The role of community pharmacists in primary and secondary prevention of skin cancer: an evaluation of a Flemish skin cancer prevention campaign.
Skin cancer is a leading form of cancer in Belgium. Prevention of skin cancer by community pharmacists can play a role in increasing awareness and promoting sun protection. However, which persons could be reached by community pharmacists for skin cancer awareness in Belgium and whether this increased awareness is associated with increased sun protection and early detection remains unclear. Demographics of approached persons in Flemish community pharmacies during the months of May-June 2022 and the content of the skin cancer counseling were retrieved from the pharmacy database. Sunscreen purchases and dermatologist visits were evaluated up to 180 days after the skin cancer counseling. Community pharmacists provided skin cancer counseling to a broad population of visitors (n = 822, 69% females, median age of 59 years Q1-Q3: 44-71 years). During the campaign, 822 visitors received a leaflet with skin cancer prevalence and sunscreen importance. On top of that, 335 visitors (41%) received additional counseling: skin type sensitivity was checked for 198 visitors (24%), typical characteristics of melanoma were discussed with 100 visitors (12%) and 37 visitors (5%) were referred to a physician for further information or concerns regarding a skin spot. Overall, one out of three visitors purchased sunscreen on the day of the counseling (33%, increasing up to 38% after 180 days). Among people under 20 years, this was even higher (51%). Additional counseling increased the likelihood of a dermatologist visit within 180 days (OR = 1.80; 95%CI: 1.12-2.88). By providing skin cancer counseling in Belgian community pharmacies, a broad range of citizens was reached and triggered to purchase sunscreen, often on the same day as the counseling. Notably, young people were likely to purchase sunscreen. Citizens receiving additional counseling were more likely to visit a dermatologist within 180 days.


The acute-phase protein response in parasite infection. Nippostrongylus brasiliensis and Trichinella spiralis in the rat.
During acute inflammation, the mammalian liver responds with increased production and secretion of a series of plasma glycoproteins, collectively termed the acute-phase proteins, resulting from the release at the site of inflammation of polypeptide cytokines, including IL-1 and IL-6, which interact with receptors on hepatocytes and alter gene expression. This attribute of the systemic acute-phase response was studied throughout the course of infection with two nematode parasites in rats. Significant increases in serum haptoglobin, alpha 1-acid glycoprotein and alpha 1-cysteine protease inhibitor were detected coincident with episodes of skin, lung and intestinal pathology during Nippostrongylus brasiliensis, but were not seen during Trichinella spiralis, infection of the rat despite similar intestinal pathology. These changes were seen at both the protein and mRNA levels in the liver. Infection with T. spiralis was not anti-inflammatory, as macrophages from various sites could be induced in vitro to release inflammatory cytokines, and in vivo induction of inflammation by turpentine injection was similar in control and infected animals. However, macrophage populations recovered from animals infected with T. spiralis were not activated. Moreover, intestinal infection alone with intestinal stages of N. brasiliensis also failed to elicit the systemic acute-phase protein response, requiring an explanation involving skin and lung for the acute-phase response during gut inflammation in a primary infection with N. brasiliensis. Taken together, these data suggest that during the intestinal phase of nematode infection, with pathological changes to the gut, the systemic acute-phase response is not elicited through compromise or lack of stimulation of inflammatory cells in the intestine. The systemic parameters of the acute-phase response may not be a component of gastrointestinal pathology.


Determination of generic body-seat interface shapes by cluster analysis.
The purpose of this study was to determine typical or generic shape patterns of the buttock-seat interface for elderly wheelchair users. The group of subjects was composed of 30 elderly people (aged 65 or older) and the shapes of the body-seat interface were measured by the electronic shape sensor (ESS). By analyzing the dissimilarity in geometrical shape descriptors or parameters, four distinct generic shapes were identified by means of the cluster analysis method. The results suggest that the generic shapes were mainly characterized by the lateral symmetry of the shapes. The determination of elderly people's seat interface shapes into distinct clusters may lead to a more comprehensive understanding of the seat support interface and more effective seat cushion designs.


New soft-tipped instruments for foveal translocation surgery with 360 degrees retinotomy.
Foveal translocation surgery with 360 degrees retinotomy involves several surgical procedures, including creation of a total retinal detachment, rotation of the retina, and complete reattachment of the retina. Some of these procedures, which are time-consuming and difficult to perform, may damage the retina when conventional surgical instruments are used. To make these procedures safer and easier, we have developed 3 soft instruments: an atraumatic forceps, a modified Chang double-barrel cannula with a silicone tip, and a light pipe with a silicone tip. The atraumatic forceps allows the surgeon to grasp and peel off the retina with less damage during the creation of retinal detachment. A bimanual technique using the other 2 instruments allows surgeons to rotate and reattach the detached retina easily and safely. We believe that these soft-tipped instruments make foveal translocation a less complicated surgery.


Increased mitochondrial energy efficiency in skeletal muscle after long-term fasting: its relevance to animal performance.
In the final stage of fasting, skeletal muscle mass and protein content drastically decrease when the maintenance of efficient locomotor activity becomes crucial for animals to reactivate feeding behaviour and survive a very long period of starvation. As mitochondrial metabolism represents the main physiological link between the endogenous energy store and animal performance, the aim of this study was to determine how a very long, natural period of fasting affected skeletal muscle mitochondrial bioenergetics in king penguin (Aptenodytes patagonicus) chicks. Rates of mitochondrial oxidative phosphorylation were measured in pectoralis permeabilized fibres and isolated mitochondria. Mitochondrial ATP synthesis efficiency and the activities of respiratory chain complexes were measured in mitochondria isolated from pectoralis muscle. Results from long-term (4-5 months) naturally fasted chicks were compared with those from short-term (10 day) fasted birds. The respiratory activities of muscle fibres and isolated mitochondria were reduced by 60% and 45%, respectively, on average in long-term fasted chicks compared with short-term fasted birds. Oxidative capacity and mitochondrial content of pectoralis muscle were lowered by long-term fasting. Bioenergetic analysis of pectoralis muscle also revealed that mitochondria were, on average, 25% more energy efficient in the final stage of fasting (4-5 months) than after 10 days of fasting (short-term fasted birds). These results suggest that the strong reduction in respiratory capacity of pectoralis muscle was partly alleviated by increased mitochondrial ATP synthesis efficiency. Such oxidative phosphorylation optimization can impact animal performance, e.g. the metabolic cost of locomotion or the foraging efficiency.


Study of the Distribution of Acetaminophen and Its Metabolites in Rats, from the Whole-Body to Isolated Organ Levels, by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging after On-Tissue Chemical Derivatization.
During drug development, detailed investigations of the pharmacokinetic profile of the drug are required to characterize its absorption, distribution, metabolism, and excretion properties. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is an established technique for studies of the distribution of drugs and their metabolites. It has advantages over autoradiography, which is conventionally used for distribution studies: it does not require the radiolabeling of drugs and can distinguish between the drug and its metabolites directly in the tissue. However, its lack of sensitivity in certain cases remains challenging. Novel procedures, such as on-tissue chemical derivatization (OTCD), could be developed to increase sensitivity. We used OTCD to enhance the sensitivity of MALDI-MSI for one of the most widely used drugs, acetaminophen, and to study its distribution in tissues. Without derivatization, this drug and some of its metabolites are undetectable by MALDI-MSI in the tissues of treated rats. We used 2-fluoro-1-methylpyridinium p-toluene sulfonate as a derivatization reagent, to increase the ionization yield of acetaminophen and some of its metabolites. The OTCD protocol made it possible to study the distribution of acetaminophen and its metabolites in whole-body sections at a spatial resolution of 400 μm and in complex anatomical structures, such as the testis and epididymis, at a spatial resolution <50 μm. The OTCD is also shown to be compatible with the quantification of acetaminophen by MALDI-MSI in whole-body tissues. This protocol could be applied to other molecules bearing phenol groups and presenting a low ionization efficiency.


A model of molecular circadian clocks: multiple mechanisms for phase shifting and a requirement for strong nonlinear interactions.
A fundamental question in the field of circadian rhythms concerns the biochemical and molecular nature of the oscillator. There is strong evidence that circadian oscillators are cell autonomous and rely on periodic gene expression. In Drosophila, Neurospora, Aplysia, and vertebrates, circadian oscillators are thought to be based on molecular autoregulatory loops composed of transcription, translation, and negative feedback by proteins on nuclear transcription. By studying a mathematical model of molecular clocks based on this general concept, the authors sought to determine which features such clocks must have to generate robust and stable oscillations and to allow entrainment by external stimuli such as light. The model produced circadian oscillations as an emergent property even though a time delay in protein synthesis and rate constants of the feedback loop were much shorter than 24 h. Along with the delay in protein production, strong nonlinear interactions in macromolecular synthesis and nuclear feedback appeared to be required for the model to show well-behaved oscillatory behavior. Realistic phase-shifting patterns induced by external stimuli could be achieved by multiple mechanisms-namely, up- and downward perturbations of protein or mRNA synthesis or degradation rates. The model makes testable predictions about interactions between clock elements and mechanisms of entrainment and may help to understand the functions of the intricate molecular interactions governing circadian rhythmogenesis.


What African American male adolescents are telling us about HIV infection among their peers: cultural approaches for HIV prevention.
This study explored the beliefs of African American male adolescents concerning the high rates of HIV infection among their peers and their reasons for those beliefs. In-depth interviews were conducted with a sample of 16 male African Americans, and a thematic analysis of the data was conducted. Half of the participants believed that peers were not becoming infected at higher rates than white youths and reported high rates of sexual risk taking. Conspiracy beliefs and high rates of sexual adventurism for all teenagers were among the reasons offered to support this belief. Participants who believed the uneven incidence rates reported low levels of sexual risk taking. These participants identified early and unsafe sexual activity -- in conjunction with social factors such as negative peer and media influences, poor parental supervision, and dangerous neighborhood environments -- as contributing reasons for these disparate rates. Sexual behaviors were markedly different among both groups. The implications of these findings are discussed in the context of culturally relevant approaches to prevention of HIV infection among this group.


[Celastrol inhibits growth and increases apoptosis of human lung cancer A549 cells].
Objective To investigate the inhibitory effect of celastrol on the proliferation of human lung cancer A549 cells and its possible mechanism. Methods A549 cells were treated with 0, 1, 2, 3, 4, 5, 6 μmol/L celastrol for 0, 24, 48, 72 hours. The effects of different concentrations and durations on the cell proliferation were evaluated by MTT assay to determine the optimal concentration and treatment time. In the subsequent experiments, A549 cells were treated with (0, 1, 3) μmol/L of celastrol for 48 hours. The effects of celastrol on the expression of BAX, B-cell lymphoma 2 (Bcl2), caspase-3, caspase-8, caspase-9 mRNA in A549 cells were detected by real-time quantitative PCR. The protein levels of BAX, Bcl-2, cleaved caspase-3(c-caspase-3), c-caspase-8, c-caspase-9 were assessed by Western blot analysis. Results Celastrol inhibited the viability of A549 cells in a concentration- and time-dependent manner. Compared with the group without celastrol treatment, the mRNA and protein level of Bcl2 in A549 cells treated with (1, 3) μmol/L celastrol decreased significantly, while the expression levels of BAX, caspase-3, caspase-8, caspase-9, c-caspase-3, c-caspase-8, c-caspase-9 increased significantly. Conclusion Celastrol could suppress the proliferation and induced the apoptosis of A549 cells through mitochondrial pathway.


Polycomb gene expression and histone H3 lysine 27 trimethylation changes during bovine preimplantation development.
Trimethylation of histone H3 at lysine 27 (H3K27me3) is established by polycomb group genes and is associated with stable and heritable gene silencing. The aim of this study was to characterize the expression of polycomb genes and the dynamics of H3K27me3 during bovine oocyte maturation and preimplantation development. Oocytes and in vitro-produced embryos were collected at different stages of development. Polycomb gene expression was analyzed by real-time quantitative RT-PCR and immunofluorescence. Global H3K27me3 levels were determined by semiquantitative immunofluorescence. Transcripts for EZH2, EED, and SUZ12 were detected at all stages analyzed, with EZH2 levels being the highest of the three at early stages of development. By the time the embryo reached the blastocyst stage, the level of PcG gene mRNA levels significantly increased. Immunofluorescence staining indicated nuclear expression of EZH2 at all stages while nuclear localized EED and SUZ12 were only evident at the morula and blastocyst stages. Semiquantitative analysis of H3K27me3 levels showed that nuclear fluorescence intensity was the highest in immature oocytes, which steadily decreased after fertilization to reach a nadir at the eight-cell stage, and then increased at the blastocyst stage. These results suggest that the absence of polycomb repressive complex 2 proteins localized to the nucleus of early embryos could be responsible for the gradual decrease in H3K27me3 during early preimplantation development.


Deep brain stimulation for dystonia.
Dystonia is a painful and disabling disorder, characterised by painful, involuntary posturing of the affected body region(s). Deep brain stimulation is an intervention typically reserved for severe and drug-refractory cases, although uncertainty exists regarding its efficacy, safety, and tolerability. To compare the efficacy, safety, and tolerability of deep brain stimulation (DBS) versus placebo, sham intervention, or best medical care, including botulinum toxin and resective or lesional surgery, in adults with dystonia. We identified studies by searching the CENTRAL, MEDLINE, Embase, three other databases, four clinical trial registries, four grey literature databases, and reference lists of included articles. We ran the last search of all elements of the search strategy, with no language restrictions, on 29 May 2018. Double-blind, parallel, randomised, controlled trials (RCTs) comparing DBS with sham stimulation, best medical care, or placebo in adults with dystonia. Two independent review authors assessed records, selected included studies, extracted data onto a standardised (or prespecified) data extraction form, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third review author. We conducted meta-analyses using a random-effects model, to estimate pooled effects and corresponding 95% confidence intervals (95% CI). We assessed the quality of the evidence with GRADE methods. The primary efficacy outcome was symptom improvement on any validated symptomatic rating scale, and the primary safety outcome was adverse events. We included two RCTs, enrolling a total of 102 participants. Both trials evaluated the effect of DBS on the internal globus pallidus nucleus, and assessed outcomes after three and six months of stimulation. One of the studies included participants with generalised and segmental dystonia; the other included participants with focal (cervical) dystonia. We assessed both studies at high risk for performance and for-profit bias. One study was retrospectively registered with a clinical trial register, we judged the second at high risk of detection bias.Low-quality evidence suggests that DBS of the internal globus pallidus nucleus may improve overall cervical dystonia-related symptoms (mean difference (MD) 9.8 units, 95% CI 3.52 to 16.08 units; 1 RCT, 59 participants), cervical dystonia-related functional capacity (MD 3.8 units, 95% CI 1.41 to 6.19; 1 RCT, 61 participants), and mood at three months (MD 3.1 units, 95% CI 0.73 to 5.47; 1 RCT, 61 participants).Low-quality evidence suggests that In people with cervical dystonia, DBS may slightly improve the overall clinical status (MD 2.3 units, 95% CI 1.15 to 3.45; 1 RCT, 61 participants). We are uncertain whether DBS improves quality of life in cervical dystonia (MD 3 units, 95% CI -7.71 to 13.71; 1 RCT, 57 participants; very low-quality evidence), or emotional state (MD 2.4 units, 95% CI -6.2 to 11.00; 1 RCT, 56 participants; very low-quality evidence).Low-quality evidence suggests that DBS of the internal globus pallidus nucleus may improve generalised or segmental dystonia-related symptoms (MD 14.4 units, 95% CI 8.0 to 20.8; 1 RCT, 40 participants), overall clinical status (MD 3.5 units, 95% CI 2.33 to 4.67; 1 RCT, 37 participants), physical functioning-related quality of life (MD 6.3 units, 95% CI 1.06 to 11.54; 1 RCT, 33 participants), and overall dystonia-related functional capacity at three months (MD 3.1 units, 95% CI 1.71 to 4.48; 1 RCT, 39 participants). We are uncertain whether DBS improves physical functioning-related quality of life (MD 5.0 units, 95% CI -2.14 to 12.14, 1 RCT, 33 participants; very low-quality evidence), or mental health-related quality of life (MD -4.6 units, 95% CI -11.26 to 2.06; 1 RCT, 30 participants; very low-quality evidence) in generalised or segmental dystonia.We pooled outcomes related to safety and tolerability, since both trials used the same intervention and comparison. We found very low-quality evidence of inconclusive results for risk of adverse events (relative risk (RR) 1.58, 95% 0.98 to 2.54; 2 RCTs, 102 participants), and tolerability (RR 1.86, 95% CI 0.16 to 21.57; 2 RCTs,102 participants). DBS of the internal globus pallidus nucleus may reduce symptom severity and improve functional capacity in adults with cervical, segmental or generalised moderate to severe dystonia (low-quality evidence), and may improve quality of life in adults with generalised or segmental dystonia (low-quality evidence). We are uncertain whether the procedure improves quality of life in cervical dystonia (very low-quality evidence). We are also uncertain about the safety and tolerability of the procedure in adults with either cervical and generalised, or segmental dystonia (very-low quality evidence).We could draw no conclusions for other populations with dystonia (i.e. children and adolescents, and adults with other types of dystonia), or for other DBS protocols (i.e. other target nuclei or stimulation paradigms). Further research is needed to establish the long-term efficacy and safety of DBS of the internal globus pallidus nucleus.


Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution.
The EGFR-targeted antibodies cetuximab and panitumumab are used to treat metastatic colorectal cancers. Mutations in KRAS, NRAS, and BRAF and amplification of ERBB2 and MET drive primary (de novo) resistance to anti-EGFR treatment. Recently, the emergence of alterations in the same genes was detected in patients who responded to EGFR blockade and then relapsed. These results illuminate a striking overlap between genes that, when mutated, drive primary and secondary resistance to anti-EGFR antibodies. Remarkably, although the mechanisms of resistance are genetically heterogeneous, they biochemically converge on key signaling pathways. This knowledge is being translated in the rational design of additional lines of therapy. Anti-EGFR-targeted therapies are used for the treatment of metastatic colorectal cancer. Molecular heterogeneity impairs their efficacy by fuelling de novo and acquired resistance. In this review, we highlight how genetically distinct resistance mechanisms biochemically converge on a limited number of signaling pathways that can be therapeutically intercepted.


Ten-year comparison of all-cause mortality after endovascular or open repair of abdominal aortic aneurysms: a propensity score analysis.
This study aimed to compare the long-term survival after open (OS) or endovascular (EVAR) repair of abdominal aortic aneurysms (AAAs), exploring baseline factors that could affect long-term outcome. We identified 774 patients (501 EVAR, 273 OS, during 1996-2004) with data on perioperative risk factors including 37 variables assessed with a standardized patient response instrument. Propensity score was used to adjust for baseline differences between the two cohorts. Matched cohorts survival analysis and Cox multivariate regression were performed. Median follow-up was 6.95 (interquartile range 4.46-9.27) years. EVAR patients were older [75.0 ± 7.7 (SD) vs. 71.3 ± 8.5 years, p < 0.001] and had a higher rate of previous myocardial infarction (39.3 vs. 25.3%, p < 0.001), pulmonary disease (25.9 vs. 18.3%, p = 0.020), and history of malignancy (5.0 vs. 1.8%, p = 0.039). The 30-day mortality was comparable (1.4% EVAR, 1.5% OS). Although the unadjusted survival rate was lower (median survival: 7.4 years EVAR, 8.8 OS, p = 0.011) and early (within 4 years) hazard was higher after EVAR (p = 0.003), no difference in survival was observed after propensity score-matching (p = 0.688) or propensity score-adjusted Cox regression (hazard ratio 1.01, 95 % confidence interval 0.82-1.25, p = 0.911, EVAR vs. OS). There was a trend toward higher hazard later in both groups. A multivariate Cox regression identified age, pulmonary disease, stroke, dialysis, oral anticoagulation, cardiac enlargement, and smoking history as variables associated with poor survival. Lipid-lowering medication was found to be protective. Over long-term follow-up, survivals after endovascular and open repair of AAA are similar. Baseline patient characteristics are correlated with survival, but whether attention to the modifiable risk factor can alter outcome remains to be defined.


Intron definition is required for excision of the minute virus of mice small intron and definition of the upstream exon.
Alternative splicing of pre-mRNAs plays a critical role in maximizing the coding capacity of the small parvovirus genome. The small-intron region of minute virus of mice (MVM) pre-mRNAs undergoes an unusual pattern of overlapping alternative splicing--using two donors (D1 and D2) and two acceptors (A1 and A2) within a region of 120 nucleotides--that determines the steady-state ratios of the various viral mRNAs. In this report, we show that the determinants that govern excision of the small intron are complex and are also required for efficient definition of the upstream exon. For the MVM small intron in its natural context, the two donors appear to compete for the splicing machinery: the position of D1 favors its usage, while the primary sequence of D2 must be more like the consensus sequence than is D1 to be used efficiently. We have genetically defined the branch points that are used for generation of the major and minor spliced forms and show that recognition of components of the small-intron acceptors is likely to be the dominant determinant in alternative small-intron excision. We have also identified a G-rich intronic enhancer sequence within the small intron that is essential for splicing of the minor form (D2 to A2) but not the major form (D1 to A1) of MVM mRNAs and is required for efficient definition of the upstream NS2-specific exon. In its natural context, the small intron appears to be excised by a mechanism consistent with intron definition. When the MVM small intron is expanded, various parameters of its excision are altered, indicating that critical cis-acting signals are context dependent. Relative use of the donors and acceptors is altered, and the upstream NS2-specific exon is no longer efficiently defined. The fact that definition of the upstream NS2-specific exon can be achieved by the MVM small intron in its natural context, but not when it is expanded, suggests that the multiple determinants that govern definition and excision of the small intron are required, in concert, for upstream exon definition. Our data are consistent with a model in which alternative splicing of the MVM P4-generated pre-mRNAs is governed by a hybrid of intron- and exon-defining mechanisms.


Restriction enzyme analysis and DNA sequencing comparison for alpha-toxin gene among different types of Clostridium perfringens.
Alpha-toxin is produced by all types of Clostridium perfringens. The genes encoding alpha-toxin from the available five types of Clostridium perfringens [A (chicken strain), A (rabbit strain), B, C and D] were PCR amplified using specific primers and the PCR products were examined on 1.5% (w/v) agarose gel and demonstrated the same bands comparable to the published alpha-toxin gene. Restriction enzyme analysis using two sets of enzymes (one set known to have recognition sites; Hinf1, EcoRV and Mse1 and the other set known to lack recognition sites Hind III, Pst1 and BamH1) were carried out. The first set of enzymes revealed the same cut specific for alpha-toxin gene. However, the second set of enzymes revealed no cut which is consistent to the published data. The PCR products of alpha-toxin gene from the five types were separately sequenced and aligned with all published alpha-toxin genes of Clostridium perfringens. Identities among all studied alpha-toxin gene sequences and with the published ones were nearly 96-98%. There are no any significant differences among these nucleotide sequences. It is concluded that alpha-toxin gene sequences among different types of Clostridium perfringens are similar and highly conserved.


The association between serum magnesium levels and community-acquired pneumonia 30-day mortality.
Community acquired pneumonia (CAP) is a common illness affecting hundreds of millions worldwide. Few studies have investigated the relationship between serum magnesium levels and outcomes of these patients. We aimed to study the association between serum magnesium levels and 30-day mortality among patients with CAP. Retrospective overview of patients hospitalized with CAP between January 1, 2010 and December 31, 2016. Participants were analyzed retrospectively in order to identify the risk factors for a primary endpoint of 30-day mortality. Normal levels of magnesium levels in our laboratory varies between 1.35 and 2.4 mg/dl. 3851 patients were included in our cohort. Age > 75 years, blood urea nitrogen (BUN) > 20 mg/dl, hypoalbuminemia, and abnormal levels of magnesium were all associated with increased risk of 30-day mortality. Normal magnesium levels were associated with the lowest mortality rate (14.7%). Notably, within the normal levels, high normal magnesium levels (2-2.4 mg/dl) were correlated with higher mortality rates (30.3%) as compared to levels that ranged between 1.35-2 mg/dl (12.9%). Hypomagnesemia and hypermagnesemia were both associated with excess of 30-day mortality, 18.4 and 50%, respectively. Hypomagnesemia and hypermagnesemia on admission were associated with an increased rate of 30-day mortality among adult patients hospitalized with CAP. Interestingly, magnesium levels within the upper normal limits were associated with higher mortality.


[Evaluation of oxacillin resistance screening agar and chromogenic MRSA agar media for the detection of methicillin resistance in Staphylococcus aureus clinical isolates].
Methicillin-resistant Staphylococcus aureus (MRSA) strains which are the most frequent causes of hospital acquired infections, are also currently encountered with increasing frequency in community acquired infections. Therefore rapid and accurate identification of MRSA strains is essential in both implementation of infection control measures and prevention of the nosocomial spread of this microorganism. The aim of this study was to determine the specifisity, sensitivity, positive and negative predictive values of two commercial media, one was Oxacillin Resistance Screening Agar Base (ORSAB; Oxoid, England) and the other was chromogenic MRSA agar (BBL CHROMagar MRSA; BD, Paris, France), for the identification of MRSA strains. A total of 175 clinical S. aureus isolates, of which 45 were MRSA, and 130 were methicillin-susceptible S. aureus (MSSA), whose susceptibility to methicillin were determined by disk diffusion method using oxacillin and cefoxitin disks in Mueller-Hinton agar medium, were included in the study. When oxacillin disk diffusion test was accepted as the reference method, the specificity, sensitivity, positive and negative predictive values of ORSAB were found as 97.7%, 40%, 36.5% and 98.1%, respectively; while these values were detected as 95.5%, 37.6%, 35.7% and 96.1% for CHROMagar MRSA, respectively. These results indicated that both media may be used in laboratories where work load is high and the number of personnel is inadequate especially in screening studies together or in addition to another medium (mannitol-salt agar). However, since these methods exhibit low specifity (high false positive results), positive results should be confirmed using other methods such as disk diffusion, E-test or microdilution susceptibility testing.


Osmolarity influences chondrocyte death in wounded articular cartilage.
Mechanical injury results in chondrocyte death in articular cartilage. The purpose of the present study was to determine whether medium osmolarity affects chondrocyte death in injured articular cartilage. Osteochondral explants (n = 48) that had been harvested from the metacarpophalangeal joints of three-year-old cows were exposed to media with varying osmolarity (0 to 480 mOsm) for ninety seconds to allow in situ chondrocytes to respond to the altered osmotic environment. Explants were then wounded with a scalpel through the full thickness of articular cartilage, incubated in the same media for 2.5 hours, and transferred to 340-mOsm Dulbecco's Modified Eagle Medium (control medium) with further incubation for seven days. The spatial distribution of in situ chondrocyte death, percentage cell death, and marginal cell death at the wounded cartilage edge were compared as a function of osmolarity and time (2.5 hours compared with seven days) with use of confocal laser scanning microscopy. In situ chondrocyte death was mainly localized to the superficial tangential zone of injured articular cartilage for the range of medium osmolarities (0 to 480 mOsm) at 2.5 hours and seven days. Therefore, a sample of articular cartilage from the superficial region (which included the scalpel-wounded cartilage edge) was studied with use of confocal laser scanning microscopy to compare the effects of osmolarity on percentage and marginal cell death in the superficial tangential zone. Compared with the control explants exposed to 340-mOsm Dulbecco's Modified Eagle Medium, percentage cell death in the superficial tangential zone was greatest for explants exposed to 0-mOsm (distilled water) and least for explants exposed to 480-mOsm Dulbecco's Modified Eagle Medium at 2.5 hours (13.0% at 340 mOsm [control], 35.5% at 0 mOsm, and 4.3% at 480 mOsm; p <or= 0.02 for paired comparisons) and seven days (9.9% at 340 mOsm [control], 37.7% at 0 mOsm, and 3.5% at 480 mOsm; p <or= 0.01 for paired comparisons). Marginal cell death in the superficial tangential zone decreased with increasing medium osmolarity at 2.5 hours (p = 0.001) and seven days (p = 0.002). There was no significant change in percentage cell death from 2.5 hours to seven days for explants initially exposed to any of the medium osmolarities. Medium osmolarity significantly affects chondrocyte death in wounded articular cartilage. The greatest chondrocyte death occurs at 0 mOsm. Conversely, increased medium osmolarity (480 mOsm) is chondroprotective. The majority of cell death occurs within 2.5 hours, with no significant increase over seven days.


Phytoremediation of MTBE with hybrid poplar trees.
This research investigates the fate and transport of methyl tert-butyl ether (MTBE) in phytoremediation, particularly the uptake and volatilization of MTBE in lab-scale hydroponic systems. The research reveals that MTBE was taken up by hybrid poplar cuttings and volatilized to the atmosphere. Volatilization of MTBE occurred through both stems and leaves. The concentration of MTBE in the transpiration stream declined exponentially with height, indicating that the uptake and volatilization along the stems are an important removal mechanism of MTBE in phytoremediation. Volatilization, via diffusion from the stems, has not been directly measured previously. No volatile MTBE metabolites were detected; however, mass balance closure and metabolite detection were not primary objectives of this study. The greatest amount of MTBE in plant biomass was associated with the woody stems from the previous year's growth, owing in part to the large biomass of stems. MTBE in the plant tissues appears to reach a steady state concentration and there does not appear to be an accumulation process that could lead to highly elevated concentrations relative to the groundwater source.


Hydroxyl-functionalized and N-doped multiwalled carbon nanotubes decorated with silver nanoparticles preserve cellular function.
The present study aims to investigate biocompatibility of silver nanoparticles (Ag-NPs) anchored to different types of multiwalled carbon nanotubes (MWNTs). The MWNTs were decorated with Ag-NPs via a novel chemical route without using any sulfur containing reagent. Three different MWNTs were used as substrate materials for anchoring Ag-NPs: MWNTs-Ag (pure carbon), COx-MWNTs-Ag (carboxyl functionalized), and CNx-MWNTs-Ag (nitrogen-doped). The Ag-NPs, synthesized without thiol capping groups, and which were strongly anchored to the nanotubes surfaces, exhibit an average size of 7 ± 1, 10 ± 1, and 12 ± 1 nm in MWNTs, COx-MWNTs, and CNx-MWNTs, respectively. To determine biocompatibility of these three types of novel hybrid Ag-nanotube materials, cellular function and immune response were evaluated in the human keratinocyte cell line (HaCaT). Cellular assays revealed marginal toxicity after 24 h, and full cellular recovery was observed at 48 h based on an MTS assay for cellular viability. Therefore, Ag-nanotube systems appear to be very different from isolated dispersed Ag-NPs, and due to the strong interactions between the Ag-NPs and the doped nanotube surfaces, they make the Ag particles less toxic because they are not released easily to the cells. Pure carbon MWNTs appear to start releasing Ag-NPs at periods longer than 1 week by an observed decrease in cell proliferation. However, the use of N- and COx-doped MWNTs do not appear to release Ag-NPs to the cells due to the strong binding to the tube surfaces caused by the doped sites. We envisage the use of COx-MWNTs, and CNx-MWNTs anchored with Ag-NP as efficient drug delivery carriers and biosensors.


Adverse effects of daily oral pre-exposure prophylaxis in men who have sex with men and transgender women: a systematic review and meta-analysis.
The adverse effects of oral pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate are barriers to PrEP initiation and continuation. Although serious effects are rare and predictable, evidence for this assessment among men who have sex with men (MSM) and transgender women (TGW) is still limited. This study assesses the adverse effects of daily oral PrEP in MSM and TGW. This is a systematic review and meta-analysis of clinical trials and cohort studies on the use of daily oral PrEP selected from the PubMed/MEDLINE, Embase, LILACS, and Cochrane CENTRAL databases. Data extraction included adverse effects and changes in renal and hepatic markers. Random effects models were used to summarize the risk of adverse effects throughout the study. Heterogeneity was assessed using the Cochran's Q test and the inconsistency test (I2). The risk of bias and the certainty of the evidence were assessed using the Cochrane Collaboration recommendations. The search identified 653 references. Of these, 10 were selected. All studies assessed the eligibility of renal and hepatic markers. The use of daily oral PrEP was not associated with grade 3 or 4 adverse events (RR = 0.99; 95%CI: 0.83-1.18; I2 = 26.1%), any serious adverse event (RR = 1.04; 95%CI: 0.58-1.87; I2 = 88.4%), grade 3+4 creatinine level (RR = 0.66; 95%CI: 0.24-1.84; I2 = 79.9%), and grade 3 or 4 hypophosphatemia (RR = 0.56; 95%CI: 0.15-2.10). The certainty of the evidence ranged from high to moderate for the outcomes analyzed. Daily oral PrEP is safe and well tolerated by MSM and TGW. Adverse effects were minimal and evenly distributed between intervention and control.


Important Role of Menarche in Development of Estrogen Receptor-Negative Breast Cancer in African American Women.
Menarche is a critical time point for diverging fates of mammary cells of origin. African American women have young age at menarche, which could be associated with their high rates of estrogen receptor-negative (ER-) breast cancer. In the AMBER Consortium, using harmonized data from 4426 African American women with breast cancer and 17 474 controls, we used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for ages at menarche and first live birth (FLB), and the interval between, in relation to ER+ and ER- breast cancer. All statistical tests were two-sided. Risk of ER- breast cancer was reduced with later age at menarche among both parous and nulliparous women (≥15 vs <11 years OR = 0.62, 95% CI = 0.48 to 0.81 and OR = 0.56, 95% CI = 0.29 to 1.10, respectively), with no effect of age at FLB. For ER+ breast cancer, the inverse association was weaker among nulliparous women. While longer intervals between menarche and FLB were associated with increased risk of ER+ breast cancer in a dose-response fashion (OR for 20 year interval = 1.39, 95% CI = 1.08 to 1.79, P trend = .003), ER- risk was only increased for intervals up to 14 years and not beyond (P trend = .33). While ER- breast cancer risk was markedly reduced in women with a late age at menarche, there was not a clear pattern of increased risk with longer interval between menarche and FLB, as was observed for ER+ breast cancer. These findings indicate that etiologic pathways involving adolescence and pregnancy may differ for ER- and ER+ breast cancer.


Delleman syndrome: a case report and review.
A case of oculocerebrocutaneous syndrome is presented, to our knowledge the first to be reported in West Bank and Gaza. The child was of consanguinous parents. The clinical features of orbital cyst, periorbital cutaneous malformations, and cerebral malformations are described, together with a brief review of previous reports. The need for neurological follow-up of these cases is emphasised.


Neovascularization of poly(ether ester) block-copolymer scaffolds in vivo: long-term investigations using intravital fluorescent microscopy.
Poly(ether ester) block-copolymer scaffolds of different pore size were implanted into the dorsal skinfold chamber of balb/c mice. Using intravital fluorescent microscopy, the temporal course of neovascularization into these scaffolds was quantitatively analyzed. Three scaffold groups (diameter, 5 mm; 220-260 thickness, microm; n = 30) were implanted. Different pore sizes were evaluated: small (20-75 microm), medium (75-212 microm) and large pores (250-300 microm). Measurements were performed on days 8, 12, 16, and 20 in the surrounding normal tissue, in the border zone, and in the center of the scaffold. Standard microcirculatory parameters were assessed (plasma leakage, vessel diameter, red blood cell velocity, and functional vessel density). The large-pored scaffolds showed significantly higher functional vessel density in the border zone and in the center (days 8 and 12) compared with the scaffold with the small and medium-sized pores. These data correlated with a larger vessel diameter and a higher red blood cell velocity in the large-pored scaffold group. Interestingly, during the evaluation period the microcirculatory parameters on the edge of the scaffolds returned to values similar to those found in the surrounding tissue. In the center of the scaffold, however, neovascularization was still active 20 days after implantation. Plasma leakage and vessel diameter were higher in the center of the scaffold. Red blood cell velocity and functional vessel density were 50% lower than in the surrounding tissue. In conclusion, the dorsal skinfold chamber model in mice allows long-term study of blood vessel growth and remodeling in porous biomedical materials. The rate of vessel ingrowth into poly(ether ester) block-copolymer scaffolds is influenced by pore size and was highest in the scaffold with the largest pores. The data generated with this model contribute to knowledge about the development of functional vessels and tissue ingrowth into biomaterials.


[Cancer of the right half of the colon: clinical aspects, diagnosis and immediate results of surgical treatment].
Carcinoma of the right half of the colon (CRHC) is diagnosed in 21-35% of patients with colorectal carcinomas. The Research Institute of Proctology of the RSFSR Ministry of Health has an experience with treatment of 338 patients with CRHC. Most of them (84.9%) were admitted to the clinic with advanced forms of the disease because of poor clinical manifestations at early stages of the disease and resulting in late consultations with the doctor. Surgical treatment was performed in 332 patients. The operation of choice for locally removable tumors of the right half of the colon still remains right-side hemicolectomy. For locally spread CRHC combined operations are thought to be expedient. Immediate results of the surgical treatment of CRHC by the correct curative methods are perfectly favorable, the amount of postoperative complications was 14.5%, lethality--6.6%.


Effect of L-thyroxine supplementation on very low birth weight infants with transient hypothyroxinemia of prematurity at 3 years of age.
To evaluate the effects of levothyroxine (L-T4) supplementation on growth and neurodevelopmental outcomes at 3 years of age in very low birth weight (VLBW) infants with transient hypothyroxinemia of prematurity (THOP). VLBW infants with plasma thyroid-stimulating hormone concentrations <10 mIU l-1 and free thyroxine concentrations <0.8 ng dl-1 were defined as having THOP and randomly assigned to the Treated (20 infants) or Untreated (31 infants) group. The Treated group received L-T4 at a dose of 5 μg kg-1 day-1. Growth and neurodevelopmental outcomes at 3 years of age were compared between the two groups. There were no significant differences in body length, body weight or head circumference mean s.d. scores or in neurodevelopmental outcomes between the two groups. L-T4 supplementation in VLBW infants with THOP demonstrated no beneficial effect at 3 years of age.


Genetic Architecture of a Rice Nested Association Mapping Population.
Describing the genetic diversity in the gene pool of crops will provide breeders with novel resources for varietal improvement. Nested Association Mapping (NAM) populations are uniquely suited for characterizing parental diversity through the shuffling and fixation of parental haplotypes. Here, we describe a set of 1879 rice NAM lines created through the selfing and single-seed descent of F1 hybrids derived from elite IR64 indica crossed with 10 diverse tropical japonica lines. Genotyping data indicated tropical japonica alleles were captured at every queried locus despite the presence of segregation distortion factors. Several distortion loci were mapped, both shared and unique, among the 10 populations. Using two-point and multi-point genetic map calculations, our datasets achieved the ∼1500 cM expected map size in rice. Finally, we highlighted the utility of the NAM lines for QTL mapping, including joint analysis across the 10 populations, by confirming known QTL locations for the trait days to heading.


Ursolic acid induces apoptosis via Akt/NF-κB signaling suppression in T24 human bladder cancer cells.
The Akt/NF-κB pathway is involved in numerous anti‑apoptotic and drug resistance events which occur in various types of bladder cancer. The present study investigated the role of ursolic acid in the regulation of anti-apoptotic Akt and NF-κBp65 signaling. T24 human bladder cancer cells were treated with ursolic acid at final concentrations of 12.5, 25 or 50 µmol/l for 48 h. Quantitative PCR (qPCR) and western blotting were performed to detect mRNA and protein expression, respectively. The results showed that anti-apoptotic phospho-Akt1 (pAkt1), phospho-IκBα (pIκBα), NF-κBp65 and Bcl-2 were inhibited and pro-apoptotic caspase-3 was upregulated in a dose‑dependent manner. A 50 µmol/l dose of ursonic acid decreased the mRNA expression levels of anti-apoptotic NF-κBp65 and Bcl-2 0.17 (8.9/52.6)-fold and 0.22 (9.5/42.3)‑fold, respectively. The pro-apoptotic caspase-3 mRNA expression levels were upregulated 4.78 (38.7/8.1)-fold. The anti-apoptotic pAkt1, pIκBα, NF-κBp65 and Bcl-2 protein levels were downregulated to 5.1 (blot grayscales vs. control at 32.3), 3.2 (vs. 24.2), 8.5 (vs. 45.1) and 9.2 (vs. 40.3). The protein levels of pro-apoptotic caspase-3 were upregulated to 20.7 (vs. 4.7). The proliferative activity of T24 cells treated with 12.5, 25.0 and 50.0 µmol/l ursolic acid was significantly reduced compared with that of control cells (83.8, 56.2 and 31.5 vs. 97.6%, respectively, P<0.05 for each). In conclusion, ursolic acid is important in inducing apoptosis via the suppression of Akt/NF-κB signaling in T24 human bladder cancer cells and this occurs in a dose-dependent manner. Ursolic acid may therefore serve as a naturally occurring candidate drug for the prevention and treatment of bladder cancer.


The aprosodias: further functional-anatomical evidence for the organisation of affective language in the right hemisphere.
Fourteen right-handed patients with right hemispheric strokes were examined for disorders of affective language in order to further define the clinical-anatomical correlates of the aprosodias. A bedside evaluation strategy and CT scan mappings were utilised to make these comparisons. There were six patients with motor aprosodia, one with global aprosodia, two with conduction aprosodia, one with sensory aprosodia, one with transcortical sensory aprosodia, one with pure affective deafness and two with normal examinations of affect. Functional-anatomical correlations were consistent with those predicted previously. Recovery of affective language function in selected cases was characterised by improvements in affective-prosodic repetition and/or evolution into other aprosodic subtypes. Our results lend further support to the hypothesis that the organisation of affective language in the right hemisphere mirrors that of propositional language in the left hemisphere.


Thermoelectricity in molecular junctions.
By trapping molecules between two gold electrodes with a temperature difference across them, the junction Seebeck coefficients of 1,4-benzenedithiol (BDT), 4,4'-dibenzenedithiol, and 4,4''-tribenzenedithiol in contact with gold were measured at room temperature to be +8.7 +/- 2.1 microvolts per kelvin (muV/K), +12.9 +/- 2.2 muV/K, and +14.2 +/- 3.2 muV/K, respectively (where the error is the full width half maximum of the statistical distributions). The positive sign unambiguously indicates p-type (hole) conduction in these heterojunctions, whereas the Au Fermi level position for Au-BDT-Au junctions was identified to be 1.2 eV above the highest occupied molecular orbital level of BDT. The ability to study thermoelectricity in molecular junctions provides the opportunity to address these fundamental unanswered questions about their electronic structure and to begin exploring molecular thermoelectric energy conversion.


Calcium wave for cytoplasmic streaming of Physarum polycephalum.
The plasmodium Physarum polycephalum exhibits periodic cycles of cytoplasmic streaming in association with those of contraction and relaxation movement. In the present study, we injected Calcium Green dextran as a fluorescent Ca2+ indicator into the thin-spread living plasmodium. We found changes in the [Ca2+]i (intracellular concentration of Ca2+), which propagated in a wave-like form in its cytoplasm. The Ca2+ waves were also detected when we used Fura dextran which detected [Ca2+]i by the ratio of two wavelengths. We prepared the plasmodial fragment from the thin-spread and found that the cycles of the contraction-relaxation movement was so synchronized that the measurement of its area provided an indication of the movement. We observed that [Ca2+]i also synchronized in the entire fragment and that the relaxation ensued upon the reduction in [Ca2+]i. We suggest that the Ca2+ wave generated periodically is one of the major factors playing a crucial role in the relaxation of P. polycephalum.


Human immunodeficiency virus-1 (HIV-1) gp120 superantigen-binding serum antibodies. A host factor in homosexual HIV-1 transmission.
HIV-1 gp120 is an immunoglobulin superantigen which can bind to preimmune serum Ig. We hypothesize that levels of such preimmune antibodies vary in the population and might affect host resistance or susceptibility to viral transmission. This study tests two predictions: (a) levels of preimmune anti-gpl20 Igs are a polymorphic trait; and, (b) these levels are correlated with resistance or susceptibility to HIV-1 transmission. The first prediction was confirmed in a longitudinal study of a low-risk seronegative population. In this group, levels of both endogenous anti-gpl20 IgM and IgG varied widely, but were characteristic and stable for each individual. The second prediction was addressed in a study of participants of the Multicenter AIDS Cohort Study, in which men "susceptible" and "resistant" to HIV infection were identified based on numbers of sexual partners and eventual seroconversion. Specimens consisted of archival sera obtained > 2 yr before seroconversion. Men in the susceptible population (low-risk seroconverters) were distinguished by low levels of anti-gpl20 IgG. We conclude that the level of preimmune anti-gpl20 IgG is a polymorphic population trait, and low levels are a potentially specific and significant factor in homosexual transmission of HIV infection.


Bench-to-bedside review: the role of nitric oxide in sepsis.
Sepsis is a state of systemic inflammation directed at microbes or their toxins in blood or tissues. Nitric oxide (NO) is one of many vasoactive molecules released from a variety of cell types during sepsis. Almost two decades ago, NO emerged as a potential therapeutic target in sepsis. NO produced by the constitutive NO synthase (NOS) isoform (endothelial NOS and neuronal NOS) in the vascular endothelium and elsewhere acts as a nonadrenergic, noncholinergic neurotransmitter, an inhibitor of platelet aggregation and a vasodilator. During sepsis, activation of inducible NOS (iNOS) in the lung epithelium and other organs occurs, leading to NO overproduction. The result of excessive circulating NO is enhanced bacterial destruction, but also profound vasodilatation, activation of inflammatory cascades and depression of cardiac function. Trials of nonselective NOS inhibitors have shown increased mean arterial pressure, but also increased pulmonary artery pressure and reduced cardiac output. Small animal studies of iNOS selective inhibition have produced dichotomous results, but larger clinical studies assessing mortality are lacking. Inhaled NO has been touted as a therapeutic option to improve systemic oxygenation in the acute lung injury of sepsis (hypoxic pulmonary vasoconstriction and pulmonary hypertension); however, studies of inhaled NO in acute respiratory distress syndrome have not shown survival efficacy. Further investigation into the role of NO in human sepsis, and the development of methods to assess NO balance in patients with sepsis is essential in this field. In this review, we outline the effects of NO in sepsis, and summarize the therapeutic outcomes of NOS inhibitors, and inhaled NO in sepsis and acute respiratory distress syndrome.


Postpartum deaths: piglet, placental, and umbilical characteristics.
The fetal growth of the piglet is highly dependent on its placenta, and the newborn piglet birth weight is highly associated with postpartum death. However, there is little information available in the literature on the assessment of the placenta in relation to postpartum death in piglets. The aim of this study was to evaluate the impact of the placental area and placental weight, status of the umbilical cord, and piglet birth characteristics, such as blood parameters, vitality score, and birth weight on postpartum death. All live born piglets in litters from 26 Landrace-Yorkshire sows were monitored during farrowing and the status of each was recorded, including placental area and placental weight and blood variables obtained from the piglets and umbilical veins. Out of the 386 live-born piglets, 16.8% died before weaning at 5 wk. Among these, 78.5% died within the first 3 d of life. Mean blood concentration of lactate was increased in piglets that did not survive to weaning (P = 0.003). Concentrations of hemoglobin and hematocrit were decreased (P < 0.001) compared with survivors. Piglets born with a broken umbilical cord had a reduced vitality score vs. piglets born with an intact umbilical cord (P = 0.021), and they had an increased probability of dying before weaning (P = 0.050). Mean birth weight, body mass index, placental area (P < 0.001), and placental weight (P = 0.020) were reduced in piglets that died before weaning vs. those that survived. Birth weight and placental area were furthermore negatively associated with live litter size. Blood concentrations of IgG and albumin recorded at d 1 were decreased in piglets that died before weaning (P < 0.01), and blood concentration of albumin was positively associated with placental area (P < 0.001). We conclude that placental area and placental weight, status of the umbilical cord, birth weight, body mass index, blood concentrations of lactate, hemoglobin, and hematocrit recorded at birth, and blood concentrations of IgG and albumin recorded at d 1 were associated with postpartum death in this study. These results may indicate that there is an upper uterine limitation of litter size and that placental area and placental weight influence postpartum survival.


Methanolic extract of Kigelia africana and wound healing: an in vitro study.
Kigelia africana (Lam.) Benth. (Bignoniaceae) syn. Kigelia pinnata (Jacq. DC) is a tropical plant that is native to tropical Africa. The aim of this study was to determine if a methanolic extract prepared from Kigelia africana (KAE) can promote wound healing in treated human normal epidermal keratinocyte (HaCaT) cells and human normal foreskin fibroblast cell line (BJ) cells compared with untreated cells. Experimental steps included: the methanolic extraction of the leaf and fruit of the Kigelia africana plant; the preparation of HaCaT and BJ cell lines; cell culture with a stable tetrazolium salt-based proliferation assay; and the evaluation of the wound healing effect of KAE (2μg/ml) in BJ and HaCaT cells. The phytochemical contents of KAE were determined using liquid chromatography quadrupole time-of-flight mass spectrometry. The following molecules were identified as being present in the KAE, among others: cholesterol sulfate; lignoceric acid; embelin; isostearic acid; linoleic acid; dioctyl phthalate; arg-pro-thr; 15-methyl-15(S)-PGE1; sucrose; benzododecinium (Ajatin); and 9-Octadecenamide (oleamide). KAE effected faster wound healing in treated cells compared with untreated cells for both cell lines. HaCaT cells that had been mechanically injured and treated with KAE healed completely in 48 hours compared with 72 hours for untreated HaCaT cells. Treated BJ cells healed completely in 72 hours compared with 96 hours for untreated BJ cells. Concentrations of KAE up to 300μg/ml had a very low cytotoxic effect on treated BJ and HaCaT cells. The experimental data in this study support the potential of KAE-based wound healing treatment to accelerate wound healing.


The dermis.
All the dermal structures are less well developed in the newborn than in the older infant or child, but there are few important consequences of this. Sweating in response to a thermal stimulus occurs at birth in the term infant and can be detected in most preterm infants from 2 weeks of age. It is poorly developed though. Emotional (palmar/plantar) sweating is present from birth in term infants only. Skin blood flow can be regulated in term and preterm infants, and is often measured indirectly as a temperature gradient. Such a gradient is temperature as well as illness dependent which limits its use as a clinical tool. Sensory nerve endings are readily stimulated in the most immature infants. Finally, damage to the skin in the newborn period commonly leads to scarring, although this usually improves with time.


Changes in serum creatine kinase, leg muscle tightness, and delayed onset muscle soreness after a full marathon race.
Muscle tightness (MT) is believed to be an important cause of injury for runners. This study evaluated the change of serum creatine kinase (CK), MT in the leg muscles, and delayed onset muscle soreness after running. We evaluated 11 college students who completed a full marathon race. Participants completed a questionnaire on the right quadriceps muscle soreness. The CK activity and MT (iliopsoas, rectus femoris, hamstrings, gastrocnemius, and soleus muscles) were measured. The time points for CK measurements were before; immediately after; and at 1, 2, and 5 days after the race. The time points for MT measurements were the same as for CK except MT was not measured one day after the race. The time points for muscle soreness analysis were before the race and then every morning and night for 5 days after the race. Long-distance running led to significant increases in CK, MT, and muscle soreness. The CK levels peaked day 1 after the race. MT of iliopsoas peaked on day 5; of rectus femoris immediately after the race; and of hamstrings, gastrocnemius, and soleus on day 2. muscle soreness peaked at night on day 1. MT did not decrease to the pre-race levels on day 5. There were no significant changes but CK tended to correlate with the peak of MT of the rectus femoris (r=0.55, P=0.082) and hamstrings (r=0.57, P=0.065). Long-distance running may cause muscle fiber microdamage that may consequently increase CK, MT, and muscle soreness.


Potassium deficiency affects the carbon-nitrogen balance in cotton leaves.
Potassium (K) plays important roles in the metabolism of carbon (C) and nitrogen (N), but studies of K deficiency affecting C-N balance are lacking. This study explored the influence of K deficiency on C-N interaction in cotton leaves by conducting a field experiment with cotton cultivar DP0912 under two K rates (K0: 0 kg K2O ha-1 and K67: 67 kg K2O ha-1) and a controlled environment experiment with K-deficient solution (K1: 0 mM K+) and K-sufficient solution (K2: 6 mM K+). The results showed that leaf K content, leaf number, leaf area, boll number, reproductive dry weight and total dry weight were significant lower under K deficiency (K0 or K1). Lower total chlorophyll content and Chl a/b ratio, and decreased Pn along with lower Gs and higher Ci were measured under K deficiency, suggesting that the decrease in Pn was resulted from non-stomatal limitation. Leaf glucose, fructose, sucrose and starch contents were higher under K deficiency, because lower sucrose export was detected in phloem. Although leaf nitrate and ammonium contents significantly decreased, free amino acid content was increased by 40-63% under K deficiency, since lower amino acid export was also measured in phloem. K deficiency also induced lower soluble protein content in leaves. Leaf ATP level was significantly increased under K deficiency, indicating ATP utilization was lower, so that less energy was supplied to C and N metabolism. The ratio of soluble sugar to free amino acid and the C/N ratio markedly increased under K deficiency, and one reason was that the phloem export reduced more prominent for sucrose (54.6-78.0%) than amino acid (36.7-85.4%) under K deficiency. In addition, lower phosphoenolpyruvate carboxylase activity limited malate and citrate biosynthesis under K deficiency, causing a decrease of C flux into the amino acids, which was not beneficial for maintaining C-N balance. Sucrose phosphate synthase and nitrate reductase activities were lower under K deficiency, which would limit sucrose biosynthesis and nitrate assimilation. This was another factor altering soluble sugar to free amino acid ratio and C/N ratio in the K-deficient leaves.


Clostridium difficile toxin-induced inflammation and intestinal injury are mediated by the inflammasome.
Clostridium difficile-associated disease (CDAD) is the leading cause of nosocomial diarrhea in the United States. C difficile toxins TcdA and TcdB breach the intestinal barrier and trigger mucosal inflammation and intestinal damage. The inflammasome is an intracellular danger sensor of the innate immune system. In the present study, we hypothesize that TcdA and TcdB trigger inflammasome-dependent interleukin (IL)-1beta production, which contributes to the pathogenesis of CDAD. Macrophages exposed to TcdA and TcdB were assessed for IL-1beta production, an indication of inflammasome activation. Macrophages deficient in components of the inflammasome were also assessed. Truncated/mutated forms of TcdB were assessed for their ability to activate the inflammasome. The role of inflammasome signaling in vivo was assessed in ASC-deficient and IL-1 receptor antagonist-treated mice. TcdA and TcdB triggered inflammasome activation and IL-1beta secretion in macrophages and human mucosal biopsy specimens. Deletion of Nlrp3 decreased, whereas deletion of ASC completely abolished, toxin-induced IL-1beta release. TcdB-induced IL-1beta release required recognition of the full-length toxin but not its enzymatic function. In vivo, deletion of ASC significantly reduced toxin-induced inflammation and damage, an effect that was mimicked by pretreatment with the IL-1 receptor antagonist anakinra. TcdA and TcdB trigger IL-1beta release by activating an ASC-containing inflammasome, a response that contributes to toxin-induced inflammation and damage in vivo. Pretreating mice with the IL-1 receptor antagonist anakinra afforded the same level of protection that was observed in ASC-/- mice. These data suggest that targeting inflammasome or IL-1beta signaling may represent new therapeutic targets in the treatment of CDAD.


Upregulation of lncRNA HNF1A-AS1 promotes cell proliferation and metastasis in osteosarcoma through activation of the Wnt/β-catenin signaling pathway.
HNF1A-antisense 1 (HNF1A-AS1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies demonstrated that HNF1A-AS1 play important roles in cacinogenesis. However, the exact effects and molecular mechanisms of HNF1A-AS1 in osteosarcoma (OS) progression is still unclear. In the present study, we found that HNF1A-AS1 was markedly up-regulated in OS tissues compared to their adjacent non-tumor tissues. HNF1A-AS1 expression levels were positively associated with the clinical stage, distant metastasis, and reduced overall survival of OS patients. In addition, knockdown HNF1A-AS1 expression inhibited cell proliferation, metastasis and influences the activity of the Wnt/β-catenin pathway in OS cells. Wnt/β-catenin pathway activator (LiCl) rescued the anticancer effect of knockdown HNF1A-AS1 expression in OS cells. In conclusion, our study demonstrated that HNF1A-AS1 promoted the progression of OS via regulating the activity of the Wnt/β-catenin pathway, indicating that HNF1A-AS1 might be a potential target for the treatment of OS.


Development of a list with renally relevant drugs as a tool to increase medicines optimisation in patients with chronic kidney disease.
Chronic kidney disease (CKD) is a common disorder all over the world. Therapeutic goals are early detection of declining renal function and implementation of adequate pharmacological treatments regarding underlying and secondary diseases. As therapy becomes more complex with increasing stages of CKD, a decision-making tool for healthcare professionals could help to ensure safe drug treatment in patients with CKD in the outpatient setting. Therefore, a list of renally relevant drugs as a decision-making tool was developed to improve medicines optimisation for CKD patients in the outpatient setting long term. A renally relevant drug list (RRD-list) with renally relevant drugs, based on data from a study on medicines optimisation in patients with CKD from June 2015 to March 2018, was developed at the nephrological outpatient clinic at the Klinikum Fulda, Germany. The whole study is published elsewhere. A clinical pharmacist reviewed the patients' medications, current drug-related problems and all nephrologists' recommendations, and categorised all detected drugs into renally relevant and non-renally relevant groups. The 10 most frequently detected renally relevant drug groups were summarised in the RRD-list and extended by treatment alternatives and advice. The medication of 160 patients, who were receiving overall 1376 drugs, was analysed; 831 drugs were defined as renally relevant. Drug-related problems were caused by 543 renally relevant drugs. The nephrologists made 292 recommendations regarding 28 drug classes. Considering the 10 most frequent drug groups, in total 16 renally relevant drug groups with 36 drug classes were added to the RRD-list. The RRD-list could be an essential tool for all healthcare professionals in their daily work, such as general practitioners and community pharmacists, for the treatment of patients with renal insufficiency.


Duffy antigen is expressed during erythropoiesis in Duffy-negative individuals.
The erythrocyte silent Duffy blood group phenotype in Africans is thought to confer resistance to Plasmodium vivax blood-stage infection. However, recent studies report P. vivax infections across Africa in Fy-negative individuals. This suggests that the globin transcription factor 1 (GATA-1) SNP underlying Fy negativity does not entirely abolish Fy expression or that P. vivax has developed a Fy-independent red blood cell (RBC) invasion pathway. We show that RBCs and erythroid progenitors from in vitro differentiated CD34 cells and from bone marrow aspirates from Fy-negative samples express a functional Fy on their surface. This suggests that the GATA-1 SNP does not entirely abolish Fy expression. Given these results, we developed an in vitro culture system for P. vivax and show P. vivax can invade erythrocytes from Duffy-negative individuals. This study provides evidence that Fy is expressed in Fy-negative individuals and explains their susceptibility to P. vivax with major implications and challenges for P. vivax malaria eradication.


Shape-based tracking of left ventricular wall motion.
An approach for tracking and quantifying the nonrigid, nonuniform motion of the left ventricular (LV) endocardial wall from two-dimensional (2-D) cardiac image sequences, on a point-by-point basis over the entire cardiac cycle, is presented. Given a set of boundaries, motion computation involves first matching local segments on one contour to segments on the next contour in the sequence using a shape-based strategy. Results from the match process are incorporated with a smoothness term into an optimization functional. The global minimum of this functional is found, resulting in a smooth flow field that is consistent with the match data. The computation is performed for all pairs of frames in the temporal sequence and equally sampled points on one contour are tracked throughout the sequence, resulting in a composite flow field over the entire sequence. Two perspectives on characterizing the optimization functional are presented which result in a tradeoff resolved by the confidence in the initial boundary segmentation. Experimental results for contours derived from diagnostic image sequences of three different imaging modalities are presented. A comparison of trajectory estimates with trajectories of gold-standard markers implanted in the LV wall are presented for validation. The results of this comparison confirm that although cardiac motion is a three-dimensional (3-D) problem, two-dimensional (2-D) analysis provides a rich testing ground for algorithm development.


State-level Medicaid expenditures attributable to smoking.
Medicaid recipients are disproportionately affected by tobacco-related disease because their smoking prevalence is approximately 53% greater than that of the overall US adult population. This study estimates state-level smoking-attributable Medicaid expenditures. We used state-level and national data and a 4-part econometric model to estimate the fraction of each state's Medicaid expenditures attributable to smoking. These fractions were multiplied by state-level Medicaid expenditure estimates obtained from the Centers for Medicare and Medicaid Services to estimate smoking-attributable expenditures. The smoking-attributable fraction for all states was 11.0% (95% confidence interval, 0.4%-17.0%). Medicaid smoking-attributable expenditures ranged from $40 million (Wyoming) to $3.3 billion (New York) in 2004 and totaled $22 billion nationwide. Cigarette smoking accounts for a sizeable share of annual state Medicaid expenditures. To reduce smoking prevalence among recipients and the growth rate in smoking-attributable Medicaid expenditures, state health departments and state health plans such as Medicaid are encouraged to provide free or low-cost access to smoking cessation counseling and medication.


An immunohistochemical study of the GnRH neuron morphology and topography in the adult female rabbit hypothalamus.
The morphology and distribution of immunoreactive (GnRH) neural elements in the hypothalamus of the adult nulliparous female rabbit were examined. Approximately 1,000 GnRH cells (range 890-1136) were counted in the right half of the hypothalamus. Two distinct GnRH cell types were observed: GnRH cells with rough or spiny contours accounted for 64% of the total immunoreactive cells, and smooth-contoured cells represented 34% of the total. The majority of immunoreactive neural elements were found in the anterior hypothalamus. GnRH cells and processes were located primarily in the ventral and medial anterior hypothalamus forming an inverted V pattern. Processes were followed from the medial preoptic area and suprachiasmatic nucleus to the infundibular stem. Extrahypothalamic projections of GnRH cells were observed. Immunoreactive fibers were also found to contact the ependymal lining of the third ventricle. It is concluded that two morphologically distinct GnRH cell types exist and have a broad distribution in the rabbit hypothalamus. The functional significance of these cell types requires further study.


SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium.
The genes encoding Slits and their Robo receptors are silenced in many types of cancer, including breast, suggesting a role for this signaling pathway in suppressing tumorigenesis. The molecular mechanism underlying these tumor-suppressive effects has not been delineated. Here, we show that loss of Slits, or their Robo1 receptor, in murine mammary gland or human breast carcinoma cells results in coordinate up-regulation of the Sdf1 and Cxcr4 signaling axis, specifically within mammary epithelium. This is accompanied by hyperplastic changes in cells and desmoplastic alterations in the surrounding stroma. A similar inverse correlation between Slit and Cxcr4 expression is identified in human breast tumor tissues. Furthermore, we show in a xenograft model that Slit overexpression down-regulates CXCR4 and dominantly suppresses tumor growth. These studies classify Slits as negative regulators of Sdf1 and Cxcr4 and identify a molecular signature in hyperplastic breast lesions that signifies inappropriate up-regulation of key prometastatic genes.


Unique biological properties and molecular mechanism of 5,6-bridged quinolones.
We have characterized an early series of 5,6-bridged dioxinoquinolones which behaved strikingly different from typical quinolones. The 5,6-bridged dioxinoquinolones inhibited Escherichia coli DNA gyrase supercoiling activity but, unlike typical quinolones, failed to stimulate gyrase-dependent cleavable complex formation. Analogous unsubstituted compounds stimulated cleavable complex formation but were considerably less potent than the corresponding 5,6-bridged compounds. Consistent with a previous report (M. Antoine et al., Chim. Ther. 7:434-443, 1972) and contrary to established quinolone SAR trends, a compound with an N-1 methyl substitution (PGE-8367769) was more potent than its analog with an N-1 ethyl substitution (PGE-6596491). PGE-8367769 was shown to antagonize ciprofloxacin-mediated cleavable complex formation in a dose-dependent manner, suggesting an interaction with the gyrase-DNA complex that overlaps that of ciprofloxacin. Resistance to PGE-8367769 in E. coli was found to arise through missense mutations in gyrA, implicating DNA gyrase as the primary antibacterial target. Notably, only 1 of 15 distinct mutations selected on PGE-8367769 (D87G) has previously been implicated in quinolone resistance in E. coli. The remaining 14 mutations (E16V, G31V, R38L, G40A, Y50D, V70A, A84V, I89L, M135T, G173S, T180I, F217C, P218T, and F513C) have not been previously reported, and most were located outside of the traditional quinolone resistance-determining region. These novel GyrA mutations decreased sensitivity to 5,6-bridged dioxinoquinolones by four- to eightfold, whereas they did not confer resistance to other quinolones such as ciprofloxacin, clinafloxacin, or nalidixic acid. These results demonstrate that the 5,6-bridged quinolones act via a mechanism that is related to but qualitatively different from that of typical quinolones.


Primary cutaneous anaplastic large cell lymphoma.
Anaplastic large cell lymphoma (ALCL) is characterized by proliferation of anaplastic large CD 30+ T-cell lymphoid cells with abundant cytoplasm. Primary cutaneous ALCL is a rare form of ALCL, usually seen in elderly patients. In this report, the authors present an unusual case of 15-year-old boy with a solitary left ear lobe mass, previously reported as keratoacanthoma which was later histopathologically and immunohistochemically diagnosed as T-cell phenotype, anaplastic lymphoma kinase (ALK)-negative primary cutaneous anaplastic large cell lymphoma. The patient's response to chemotherapy was good and he is receiving the continuation phases of his chemotherapy.


Deterministic and probabilistic control of the behavior of rats ingesting liquid diets.
The probability distributions of bouts of licking and pauses between them in rats ingesting sucrose solutions were studied to determine if the durations of these ingestive and noningestive acts were controlled by a deterministic or probabilistic decision rule in the central nervous system. The duration of the bouts of licking could be modeled by a Poisson process, indicating that these bouts were terminated by a probabilistic rule. Three different types of pauses terminated the bouts of licking. Each averaged 0.3, 1.5, or 50-60 s in duration. The two longer pauses could be modeled by a Poisson process, indicating that their termination was also probabilistic in nature. The shorter pauses averaging 0.3 s could not and are more likely deterministically controlled.


A Unified Approach to Decarboxylative Halogenation of (Hetero)aryl Carboxylic Acids.
Aryl halides are a fundamental motif in synthetic chemistry, playing a critical role in metal-mediated cross-coupling reactions and serving as important scaffolds in drug discovery. Although thermal decarboxylative functionalization of aryl carboxylic acids has been extensively explored, the scope of existing halodecarboxylation methods remains limited, and there currently exists no unified strategy that provides access to any type of aryl halide from an aryl carboxylic acid precursor. Herein, we report a general catalytic method for direct decarboxylative halogenation of (hetero)aryl carboxylic acids via ligand-to-metal charge transfer. This strategy accommodates an exceptionally broad scope of substrates. We leverage an aryl radical intermediate toward divergent functionalization pathways: (1) atom transfer to access bromo- or iodo(hetero)arenes or (2) radical capture by copper and subsequent reductive elimination to generate chloro- or fluoro(hetero)arenes. The proposed ligand-to-metal charge transfer mechanism is supported through an array of spectroscopic studies.


Prenatal developmental toxicity testing of petroleum substances using the zebrafish embryotoxicity test.
The present study evaluates the applicability of the zebrafish embryotoxicity test (ZET) to assess prenatal developmental toxicity (PDT) potency of the DMSO-extracts of 9 petroleum substances (PS), with variable polycyclic aromatic hydrocarbon (PAH) content, and 2 gas-to-liquid (GTL) products, without any PAHs but otherwise similar properties to PS. The results showed that all PS extracts induced concentration-dependent in vitro PDT, as quantified in the ZET and that this potency is associated with their 3-5 ring PAH content. In contrast and as expected, GTL products did not induce any effect at all. The potencies obtained in the ZET correlated with those previously reported for the embryonic stem cell test (EST) (R2=0.61), while the correlation with potencies reported in in vivo studies were higher for the EST (R2=0.85) than the ZET (R2=0.69). Combining the results of the ZET with those previously reported for the EST (Kamelia et al., 2017), the aryl hydrocarbon (AhR) CALUX assay (Kamelia et al., 2018), and the PAH content, ranked and clustered the test compounds in line with their in vivo potencies and chemical characteristics. To conclude, our findings indicate that the ZET does not outperform the EST as a stand-alone assay for testing PDT of PS, but confirms the hypothesis that PAHs are the major inducers of PDT by some PS, while they also indicate that the ZET is a useful addition to a battery of in vitro tests able to predict the in vivo PDT of PS.


[Spontaneous remission of congenital liver cysts].
A six-weeks old infant presented with vomiting, malnutrition, pneumonia and signs of biliary obstruction. The liver was enlarged; ultrasonography showed three large cysts in the right lobe. The cysts were thought to be congenital. Before we could differentiate them from other causes they disappeared spontaneously. To our knowledge, spontaneous regression of congenital cysts of the liver has not been reported previously.


Polyotia: the Confusing Auricular Malformation.
Polyotia is a very rare auricular malformation, and only few cases have been reported to date. Polyotia has been ambiguously defined, and due to the instability of its shape and condition, no uniform surgical technique has been established up to now. Thus, it is necessary to standardize the diagnosis and treatment of polyotia. The aim of the present study was to present a new set of objective diagnostic criteria for discussion, and introduce our surgical design for polyotia. A retrospective analysis was performed on 34 cases of polyotia, which were diagnosed and treated in our Plastic Surgery Department during a 3-year period from January 2016 to March 2019. The preoperative photographs, manifestations and operation records of these 34 cases were reviewed. On the basis of the new set of objective diagnostic criteria, only 12 of 34 cases were diagnosed as polyotia, while the remaining 22 cases were diagnosed as accessory tragus. Polyotia was redefined as the presence of a broad-based accessory auricle in the tragus area along with accessory cavitas conchae similar to cavitas conchae. The new surgical design emphasized the use of cartilage and skin to fill up the concavity and reconstruct the tragus. The diagnosis of polyotia was presented on the basis of a new set of objective criteria, which include an accessory auricle and accessory cavitas conchae. The use of cartilage and skin to fill up the concavity and reconstruct the tragus were the emphases.


Differential pattern of brain functional connectome in obsessive-compulsive disorder versus healthy controls.
Researchers believe that recognition of functional impairment in some of brain networks such as frontal-parietal, default mode network (DMN), anterior medial prefrontal cortex (MPFC) and striatal structures could be a beneficial biomarker for diagnosis of obsessive-compulsive disorder (OCD). Although it is well recognized brain functional connectome in OCD patients shows changes, debate still remains on characteristics of the changes. In this regard, little has been done so far to statistically assess the altered pattern using whole brain electroencephalography. In this study, resting state EEG data of 39 outpatients with OCD and 19 healthy controls (HC) were recorded. After, brain functional network was estimated from the cleaned EEG data using the weighted phase lag index algorithm. Output matrices of OCD group and HCs were then statistically compared to represent meaningful differences. Significant differences in functional connectivity pattern were demonstrated in several regions. As expected the most significant changes were observed in frontal cortex, more significant in frontal-temporal connections (between F3 and F7, and T5 regions). These results in OCD patients are consistent with previous studies and confirm the role of frontal and temporal brain regions in OCD.


Integrin ανβ5 in vitro inhibition limits pro-fibrotic response in cardiac fibroblasts of spontaneously hypertensive rats.
To date the TGF-β1 activation mediated by integrin ανβ5 during fibrosis is well-known. This process has been shown also in the heart, where cardiac fibroblasts (CF) differentiate into α-smooth muscle actin (α-SMA)-positive myofibroblasts (MyoFB). Here, we studied the effects on CF, isolated by spontaneously hypertensive rats (SHR), of integrin ανβ5 inhibition in MyoFB differentiation. Staining and immunohistochemistry were performed on rat cardiac tissue. CF were isolated by enzymatic digestion from SHR (SHR-CF) and normotensive WKY (WKY-CF) rat hearts and then treated for in vitro evaluation. SHR heart tissues revealed a higher TGF-β1 expression vs. WKY samples. SHR-CF showed an enhanced SMAD2/3 activation and an up-regulated expression of α-SMA, a typical MyoFB marker, especially after TGF-β1 treatment. Immunostaining on cardiac tissues revealed a higher expression of integrin ανβ5 in SHR vs. WKY rat hearts. In vitro results confirmed the up-regulation of integrin ανβ5 expression in SHR-CF at basal condition and after TGF-β1 treatment, in comparison with WKY-CF. Inhibition of integrin ανβ5 by cilengitide treatment led a decreased expression of ανβ5, collagen I, and α-SMA in SHR-CF vs. WKY-CF, resulting in a diminished differentiation of CF into MyoFB. Taking together, results suggested that SHR-CF are more susceptible to TGF-β1, showing an up-regulated activation of SMAD2/3 signaling, and an increased ανβ5, α-SMA, and collagen I expression. Hypertension stimulus promoted an up-regulation of integrin ανβ5 on SHR cardiac tissue and its in vitro inhibition reverted pro-fibrotic events of SHR-CF. Inhibition of integrin ανβ5 exerted by cilengitide strongly diminished SHR-CF differentiation into detrimental MyoFB. So, integrin ανβ5 might be considered a novel therapeutic target and cilengitide an effective pharmacological tool to limit the progression of hypertension-induced cardiac fibrosis.


How do veterinary students engage when reflecting on their development towards being veterinary surgeons?
Reflection has been widely acknowledged to contribute to professional development, the ability to manage tension and enhanced resilience. However, many practitioners struggle to reflect productively due to a lack of clarity of what constitutes effective reflection. To help develop reflective competence among future professionals, 30 veterinary students' reflective assignments were analysed by thematic text analysis. Theoretical frameworks were based on published criteria for critical and core reflection. Reflection was described through resources (the tools used), practices (the ways of using these tools) and outcomes (what was achieved). This helped to distinguish simple skills based reflection from higher-level core reflection. Simple skills-based reflection was associated with an identity of expert learner: students perceive that their task is to identify a knowledge deficit that can be easily rectified through new learning. Core reflection was associated with students articulating an identity of adaptable professionals: rather than veterinary challenges being resolved simply through application of a body of knowledge, wider complexities of professional practice are recognised, including a need to resolve tension between their own and other stakeholders' priorities, values and beliefs. Scaffolding an iterative, cyclical reflection process may support outcomes oriented towards resilience and the management of tension.


Louis H. Bauer, M.D., and the first civil U.S. aeromedical standards: his continuing legacy.
Louis Hopewell Bauer, M.D. (1888-1964) promulgated the first civil aviation medicine regulations for U.S. civil airmen on December 31, 1926. Major elements of these regulations are reflected in the current Federal Aviation Administration Civil Airman Medical Standards, these latter including modifications resulting from medical and aeronautical technical advances. Dr. Bauer's plans covering periodic examinations, waivers, and a system implemented through designated "Aviation Medical Examiners" are continued to this day. Dr. Bauer founded the progenitor of the present Aerospace Medical Association in 1929, the Aero Medical Association. Further, he founded the Journal of Aviation Medicine, the predecessor of the present Aviation, Space, and Environmental Medicine journal, the first issue published in March, 1930. Dr. Bauer's influence in medicine broadened to include the presidency of the American Medical Association (1952-3) and a long standing leadership role with the World Medical Association. His 1926 textbook, Aviation Medicine, stands as an historic centerpiece in the evolution of aviation medicine. Bauer's leadership and contributions to civil aviation medicine came at the right time to enhance the development of U.S. civil aviation and civil aviation safety.


Aerosolized Cyanobacterial Harmful Algal Bloom Toxins: Microcystin Congeners Quantified in the Atmosphere.
Cyanobacterial harmful algal blooms (cHABs) have the potential to adversely affect public health through the production of toxins such as microcystins, which consist of numerous molecularly distinct congeners. Microcystins have been observed in the atmosphere after emission from freshwater lakes, but little is known about the health effects of inhaling microcystins and the factors contributing to microcystin aerosolization. This study quantified total microcystin concentrations in water and aerosol samples collected around Grand Lake St. Marys (GLSM), Ohio. Microcystin concentrations in water samples collected on the same day ranged from 13 to 23 μg/L, dominated by the d-Asp3-MC-RR congener. In particulate matter <2.5 μm (PM2.5), microcystin concentrations up to 156 pg/m3 were detected; the microcystins were composed primarily of d-Asp3-MC-RR, with additional congeners (d-Asp3-MC-HtyR and d-Asp3-MC-LR) observed in a sample collected prior to a storm event. The PM size fraction containing the highest aerosolized MC concentration ranged from 0.44 to 2.5 μm. Analysis of total bacteria by qPCR targeting 16S rDNA revealed concentrations up to 9.4 × 104 gc/m3 in aerosol samples (≤3 μm), while a marker specific to cyanobacteria was not detected in any aerosol samples. Concentrations of aerosolized microcystins varied even when concentrations in water were relatively constant, demonstrating the importance of meteorological conditions (wind speed and direction) and aerosol generation mechanism(s) (wave breaking, spillway, and aeration systems) when evaluating inhalation exposure to microcystins and subsequent impacts on human health.


Disposable Isolation Device to Reduce COVID-19 Contamination During CT Scanning.
The use of chest computed tomography (CT) in the era of the COVID-19 pandemic raises concern regarding the transmission risks to patients and staff caused by CT room contamination. Meanwhile the Center for Disease Control guidance for air exchange in between patients may heavily impact workflows. To design a portable custom isolation device to reduce imaging equipment contamination during a pandemic. Center for Disease Control air exchange guidelines and requirements were reviewed. Device functional requirements were outlined and designed. Engineering requirements were reviewed. Methods of practice and risk mitigation plans were outlined including donning and doffing procedures and failure modes. Cost impact was assessed in terms of CT patient throughput. CT air exchange solutions and alternatives were reviewed. Multiple isolation bag device designs were considered. Several designs were custom fabricated, prototyped and reduced to practice. A final design was tested on volunteers for comfort, test-fit, air seal, and breathability. Less than 14 times enhanced patient throughput was estimated, in an ideal setting, which could more than counterbalance the cost of the device itself. A novel isolation bag device is feasible for use in CT and might facilitate containment and reduce contamination in radiology departments during the COVID Pandemic.


A selective M1 and M3 receptor antagonist, penehyclidine hydrochloride, prevents postischemic LTP: involvement of NMDA receptors.
Our previous and other studies have confirmed that a selective M1 and M3 receptor antagonist, Penehyclidine hydrochloride (PHC), has neuroprotection activity in cerebral ischemia. However, the precise mechanisms of protection of PHC are still elusive. In this study we analyzed PHC-mediated neuroprotection on a model of brain ischemia (oxygen and glucose deprivation), named postischemic LTP (i-LTP). We found that the activation of NMDA receptor was required for the induction of i-LTP. Compared with scopolamine, PHC could prevent it due to selectively blocking M1 receptor, not M2 receptor, to decrease NMDAR activation. Our findings further showed that the inhibition of SK2 channels occluded the prevention of PHC on NMDAR activation. Furthermore, we confirmed that PHC exerted its roles through directly disinhibition of SK2 channels by blocking M1 receptor and subsequent restricting PKC activation. Moreover, our studies further revealed the critical roles of SK2 channels in i-LTP. Thus, the mechanisms of PHC in brain protection may be involved in suppression of NMDAR by regulation of SK2 channels. Our results obtained in effects of PHC on i-LTP further provided a better understanding of the therapy strategy during stroke and identified potential therapeutic targets to prevent development of ischemia.


Functional characterization of Ape1 variants identified in the human population.
Apurinic/apyrimidinic (AP) sites are common mutagenic and cytotoxic DNA lesions. Ape1 is the major human repair enzyme for abasic sites and incises the phosphodiester backbone 5' to the lesion to initiate a cascade of events aimed at removing the AP moiety and maintaining genetic integrity. Through resequencing of genomic DNA from 128 unrelated individuals, and searching published reports and sequence databases, seven amino acid substitution variants were identified in the repair domain of human Ape1. Functional characterization revealed that three of the variants, L104R, E126D and R237A, exhibited approximately 40-60% reductions in specific incision activity. A fourth variant, D283G, is similar to the previously characterized mutant D283A found to exhibit approximately 10% repair capacity. The most common substitution (D148E; observed at an allele frequency of 0.38) had no impact on endonuclease and DNA binding activities, nor did a G306A substitution. A G241R variant showed slightly enhanced endonuclease activity relative to wild-type. In total, four of seven substitutions in the repair domain of Ape1 imparted reduced function. These reduced function variants may represent low penetrance human polymorphisms that associate with increased disease susceptibility.


Improving filtered backprojection reconstruction by data-dependent filtering.
Filtered backprojection, one of the most widely used reconstruction methods in tomography, requires a large number of low-noise projections to yield accurate reconstructions. In many applications of tomography, complete projection data of high quality cannot be obtained, because of practical considerations. Algebraic methods tend to handle such problems better, but are computationally more expensive. In this paper, we introduce a new method that improves the filtered backprojection method by using a custom data-dependent filter that minimizes the projection error of the resulting reconstruction. We show that the computational cost of the new method is significantly lower than that of algebraic methods. Experiments on both simulation and experimental data show that the method is able to produce more accurate reconstructions than filtered backprojection based on popular static filters when presented with data with a limited number of projections or statistical noise present. Furthermore, the results show that the method produces reconstructions with similar accuracy to algebraic methods, but is faster at producing them. Finally, we show that the method can be extended to exploit certain forms of prior knowledge, improving reconstruction accuracy in specific cases.