver of informed consent. Diffusion-tensor imaging and serial neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Testing evaluation were performed in 45 patients with mTBI (38 with irritability, 32 with depression, and 18 with anxiety). Control subjects consisted of 29 patients with mTBI without neuropsychiatric symptoms. Fractional anisotropy and diffusivity maps were analyzed by using tract-based spatial statistics with a multivariate general linear model. Diffusion-tensor imaging findings were correlated with symptom severity, neurocognitive test scores, and time to recovery with the Pearson correlation coefficient. Compared with control subjects, patients with mTBI and depression had decreased fractional anisotropy in the superior longitudinal fasciculus (P = .006), white matter around the nucleus accumbens (P = .03), and anterior limb of the internal capsule (P = .02). Patients with anxiety had diminished fractional anisotropy in the vermis (P = .04). No regions of significantly decreased fractional anisotropy were seen in patients with irritability relative to control subjects. Injury in the region of the nucleus accumbens inversely correlated with recovery time in patients with depression (r = -0.480, P = .005). Unique white matter injury patterns were seen for two major posttraumatic neuropsychiatric symptoms. Injury to the cerebellar vermis in patients with mTBI and anxiety may indicate underlying dysfunction in primitive fear conditioning circuits in the cerebellum. Involvement of the nucleus accumbens in depression after mTBI may suggest an underlying dysfunctional reward circuit that affects the prognosis in these patients.


Matrix delivery transdermal 17beta-estradiol for the prevention of bone loss in postmenopausal women. The International Study Group.
A total of 277 early postmenopausal women were enrolled in this placebo-controlled 2-year study to examine the efficacy of a matrix transdermal 17beta-estradiol system, at three different dosages (25, 50 and 75 mg/day) combined with sequential oral dydrogesterone 20 mg/day, in preventing bone loss. At 2 years, the difference from placebo in percentage change from baseline of L1-4 lumbar spine bone mineral density (BMD) (assessed by dual-energy X-ray absorptiometry) was 4.7% +/- 0.7% with estradiol 25 mg/day, 7.3% +/- 0.7% with estradiol 50 mg/day and 8.7% +/- 0.7% with estradiol 75 mg/day (all values mean +/- SEM). There were also significant increases in femoral neck, trochanter and total hip BMD with all doses of estradiol compared with placebo. Additionally, most patients had a significant gain (increase greater than 2.08%) in lumbar spine bone mass compared with placebo. Patients who received estradiol also experienced clinically significant and dose-related decreases in total serum osteocalcin, serum bone alkaline phosphatase and urinary C-telopeptide, with all three markers of bone turnover returning to premenopausal levels. Estradiol was well tolerated during the 2-year treatment period. Transdermal estradiol is effective and well tolerated at dosages between 25-75 mg/day in the prevention of bone loss in postmenopausal women; 25 mg/day offers an effective option for those women who cannot tolerate higher doses.


[Elevated level of TGF-alpha in the mucosa of small intestine of the rat following massive small bowel resection].
This study was performed to determine the changes in TGF-alpha production during compensatory regeneration of small intestine. For this purpose rats underwent either 70% small bowel resection or sham operation. Levels of TGF-alpha production were evaluated by radioreceptor assay and Western blotting. When compared with sham operation, small bowel resection resulted in threefold increase in the production of TGF-alpha at postoperative day 3. Possible mechanisms of TGF-alpha involvement in intestinal adaptation following massive small bowel resection are discussed.


The ATPase domain but not the acidic region of Cockayne syndrome group B gene product is essential for DNA repair.
Cockayne syndrome (CS) is a human genetic disorder characterized by UV sensitivity, developmental abnormalities, and premature aging. Two of the genes involved, CSA and CSB, are required for transcription-coupled repair (TCR), a subpathway of nucleotide excision repair that removes certain lesions rapidly and efficiently from the transcribed strand of active genes. CS proteins have also been implicated in the recovery of transcription after certain types of DNA damage such as those lesions induced by UV light. In this study, site-directed mutations have been introduced to the human CSB gene to investigate the functional significance of the conserved ATPase domain and of a highly acidic region of the protein. The CSB mutant alleles were tested for genetic complementation of UV-sensitive phenotypes in the human CS-B homologue of hamster UV61. In addition, the CSB mutant alleles were tested for their ability to complement the sensitivity of UV61 cells to the carcinogen 4-nitroquinoline-1-oxide (4-NQO), which introduces bulky DNA adducts repaired by global genome repair. Point mutation of a highly conserved glutamic acid residue in ATPase motif II abolished the ability of CSB protein to complement the UV-sensitive phenotypes of survival, RNA synthesis recovery, and gene-specific repair. These data indicate that the integrity of the ATPase domain is critical for CSB function in vivo. Likewise, the CSB ATPase point mutant failed to confer cellular resistance to 4-NQO, suggesting that ATP hydrolysis is required for CSB function in a TCR-independent pathway. On the contrary, a large deletion of the acidic region of CSB protein did not impair the genetic function in the processing of either UV- or 4-NQO-induced DNA damage. Thus the acidic region of CSB is likely to be dispensable for DNA repair, whereas the ATPase domain is essential for CSB function in both TCR-dependent and -independent pathways.


Identifying Liver Metastasis-Related Genes Through a Coexpression Network to Construct a 5-Gene Model for Predicting Pancreatic Ductal Adenocarcinoma Patient Prognosis.
This study aimed to develop a liver metastasis-related gene prognostic index (LMPI) for pancreatic ductal adenocarcinoma prognosis and therapy. The Cancer Genome Atlas data set was used to identify liver metastasis-related hub genes via weighted gene coexpression network analysis. The core genes were identified to construct an LMPI by using the Cox regression method. An immune cell abundance identifier was applied to determine the immune cell abundance. A total of 78 hub liver metastasis-related genes in the black module were significantly enriched in complement and coagulation cascades, fat digestion and absorption, and the PPAR signaling pathway. Then, an LMPI was constructed on the basis of the 5 prognostic genes (MOGAT3, ASGR1, TRPM8, SGSM1, and LOC101927851). Patients with higher LMPI scores had poor overall survival, more co-occurring or mutually exclusive pairs of driver gene mutations, and less benefit from immunotherapy than patients with lower LMPI scores. In addition, a high correlation was also found between LMPI scores and immune infiltration, such as CD4 naive, CD8 T, cytotoxic T, T helper 2, follicular helper T, and natural killer cells. The core genes of the LMPI developed may be independent factors for predicting prognosis, immune characteristics, and immunotherapy efficacy in pancreatic ductal adenocarcinoma.


Time series modelling and forecasting of emergency department overcrowding.
Efficient management of patient flow (demand) in emergency departments (EDs) has become an urgent issue for many hospital administrations. Today, more and more attention is being paid to hospital management systems to optimally manage patient flow and to improve management strategies, efficiency and safety in such establishments. To this end, EDs require significant human and material resources, but unfortunately these are limited. Within such a framework, the ability to accurately forecast demand in emergency departments has considerable implications for hospitals to improve resource allocation and strategic planning. The aim of this study was to develop models for forecasting daily attendances at the hospital emergency department in Lille, France. The study demonstrates how time-series analysis can be used to forecast, at least in the short term, demand for emergency services in a hospital emergency department. The forecasts were based on daily patient attendances at the paediatric emergency department in Lille regional hospital centre, France, from January 2012 to December 2012. An autoregressive integrated moving average (ARIMA) method was applied separately to each of the two GEMSA categories and total patient attendances. Time-series analysis was shown to provide a useful, readily available tool for forecasting emergency department demand.


Comparison of outcomes of one-stage basilic vein transpositions and two-stage basilic vein transpositions.
Basilic vein transpositions (BVTs) provide autologous hemodialysis access in the upper extremity. We report and compare our experience using the two techniques that are commonly performed to create BVTs: the one-stage and the two-stage technique. A retrospective review was performed on patients who underwent BVT from June 2006 to June 2010 from a database of all patients undergoing dialysis access procedures. One hundred six patients, mean age of 54 years (41% male), who received upper-arm basilic vein-only transposition were identified and were stratified based on one-stage and two-stage BVTs. Anatomic outcomes and functionality were determined and compared between stages. Seventy-seven patients underwent two-stage BVT, and 29 underwent one-stage BVT. Fifty-one percent and 79% of the two-stage group and the one-stage group, respectively, had had a previous failed ipsilateral permanent access. Catheter dialysis at time of surgery was 14% in one-stage BVT and 43% in two-stage BVT. Immediate technical success was obtained in all cases. The rate of primary failure was 21% in the one-stage group and 18% in the two-stage group. Reintervention rates for the one-stage group and the two-stage group were 62% and 66%, respectively. Primary patency for the one-stage group and the two-stage group at 1 year was 82% and 67%, at 2 years was 81% and 27%, and at 3 years was 51% and 18%, respectively. Secondary patency for the one-stage group and the two-stage group at 1 year was 91% and 81%, at 2 years was 80% and 61%, and at 3 years was 58% and 45%, respectively. Thirty-day mortality was 0% in both groups, and all-cause morbidity was 12% in both groups (counting all stages). One-stage BVTs have a similar number of initial failures and secondary interventions as two-stage BVTs. One-stage BVTs achieved better primary and cumulative patencies. There appears to be no advantage to a two-stage BVT in equally matched patients.


The role of R21 expression in differential diagnosis of melanocytic lesions.
Cyclic adenosine monophosphate (cAMP) is an intracellular signal transmitter involved in the regulation of melanocyte growth, proliferation, and melanogenesis. R21 is a monoclonal antibody against the soluble adenylyl cyclase (sAC) protein. Various nuclear and cytoplasmic R21 expression patterns in melanocytic lesions have been previously reported. Pan-nuclear staining was defined as specific for melanoma and was found supportive in the assessment of surgical margins. The aim of this study is to evaluate the different expression patterns of R21 immunostain and investigate its effectiveness in the differential diagnosis of cutaneous malignant and benign melanocytic lesions. Fifty invasive cutaneous melanoma and 50 benign melanocytic proliferation were included in the study. Paraffin blocks that best reflected tumor morphology were studied via immunohistochemical staining for R21. For all patterns, the cases showing staining in 25% or more tumor cells were considered as positive. Yates' Chi-square, Pearson Chi-square exact test, Spearman correlation were used. Dot-like Golgi staining was characteristic for nevi (12/50) and seen only in one melanoma. Pan-nuclear staining was striking for melanoma (36/50). This pattern was observed in 2 dysplastic and 3 common melanocytic nevi too. None of the Spitz nevi expressed R21 in pan-nuclear pattern. For the diagnosis of melanoma, sensitivity and specificity of the pan-nuclear expression were 72% and 90%, respectively. Positive and negative predictive values were found as 87% and 76%. R21, a second-generation immunohistochemical marker, can be used in the differential diagnosis of benign and malignant melanocytic lesions.


Iteravirus-like genome organization of a densovirus from Sibine fusca Stoll.
The complete genome of Sibine fusca densovirus was cloned and sequenced. The genome contained 5,012 nucleotides (nt), including inverted terminal repeats (ITRs) of 230 nt with terminal hairpins of 161 nt. Its DNA sequence and monosense organization with 3 open reading frames (ORFs) is typical of the genus Iteravirus in the subfamily Densovirinae of the Parvoviridae.


Optical coherence tomography findings in a case of cone-rod dystrophy.
A patient with cone-rod dystrophy, who was examined thoroughly with biomicroscopy, fluorescein angiography, optical coherence tomography, and electrophysiology, is presented. Although fluorescein angiography depicted only window-defect type of hyperfluorescence, optical coherence tomography disclosed detachment of the neurosensory retina, focal absence of the outer parts of the photoreceptors' layer in the fovea, and cystoid edema in the macula. To the authors' knowledge, these findings have not been described in cone-rod dystrophy so far.


Gender differences in hypertension control among older korean adults: Korean social life, health, and aging project.
Controlling blood pressure is a key step in reducing cardiovascular mortality in older adults. Gender differences in patients' attitudes after disease diagnosis and their management of the disease have been identified. However, it is unclear whether gender differences exist in hypertension management among older adults. We hypothesized that gender differences would exist among factors associated with hypertension diagnosis and control among community-dwelling, older adults. This cross-sectional study analyzed data from 653 Koreans aged ≥60 years who participated in the Korean Social Life, Health, and Aging Project. Multiple logistic regression was used to compare several variables between undiagnosed and diagnosed hypertension, and between uncontrolled and controlled hypertension. Diabetes was more prevalent in men and women who had uncontrolled hypertension than those with controlled hypertension or undiagnosed hypertension. High body mass index was significantly associated with uncontrolled hypertension only in men. Multiple logistic regression analysis indicated that in women, awareness of one's blood pressure level (odds ratio [OR], 2.86; p=0.003) and the number of blood pressure checkups over the previous year (OR, 1.06; p=0.011) might influence the likelihood of being diagnosed with hypertension. More highly educated women were more likely to have controlled hypertension than non-educated women (OR, 5.23; p=0.013). This study suggests that gender differences exist among factors associated with hypertension diagnosis and control in the study population of community-dwelling, older adults. Education-based health promotion strategies for hypertension control might be more effective in elderly women than in elderly men. Gender-specific approaches may be required to effectively control hypertension among older adults.


Clinical evaluation of pituitary insufficiency in adult population
This retrospective study aimed to investigate the clinical profile of pituitary insufficiency (PI) in adult population. One hundred and fifty patients who were diagnosed as having PI between 2012 and 2018 (53.3% female, mean age 48.13 ± 15.83 years) were retrospectively analyzed. Age at diagnosis was higher in females as compared with males (51.13 ± 15.95 vs. 44.70 ± 15.08 years, P = 0.012). The most frequent presenting signs were headache (29.4%) and visual disturbance (19.6%) in general. Females frequently presented with headache (33.3%), whereas males presented with sexual dysfunction (34.4%). The most frequent cause of PI was nonfunctional pituitary adenoma (28.8%) in general population. A frequent cause of PI was Sheehan's syndrome (33.8%) among females and nonfunctional pituitary adenoma (38.6%) among males. Pituitary macroadenoma (75.8%) was frequent in pituitary tumors with PI. 55.3 % of the patients had 4 pituitary hormones deficiencies and 26.0% of patients had 3 pituitary hormones deficiencies. Gonadotropin deficiency was the leading pituitary hormone deficiency. The frequency of posttraumatic PI was 4.7% in the general population. Nonfunctional pituitary adenoma was the most common cause of PI among males and Sheehan's syndrome was a major etiologic factor in females. Sheehan's syndrome remains an important health problem in Turkey although obstetric care has improved. Posttraumatic PI should be considered in the differential diagnosis of idiopathic PI.


Study on endocrine disruptors levels in raw milk from cow's farms: Risk assessment.
Diet represents the primary route for human exposure to bisphenol A (BPA). As endocrine disruptor (ED), BPA has raised concerns about its adverse effects on human health. Therefore, EFSA recommended a tolerable daily intake (t-TDI) of 4 μg/kg bw/day and the EU Regulation n. 2018/213 fixed a specific migration limit (SML) of 0.05 mg/kg for BPA in food from plastic materials intended to come in contact with food. BPA could be present in milk due to environmental contamination, and also as a result of the migration from contact materials used during milking and storage. Considering the widespread consumption of milk and milk products, the contamination of dairy products is a matter of public health concern. The aim of the study was to investigate the BPA contamination levels of raw cow's milk from two farms located in Campania region, Italy. The milk samples (n=22), weekly collected from the cooling tank, were analyzed using liquid chromatography with fluorescence detection. In raw milk from both farms, preliminary results showed the occurrence of BPA levels lower than the SML limit, ranging from not detected to 2.34 μg/L. The consumer exposure, calculated considering a hypothetical raw milk consumption and three possible scenarios, was below the t-TDI. Despite the low levels of exposure through milk consumption, low doses can have lasting effects during human development. Thus, new approaches, methods, and plans should be applied to monitor ED contamination, such as BPA and other pollutants, and to assure milk safety.


Multiple primary cancers including mesothelioma of the tunica vaginalis: case report and literature review with primary care focus.
The development of multiple primary malignancies in an individual is rare and unfortunate, and the care of such a patient presents specific challenges. We report the diagnosis and progression of 3 histologically different primary cancers in 1 patient over the course of 15 years. At age 50 years, the patient received a diagnosis of transitional cell carcinoma of the bladder; treatment was successful. When the patient was 64 years old, mesothelioma of the tunica vaginalis was diagnosed, and computed tomography performed for staging purposes revealed a lung lesion, which was later diagnosed as adenocarcinoma. Treatment for the adenocarcinoma was also successful, but the patient continues to have recurrence of mesothelioma. To our knowledge, the present report is the first description of a case of 3 primary cancers that includes a mesothelioma of the tunica vaginalis. Because mesothelioma of the tunica vaginalis is rare, we reviewed the literature on its prevalence, presentation, management, and prognosis.


Costs and benefits of polyandry in a sexually cannibalistic mantis.
Mating with more than one male often provides direct or indirect benefits to female fitness but can also increase the chance of injury and death. Costs of mating are expected to increase linearly with increasing mating number. But how such costs interact with benefits to determine the net payoff of mating multiply is not well understood. Using the highly cannibalistic Springbok mantis, Miomantis caffra, a species where females are stabbed in the abdomen by males during violent premating struggles that males initiate to avoid being cannibalized, we took an experimental approach to assess the economics of polyandry under the risk of external, male-inflicted injury. We predicted that females that mate multiply would be more likely to show abdominal injuries, have higher prereproductive mortality, produce fewer offspring and be more likely to engage in pre-mating cannibalism to avoid unwanted matings. In line with our predictions, we found that the likelihood of abdominal injury was highest among females that mated at least once, and prereproductive death was highest among females that mated twice or three times. Virgin females completely avoided these costs and produced some offspring parthenogenetically but not enough to provide a net benefit. Although mating was better than not mating, there was no singularly optimal mating number: females that mated once and three times produced similarly high numbers of offspring from the first ootheca, which resulted in an intermediate trough in offspring production at two matings. We also found little evidence that cannibalism was deployed as a mate-avoidance strategy: females consistently attacked and consumed males regardless of how many times they mated or how long they were housed with males. Our results suggest the possibility of two distinct mating strategies in M. caffra, where females either mate at a lower frequency to minimize costs or at a higher frequency to maximize benefits. We discuss possible explanations for this bimodal pattern in offspring production.


Rectal-wall dose dependence on postplan timing after permanent-seed prostate brachytherapy.
Dose to rectal wall after permanent-seed prostate brachytherapy is dependent on distance between posterior prostatic seeds and anterior rectal wall and is influenced by postimplant periprostatic edema. We analyzed the effect of postplan timing on anterior rectal-wall dose. Twenty patients received permanent seed 125I brachytherapy as monotherapy (145 Gy). Implants were preplanned by use of transrectal ultrasound (TRUS) and carried out by use of preloaded needles. Postimplant dosimetry was calculated by use of magnetic resonance imaging-computed tomography fusion on Days 1, 8, and 30. The anterior rectal-wall dose is reported as the isodose enclosing 1.0 or 2.0 cc of rectal wall and as the RV100 in cc. The dose to rectal wall increased progressively over time. The median increase in dose to 1.0 cc of rectal wall (RD [1 cc]) from Day 1 to 30 was 39.2 Gy (p < 0.001). RV100 increased from a median of 0.07 cc on Day 1 to 0.67 cc on Day 30. The most significant predictor of rectal-wall dose (RD [1 cc], RD [2 cc], or RV100) was the time of evaluation (p < 0.001). Although periprostatic edema cannot be quantified by postimplant imaging, the dose to the anterior rectal wall increases significantly over time as prostatic and periprostatic edema resolve. Critical-organ dose reporting and guidelines for minimizing toxicity must take into account the time of the assessment.


Comparison of finite-difference transport and diffusion calculations for photon migration in homogeneous and heterogeneous tissues.
We analyse the limits of the diffusion approximation to the time-independent equation of radiative transfer for homogeneous and heterogeneous biological media. Analytical calculations and finite-difference simulations based on diffusion theory are compared with discrete-ordinate, finite-difference transport calculations. The influence of the ratio of absorption and transport scattering coefficient (mu(a)/mu'(s)) on the accuracy of the diffusion approximation are quantified and different definitions for the diffusion coefficient, D, are discussed. We also address effects caused by void-like heterogeneities in which absorption and scattering are very small compared with the surrounding medium. Based on results for simple homogeneous and heterogeneous systems, we analyse diffusion and transport calculation of light propagation in the human brain. For these simulations we convert density maps obtained from magnetic resonance imaging (MRI) to optical-parameter maps (mu(a) and mu'(s)) of the brain. We show that diffusion theory fails to describe accurately light propagation in highly absorbing regions, such as haematoma, and void-like spaces, such as the ventricles and the subarachnoid space.


Vertebral compression fractures: Still an unpredictable aspect of osteoporosis
Vertebral compression fracture is a hallmark of osteoporosis (OP) and by far the most prevalent fragility fracture. It is well proven that patients who develop a vertebral compression fracture are at substantial risk for additional fractures. Diagnosis is based on adequate clinical evaluation, imaging, and laboratory tests. The imaging of OP and fragility fractures includes conventional radiology to evaluate spinal fractures, bone mineral density (BMD) testing by dual energy x-ray densitometry, quantitative computerized tomography, magnetic resonance imaging, bone scintigraphy (if necessary), and ultrasound. Screening and treatment of individuals with high risk of osteoporotic fracture are cost-effective, but approximately two-thirds of the vertebral compression fractures (VCF) that occur each year are not accurately diagnosed and, therefore, not treated. Evaluation of VCFs, even though they may be asymptomatic, seems essential to health-related and/or clinical research on OP.


A c-fos-monomeric red fluorescent protein 1 fusion transgene is differentially expressed in rat forebrain and brainstem after chronic dehydration and rehydration.
We have previously shown that an acute osmotic stimulation induces the expression of a c-fos and monomeric red fluorescent protein 1 (mRFP1) fusion transgene in osmosensitive rat brain areas, including the supraoptic (SON) and paraventricular nuclei (PVN). However, the effects of chronic stimuli, such as dehydration, have not been investigated. In the present study, the expression patterns of the c-fos-mRFP1 fusion gene in the forebrain and the brainstem of male and female transgenic rats were studied in seven experimental groups: ad lib. water (euhydration), water deprivation for 12, 24 or 48 h (dehydration) and water deprivation for 46 h + ad lib. water for 2, 6 or 12 h (rehydration). The number of cells that express nuclear mRFP1 fluorescence was quantified in the hypothalamus, the circumventricular organs and the brainstem. Compared to the euhydrated state, the number of transgene expressing cells significantly increased in all forebrain areas and in the rostral ventrolateral medulla after dehydration and 2 h of rehydration. In the nucleus of the solitary tract and area postrema, the number of mRFP1 fluorescent cells was markedly increased after 2 h of rehydration. Although the number of mRFP1 fluorescent cells in the organum vasculosum laminae terminalis, median preoptic nucleus and subfornical organ remained significantly increased after 6 h of rehydration, reaching control levels after 12 h of rehydration, the number of mRFP1 fluorescent cells in the SON and the PVN reached control levels after 6 h of rehydration. There were no significant differences between male and female rats. These results show that the expression of the c-fos-mRFP1 fusion gene changes in the forebrain and the brainstem not only after acute osmotic stimulation, but also after chronic osmotic stimulation. Interestingly, these studies reveal the differential activation of different neuronal groups over the time course of dehydration and rehydration.


From asymptomatic to critical illness: decoding various clinical stages of COVID-19
The clinical course of COVID-19 is variable, with clinical manifestation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. The asymptomatic course is reported to potentially range between 20% and 70% (avg. 33%). A more severe course is seen in the elderly, those with various chronic diseases, and the immunosuppressed, where the case fatality rate is higher in these risk groups. The disease progresses with various symptoms, such as fever, cough, shortness of breath, malaise, myalgia, taste and smell disorders, diarrhea, sore throat, headache, and conjunctivitis. The disease begins with shortness of breath, indicative of lung damage, after an average of 7 to 10 days, and progresses in ARDS, sepsis, and septic shock. Some patients quickly enter shortness of breath, while others gradually develop shortness of breath and chest tightness and burning. The risk factors for a poor prognosis are age, comorbidities, and changes in laboratory tests. Secondary bacterial and fungal infections frequently develop with steroids and immunosuppressants, especially in the intensive care unit. Frequent complications in hospitalized patients include pneumonia (75%), ARDS (15%), acute renal failure (9%), and acute liver injury (19%). An increased incidence of heart damage is observed, including acute heart failure, arrhythmias, and myocarditis. Of the patients hospitalized due to COVID-19, 10%–25% present with prothrombotic coagulopathy, resulting in venous and arterial thromboembolic events. The most common extrapulmonary symptom is neuropsychiatric involvement, frequently accompanied by insomnia, an impediment to remembering, and an altered state of consciousness. During the course of COVID-19, patients undergo some pathological changes (severe lymphopenia, high levels of C-reactive protein, D-dimer, ferritin, etc.) depending on the condition and exposure level of the affected systems as shown by various laboratory tests. The relevant tests are the guiding elements of risk assessment, clinical monitoring, disease severity, and prognosis setting and therapy decision-making processes.


[Differential diagnosis of normocalcemic hyperparathyroidism and idiopathic hypercalciuria on the example of clinical case].
Idiopathic hypercalciuria is a heterogeneous generalized disorder caused by various defects in calcium transport and increased urinary calcium excretion. The main etiopathogenetic factors are violations of vitamin D metabolism, changes in the sensitivity of calcitriol receptors and violations of the processes of calcium reabsorption in the proximal tubules and in the ascending knee of the Henle loop. This article presents a clinical observation of patient with idiopathic hypercalciuria, initially high levels of parathyroid hormone (PTH) in the absence of hyperparathyroidism. Therapy with thiazide diuretics allowed to achieve normalization of daily urinary calcium excretion and reducing PTH. Despite the low prevalence of idiopathic hypercalciuria, differential diagnosis of this metabolic disorder should be carried out with mandatory consideration of clinical and laboratory data, as well as with diseases that may cause increased PTH production.


Hypotonic shock mediation by p38 MAPK, JNK, PKC, FAK, OSR1 and SPAK in osmosensing chloride secreting cells of killifish opercular epithelium.
Hypotonic shock rapidly inhibits Cl(-) secretion by chloride cells, an effect that is osmotic and not produced by NaCl-depleted isosmotic solutions, yet the mechanism for the inhibition and its recovery are not known. We exposed isolated opercular epithelia, mounted in Ussing chambers, to hypotonic shock in the presence of a variety of chemicals: a general protein kinase C (PKC) inhibitor chelerythrine, Gö6976 that selectively blocks PKC alpha and beta subtypes, H-89 that blocks PKA, SB203580 that blocks p38 mitogen-activated protein kinase (MAPK), as well as serine/threonine protein phosphatase (PP1 and 2A) inhibitor okadaic acid, and finally tamoxifen, a blocker of volume-activated anion channels (VSOAC). Chelerythrine has no effect on hypotonic inhibition but blocked the recovery, indicating PKC involvement in stimulation. Gö6976 had little effect, suggesting that PKC alpha and PKC beta subtypes are not involved. H-89 did not block hypotonic inhibition but decreased the recovery, indicating PKA may be involved in the recovery and overshoot (after restoration of isotonic conditions). SB203580 significantly enhanced the decrease in current by hypotonic shock, suggesting an inhibitory role of p38 MAPK in the hypotonic inhibition. Okadaic acid increased the steady state current, slowed the hypotonic inhibition but made the decrease in current larger; also the recovery and overshoot were completely blocked. Hypotonic stress rapidly and transiently increased phosphorylated p38 MAPK (pp38) MAPK (measured by western analysis) by eightfold at 5 min, then more slowly again to sevenfold at 60 min. Hypertonic shock slowly increased p38 by sevenfold at 60 min. Phosphorylated JNK kinase was increased by 40-50% by both hypotonic and hypertonic shock and was still elevated at 30 min in hypertonic medium. By immunoblot analysis it was found that the stress protein kinase (SPAK) and oxidation stress response kinase 1 (OSR1) were present in salt and freshwater acclimated fish with higher expression in freshwater. By immunocytochemistry, SPAK, OSR1 and phosphorylated focal adhesion kinase (pFAK) were colocalized with NKCC at the basolateral membrane. The protein tyrosine kinase inhibitor genistein (100 micromol l(-1)) inhibited Cl(-) secretion that was high, increased Cl(-) secretion that was low and reduced immunocytochemical staining for phosphorylated FAK. We present a model for rapid control of CFTR and NKCC in chloride cells that includes: (1) activation of NKCC and CFTR via cAMP/PKA, (2) activation of NKCC by PKC, myosin light chain kinase (MLCK), p38, OSR1 and SPAK, (3) deactivation of NKCC by hypotonic cell swelling, Ca(2+) and an as yet unidentified protein phosphatase and (4) involvement of protein tyrosine kinase (PTK) acting on FAK to set levels of NKCC activity.


Defining excellence in health service management: evidence from an international study.
Health service executives are striving to implement the best managerial practices amid the major turbulence and restructuring which is prevalent in many health care systems today. All too often, guidance about what the best practices are needs to be sought from studies contained within the general management literature. It is problematical whether this literature is applicable to health service organizations. This article reports the results of a study which examined the views of 93 executives in 14 hospitals in Britain, Canada and the United States about what constitutes managerial excellence. The hospitals were selected on the basis of their reputed success in health service management. Using grounded theory methodology, eight factors of excellence were derived from the interview data which were supplemented by data made available from hospital documentation supplied by participants. The results of this study are compared with those of Peters and Waterman (1982). This is the most frequently cited study of managerial excellence in the general management literature. The main conclusions drawn are that a current definition of health service management excellence has been identified; there was a high degree of unanimity among participant executives about the constituents of success and excellence in health service management; and, that there are some marked differences between this definition of excellence and that propounded by Peters and Waterman (1982). The implications of this definition of excellence for health service executives are discussed.


Kinetics of p53 binding to promoter sites in vivo.
Downstream target genes of p53 are thought to mediate its tumor-suppressive activity, but it is unknown whether differential transactivation of these genes is regulated at the level of p53 binding to their promoters. To address this issue, p53 binding in vivo to consensus sites in the p21(Waf1), MDM2, and PIG3 promoters was investigated in cells exposed to adriamycin (ADR) or ionizing radiation as well as in an inducible p53 cell line. p53-DNA complexes were cross-linked in vivo by treating the cells with formaldehyde and processed by chromatin immunoprecipitation-PCR. This methodology allowed for the analysis of relevant p53-DNA complexes by preventing redistribution of cellular components upon collection of cell extracts. Increased p53 binding to the p21(Waf1), MDM2, and PIG3 promoters occurred within 2 h after p53 activation; however, significant increases in PIG3 transcription did not occur until 15 h after p53 binding. Gel shift analyses indicated that p53 had lower affinity for the consensus binding site in the PIG3 promoters compared to its consensus sites in the p21 and MDM2 genes, which suggests that additional factors may be required to stabilize the interaction of p53 with the PIG3 promoter. Further, acetylated p53 (Lys382) was found in chemically cross-linked complexes at all promoter sites examined after treatment of cells with ADR. In summary, the kinetics of p53 binding in vivo to target gene regulatory regions does not uniformly correlate with target gene mRNA expression for the p53 target genes examined. Our results suggest that target genes with low-affinity p53 binding sites may require additional events and will have delayed kinetics of induction compared to those with high-affinity binding sites.


Highlights of Skin Disease Education Foundation's 41st Annual Hawaii Dermatology Seminar™.
New therapies, recent pathophysiological findings, and updated guidelines combined to create compelling presentations at the Skin Disease Education Foundation's 41st Annual Hawaii Dermatology Seminar™. This educational supplement summarizes the highlights of clinical sessions presented during this CME/CE conference. A growing understanding of the biology of psoriasis has facilitated the development of increasingly efficacious medications. Skin clearance used to be regarded as an impractical goal for psoriasis therapy. Now, some clinical trials of newer medications report more than half of participants attaining Psoriasis Area and Severity Index (PASI) scores of 90. Two leading investigators review the latest findings about the treatment of this condition. Recent evidence demonstrates that psoriasis and psoriatic arthritis share multiple pathological underpinnings. A T helper type 17 (Th17) lymphocyte-based pathogenesis, genes, and microbiome changes have been identified in both conditions. Many therapeutics used in psoriasis care are efficacious in psoriatic arthritis. An expert in psoriatic arthritis updates readers about this condition. Cutaneous fungal infections, including onychomycosis, pose diagnostic and treatment challenges. New topical therapies and an investigational oral agent offer expanded options for management. The American Academy of Dermatology has issued new guidelines for the treatment of acne. Appropriate antibiotic use is a prominent theme. The US Food and Drug Administration has issued a communication about the risk of unintentional injection of soft tissue fillers into facial blood vessels-including blindness. The lead author of a recent review about this topic discusses how to prevent this serious outcome. The volume of new information about pathophysiology, diagnosis, therapy, and safety challenges our ability to keep current while enabling us to improve patient care. We hope that the highlights of this seminar offer you information that can be applied to your busy practices.


Incidence of free-living amoebae in the nasal passages of local population in Zaria, Nigeria.
Following the observation of cases of primary amoebic meningoencephalitis (PAME) during the dusty harmattan period in Zaria, a survey was carried out in randomly selected local populations of Zaria, to find out the incidence of free-living amoebae in the nasal passages. The times of sampling were spaced so as to cover both the rainy (non-harmattan) abd dry (harmattan) seasons. In all 1250 individuals were sampled, and were grouped in the three age groups of above 18 years, between 4 and 18 years and below 4 years. The overall incidence was 4.2% (52 out of 1250). There was no marked difference in the three age groups studied. The incidence rate in males was 4.8% (30 of 630) and that in females was 3.5% (22 of 620). Nine different species of free-living amoebae were isolated. Six belonged to the Genus Hartmannella, two to the genus Naegleria, and one to the genus Schizopyrenus. Three species were found to be pathogenic for mice: H. culbertsoni, H. rhysodes and N. fowleri. It was observed from this study that a significant percentage of the Zaria population carry free-living amoebae in the nasal passages. The monthly incidence rate in population ranged from 1.8 to 3.1% during the rainy (non-harmattan) season whereas in the dry (harmattan) season it ranged from 4.2 to 7.9%. The highest incidence rate coincided with the peak of the dry (harmattan) season. The possible role of harmattan winds on the nasal carriage as well as the necessity to investigate fully the disease PAME in this environment is discussed.


Investigating the effects of cerebellar transcranial direct current stimulation on saccadic adaptation and cortisol response.
Transcranial Direct Current Stimulation (tDCS) over the prefrontal cortex has been shown to modulate subjective, neuronal and neuroendocrine responses, particularly in the context of stress processing. However, it is currently unknown whether tDCS stimulation over other brain regions, such as the cerebellum, can similarly affect the stress response. Despite increasing evidence linking the cerebellum to stress-related processing, no studies have investigated the hormonal and behavioural effects of cerebellar tDCS. This study tested the hypothesis of a cerebellar tDCS effect on mood, behaviour and cortisol. To do this we employed a single-blind, sham-controlled design to measure performance on a cerebellar-dependent saccadic adaptation task, together with changes in cortisol output and mood, during online anodal and cathodal stimulation. Forty-five participants were included in the analysis. Stimulation groups were matched on demographic variables, potential confounding factors known to affect cortisol levels, mood and a number of personality characteristics. Results showed that tDCS polarity did not affect cortisol levels or subjective mood, but did affect behaviour. Participants receiving anodal stimulation showed an 8.4% increase in saccadic adaptation, which was significantly larger compared to the cathodal group (1.6%). The stimulation effect on saccadic adaptation contributes to the current body of literature examining the mechanisms of cerebellar stimulation on associated function. We conclude that further studies are needed to understand whether and how cerebellar tDCS may module stress reactivity under challenge conditions.


Normative social influence is underdetected.
The present research investigated the persuasive impact and detectability of normative social influence. The first study surveyed 810 Californians about energy conservation and found that descriptive normative beliefs were more predictive of behavior than were other relevant beliefs, even though respondents rated such norms as least important in their conservation decisions. Study 2, a field experiment, showed that normative social influence produced the greatest change in behavior compared to information highlighting other reasons to conserve, even though respondents rated the normative information as least motivating. Results show that normative messages can be a powerful lever of persuasion but that their influence is underdetected.


To test or not to test: psychosocial barriers to HIV testing in high-income countries.
To contribute to the evidence-based understanding of the psychosocial factors that influence individuals' uptake of testing for HIV, we assessed and synthesized the pertinent published literature in the fields of public health, behavioural medicine, and (health) psychology. Although the evidence base appears too limited to allow firm conclusions and definition on psychological barriers to HIV testing in high-income countries, we identified convergent themes from the available studies. Testing for HIV seems to be more likely when individuals perceive that they have been at risk, though this association is not perfectly observed. Fear of the consequences of testing positive -mainly worries related to discrimination and rejection - also hinders HIV testing. Finally, individuals appear more likely to test for HIV when they perceive more benefits from testing. The perspective of targeted individuals, in particular the social connotations and consequences of HIV diagnoses, is crucial to understand testing decisions.


Intracardiac Shunt-Use of the Hydrogen-Sensitive Catheter to Clarify False Positive Diagnosis of Left-to-Right Shunt.
The charts of 142 patients who had diagnostic right heart catheterization with conventional oximetry, oxygen content determinations and hydrogen electrode curve recording for left-to-right shunt were reviewed. A false positive diagnosis of surgical significance would have been made in nine patients if the hydrogen electrode had not been used. In addition, a diagnosis of left-to-right shunt could have been made at the wrong chamber level in three additional cases.


Field evaluation of a blood based test for active tuberculosis in endemic settings.
Over 9 million new active tuberculosis (TB) cases emerge each year from an enormous pool of 2 billion individuals latently infected with Mycobacterium tuberculosis (M. tb.) worldwide. About 3 million new TB cases per year are unaccounted for, and 1.5 million die. TB, however, is generally curable if diagnosed correctly and in a timely manner. The current diagnostic methods for TB, including state-of-the-art molecular tests, have failed in delivering the capacity needed in endemic countries to curtail this ongoing pandemic. Efficient, cost effective and scalable diagnostic approaches are critically needed. We report a multiplex TB serology panel using microbead suspension array containing a combination of 11 M.tb. antigens that demonstrated overall sensitivity of 91% in serum/plasma samples from TB patients confirmed by culture. Group wise sensitivities for sputum smear positive and negative patients were 95%, and 88%, respectively. Specificity of the test was 96% in untreated COPD patients and 91% in general healthy population. The sensitivity of this test is superior to that of the frontline sputum smear test with a comparable specificity (30-70%, and 93-99%, respectively). The multiplex serology test can be performed with scalability from 1 to 360 patients per day, and is amenable to automation for higher (1000s per day) throughput, thus enabling a scalable clinical work flow model for TB endemic countries. Taken together, the above results suggest that well defined antibody profiles in blood, analyzed by an appropriate technology platform, offer a valuable approach to TB diagnostics in endemic countries.


VIP reverses the expression profiling of TLR4-stimulated signaling pathway in rheumatoid arthritis synovial fibroblasts.
Since recent evidences point out the potential involvement of Toll-like receptors (TLRs) in the therapeutic effect of vasoactive intestinal peptide (VIP), the purpose of this study is to elucidate the role of VIP as a negative regulator of TLR-signaling. To this aim, we analyzed in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), the expression profile of TLR-pathway related molecules, as well as the alterations induced by LPS stimulation in RA-FLS and the effect of VIP treatment. Cultured FLS were obtained from patients with RA or OA. RA-FLS were next stimulated with lipopolysaccharide (LPS) in presence or absence of VIP. The gene expression profiling of molecules involved in LPS-mediated TLR4-signaling was studied by cRNA microarray analysis. Twenty three molecules involved in TLR signaling resulted over-expressed at mRNA level in basal RA-FLS compared to OA-FLS. Moreover, in RA-FLS, 23 of the analyzed genes were found to be up-regulated by LPS stimulation whereas 30 were not affected. VIP down-regulated the LPS-induced RNA expression of molecules involved in TLR signaling pathway. Up-regulation of RNA expression of CD14, MD2, TRAM, TRIF, IRAK4, TAB2, TRAF6 and TBK1 was corroborated by RT-PCR as well as the VIP regulatory effect. Increased protein levels of TRAF6, TBK1 and pIRAK1 after exposure to LPS, and the inhibitory effect of VIP, were described by Western blotting. As functional consequences, it was observed the VIP-induced impaired production of IL-6 and RANTES/CCL5 after LPS stimulation. In conclusion, VIP acts as a negative modulator of the TLR4-signaling by overturning the production of several checkpoints molecules of the cascade and thus, widening its potential therapeutic effects.


Determinant analysis and developing evaluation indicators of grade of execution score of double axel jump in figure skating.
A figure skating jump score is determined by the sum of the base value based on the difficulty and grade of execution (GOE) that indicates the performance quality. Therefore, performing a high-quality jump to obtain a high GOE is essential to win a competition. However, the relationship between the GOE and kinematic parameters remains unclear. We analysed the horizontal distance, vertical height, and landing speed of double axel jumps in the Ladies' Short Program at the 2019 World Championships. The highest GOE group had significantly larger horizontal distances than the middle and lower groups, while the landing speed and vertical height were not significantly different. A principal component regression analysis was conducted to clarify the contrast between the three variables affecting the GOE. The results showed that greater horizontal distance and landing speed compared to vertical height (component 1) and greater horizontal distance compared to landing speed (component 3) contributed to higher GOE. We divided skaters into four clusters using these two components and provided general GOE acquisition strategies for each cluster. Finally, to apply our results to the industry, we proposed two new evaluation indicators which are highly correlated with the two components and easy to interpret.


Does breast carcinoma belong to the Lynch syndrome tumor spectrum? - Somatic mutational profiles vs. ovarian and colorectal carcinomas.
Inherited DNA mismatch repair (MMR) defects cause predisposition to colorectal, endometrial, ovarian, and other cancers occurring in Lynch syndrome (LS). It is unsettled whether breast carcinoma belongs to the LS tumor spectrum. We approached this question through somatic mutational analysis of breast carcinomas from LS families, using established LS-spectrum tumors for comparison. Somatic mutational profiles of 578 cancer-relevant genes were determined for LS-breast cancer (LS-BC, n = 20), non-carrier breast cancer (NC-BC, n = 10), LS-ovarian cancer (LS-OC, n = 16), and LS-colorectal cancer (LS-CRC, n = 18) from the National LS Registry of Finland. Microsatellite and MMR protein analysis stratified LS-BCs into MMR-deficient (dMMR, n = 11) and MMR-proficient (pMMR, n = 9) subgroups. All NC-BCs were pMMR and all LS-OCs and LS-CRCs dMMR. All but one dMMR LS-BCs were hypermutated (> 10 non-synonymous mutations/Mb; average 174/Mb per tumor) and the frequency of MMR-deficiency-associated signatures 6, 20, and 26 was comparable to that in LS-OC and LS-CRC. LS-BCs that were pMMR resembled NC-BCs with respect to somatic mutational loads (4/9, 44%, hypermutated with average mutation count 33/Mb vs. 3/10, 30%, hypermutated with average 88 mutations/Mb), whereas mutational signatures shared features of dMMR LS-BC, LS-OC, and LS-CRC. Epigenetic regulatory genes were significantly enriched as mutational targets in LS-BC, LS-OC, and LS-CRC. Many top mutant genes of our LS-BCs have previously been identified as drivers of unselected breast carcinomas. In conclusion, somatic mutational signatures suggest that conventional MMR status of tumor tissues is likely to underestimate the significance of the predisposing MMR defects as contributors to breast tumorigenesis in LS.


[Activity of purine enzyme metabolism in rat thymocytes after irradiation and after administration of riboxine].
It has been established, that the total X-ray irradiation of animals takes influence upon the functional activity of key enzymes of adenine nucleotides metabolism: adenylatekinase, AMP deaminase, 5'-nucleotidase, adenosine deaminase and purine nucleoside phosphorylase in rat's thymocytes. The increase of activity of the investigated enzymes is observed in our experiment, except 5'-nucleotidase, which activity is authentically decreasing after irradiation (1.0 and 7.78 Gy). The injection of the preparation riboxine to experimental animals 15 min prior to the exposure has normalized the purine exchange enzymes activity.


Screening of food raw materials for the presence of Shiga toxin-producing Escherichia coli O91:H21.
To provide information on the prevalence and detection, in foods, of Shiga toxin-producing Escherichia coli (STEC) O91:H21. Seven hundred fifteen minced beef meats and 205 raw milk samples were analysed by stx-specific PCR-ELISA. Samples positive for stx were subsequently tested for the presence of wzy-O91, fliC-H21 and the adhesin-encoding gene saa. For minced meat, 16 (2.2%) and 11 (1.5%) samples were found positive for (stx, wzy-O91, fliC-H21) and (stx, wzy-O91, fliC-H21, saa) combinations, respectively. For raw milk, seven (3.4%) samples were found positive for the (stx, wzy-O91, fliC-H21) combination but none of these contained saa. Two STEC O91:H21 saa-positive strains and three STEC O91 H21- and saa-negative strains were isolated by colony hybridization. A low prevalence of potentially pathogenic STEC O91:H21 in food products was found using a combination of PCR assays targeting stx, wzy-O91, fliC-H21 and saa. The PCR-based approach described here represents a valuable method for rapid screening of food samples contaminated by STEC O91:H21.


Zika Virus-Induction of the Suppressor of Cytokine Signaling 1/3 Contributes to the Modulation of Viral Replication.
Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged and caused global outbreaks since 2007. Although ZIKV proteins have been shown to suppress early anti-viral innate immune responses, little is known about the exact mechanisms. This study demonstrates that infection with either the African or Asian lineage of ZIKV leads to a modulated expression of suppressor of cytokine signaling (SOCS) genes encoding SOCS1 and SOCS3 in the following cell models: A549 human lung adenocarcinoma cells; JAr human choriocarcinoma cells; human neural progenitor cells. Studies of viral gene expression in response to SOCS1 or SOCS3 demonstrated that the knockdown of these SOCS proteins inhibited viral NS5 or ZIKV RNA expression, whereas overexpression resulted in an increased expression. Moreover, the overexpression of SOCS1 or SOCS3 inhibited the retinoic acid-inducible gene-I-like receptor-mediated activation of both type I and III interferon pathways. These results imply that SOCS upregulation following ZIKV infection modulates viral replication, possibly via the regulation of anti-viral innate immune responses.


The nature of the phosphate inhibitor complex of sulphite oxidase from electron-paramagnetic-resonance studies using oxygen-17.
Studies of the effect of substitution with 17O on the e.p.r. spectra at 9 and 35 GHz of Mo(V) in the phosphate complex of sulphite oxidase are reported. Substitution of 17O-enriched water for normal water, for samples of the enzymes reduced by sulphite in the presence of normal phosphate, produced no detectable effect on the e.p.r. signal. If phosphate substituted with 17O was used, coupling due to 17O, producing large anisotropic splittings in the spectrum, was clearly detectable. It is concluded that phosphate is co-ordinated directly to molybdenum in the active site of the enzyme, in an equatorial type of ligand position. An oxygen ligand must be displaced from the molybdenum in the process of binding the phosphate. Implications concerning the mechanism of the enzyme reactions are discussed.


Compassion in emergency departments. Part 1: nursing students' perspectives.
Compassion is a topical issue in clinical nursing practice, nurse education and policy, but a review of the literature reveals that nursing students' experiences of compassionate care receives little attention. In this three-part series David Hunter and colleagues explore compassion in emergency departments (EDs) from nursing students' point of view. Part 1 provides findings of a professional doctorate study of nursing students' experiences of compassionate care in EDs, part 2 explores the barriers to compassionate care in this clinical setting that emerged from the study, and part 3 considers factors that enable and support compassionate care provision in EDs. The aim of the study was to explore nursing students' experiences of the provision of compassionate care in EDs. The underpinning methodology was an exploratory-descriptive qualitative design. A total of 15 nursing students from across the west of Scotland, who had been placed in eight different EDs, participated in face-to-face interviews which were audio recorded, transcribed and analysed. Two major themes emerged 'doing the little things' and 'a strange, new world: the uniqueness of the ED'. The students also identified barriers and enablers to providing compassionate care which are discussed in parts two and three. Despite the challenges of working in the most acute of clinical settings, nurses can provide compassionate care to patients and their relatives. However, this is not universal because certain groups of patients considered 'challenging' do not receive equitable compassionate care.


Emotion-related brain regions.
Converging data from human functional imaging in healthy subjects, neuropsychological studies of brain-damaged patients, and non-human neurophysiology indicate that emotional processing is linked to anatomically distinct and well-defined brain regions. A main characteristic of emotion-related brain regions (orbitofrontal cortex, anterior cingulated cortex, amygdala, insula) is their reciprocal anatomical connectivity with each other as well as with neuromodulatory systems (e.g., serotonergic dorsal raphe, cholinergic nucleus basalis of Meynert, and dopaminergic ventral tegmentum) and with other brain areas involved in sensory, motor, and cognitive functions. These structures mediate the representation of stimulus values, the affect-leaden enhancement of sensory processing, and the predictions of values associated with actions in order to bias decision-making in uncertain situations. In this review, we discuss new results from the functional neuroanatomy of these brain circuits and outline their significance in the emergence of various psychopathological phenomena.


The effect of Schistosoma mansoni infection of the productivity of cane cutters on a sugar estate in Tanzania.
In an attempt to justify future snail control on an irrigated sugar estate in Tanzania, the effects of Schistosoma mansoni infection on the productivity of apparently healthy cane cutters were investigated. The bonus earnings of cane cutters who were found to be infected with S. mansoni were compared, retrospectively, with earnings of uninfected cane cutters during the years 1968-69. For one 6-month period a more detailed study was made to correlate bonus earnings with actual output in tons of cane cut. It was found that in the four 6-month periods the mean bonus earnings of the uninfected cane cutters exceeded the mean bonus earnings of the infected men by 11.0%, 11.4%, 6.0%, and 13.7%, respectively. In all except the third period these differences were statistically significant. After treatment for S. mansoni infection, the workers were able to improve their earnings relative to both infected and uninfected workers. In a more detailed study of some of the workers during the third 6-month period, it was discovered that a 4% difference in bonus earnings represented a 1% difference in output. Taking into account the variations of bonus earnings it was estimated that the overall difference in productivity between infected and uninfected workers was 3-5%.


Congenital contractural arachnodactyly. Report of four additional families and review of literature.
We report here four families with congenital contractural arachnodactyly (CCA) in which a wide range of phenotypic expression is observed. In one family with a large number of affected individuals the condition is mildly expressed. These individuals usually have crumpled ears, camptodactyly with ulnar deviation of the fingers, adducted thumbs, limited elbow and/or knee extension, and hypoplasia of the calf muscles. Arachnodactyly is not a constant feature. No spinal deformities are present and only the proband has clubfoot deformities. With time, affecteds have experienced spontaneous improvement of their contractures and their condition in adulthood has not interfered with a normal lifestyle. Within this family there is little phenotypic variation between affected individuals. Those affected within each of the other families have had varying degrees of severity of the condition. A review of 29 other kindreds described in the literature with congenital contractural arachnodactyly shows that in this condition the most common features are abnormally formed ears, camptodactyly, arachnodactyly, adducted thumbs, limited movement of the elbows and knees, and underdevelopment of the calf muscles. Spontaneous improvement of the contractures with age is reported in 94% of cases. Kyphosis, scoliosis or kyphoscoliosis occurred in 50% and these defects were present in those who where more severely affected with CCA. No ocular problems have been reported in this syndrome, but congenital heart defects have occurred in 14.7%. Marfan syndrome is the most important condition to differentiate from congenital contractural arachnodactyly since these two conditions are similar phenotypically. However, in the former there are frequently serious ocular and cardiovascular problems which lead to significant morbidity and/or early death.


The recycling of the coal fly ash in glass production.
The recycling of fly ash obtained from the combustion of coal in thermal power plant has been studied. Coal fly ash was vitrified by melting at 1773 K for 5 hours without any additives. The properties of glasses produced from coal fly ash were investigated by means of Differential Thermal Analysis (DTA), X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) techniques. DTA study indicated that there was only one endothermic peak at 1003 K corresponding to the glass transition temperature. XRD analysis showed the amorphous state of the glass sample produced from coal fly ash. SEM investigations revealed that the coal fly ash based glass sample had smooth surface. The mechanical, physical and chemical properties of the glass sample were also determined. Recycling of coal fly ash by using vitrification technique resulted to a glass material that had good mechanical, physical and chemical properties. Toxicity characteristic leaching procedure (TCLP) results showed that the heavy metals of Pb, Cr, Zn and Mn were successfully immobilized into the glass. It can be said that glass sample obtained by the recycling of coal fly ash can be taken as a non-hazardous material. Overall, results indicated that the vitrification technique is an effective way for the stabilization and recycling of coal fly ash.


Abdominal MR imaging with a volumetric interpolated breath-hold examination.
To compare a T1-weighted, three-dimensional (3D), gradient-echo (GRE) sequence for magnetic resonance (MR) imaging of the body (volumetric interpolated breath-hold examination, or VIBE) with a two-dimensional (2D) GRE breath-hold equivalent. Twenty consecutive patients underwent 1.5-T MR imaging. The examinations included pre- and postcontrast (20 mL gadopentetate dimeglumine) fat-saturated 2D GRE breath-hold imaging and fat-saturated volumetric interpolated breath-hold imaging before, during (arterial phase), and after injection, with thin (2-mm source images) and thick (8-mm reconstruction images) sections. The three images were compared qualitatively and quantitatively (signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]). Qualitatively, the 2-mm source images had poorer pancreatic edge definition on precontrast images compared with the other two data sets (P < .05). On gadolinium-enhanced images, scores for clarity of pancreatic edge, number of vessels visualized, and arterial ghosting were significantly lower for the postcontrast 2D GRE images. Quantitatively, SNR measurements in the liver, aorta, and renal cortex on pre- and postcontrast images were significantly higher for the 8-mm reconstruction images than for the 2D GRE or 2-mm source images (P < .05). Aorta-to-fat CNR was significantly higher on the 8-mm reconstruction images. Fat-saturated volumetric interpolated breath-hold images have quality comparable to that of conventional fat-saturated 2D GRE images.


[Restriction analysis of the genome of swine abortion parvovirus and cloning of its PstI-EcoRI fragment].
The cultured pig kidney cells infected by the porcine parvovirus (PPV) produced the virions and viral DNA. The latter was used as a matrix to synthesize the double stranded DNA. The obtained preparation is more homogenic than the natural replicative form and was used for restriction analysis of porcine parvovirus genome and for molecular cloning of its fragment. The isolated recombinant plasmids contained the PstI-EcoRI fragment of PPV DNA, containing 70% of the viral genome. The restriction analysis of replicative PPV DNA isolated from the infected cells has resulted in finding of the replicative form containing a 300 bp deletion in the 5'-region of PPV genome.


Hyperlipidemia with hypoglycemia reduces myocardial oxygen utilization efficiency but not contractile function during coronary hypoperfusion.
This study was designed to determine changes in myocardial contractile function and fuel selection during moderate coronary hypoperfusion in the presence of elevated plasma free fatty acid (FFA) at normal and reduced blood glucose concentrations. Coronary perfusion pressure (CPP) was sequentially lowered from 100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery (LAD) of anesthetized, open-chest dogs. Regional glucose uptake (GU), fatty acid uptake (FAU), percentage segment shortening (%SS), and oxygen consumption (MV O(2)) were determined with normal arterial plasma FFA concentrations (Group 1) or with elevated FFA concentrations (Groups 2 and 3). In Group 3, glucose in the coronary perfusate blood was reduced from 3.53+/-0.36 to 0.15+/-0.03 m M by hemodialysis. In Group 1, FAU fell by 85% as CPP was lowered to 60 mmHg and remained depressed as CPP was reduced further; GU did not fall significantly. Hyperlipidemia in Group 2 did not alter GU at any CPP, but maintained FAU at baseline levels until CPP was lowered to 40 mmHg. At 40 mmHg CPP, myocardial function and metabolic variables were similar in Groups 1 and 2. In Group 3 at 40 mmHg, FAU increased four-fold and MV O(2)doubled v Groups 1 and 2, and GU fell to zero. Despite these metabolic changes, %SS in Group 3 was unchanged relative to Group 2. Addition of glucose to the dialysate prevented the effects of dialysis on FAU, GU, and MV O(2). Thus, preferential glucose oxidation sustains myocardial oxygen utilization efficiency [(heart rate x %SS x maximum left ventricular pressure)/MV O(2)] during hypoperfusion. Blocking preferential glucose oxidation by combined hyperlipidemia and hypoglycemia lowers oxygen utilization efficiency, but does not compromise myocardial contractile function.


Perceived Mentoring Practices in Developmental-Behavioral Pediatrics Fellowship Programs.
Junior physicians describe mentoring relationships as integral to their career development and success. Current evidence suggests that mentoring is under-utilized despite interest from trainees. The purpose of this study is to describe the mentoring practices in developmental-behavioral pediatric (DBP) fellowship programs and identify mentoring needs of DBP fellows and recent graduates. DBP fellows and recent graduates less than 5 years out of training from US-based DBP fellowship programs were contacted to complete a survey on their mentoring experiences in fellowship and early career. A total of 90 respondents completed the entire survey including 47 current DBP fellows and 43 recent graduates. Only 52% of respondents reported having a formal faculty mentor during their fellowship. Only 45% of recent graduates reported that they currently have a mentor, of those without a current mentor 83% said they would like to have a mentor. Adequate mentoring during fellowship was lowest for career development and research (34% and 27%). Satisfaction with mentoring was associated with having a formal mentor (p < .001) and receiving mentoring in multiple areas (p < .001). Qualitative responses suggested that effective mentoring addresses the mentee's career goals, provides insight into being a developmental-behavioral pediatrician, assists in navigating academics, and involves a personal relationship. Results suggest opportunities for improved mentoring in DBP fellowship programs, particularly in the areas of career development and research and that there is a significant need for mentorship among recent graduates. Findings from this study can inform program improvement in mentoring for DBP fellows and recent graduates.


Dietary Protein Intake and Lean Muscle Mass in Survivors of Childhood Acute Lymphoblastic Leukemia: Report From the St. Jude Lifetime Cohort Study.
Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for low lean muscle mass and muscle weakness, which may contribute to inactivity and early development of chronic diseases typically seen in older adults. Although increasing protein intake, in combination with resistance training, improves lean muscle mass in other populations, it is not known whether muscular tissue among survivors of ALL, whose impairments are treatment-related, will respond similarly. The aim of this study was to evaluate associations among dietary protein intake, resistance training, and lean muscle mass in survivors of ALL and age-, sex-, and race-matched controls. This was a cross-sectional study. Lean muscle mass was determined with dual-energy x-ray absorptiometry, dietary information with 24-hour recalls, and participation in resistance training with a questionnaire. Participants were 365 survivors of ALL (52% male; 87% white; median age=28.5 years, range=23.6-31.7) and 365 controls with no previous cancer. Compared with controls, survivors of ALL had lower lean muscle mass (55.0 versus 57.2 kg, respectively) and lower percentage of lean muscle mass (68.6% versus 71.4%, respectively) than controls. Similar proportions of survivors (71.1%) and controls (69.7%) met recommended dietary protein intake (0.8 g/kg/d). Survivors (45.4%) were less likely to report resistance training than controls (53.8%). In adjusted models, 1-g higher protein intake per kilogram of body mass per day was associated with a 7.9% increase and resistance training ≥1×wk, with a 2.8% increase in lean muscle mass. The cross-sectional study design limits temporal evaluation of the association between protein intake and lean muscle mass. The findings suggest that survivors of childhood ALL with low lean muscle mass may benefit from optimizing dietary protein intake in combination with resistance training. Research is needed to determine whether resistance training with protein supplementation improves lean muscle mass in survivors of childhood ALL.


Immune serum-mediated effects on brucellosis evolution in mice.
Immune serum injected into mice before a footpad challenge of virulent strain Brucella abortus 544 can prevent dissemination of infection to the spleen. Sera from mice infected with Brucella for at least 2 months or from mice vaccinated with a protein-bound cell wall peptidoglycan Brucella fraction completely stopped dissemination. Brucella lipopolysaccharide and polysaccharide cross-reacting Yersinia immune sera reduced dissemination. Both peptidoglycan and lipopolysaccharide immune sera injected simultaneously with an intravenous challenge caused a shift in Brucella from spleen to liver. When immune sera were injected simultaneously with an intravenous challenge, the kinetics of splenic infection showed two effects: an early one, optimally measured at day 7 postchallenge, showed reduced numbers in the spleen due to the shift of Brucella to the liver; a late effect, measured at day 21 postchallenge, showed reduced numbers in spleen and liver with nearly complete clearance by day 49 postchallenge. Brucella lipopolysaccharide and cross-reacting bacterial antisera induced the early effect only, whereas peptidoglycan and infected mouse sera induced both effects. When peptidoglycan immune serum was injected 2 or 7 days after intravenous challenge, the late effect was somewhat reduced. Hence, immune sera to protein and polysaccharide surface antigens can (i) prevent dissemination of systemic infection and (ii) help destroy intercellular bacteria (protein antigen only). These effects may represent a large part of vaccinal immunity.


A model of disturbed flow-induced atherosclerosis in mouse carotid artery by partial ligation and a simple method of RNA isolation from carotid endothelium.
Despite the well-known close association, direct evidence linking disturbed flow to atherogenesis has been lacking. We have recently used a modified version of carotid partial ligation methods to show that it acutely induces low and oscillatory flow conditions, two key characteristics of disturbed flow, in the mouse common carotid artery. Using this model, we have provided direct evidence that disturbed flow indeed leads to rapid and robust atherosclerosis development in Apolipoprotein E knockout mouse. We also developed a method of endothelial RNA preparation with high purity from the mouse carotid intima. Using this mouse model and method, we found that partial ligation causes endothelial dysfunction in a week, followed by robust and rapid atheroma formation in two weeks in a hyperlipidemic mouse model along with features of complex lesion formation such as intraplaque neovascularization by four weeks. This rapid in vivo model and the endothelial RNA preparation method could be used to determine molecular mechanisms underlying flow-dependent regulation of vascular biology and diseases. Also, it could be used to test various therapeutic interventions targeting endothelial dysfunction and atherosclerosis in considerably reduced study duration.


Synthesis and evaluation of biological properties of ferrocenyl-podophyllotoxin conjugates.
Three types, esters, amides and 1,2,3-triazoles, of ferrocenyl-podophyllotoxin conjugates were synthesised, and their anticancer activity was evaluated. We observed that the most potent ferrocenyl derivatives were esters. Esters 15, 16 and 17 acted in a similar way to podophyllotoxin, i.e. reduced the number of G1 phase cells and induced G2/M blockage, while esters 14 and 18 and amide 19 blocked cells in S phase in a similar manner to etoposide.