Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells.
Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we investigate whether primary human bone marrow derived mesenchymal stromal cells (BMSC) EVs isolated from two different origins, fetal (fEV) and adult (aEV) tissue, can increase the relative low number of HSPCs found in umbilical cord blood (UCB) and which EV-derived components are responsible for ex vivo HSPC expansion. Interestingly, aEVs and to a lesser extent fEVs, showed supportive ex vivo expansion capacity of UCB-HSPCs. Taking advantage of the two BMSC sources with different supportive effects, we analyzed the EV cargo and investigated how gene expression is modulated in HSPCs after incubation with aEVs and fEVs. Proteomics analyses of the protein cargo composition of the supportive aEV vs. the less-supportive fEV identified 90% of the Top100 exosome proteins present in the ExoCarta database. Gene Ontology (GO) analyses illustrated that the proteins overrepresented in aEVs were annotated to oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport, or protein folding. In contrast, the proteins overrepresented in fEVs were annotated to extracellular matrix organization positive regulation of cell migration or transforming growth factor beta receptor (TGFBR) signaling pathway. Small RNA sequencing identified different molecular signatures between aEVs and fEVs. Interestingly, the microRNA cluster miR-99b/let-7e/miR-125a, previously identified to increase the number of HSPCs by targeting multiple pro-apoptotic genes, was highly and significantly enriched in aEVs. Although we identified significant differences in the supportive effects of aEVs and fEVs, RNAseq analyses of the 24 h treated HSPCs indicated that a limited set of genes was differentially regulated when compared to cells that were treated with cytokines only. Together, our study provides novel insights into the complex biological role of EVs and illustrates that aEVs and fEVs differentially support ex vivo expansion capacity of UCB-HSPCs. Together opening new means for the application of EVs in the discovery of therapeutics for more efficient ex vivo HSPC expansion.


The Extended Congress: Reimagining scientific meetings after the COVID-19 pandemic.
This article was migrated. The article was marked as recommended. The COVID-19 pandemic has profoundly impacted the medical meetings planned for 2020. This health crisis has caused the cancellation, postponement or a pivot in educational design to virtual formats. In the latter case, the format for virtual meetings has remained very similar to the cancelled face-to-face meeting, by using primarily web conferencing systems. This article intends to start a dialogue with the medical education and events community about possible delivery formats. Among them, the concept of an "Extended Congress" is introduced. The extended congress uses the extension of time, space and languages to a scientific meeting. It aims to: 1) unleash the reach of traditional meetings through the use of technology to access larger audiences in different languages, across a country and internationally, with local leaders to help interpret the knowledge and localize it, and 2) to improve knowledge translation into practice through a sequential and active learning process. An ongoing example is described as a proof of concept: the Latin American Peritoneal Dialysis Extended Congress attracted 774 remote participants from over 20 countries, 93% of whom were paid registrants. Initially designed as a hybrid (live plus remote) event scheduled for March 2020, it had to be reframed as a remote only meeting due to the COVID-19 pandemic, thus protecting the health of members while providing continued value to the organization and attendees of the event. With this experience in mind, the authors are currently designing programs in the United States, through collaboration with the University of Virginia Office of Continuing Medical Education. In summary, the design of meetings can better utilize and integrate technology and reach larger audiences with a blend of formats. Those organizations that adapt more quickly to offer these events will concentrate more of the share, as seen with the adoption of technology by other industries.


The Relationship between Older Drivers' Performance on the Driving Observation Schedule (eDOS) and Cognitive Performance.
The Driving Observation Schedule (eDOS) was developed for use in the Candrive/Ozcandrive five-year prospective study of older drivers to observe the driving behavior of older drivers and monitor changes in driving behaviors over time. The aim of this study is to describe participants' driving performance during the eDOS driving task and investigate the association between driving performance and cognitive measures. A subset of Ozcandrive participants (n = 144, 104 male [72%], 40 female [28%], Mean age = 81.49 years, SD = 3.58 years, Range: 76 - 96 years) completed the eDOS driving task. Participants drove to their selected destinations (up to 4 locations), with observations of driving behaviors (both inappropriate and appropriate) recorded for specific driving maneuvers: intersection negotiation, lane-changing, merging, low speed maneuvers and maneuver-free driving. Driving behaviors (e.g. signalling, speed regulation, gap acceptance, lane position, 'critical errors') were scored by a trained observer and participants received an overall eDOS driving task score (Maximum = 100 points). Participants also completed a series of cognitive assessments as part of the Year 2 Candrive/Ozcandrive assessment protocols. The overall eDOS driving task score was very high (M = 95.77; SD = 5.15; Range = 65.63 - 100). Detailed analyses of participants' driving behavior revealed a high level of appropriate driving behavior (96%, n = 5,935 maneuvers), with few errors (4%, n = 252 maneuvers). While most participants' performance on the cognitive assessments was high, some scores were below the criteria for cogntive impairment (BIC) according to conventional benchmarks: (MoCA: M = 26.56, SD = 2.12, Range = 19 - 30, % BIC = 28%; MMSE: M = 29.10, SD = 1.01, Range = 26-30, %BIC = 0%; Trails B: M = 111.66, SD = 43.53, Range = 50 - 301, %BIC = 6%). There was no significant relationship observed between participants' overall eDOS driving task scores and age (r (144) = -0.17, p > 0.05), and performance on various cognitive assessments including: MoCA (r (144) = 0.07, p > 0.1), MMSE (r (144) = 0.03, p > 0.5), Trail Making Test B (r (144) = 0.09, p > 0.1). Preliminary analyses of the eDOS driving task revealed a high level of appropriate driving behavior among Ozcandrive older drivers. Despite some participants' cognitive performance suggesting impairment, participants' overall eDOS driving task scores were not significantly related to cognitive performance. This finding is consistent with previous research suggesting some older drivers are able to compensate well for age-related cognitive impairment.


Auxin deprivation induces synchronous Golgi differentiation in suspension-cultured tobacco BY-2 cells.
To date, the lack of a method for inducing plant cells and their Golgi stacks to differentiate in a synchronous manner has made it difficult to characterize the nature and extent of Golgi retailoring in biochemical terms. Here we report that auxin deprivation can be used to induce a uniform population of suspension-cultured tobacco (Nicotiana tabacum cv BY-2) cells to differentiate synchronously during a 4-d period. Upon removal of auxin, the cells stop dividing, undergo elongation, and differentiate in a manner that mimics the formation of slime-secreting epidermal and peripheral root-cap cells. The morphological changes to the Golgi apparatus include a proportional increase in the number of trans-Golgi cisternae, a switch to larger-sized secretory vesicles that bud from the trans-Golgi cisternae, and an increase in osmium staining of the secretory products. Biochemical alterations include an increase in large, fucosylated, mucin-type glycoproteins, changes in the types of secreted arabinogalactan proteins, and an increase in the amounts and types of molecules containing the peripheral root-cap-cell-specific epitope JIM 13. Taken together, these findings support the hypothesis that auxin deprivation can be used to induce tobacco BY-2 cells to differentiate synchronously into mucilage-secreting cells.


Should ongoing airway education be a mandatory component of continuing professional development for College of Intensive Care Medicine Fellows?
This study aimed to determine whether airway education should be introduced to the continuing professional development (CPD) program for College of Intensive Care Medicine (CICM) Fellows. A random representative sample of 11 tertiary intensive care units (ICUs) was chosen from the list of 56 units accredited for 12 or 24 months of CICM training. All specialist intensive care Fellows (n=140) currently practising at the eleven ICUs were sent the questionnaire via email. Questionnaire data collection and post-collection data analysis was used to determine basic respondent demographics, frequency of certain airway procedures in the past 12 months, confidence with advanced airway practices in ICU, participation in airway education in the past three years, knowledge of can't intubate, can't oxygenate (CICO) algorithms, preference for certain airway equipment/techniques, and support for required airway education as a component of the CICM CPD program. All responses were tabled for comparison. Data was analysed to establish any significant effect of another specialty qualification and current co-practice in anaesthesia on volume of practice, confidence with multiple airway procedures, use of airway equipment, and support for airway education. In total, 112 responses (response rate 80%) to the questionnaire were received within four weeks; 107 were completed in full (compliance 96%). All results were tabled. There is currently widespread support amongst CICM Fellows for airway skills education as a CPD requirement for CICM Fellows. Volumes of practice and confidence levels with different airway procedures vary amongst Fellows and further support the need for education.


Deslorelin and naltrexone stimulate follicular development in mares during autumn transition and early anestrus.
Horses are long-day breeders and commence ovarian follicular activity during the spring. Evidence suggests that there is an endogenous circannual rhythm in mares, and it is uncertain whether hormonal manipulation during or immediately following the fall transition induces follicular development. The current study was designed to test the hypothesis that both deslorelin and naltrexone induce follicular development in late fall transitioning or anestrous mares. Five of six mares treated with deslorelin, and 4 of 6 mares treated with naltrexone, developed a pre-ovulatory-sized follicle and were inseminated. Zero of three deslorelin-control mares and 1 of 3 naltrexone-control mares were inseminated. The number of mares bred in the deslorelin treatment group was significantly higher than in the corresponding control group (P < 0.05). Six of nine mares inseminated were pregnant 14 days after insemination. In conclusion, we were able to induce follicular development resulting in fertile ovulations during and shortly after the fall transition.


Asthma exacerbations in African Americans treated for 1 year with combination fluticasone propionate and salmeterol or fluticasone propionate alone.
This long-term prospective study was conducted in African Americans with persistent asthma to examine the safety and effectiveness of the combination of the inhaled corticosteroid, fluticasone propionate (FP), and the long-acting beta-agonist, salmeterol, compared with FP alone. This was a randomized, double-blind, parallel group, multi-center trial in adolescent and adult subjects >/=12 years of age symptomatic on a low dose of an inhaled corticosteroid (ICS). The study consisted of a 2-week screening period on low dose ICS; a 4-week open-label FP 250 mcg twice daily (BID) run-in; a 52-week double-blind period (FP/salmeterol [FSC] 100/50 mcg [n=239] or FP 100 mcg [n=236] BID), and a 4-week FP 250 mcg BID run-out period. Annualized exacerbation rate was the primary outcome for comparing the two treatments. Other measures of asthma control included peak expiratory flow, asthma symptoms, and albuterol use. Safety was assessed through adverse events. Exacerbation rates were not significantly different in those treated with FSC 100/50 mcg (0.449 per year) compared with FP 100 mcg (0.529 per year, p=0.169). When the per-protocol analysis was applied, the rates were 0.465 and 0.769 per year for FSC 100/50 mcg and FP 100 mcg, respectively. Treatment with FSC 100/50 mcg provided statistically greater improvements in lung function measures and nighttime awakenings (p</=0.050) and demonstrated numerically lower daily symptoms (p=0.216) and albuterol use (p=0.122). Two subjects treated with FSC 100/50 mcg were hospitalized for an asthma exacerbation compared to three treated with FP 100 mcg. The overall incidence of adverse effects during double-blind treatment was similar between the FSC 100/50 mcg and FP 100 mcg treatment groups (61% and 68%, respectively). Frequent study visits were required of subjects during this long-term study, and it remains unknown whether this intervention may affect generalizability. In this large, prospective study among African Americans with asthma, the addition of salmeterol to FP resulted in a similar low rate of exacerbations and improved other markers of asthma control. Both FSC 100/50 mcg and FP 100 mcg were well-tolerated, and the overall safety-profiles were similar over 1 year of treatment.


Effects of game-based rehabilitation on upper limb function in adults within the first six months following stroke: protocol for a systematic review and meta-analysis.
To evaluate and summarize the level of evidence for the immediate, short-term, and long-term effects of game-based rehabilitation on upper limb function in adults within the first six months following stroke. A game-based intervention is a valuable therapeutic tool for incorporating principles of motor learning and neuroplasticity in the rehabilitation of upper limb function post-stroke. Most of the existing reviews on game-based rehabilitation are focused on the chronic phase of stroke. However, as maximum upper limb motor recovery occurs in the first six months after stroke, further exploration of the effects of game-based rehabilitation in this phase is necessary. We will include randomized clinical trials assessing the immediate, short-term, and long-term effects of game-based rehabilitation on upper limb function in adults within the first six months following stroke. The systematic review will follow the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) checklist and JBI methodology for systematic reviews of effectiveness. A database-specific search strategy will be used in CINAHL, PubMed, Scopus, Web of Science, ProQuest, PEDro, OT Seeker, and Ovid MEDLINE to identify studies in the English language with no date limit. Two reviewers will independently screen, extract data from, and assess risk of bias in the eligible studies. Meta-analysis and publication bias evaluation will be done when adequate data are available. If a meta-analysis is precluded, then a narrative synthesis will be done. The Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria will be used to assess the certainty of evidence for the outcome measures of interest. PROSPERO CRD42020190100.


Challenges and Strategies of Providing Effective Antenatal Education Services in Oman's Public Healthcare System: Perspectives of service providers and pregnant women.
This study aimed to explore the challenges of providing quality antenatal education from the perspectives of the healthcare service providers and pregnant women. Globally, maternal mortality is considered a critical healthcare issue because statistics consistently show that many deaths and injuries that occur during pregnancy and childbirth are avoidable. This qualitative study was conducted from January 2021 to March 2021 at 9 outpatient antenatal clinics located in the public health centres of Muscat governorate, Oman. A purposive sampling technique was used, and data were collected through in-depth interviews and field notes and analysed manually using thematic analysis. A total of 30 participants were included in this study. The challenges identified by the healthcare service providers included the lack of a consultation room and designated space for health education, work overload, time constraints, under-staffing, lack of educational materials, language barriers, lack of authority and negative attitude. The pregnant women identified lack of focus on women's needs, superficial antenatal education, overcrowding, lack of educational facilities, use of medical jargon and unprofessional staff attitude towards women as key barriers to receiving quality antenatal service. Suggested solutions included improving staffing levels, designating a space for antenatal education, expanding educational activities, continuing education for caregivers, establishing midwife-led units, providing focused antenatal education and improving communication between the providers and users. Both healthcare service providers and pregnant women experience significant barriers that hinder them from providing and accessing quality antenatal education services, respectively. Therefore, policymakers, health planners and hospital administrators should remove these barriers and integrate some of the recommendations in this study to promote better health outcomes.


Robust entropy requires strong and balanced excitatory and inhibitory synapses.
It is widely appreciated that balanced excitation and inhibition are necessary for proper function in neural networks. However, in principle, balance could be achieved by many possible configurations of excitatory and inhibitory synaptic strengths and relative numbers of excitatory and inhibitory neurons. For instance, a given level of excitation could be balanced by either numerous inhibitory neurons with weak synapses or a few inhibitory neurons with strong synapses. Among the continuum of different but balanced configurations, why should any particular configuration be favored? Here, we address this question in the context of the entropy of network dynamics by studying an analytically tractable network of binary neurons. We find that entropy is highest at the boundary between excitation-dominant and inhibition-dominant regimes. Entropy also varies along this boundary with a trade-off between high and robust entropy: weak synapse strengths yield high network entropy which is fragile to parameter variations, while strong synapse strengths yield a lower, but more robust, network entropy. In the case where inhibitory and excitatory synapses are constrained to have similar strength, we find that a small, but non-zero fraction of inhibitory neurons, like that seen in mammalian cortex, results in robust and relatively high entropy.


Advanced fiber tracking in early acquired brain injury causing cerebral palsy.
Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury.


[Readiness for intersectoral cooperation to preserve health of megalopolis population].
For a better understanding of issues related to health-preserving activities for the benefit of city population, theoretical knowledge about the attitude and readiness of all interested parties for intersectoral cooperation is needed. The purpose of the study is to analyze readiness of the participants of health-preserving activities for intersectoral cooperation in Moscow. In 2023, a one-time, one-time study of intersectoral responsibility, commitment and awareness, as well as satisfaction with individual health care (original test cards) was conducted among different participants in the health care of the population of the city of Moscow (n = 1007). From among them, participants were identified -workers of «medical» infrastructure facilities of urban space, participants-workers of other facilities (sports, culture, industry, waste disposal, transport, food, trade, education and others) and the population as a participant in intersectoral health saving. The research based on the original integrated assessment methodology shows insufficient readiness for intersectoral cooperation to implement health-saving activities for the benefit of Moscow population. Immature intersectoral responsibility, literacy, motivation for teamwork noted among the participants of the unified health-preserving city space determines the lack of internal conviction that it is necessary to deal with both own health, and health of other members of the urban community. The data obtained can form basis for new methodological approaches to prioritize control measures to improve intersectoral cooperation between the participants of health-preserving activities in the metropolis.


The antitumor and antiangiogenic activity of vascular endothelial growth factor receptor inhibition is potentiated by ErbB1 blockade.
Receptor tyrosine kinases of the ErbB family play important roles in the control of tumor growth. Vascular endothelial growth factor (VEGF) stimulates endothelial cell proliferation, enhances vascular permeability, and plays an important role in tumor vascularization. We evaluated the effects of selective VEGF receptor (VEGFR; PTK787/ZK222584) and ErbB (PKI166 and ZD1839) inhibitors on tumor growth and angiogenesis and asked whether additional therapeutic benefit was conferred by combination treatment. The antitumor activity of each inhibitor alone or in combination was assessed in human cancer models in immunocompromised mice. ErbB receptor expression and activation of downstream signaling pathway was evaluated in both tumor and endothelial cells. Both ErbB inhibitors significantly enhanced the antitumor activity of PTK787/ZK222584. In vitro, ErbB1 inhibition blocked VEGF release by tumor cells and proliferation of both tumor and endothelial cells. In an in vitro angiogenesis assay, epidermal growth factor (EGF) stimulated the release of VEGF by smooth muscle cells resulting in increased angiogenesis, a response blocked by administration of PTK787/ZK222584. Under basal condition, both ZD1839 and PTK787/ZK222584 blocked sprouting, likely via inhibition of an autocrine ErbB1 loop and VEGFR signaling, respectively, in endothelial cells. In conditions of limiting VEGF, EGF plays an important role in endothelial cell proliferation, survival, and sprouting. We have shown that activation of ErbB1 triggers a plethora of effects, including direct effects on tumor and endothelial cells and indirect effects mediated via induction of VEGF release. Simultaneous blockade of ErbB1 and VEGFR pathways results in a cooperative antitumor effect, indicating that this combination may represent a valid therapeutic strategy.


[Short-term and end-results of combined treatment of patients with stage-II cervical cancer].
The short-term and end-results of combined therapy of 109 patients with stage II epidermal carcinoma of cervix uteri are presented. Preoperative intracavitary large-fraction contact gamma therapy from the AGAT-B installation was followed by Wertheim's or simple hysterectomy, lymphadenectomy and distant gamma therapy. Postoperative mortality rate was 0.8%; five-year survival--81.8 +/- 4.4%. Early- and late-onset postoperative complication frequency was largely determined by extent of surgery rather than preoperative intracavitary irradiation.


Trends in fall-related hospital admissions in older persons in the Netherlands.
Fall-related injuries, hospitalizations, and mortality among older persons represent a major public health problem. Owing to aging societies worldwide, a major impact on fall-related health care demand can be expected. We determined time trends in numbers and incidence of fall-related hospital admissions and in admission duration in older adults. Secular trend analysis of fall-related hospital admissions in the older Dutch population from 1981 through 2008, using the National Hospital Discharge Registry. All fall-related hospital admissions in persons 65 years or older were extracted from this database. Outcome measures were the numbers, and the age-specific and age-adjusted incidence rates (per 10,000 persons) of fall-related hospital admissions in each year of the study. From 1981 through 2008, fall-related hospital admissions increased by 137%. The annual age-adjusted incidence growth was 1.3% for men vs 0.7% for women (P < .001). The overall incidence rate increased from 87.7 to 141.2 per 10,000 persons (an increase of 61%). Age-specific incidence increased in all age groups, in both men and women, especially in the oldest old (>75 years). Although the incidence of fall-related hospital admissions increased, the total number of fall-related hospital days was reduced by 20% owing to a reduction in admission duration. In the Netherlands, numbers of fall-related hospital admissions among older persons increased drastically from 1981 through 2008. The increasing fall-related health care demand has been compensated for by a reduced admission duration. These figures demonstrate the need for implementation of falls prevention programs to control for increases of fall-related health care consumption.


Four orchid (Oncidium Gower Ramsey) AP1/AGL9-like MADS box genes show novel expression patterns and cause different effects on floral transition and formation in Arabidopsis thaliana.
Four AP1/AGL9 functional MADS box genes were characterized from the orchid (Oncidium Gower Ramsey). OMADS6 is a SEP3 ortholog, OMADS11 is a SEP1/2 ortholog, OMADS7 is an AGL6-like gene and OMADS10 is a putative paleoAP1 ortholog. The identity of these four genes was further supported by the presence of conserved motifs in the C-terminal regions of the proteins. OMADS6 showed an expression pattern different from SEP3 orthologs, with expression in the sepal, petal, lip and carpel, and was barely detected in the stamen. The expression pattern for OMADS11 was similar to OMADS6 and different from SEP1/2 orthologs since its expression was undetectable in the stamen. The expression pattern for OMADS7 was nearly identical to OMADS6. The similarities in the expression patterns of the SEP/AGL6-like genes OMADS6, 11 and 7 indicated that their transcriptional regulation is highly evolutionarily conserved in the orchid. Unlike OMADS6/11/7, OMADS10 was only expressed in vegetative leaves and in the lip and carpel of mature flowers, which distinguishes it from most genes in the SQUA subfamily. Ectopic expression of OMADS6, 11 or 7 caused extremely early flowering, whereas 35S::OMADS10 only caused moderately early flowering in transgenic Arabidopsis plants. In addition, flower organ conversions, such as carpelloid sepals and staminoid petals, were observed in 35S::OMADS6 and carpelloid sepals were produced in 35S::OMADS7, while flower organ conversions were not observed in 35S::OMADS11 or 35S::OMADS10 transgenic flowers. This result reveals possible functional diversification of the orchid AP1/AGL9 genes OMADS6, 11, 7 and 10 in regulating flower transition and formation.


The testing of dominants for heterozygoisty.
A simple method of estimating the frequency of heterozygotes among the dominants by test-making has been described; and then a maximum likelihood estimate is obtained by an iterative counting procedure. Eearly results of Haldane have been review and modified. Methods of estimating the gene frequencies, their ratio, and the inbreeding coefficient from test-mating results have also been given.


Control of spectral interference patterns in broad Rabi sidebands toward quasi-comb structures.
The pattern of spectral interference fringes in broad dynamic Rabi sidebands allows for a considerable degree of control by shaping the picosecond driving pulse. We demonstrate experimental evidence of such control and report an analytic and numerical investigation of possibilities to control the fringe pattern to produce a comb-like optical structure. The temporal phase and amplitude shaping of a picosecond driving pulse influence the spectrum envelope, fringe contrast, and fringe spacing variation in the sideband spectra. The sideband spectrum envelope depends on the sharpness of the driving pulse, that is, on the rate at which the temporal distance between the leading and trailing edges grows away from the pulse maximum. Increasing this parameter reduces the variation of the envelope amplitude across the sideband. The fringe contrast, defined by the maximum-to-minimum difference, depends strongly on the asymmetry of the driving pulse. The imbalance between the leading and trailing edges leads to a decrease of the contrast. The variation of interpeak distance within a sideband was controlled using the temporal shape of the driving pulse. In the particular case of a blue-shifted sideband emitted by excited oxygen atoms driven by a picosecond pulse of 800 nm carrier wavelength and ∼5×10¹⁰ W cm⁻² intensity, a Gaussian pulse shape results in an interpeak distance increasing almost five times over the interval from 1.60 to 1.66 eV, whereas a super-Gaussian shape leads to almost equidistant fringes producing a comb-like spectrum.


Coverage patterns of full-time employees under private retirement plans.
This article reports on the pension plan participation rate of full-time private wage and salary workers. Data are from a May 1979 Bureau of the Census survey on the pension plan coverage and vesting status of employed workers. The survey results indicate that about half of all full-time private sector workers were covered by a pension plan, with male employees having a 55-percent coverage rate compared with 40 percent for female employees. The survey also found significant variations in coverage by such factors as age, tenure, industry, size of establishment, occupation, income, and membership in a collective bargaining unit. The relationships between coverage and these variables are examined and comparisons are made between the May 1979 survey findings and the findings from a similar survey on coverage status conducted in April 1972.


Effects of in vitro exposure of alcohol on surface receptor expression of human platelets.
Platelet inhibition after moderate alcohol consumption in patients with ischaemic heart disease may contribute to reducing the risk for developing acute coronary syndromes. However, the mechanism by which ethanol affects platelets is not clarified. We sought to determine the in vitro effects of alcohol on the surface expression of human platelet receptors using whole blood flow cytometry. Blood samples from 10 healthy volunteers were incubated for 30 min with 25 and 50 mmol l(-1) of phosphate buffered saline diluted grain ethanol, concentrations often used in in vitro studies. The surface expression of platelet receptors was determined by flow cytometry after fixation with 2% paraformaldehyde using the following monoclonal antibodies: CD 41 (GP IIb/IIIa), CD 42b (GP Ib), CD 62p (P-selectin), CD 51/CD 61 (vitronectin receptor), CD 31 (PECAM-1), CD 107a (LAMP-1), CD 107b (LAMP-2), CD 63 (LIMP, LAMP-3) and CD 151 (PETA-3). Dose-dependent inhibition of GP IIb/IIIa, P-selectin, CD 63 and CD 107a receptor expression was observed in the ethanol-treated whole blood samples. This study for the first time establishes a direct effect of ethanol on selective major platelet receptors. Beneficial cardiovascular properties of moderate alcohol consumption may be explained by ethanol's antiplatelet action.


Outcome of high-intensity focused ultrasound and uterine artery embolization in the treatment and management of cesarean scar pregnancy: A retrospective study.
The aim of the study was to compare the efficacy and safety between high-intensity focused ultrasound (HIFU) treatment and uterine artery embolization (UAE) treatment; we retrospectively analyzed 152 cases with cesarean scar pregnancy (CSP). Based on our inclusion and exclusion criteria, 152 patients (average age, 31.8 ± 4.6 years old) with CSP were eligible for the HIFU group (85 patients) or the UAE group (77 patients). All patients in 2 groups received the treatment with suction curettage under hysteroscopy prior to HIFU or UAE treatment and followed up for 12 months. The assessment criteria of treatment efficacy included the success rate, intraoperative blood loss, duration of vaginal bleeding, normal menstrual function recovery time, time for β-human chorionic gonadotrophin (β-HCG) back to normal level, duration of hospital stays, and other adverse effects. Following up for 12 months, the HIFU group was of less intraoperative blood loss (76.38 ± 22.89 vs 114.42 ± 30.34 mL, P = .02), shorter duration of postoperative vaginal bleeding (11.28 ± 3.65 vs 15.77 ± 7.24 days, P = .01) and lower adverse effects rate comparing to the UAE group. However, the HIFU group have longer time for the β-HCG recovery to the normal level (35.28 ± 9.86 vs 29.91 ± 7.29, P = .03). Additionally, there were no significantly statistic differences between the 2 groups in baseline characteristics, success rate, and average time of gestational sac disappeared and menstrual recovery and hospital stay. Thus, we concluded that the method of both HIFU and UAE combined with suction curettage under hysteroscopy is safe and effective in the management of CSP. Meanwhile, HIFU is a better therapy option than UAE for those women who are seeking complete relieve of symptom to gain fertility.


Autopsy case of later-onset pontocerebellar hypoplasia type 1: pontine atrophy and pyramidal tract involvement.
The combination of pontocerebellar hypoplasia and anterior horn cell degeneration is classified as pontocerebellar hypoplasia type 1. Although most cases exhibit severe muscle weakness and hypotonia neonatally with short life spans, some cases exhibit a later onset with a longer life span and show cerebellar atrophy without pontine involvement. We present a child who exhibited neurological deterioration and progressive atrophy of the cerebellum and pons, with onset of symptoms at 20 months and death at 15 years of age. The pathological findings disclosed anterior horn cell degeneration and pyramidal tract involvement in addition to pontocerebellar atrophy, leading to the diagnosis of pontocerebellar hypoplasia type 1. The present case suggests that the degenerative pattern of later-onset pontocerebellar hypoplasia type 1 is similar to that of prenatal-onset cases. Further reports of later-onset cases with histopathological examination are required to elucidate the nosology and etiology of the disorder.


Timing of Early Cholecystectomy for Acute Calculous Cholecystitis: A Multicentric Prospective Observational Study.
The definition of Early Cholecystectomy (EC) is still debatable. This paper aims to find whether the timing of EC affects outcomes. The article reports a multicentric prospective observational study including patients with acute calculous cholecystitis (ACC) who had cholecystectomy within ten days from the onset of symptoms. Kruskall-Wallis test, Fisher's Exact test, and Spearman rank correlation were used for statistical analysis. The patients were divided into three groups depending on the timing of the operation: 0-3 days, 4-7 days, or 8-10 days from the onset of symptoms. 1117 patients were studied over a year. The time from the onset of symptoms to EC did not affect the post-operative complications and mortality, the conversion, and the reintervention rate. The time represented a significant risk factor for intraoperative complications (0-3 days, 2.8%; 4-7 days, 5.6%; 8-10 days, 7.9%; p = 0.01) and subtotal cholecystectomies (0-3 days, 2.7%; 4-7 days, 5.6%; 8-10 days, 10.9%; p < 0.001). ACC is an evolutive inflammatory process and, as the days go by, the local and systemic inflammation increases, making surgery more complex and difficult with a higher risk of intraoperative complications. We recommend performing EC for ACC as soon as possible, within the first ten days of the onset of symptoms.


Multiple myeloma.
Multiple myeloma is a malignancy of terminally differentiated plasma cells, and patients typically present with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine. The diagnosis of multiple myeloma is made when clear end-organ damage attributable to the plasma cell proliferative disorder or when findings that suggest a high likelihood of their development are present. Distinguishing symptomatic multiple myeloma that requires treatment from the precursor stages of monoclonal gammopathy of undetermined significance and smouldering multiple myeloma is important, as observation is the standard for those conditions. Much progress has been made over the past decade in the understanding of disease biology and individualized treatment approaches. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have joined the traditional armamentarium (corticosteroids, alkylating agents and anthracyclines) and, along with high-dose therapy and autologous haemopoietic stem cell transplantation, have led to deeper and durable clinical responses. Indeed, an increasing proportion of patients are achieving lasting remissions, raising the possibility of cure for this disease. Success will probably depend on using combinations of effective agents and treating patients in the early stages of disease, such as patients with smouldering multiple myeloma.


Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1
Hypoxia is an important microenvironmental factor significantly affecting tumor proliferation and progression. The importance of hypoxia is, however, not well known in oncogenesis of malignant melanoma. To evaluate the difference of hypoxic gene expression signatures in primary melanoma cell lines and metastatic melanoma cell lines and to find the expression changes of hypoxia-related genes in primary melanoma cell lines at experimental hypoxic conditions. Cell study. The mRNA expression levels of hypoxia-related genes in primary melanoma cell lines and metastatic melanoma cell lines and at experimental hypoxic conditions in primary melanoma cell lines were evaluated by using real-time polymerase chain reaction. Depending on the experimental data, we focused on two genes/proteins, the hypoxia-inducible factor-1 beta and the N-myc downstream regulated gene-1. The expression levels of the two proteins were investigated by immunohistochemistry methods in 16 primary and metastatic melanomas, 10 intradermal nevi, and a commercial tissue array comprised of 208 cores including 192 primary and metastatic malignant melanomas. The real-time polymerase chain reaction study showed that hypoxic gene expression signature was different between metastatic melanoma cell lines and primary melanoma cell lines. Hypoxic experimental conditions significantly affected the hypoxic gene expression signature. In immunohistochemical study, N-myc downstream regulated gene-1 expression was found to be lower in primary cutaneous melanoma compared to in intradermal nevi (p=0.001). In contrast, the cytoplasmic expression of hypoxia-inducible factor-1 beta was higher in primary cutaneous melanoma than in intradermal nevi (p=0.001). We also detected medium/strong significant correlations between the two proteins studied in the study groups. Hypoxic response consists of closely related proteins in more complex pathways. These findings will shed light on hypoxic processes in melanoma and unlock a Pandora's box for development of new therapeutic strategies.


Epidemiology of HIV among female sex workers, their clients, men who have sex with men and people who inject drugs in West and Central Africa.
The West and Central Africa (WCA) sub-region is the most populous region of sub-Saharan Africa (SSA), with an estimated population of 356 million living in 24 countries. The HIV epidemic in WCA appears to have distinct dynamics compared to the rest of SSA, being more concentrated among key populations such as female sex workers (FSWs), men who have sex with men (MSM), people who inject drugs (PWID) and clients of FSWs. To explore the epidemiology of HIV in the region, a systematic review of HIV literature among key populations in WCA was conducted since the onset of the HIV epidemic. We searched the databases PubMed, CINAHL and others for peer-reviewed articles regarding FSWs, MSM and PWID in 24 countries with no date restriction. Inclusion criteria were sensitive and focused on inclusion of any HIV prevalence data among key populations. HIV prevalence was pooled, and in each country key themes were extracted from the literature. The search generated 885 titles, 214 abstracts and 122 full articles, of which 76 met inclusion and exclusion criteria providing HIV prevalence data. There were 60 articles characterizing the burden of disease among FSWs, eight for their clients, one for both, six for MSM and one for PWID. The pooled HIV prevalence among FSWs was 34.9% (n=14,388/41,270), among their clients was 7.3% (n=435/5986), among MSM was 17.7% (n=656/3714) and among PWID from one study in Nigeria was 3.8% (n=56/1459). The disproportionate burden of HIV among FSWs appears to be consistent from the beginning of the HIV epidemic in WCA. While there are less data for other key populations such as clients of FSWs and MSM, the prevalence of HIV is higher among these men compared to other men in the region. There have been sporadic reports among PWID, but limited research on the burden of HIV among these men and women. These data affirm that the HIV epidemic in WCA appears to be far more concentrated among key populations than the epidemics in Southern and Eastern Africa. Evidence-based HIV prevention, treatment and care programmes in WCA should focus on engaging populations with the greatest burden of disease in the continuum of HIV care.


Platelet-induced differentiation of endothelial progenitor cells.
Endothelial progenitor cells (EPCs) have the potential to home at sites of vascular lesions and to contribute to revascularization. This homing is a highly concerted mechanism, which involves chemotaxis, adhesion, migration, and finally integration of the cells into the target tissue. Only recently has the platelet been identified as a central mediator of EPC homing. Adherent platelets were able to mediate chemotaxis and adhesion of EPCs, a process that involved P-selectin glycoprotein ligand 1 and very late antigen-4 (VLA-4). Recent studies suggest that platelet-derived stromal cell-derived factor-1 is also involved centrally in the recruitment of EPCs. Furthermore, platelets induce progenitor cell migration by platelet-derived growth factor AB. Recent in vivo data confirm the recruitment of EPCs to sites of vascular lesions after vessel denudation by activated platelets and fibrin. Moreover, when coincubated with platelets, EPCs differentiate to mature endothelial cells and have the potential to migrate and colonize a platelet thrombus. The described interaction of EPCs with platelets represents a novel mechanism of vascular remodeling and healing of endothelial lesions.


Current status of aortic aneurysm surgery in Hong Kong.
To determine the epidemiology and the status of open and endovascular aortic surgery for aortic aneurysm in Hong Kong. Three separate data sources were obtained: (1) the Hong Kong Hospital Authority discharge statistics for 1999 and 2000; (2) a survey on aortic aneurysms in public hospitals conducted by the working group of vascular surgery; and (3) the department of surgery, University of Hong Kong Medical Center aortic aneurysm database. The disease pattern, distribution as well as audit of operative mortality was determined. Aortic aneurysm ranked tenth as the leading causes of death in Hong Kong, and the incidence is increasing. Almost 800 new cases were diagnosed each year, with 10% presenting as rupture, but the death rate for ruptured aneurysms was 80%. About half of all operations on aortic aneurysms was performed for rupture, and a significant number of newly diagnosed patients were not receiving surgery. In experienced centers, the operative mortality for elective and ruptured aneurysm have improved to 2% and 38% in recent years. A growing interest and number of endovascular repair operations were performed which has led to some concerns on patient selection and follow up. Similar to a worldwide trend, aortic aneurysm in Hong Kong is diagnosed more frequently. With the relatively high mortality for ruptured aneurysms, effective diagnosis and elective surgery on patients with aortic aneurysms in experienced vascular centers remained the best treatment. Since a majority of aneurysms remained untreated, patient and physician education is of paramount importance.


Moral obligations of nurses and physicians in neonatal end-of-life care.
The aim of this study was to explore the obligations of nurses and physicians in providing end-of-life care. Nineteen nurses and 11 physicians from a single newborn intensive care unit participated. Using content analysis, an overarching obligation of creating the best possible experience for infants and parents was identified, within which two categories of obligations (decision making and the end of life itself) emerged. Obligations in decision making included talking to parents and timing withdrawal. End-of-life obligations included providing options, preparing parents, being with, advocating, creating peace and normalcy, and providing comfort. Nurses and physicians perceived obligations in both categories, although nurse obligations centered on the end of life while physician obligations focused on decision making. The findings demonstrate that, although the ultimate goal is shared by both disciplines, the paths to achieving that goal are often different. This has important implications for collaboration, communication, and improving the end of life.


Non-destructive analysis of polymers and polymer-based materials by compact NMR.
Low-field nuclear magnetic resonance (NMR) based on permanent magnet technologies is currently experiencing a considerable growth of popularity in studying polymer materials. Various bulk properties can be probed with compact NMR tabletop instruments by placing the sample of interest inside the magnet. Contrary to this, compact NMR sensors with open geometries give access to depth-dependent properties of polymer samples and objects of different sizes and shapes truly non-destructively by performing measurements in the inhomogeneous stray-field outside the magnet system. Some of the sensors are also portable being thus well suited for onsite measurements. The gain of both bulk and depth-dependent microscopic properties are important for establishing improved structure-property relationships needed for the rational design of new polymer formulations. Selected recent applications will be presented to illustrate this potential of compact NMR.


Conditioned Media Derived from Human Adipose Tissue Mesenchymal Stromal Cells Improves Primary Hepatocyte Maintenance.
Recent advances in cell therapy have encouraged researchers to provide an alternative for treatment and restoration of damaged liver through using hepatocytes. However, these cells quickly lose their functional capabilities in vitro. Here, we aim to use the secretome of mesenchymal stromal cells (MSCs) to improve in vitro maintenance conditions for hepatocytes. In this experimental study, following serum deprivation, human adipose tissue-derived MSCs (hAT-MSCs) were cultured for 24 hours under normoxic (N) and hypoxic (H) conditions. Their conditioned media (CM) were subsequently collected and labeled as N-CM (normoxia) and H-CM (hypoxia). Murine hepatocytes were isolated by perfusion of mouse liver with collagenase, and were cultured in hepatocyte basal (William's) medium supplemented with 4% N-CM or H-CM. Untreated William's and hepatocyte-specific media (HepZYM) were used as controls. Finally, we evaluated the survival and proliferation rates, as well as functionality and hepatocyte-specific gene expressions of the cells. We observed a significant increase in viability of hepatocytes in the presence of N-CM and H-CM compared to HepZYM on day 5, as indicated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium) assay. Indocyanine green (ICG) uptake of hepatocytes in the H-CM and HepZYM groups on days 3 and 5 also suggested that H-CM maintained the hepatocytes at about the same level as the hepatocyte-specific medium. The HepZYM group had significantly higher levels of albumin (Alb) and urea secretion compared to the other groups (P<0.0001). However, there were no significant differences in cytochrome activity and cytochrome gene expression profiles among these groups. Finally, we found a slightly, but not significantly higher concentration of vascular endothelial growth factor (VEGF) in the H-CM group compared to the N-CM group (P=0.063). The enrichment of William's basal medium with 4% hAT-MSC-H-CM improved some physiologic parameters in a primary hepatocyte culture.


Stat3 and Socs3 expression patterns during murine placenta development.
Signal transducers and activators of transcription 3 (Stat3) has been identified as an important signal transducer in the invasive phenotype of the trophoblasts cells in in vitro studies. However, the in situ distribution and patterns of expression of this molecule in trophoblast cells during the development of the placenta are still under-elucidated. Mice uteri of gestational ages between 7 and 14 days of pregnancy (dop) were fixed in methacarn and processed with immunoperoxidase techniques for detection of Stat3 and its phosphorylation at serine (p-ser727) residues, as well as the suppressor of cytokine signaling 3 (Socs3) expression. Stat3 was observed at 7 through 9 dop in both the antimesometrial and mesometrial deciduas, while continued immunoreactivity between 10 and 13 dop was seen only in the mesometrial decidua. In the placenta, Stat3 was detected in the cytotrophoblast cells of labyrinth and giant trophoblast cells between 10 and 14 dop. Immunoreactivity for Stat3 was also seen in trophoblast cells surrounding the maternal blood vessels. On days 10 and 11 of pregnancy, p-ser727 was detectable in the mesometrial decidua and in giant trophoblasts, while during 12-14 dop in the spongiotrophoblast region. In addition, Socs3 was immunodetected in maternal and placental tissues, principally in the giant trophoblast cells during the whole period of the study. The present in situ study shows the distribution of Stat3, its serine activation and Socs3 in different maternal and fetal compartments during murine placental development, thus further supporting the idea that they play a role during physiological placentation in mice.


The sustained virologic response of nonresponder hepatitis C virus patients with retreatment.
Pegylated interferon and ribavirin combination therapy remain the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the large number of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegylated interferon based therapy is not much reported. The aim of this retrospective study was to focus on the efficacy of pegylated interferon alpha and ribavirin in retreated chronic hepatitis C patients. All patients were treated with pegylated interferon alpha either 2a (180 μg) or 2b (1.5μg/kg) subcutaneously once weekly for a 48-week period, plus ribavirin 1000-1200 mg/day. The patient who had a negative HCV RNA at the end of 48 weeks were followed up for 24 weeks, and the patients who relapsed in the post-treatment follow-up period of 24 weeks were treated again with pegylated interferon alpha; but if the first treatment was administered with pegylated interferon alpha 2a, the second was administered with pegylated interferon alpha 2b and if pegylated interferon alpha 2b, then the second with pegylated interferon alpha 2a. We evaluated the outcome of our patients with chronic HCV who achieved a viral response at the end of the therapy, but did not achieve sustained virologic response; 54% (38/70) of patients did achieve sustained virologic response, while 46% (32/70) of patients did not (eight patients did not achieve early virologic response, five patients were nonresponders at 24th week of the treatment, the remaining 19 patient had negative HCV at the end of the therapy but did not achieve sustained virologic response). We began from 19 patients to 8 patients, who had negative HCV RNA at the end of the treatment, but did not achieve sustained virologic response, interferon plus ribavirin therapy again. If the patient had interferon alpha 2a, we gave in the second tour alpha 2b; and if alpha 2b, then alpha 2a. The early virologic response of these nine patients were found to be 63% (5/8). These 5 patients who had rapid virologic response and early virologic response at the second therapy achieved sustained virologic response this time. These findings suggest that the standard 48-week treatment is insufficient and that an extended course of treatment may be necessary. Relapse is a poorly understood clinical outcome in the treatment of chronic HCV patients. Retreatment can give a chance to some patients specially who have early virologic response and negative HCV RNA at the end of the first therapy.


SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation.
The synapse contains densely localized and interacting proteins that enable it to adapt to changing inputs. We describe a Ca2+-sensitive protein complex involved in the regulation of AMPA receptor synaptic plasticity. The complex is comprised of MUPPI, a multi-PDZ domain-containing protein; SynGAP, a synaptic GTPase-activating protein; and the Ca2+/calmodulin-dependent kinase CaMKII. In synapses of hippocampal neurons, SynGAP and CaMKII are brought together by direct physical interaction with the PDZ domains of MUPP1, and in this complex, SynGAP is phosphorylated. Ca2+CaM binding to CaMKII dissociates it from the MUPP1 complex, and Ca2+ entering via the NMDAR drives the dephosphorylation of SynGAP. Specific peptide-induced SynGAP dissociation from the MUPP1-CaMKII complex results in SynGAP dephosphorylation accompanied by P38 MAPK inactivation, potentiation of synaptic AMPA responses, and an increase in the number of AMPAR-containing clusters in hippocampal neuron synapses. siRNA-mediated SynGAP knockdown confirmed these results. These data implicate SynGAP in NMDAR- and CaMKII-dependent regulation of AMPAR trafficking.


Comparative responses of normal and malignant mouse mammary cells to modulation of surface properties.
We previously demonstrated that epithelial cells growing in primary cultures derived from normal and neoplastic mouse mammary tissues are indistinguishable on the basis of morphology, surface topography, agglutinability by concanavalin A, or of number, cytoplasmic location, or organization of microtubules and actin-containing microfilaments. In the present study, the modulation and interrelationships of these features were investigated using the drugs colchicine and cytochalasin B and the enzymes trypsin, collagenase, and hyaluronidase. Untreated cells of both types were only weakly agglutinable by concanavalin A. Pretreatment of the cells with colchicine, cytochalasin B, or hyaluronidase increased cytoagglutination by the lectin dramatically, whereas neither trypsin nor collagenase significantly altered reactivity of the cells. Binding studies utilizing fluorescein-tagged concanavalin A indicated that the enhanced agglutinability did not correlate with any particular distribution of lectin receptors on the cells. At the doses used, colchicine and cytocholasin B induced disruption of microtubules and microfilament networks, respectively, but no effects on either type of cytoskeletal element were observed after hyaluronidase, trypsin, or collagenase. The increased agglutinability was not associated with any specific surface conformation since scanning electron microscopy revealed that untreated cells and cells exposed to colchicine, hyaluronidase, and collagenase were flat and possessed variable numbers of small microvilli. In contrast, following incubation with cytochalasin B or trypsin, the cells underwent retraction and rounding, and developed complex surface structures such as blebs, ruffles, and filopodia. Thus, no single factor appeared responsible for determining the agglutinable or nonagglutinable state of the mammary cells. Morover, no differences were detected in the surface responses of the normal and malignant cells under any of the conditions used.


A Unique Presentation of Spontaneous Compartment Syndrome due to Acquired Hemophilia A and Associated Malignancy: Case Report and Literature Review.
Hemophilia is a bleeding diathesis that is most commonly congenital and causes a tendency for significant bleeding during procedures and often manifests as hemarthrosis. However, more rarely, hemophilia can be acquired. Our paper focuses on acquired hemophilia A (AHA), which is caused by the development of an autoantibody (an inhibitor) to factor VIII. A 61-year-old man with a past medical history of type II diabetes mellitus, hypertension, hyperlipidemia, hypothyroidism, and obstructive sleep apnea presented to the emergency department with severe right lower extremity pain and swelling of 2-day duration. He was found to have compartment syndrome and underwent emergent fasciotomy of his right leg. After surgery he still had significant bleeding, despite transfusions and administration of fresh frozen plasma (FFP) by the surgical team. He was later diagnosed with AHA, but was not adequately responsive to factor VII, factor VIII, steroids nor rituxan and unfortunately had his right lower extremity amputated. He had a prolonged hospital course, which included Streptococcus bovis bacteremia and a code stroke for which head computed tomography (CT) showed probable metastasis. It was acknowledged he had probable metastatic colon cancer, which was not confirmed as the patient transitioned to hospice care. Rather than hemarthrosis, patients with AHA tend to have bleeding in soft tissue or the gastrointestinal tract. AHA can have underlying causes, such as malignancy. AHA associated with malignancy is associated with poorer outcomes and tends to improve with treatment of the underlying malignancy. Therefore, it is important to quickly identify these patients and screen them for underlying etiologies.


Is the differential response of riparian plant performance to extreme drought and inundation events related to differences in intraspecific trait variation?
Previous research on the impacts of extreme events has focussed mainly on plant performance. Selective effects of extremes suggests that appropriate traits to withstand extremes, or the ability to modulate traits, may increase the competitive advantage and survival of a species. We tested how multiple extreme events affect riparian plant performance, and whether this relates to intraspecific trait variation. We hypothesised that species tolerant to extreme environmental conditions would show highest intraspecific trait variation. We conducted a greenhouse experiment where 25 wet to drought-tolerant species (grasses and herbs) were subjected to single and double 10 day drought and inundation events, and all combinations thereof. We measured plant performance and multiple traits. Performance was severely reduced, with clear synergistic, non-additive effects of extreme events. Adverse effects were stronger for wet-tolerant than drought-tolerant species and for grasses than herbs. Three traits were identified as predictors of species responses to extremes. Despite known trait variation for these species, no variation occurred under these conditions, indicating that responses are difficult to explain from impacts of mean environmental conditions. Our results indicate that multiple events may lead to quantitatively different impacts than single events, which hampers predicting plant response to a future climate.


Aqueous Sol-Gel Synthesis and Shaping of Covalent Organic Frameworks.
The intrinsic fragility and insoluble nature of covalent organic frameworks (COFs) have strongly impeded their processability for practical applications. Herein, an aqueous-based sol-gel synthetic strategy is reported for the synthesis and shaping of COFs with task-specific applications that satisfy the principles of green chemistry for gram-scale production of crystalline materials. Our successful approach involves three pivotal aspects: the "prodrug mimic" design of water-soluble monomers, the utilization of hydrolyzable bonds, and the manipulation of reaction kinetics. The generality of the method is demonstrated by the successful preparation of representative high-surface area two-dimensional (2D) COFs with several commonly used amines. By virtue of this strategy, a COF colloidal dispersion is achieved and can be formulated into processable fluids, structured films, and COF monoliths. Remarkably, the obtained lightweight (∼0.020 g cm-3) and robust aerogels displayed outstanding adsorption capacity (exceeding 57 times its own weight) toward a variety of organic solvents and exhibited superior thermal insulating properties compared to the widely used sponge and cotton. This work demonstrates a versatile strategy for the synthesis and shaping of processable COF materials in water that will contribute to the development of COF monoliths for advanced applications.


Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry.
The chemokine receptor CXCR4 (also designated fusin and LESTR) is a cofactor for fusion and entry of T cell-tropic strains of HIV-1. CXCR4 is expressed in various cell types; however, the mechanisms involved in the regulation of its expression remain unknown. To delineate these mechanisms, approximately 1.2 kb of DNA from the immediate 5' upstream region of CXCR4 gene was cloned, sequenced, and characterized. Transient expression assays using CXCR4 promoter/luciferase gene reporter constructs revealed that stimulation with PMA plus ionomycin up-regulates the CXCR4 promoter activity in the A3.01 CD4+ T cell line and PBL and that a DNA fragment from -93 to +59 relative to the transcription start site contributes markedly to the basal and induced activity. This fragment contains a consensus TATA box, two potential GC boxes, and a potential nuclear respiratory factor (NRF)-1 binding site, which were confirmed by gel mobility shift assays and footprinting analysis. Mutagenesis studies revealed that a NRF-1 site is especially important for the basal and induced activity of the CXCR4 promoter. Transient expression assays further revealed that stimulation of PBL with either IL-2 or Abs to CD3 and CD28 enhances the CXCR4 promoter activity. Inducibility of the CXCR4 promoter activity by T cell stimulation suggests that overexpression of CXCR4 may be one of the mechanisms whereby immune activation and/or perturbation of the cytokine network up-regulate HIV expression and replication and thus contribute to the progression of HIV disease.


Mode of adsorption and orientation of an extracellular matrix protein affect its cell-adhesion-promoting activity.
Cell adhesion to extracellular matrix contributes to the organization of tissues and modulates cell behavior. In conventional cell adhesion assays, plastic wells are coated with matrix proteins and assayed for their adhesion-promoting activity. We show here that factors such as sample composition, coating buffers, and manufacturers' plastic treatment markedly affect cell adhesion to the extracellular matrix protein laminin-5 (Ln-5). These factors were shown to affect adsorption efficiency as determined by measuring total adsorbed protein with a polyclonal anti-Ln-5 antiserum. They also influence the availability of the epitope for an adhesion-blocking anti-Ln-5 monoclonal antibody, suggesting that coating conditions affect the orientation of Ln-5. Generally, cell adhesion correlates more strongly with the availability of the epitope for the adhesion-blocking antibody than with total adsorbed Ln-5. Our data further indicate that cell adhesion to other matrix proteins may be influenced by similar factors. Adding Ln-5 samples to plastic wells that had been precoated with non-adhesion-blocking anti-Ln-5 antibodies made cell adhesion independent of factors such as sample composition, coating buffers, and source of plastic. Thus, the control of adsorption efficiency and orientation of extracellular matrix proteins is essential for creation of reliable and reproducible conditions in cell adhesion assays.


Juvenile onset of Crohn's disease: a risk factor for reduced lumbar bone mass in premenopausal women.
Crohn's disease (CD) is associated with reduced bone mass. Bone fragility is the result of both growth-related and age-related factors; thus, exposure to a chronic illness, such as CD, during skeletal growth may compromise peak bone mass. Our aim was to assess whether the onset of CD during skeletal growth had an impact on bone mass in adulthood in premenopausal women. Adult premenopausal CD patients who had a whole body, lumbar and hip bone densitometric evaluation were selected. Information regarding age, gender, weight, duration of CD, age at diagnosis, use of glucocorticoids and disease activity during the year before densitometric assessment and laboratory parameters were collected. Data from 57 patients (28+/-10 years) were analyzed. Age at diagnosis was independently associated with lumbar bone mineral content (BMC). Lean mass was independently associated with total, lumbar and hip BMC. Patients with a history of onset of CD before 16 years of age (n=20) were 11.6+/-2 years old at diagnosis. They had low lumbar and hip Z scores. They had significantly lower BMC, bone mineral density and Z scores in lumbar area and both hips than those diagnosed after the age of 16. They also had significantly lower lumbar area than those diagnosed after the age of 16. The onset of CD during skeletal growth is a risk factor for reduced lumbar and hip bone mass in adulthood in premenopausal women.


Alzheimer's disease phenotype based upon the carrier status of the apolipoprotein E ɛ4 allele.
The apolipoprotein E ɛ4 allele (APOE4) is universally acknowledged as the most potent genetic risk factor for Alzheimer's disease (AD). APOE4 promotes the initiation and progression of AD. Although the underlying mechanisms are unclearly understood, differences in lipid-bound affinity among the three APOE isoforms may constitute the basis. The protein APOE4 isoform has a high affinity with triglycerides and cholesterol. A distinction in lipid metabolism extensively impacts neurons, microglia, and astrocytes. APOE4 carriers exhibit phenotypic differences from non-carriers in clinical examinations and respond differently to multiple treatments. Therefore, we hypothesized that phenotypic classification of AD patients according to the status of APOE4 carrier will help specify research and promote its use in diagnosing and treating AD. Recent reviews have mainly evaluated the differences between APOE4 allele carriers and non-carriers from gene to protein structures, clinical features, neuroimaging, pathology, the neural network, and the response to various treatments, and have provided the feasibility of phenotypic group classification based on APOE4 carrier status. This review will facilitate the application of APOE phenomics concept in clinical practice and promote further medical research on AD.


An in vitro ethnopharmacological study on Prangos ferulacea: a wound healing agent.
Introduction: Traditionally Prangos ferulacea root is being used as an effective wound healing agent especially for pus-filled wounds both in human and stocks in the western north of Iran. Regarding the subject we decided to study P. ferulacea roots essential oil (PFE) for its antimicrobial and wound healing activities. Methods: The in vitro wound healing activity of PFE was evaluated in the mouse fibroblast cell line L929 using MTT assay of cell viability and cytotoxicity indices. Scratch assay as an in vitro model of wound healing assay was also conducted in this study. Moreover, the type I collagen content was used as an indicator of progress in wound healing process using Sircol collagen assay. Besides, PFE was subjected to GC/MS to identify the chemical constituents, and antimicrobical property was also evaluated against S. aureus, S. epidermidis, E. coli, P. aeruginosa,S. paratyphi and C. albicans using agar dilution method. Results: GC/MS analysis showed that the monoterpene hydrocarbones dominated in PFE, amounting to a total percentage of 95.1% with the major constituents: β-Phellandrene (32.1%), m-Tolualdehyde (26.2%), and δ-3-carene (25.8%). PFE inhibited the growth of S. aureus and P. aeruginusa with the MIC value of 20 µg/mL. In addition, at the second day of treatment, PFE at concentrations of 4 and 16 µg/mL significantly (P<0.001) enhanced the migration rate of L929 cells by 87.05±2.4 and 63.5±0.08 %, respectively. Moreover, the collagen production by L929 cells was increased greatly (P<0.001). Conclusion: It is proposed that the excellent antimicrobial activity along with the significant increase of migration rate and collagen production by fibroblast cells might be associated with the high content and synergistic effect of the monoterpens, corroborating the traditional usage of this plant as a wound healing agent.


General Oriented Formation of Carbon Nanotubes from Metal-Organic Frameworks.
Carbon nanotubes (CNTs) are of great interest for many potential applications because of their extraordinary electronic, mechanical and structural properties. However, issues of chaotic staking, high cost and high energy dissipation in the synthesis of CNTs remain to be resolved. Here we develop a facile, general and high-yield strategy for the oriented formation of CNTs from metal-organic frameworks (MOFs) through a low-temperature (as low as 430 °C) pyrolysis process. The selected MOF crystals act as a single precursor for both nanocatalysts and carbon sources. The key to the formation of CNTs is obtaining small nanocatalysts with high activity during the pyrolysis process. This method is successfully extended to obtain various oriented CNT-assembled architectures by modulating the corresponding MOFs, which further homogeneously incorporate heteroatoms into the CNTs. Specifically, nitrogen-doped CNT-assembled hollow structures exhibit excellent performances in both energy conversion and storage. On the basis of experimental analyses and density functional theory simulations, these superior performances are attributed to synergistic effects between ideal components and multilevel structures. Additionally, the appropriate graphitic N doping and the confined metal nanoparticles in CNTs both increase the densities of states near the Fermi level and reduce the work function, hence efficiently enhancing its oxygen reduction activity. The viable synthetic strategy and proposed mechanism will stimulate the rapid development of CNTs in frontier fields.


Fine needle aspiration at endoscopic ultrasound with a novel side-port needle: a pilot experience.
Diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) varies relating to the equipment used and the site targeted. Multiple needle passes are usually required to obtain a diagnosis. A new needle incorporating a side port carries a theoretical advantage regarding acquisition of cytological material. To demonstrate the safety and efficacy of the Olympus side-port needle across a spectrum of indications for EUS FNA, a prospective collection of 16 consecutive cases was undertaken at a tertiary gastroenterology referral centre in metropolitan Sydney, Australia. EUS FNA was performed with the novel Olympus side-port needle. EUS FNA was otherwise performed in the conventional fashion. The number of needle passes required for diagnosis, number of passes total, diagnosis on cytology and conclusive diagnosis were recorded. Diagnostic material was obtained at the first pass in 56.2% of patients. Mean number of passes required to reach a diagnosis was 2.1. Diagnosis was made on first pass in 62.5% of solid non-lymph-node lesions. The diagnosis was reached in 94%. The novel side-port needle is safe and effective; further evaluation with a prospective randomized trial is warranted.


Enhancing Multiexcitonic Emission in Metal-Halide Perovskites by Quantum Confinement.
Semiconductor metal halide perovskite nanocrystals have been under intense investigation for their promise in a variety of optoelectronic applications, which arises from their remarkable properties of defect tolerance and efficient light emission. Recently, quantum dot versions of perovskite nanocrystals have been available, enabling investigation of how quantum size effects control optical function and performance in these quantum dots (QD), past their well-known covalent II-VI analogues. We perform time-resolved photoluminescence (t-PL) experiments on CsPbBr3 perovskite nanocrystals spanning in diameter from 5.8 nm strongly confined quantum dots to 18 nm weakly confined quantum dots. Experiments are performed with sufficient time resolution of 3 ps to observe the interaction energies and recombination kinetics from excitons to multiexcitons. Comparing the same sized QD reveals that perovskite QD have a larger radiative rate constant for emission from X than CdSe QD due to a larger oscillator strength. The multiexciton (MX) regime reveals that perovskite QD emit brightly and with more focused bandwidth than equivalent sized CdSe QD enabling more spectrally pure brightness. The MX kinetics reveals that the perovskite QD maintain efficient radiative decay, effectively competing with Auger recombination. These experiments reveal that the strongly confined QD of perovskites can be efficient multiexcitonic emitters, such as in high brightness light emitting diodes, especially in the blue.


Musculoskeletal implications of preterm infant positioning in the NICU.
Alignment and shaping of the musculoskeletal system occur during each body position that infants experience while in neonatal intensive care. Neonatal nurses and physical therapists can play a major role in designing, modeling, and teaching positioning strategies that promote skeletal integrity, postural control, and sensorimotor organization. Musculoskeletal maturation processes and adverse musculoskeletal consequences are reviewed with an emphasis on clinical implications for neonatal care, discharge teaching, and follow-up. Recommendations are offered for neonatal positioning procedures to prevent extremity malalignment, skull deformities, and gross motor delay.


Effect of reference genome selection on the performance of computational methods for genome-wide protein-protein interaction prediction.
Recent progress in computational methods for predicting physical and functional protein-protein interactions has provided new insights into the complexity of biological processes. Most of these methods assume that functionally interacting proteins are likely to have a shared evolutionary history. This history can be traced out for the protein pairs of a query genome by correlating different evolutionary aspects of their homologs in multiple genomes known as the reference genomes. These methods include phylogenetic profiling, gene neighborhood and co-occurrence of the orthologous protein coding genes in the same cluster or operon. These are collectively known as genomic context methods. On the other hand a method called mirrortree is based on the similarity of phylogenetic trees between two interacting proteins. Comprehensive performance analyses of these methods have been frequently reported in literature. However, very few studies provide insight into the effect of reference genome selection on detection of meaningful protein interactions. We analyzed the performance of four methods and their variants to understand the effect of reference genome selection on prediction efficacy. We used six sets of reference genomes, sampled in accordance with phylogenetic diversity and relationship between organisms from 565 bacteria. We used Escherichia coli as a model organism and the gold standard datasets of interacting proteins reported in DIP, EcoCyc and KEGG databases to compare the performance of the prediction methods. Higher performance for predicting protein-protein interactions was achievable even with 100-150 bacterial genomes out of 565 genomes. Inclusion of archaeal genomes in the reference genome set improves performance. We find that in order to obtain a good performance, it is better to sample few genomes of related genera of prokaryotes from the large number of available genomes. Moreover, such a sampling allows for selecting 50-100 genomes for comparable accuracy of predictions when computational resources are limited.


Intensities of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis.
Clinical trials of the intensity of renal replacement therapy (RRT) for people with acute kidney injury (AKI) have produced conflicting results. A systematic review and meta-analysis was undertaken to assess the effect of different intensities of RRT on all-cause mortality and renal recovery in AKI patients. MEDLINE, EMBASE, and the Cochrane Library database were systematically searched for trials published between 1950 and 2009. Inclusion criteria were completed, prospective, adult-population, randomized controlled studies. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Summary estimates of RR were obtained using a random effects model. Heterogeneity, metaregression, publication bias, and subgroup analyses were conducted. Eight trials were identified that provided data on 3841 patients and 1808 deaths. More intense RRT (35 to 48 ml/kg per h or equivalent) had no overall effect on the risk of death (RR 0.89, 95% CI 0.76 to 1.04, P = 0.143) or recovery of renal function (RR 1.12, 95% CI 0.95 to 1.31, P = 0.181) compared with less-intensive regimens (20 to 25 ml/kg per h or equivalent). Significant heterogeneity was identified with contributing factors including publication year (P = 0.004) and Jadad score (P = 0.048). Within the intensity ranges studied, higher intensity RRT does not reduce mortality rates or improve renal recovery among patients with AKI. The results do not negate the importance of RRT intensity in the treatment of AKI patients but rather reinforce the need to better understand the effects of treatment modalities, doses, and timing in this varied, high-risk population.


Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosine Kinase Inhibitor Treatment.
The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (EGFR) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate EGFR mutational status as determined by each method with the clinical response to EGFR tyrosine kinase inhibitors (TKIs). Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the EGFR gene (exons 18-21). Mutations in the EGFR gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing. A total of 44 mutations (72%) were found by at least one of the three methods, and the concordances among the results were relatively high (82-85%; kappa coefficient, 0.713 to 0.736). There were 15 discordant cases (25%) among the three different methods. All three EGFR mutation tests had good concordance rates (over 82%) for FFPE samples. These results suggest that if the DNA quality and enrichment of tumor cells are assured, then DS, PNA clamping, and pyrosequencing are appropriate methods for the detection of EGFR mutations.


Tropical wood resistance to the West Indian drywood termite Cryptotermes brevis: If termites can't chew….
The importance and impact of invasive species are usually considered based on their economic implications, particularly the direct damage that they cause. The West Indian drywood termite Cryptotermes brevis (Walker) is an example and is a concern in structural lumber, furniture, and other wood products. Despite its importance, its tropical wood preferences and the wood physical characteristics contributing to resistance have not been investigated to date. Here, we developed wood testing units to allow the X-ray recording of termite colonization and then subsequently tested tropical wood resistance to the termite through free-choice and no-choice bioassays using these wood testing units. The relevance of wood density and hardness as determinants of such resistance was also tested, as was termite mandible wear. The wood testing units used allowed the assessment of the termite infestation and wood area loss, enabling subsequent choice bioassays to be performed. While pine (Pinus sp.), jequitiba (Cariniana sp.) and angelim (Hymenolobium petraenum) exhibited the heaviest losses and highest infestations; cumaru (Dipteryx odorata), guariuba (Clarisia racemosa), and purpleheart (Peltogyne sp.) showed the lowest losses and infestations; courbaril (Hymenaea courbaril), eucalyptus (Eucalyptus sp.), and tatajuba (Bagassa guianensis) exhibited intermediary results. Wood hardness and in particular wood density were key determinants of wood resistance to the termites, which exhibited lower infestations associated with greater mandible wear when infesting harder high-density wood. © 2017 Society of Chemical Industry.


Prostate cancer cells modulate the differentiation of THP-1 cells in response to etoposide and TLR agonists treatments.
The aim of this study was to determine the polarization of macrophages in the tumor microenvironment, as well as the effect of soluble factors secreted from these polarized macrophages on etoposide-induced cancer cell apoptosis. We investigated the effect of soluble factors secreted from the supernatant of PC3 cells treated with TLR4 and TLR8 agonists, and etoposide on macrophage polarization at the protein level through flow cytometry and enzyme-linked immunosorbent assay. We further explored the cell cycle distribution and phagocytic activity of THP-1 cells by flow cytometry. To imitate the relationship between cancer cells and tumor-associated macrophages (TAMs), we cocultured macrophages with etoposide-treated PC3 cells. After the incubation, the apoptosis in cancer cells was assessed through FACS analysis and by annexin V and PI staining. Our results demonstrate that protein expression of M1 and M2 markers confirmed the upregulation of M1 markers upon etoposide treatment, and mixed M1/M2 phenotype upon treatment with TLR agonists-treated PC3 supernatant. In coculture methods, our results demonstrate that the apoptosis of etoposide-treated cancer cells increases in the presence of M0 macrophages and THP-1 cells incubated with the supernatant of TLR4 agonists-treated PC3 cells. These results indicate clear protective effects of M0 macrophages and THP-1 cells incubated with the supernatant of PC3 cells treated with TLR4 agonists (THP-1 + SUP + TLR4a) on etoposide-induced cancer cell apoptosis.


Transjugular intrahepatic portosystemic shunt (TIPS) for severe veno-occlusive disease of the liver following bone marrow transplantation.
Severe veno-occlusive disease (VOD) of the liver is a leading cause of mortality after bone marrow transplantation (BMT). Vascular and parenchymal injuries account for acute portal hypertension and liver failure is frequently present. We describe the results of transjugular intrahepatic portosystemic shunt (TIPS) for the management of VOD after BMT. TIPS was performed in 10 patients with histologically proven severe VOD. Portal hypertension was controlled by TIPS in all patients (mean hepatic venous pressure gradient before, 20 +/- 11 vs 6 +/- 5 mm Hg after TIPS, P < 0.01) without technical complications. Five patients with rapidly worsening VOD died within 10 days of TIPS without any improvement. The five remaining patients with less advanced disease showed improvement in various clinical and biological parameters. Four patients subsequently died. The lone survivor continues to do well with resolution of VOD 6 months after TIPS. TIPS can be performed safely and controls portal hypertension in VOD after BMT. Arguments from the present series and from eight previously reported cases favour earlier application of TIPS to obtain improved overall survival. Bone Marrow Transplantation (2000) 25, 987-992.


Arabidopsis Co-expression Tool (ACT): web server tools for microarray-based gene expression analysis.
The Arabidopsis Co-expression Tool, ACT, ranks the genes across a large microarray dataset according to how closely their expression follows the expression of a query gene. A database stores pre-calculated co-expression results for approximately 21,800 genes based on data from over 300 arrays. These results can be corroborated by calculation of co-expression results for user-defined sub-sets of arrays or experiments from the NASC/GARNet array dataset. Clique Finder (CF) identifies groups of genes which are consistently co-expressed with each other across a user-defined co-expression list. The parameters can be altered easily to adjust cluster size and the output examined for optimal inclusion of genes with known biological roles. Alternatively, a Scatter Plot tool displays the correlation coefficients for all genes against two user-selected queries on a scatter plot which can be useful for visual identification of clusters of genes with similar r-values. User-input groups of genes can be highlighted on the scatter plots. Inclusion of genes with known biology in sets of genes identified using CF and Scatter Plot tools allows inferences to be made about the roles of the other genes in the set and both tools can therefore be used to generate short lists of genes for further characterization. ACT is freely available at www.Arabidopsis.leeds.ac.uk/ACT.


Mouse skin tumor initiation-promotion and complete carcinogenesis bioassays: mechanisms and biological activities of emission samples.
Extracts of soots obtained from various sources were applied to the skin of mice in an effort to identify carcinogens in these mixtures and to link these materials to the etiology of human cancer. Samples of coal chimney soot, coke oven materials, industrial carbon black, oil shale soot, and gasoline vehicle exhaust materials have been examined by this method. The studies reported here have been constructed to compare the carcinogenic and tumorigenic potency of extracts from various particulate emissions: coke ovens, diesel and gasoline vehicles and a roofing tar pot. Automobile emission samples were obtained by collecting the diluted and cooled exhaust on Teflon-coated glass fiber filters. Coke oven and roofing tar samples were particulate emission samples collected by impaction and filtration. The organic components associated with each of the particles were extracted with dichloromethane and dermally applied to SENCAR mice. All agents were applied as tumor initiators by using a five-dose protocol. Selected extracts were also applied as complete carcinogens and as tumor promotors. Statistical analyses of the resulting tumor data were performed by using nonlinear Poisson and probit models. The results from these experiments provide a suitable data base for comparative potency estimation of complex mixtures.


Adenosine receptor-mediated control of in vitro release of pain-related neuropeptides from the rat spinal cord.
Although it is well established that adenosine exerts antinociceptive effects at the spinal level in various species including human, the mechanisms responsible for such effects are still a matter of debate. We presently investigated whether adenosine-induced antinociception might possibly be related to an inhibitory influence of this neuromodulator on the spinal release of neuropeptides implicated in the transfer and/or control of nociceptive signals. For this purpose, the K(+)-evoked overflow of substance P-, calcitonin gene-related peptide (CGRP)- and cholecystokinin-like materials was measured from slices of the dorsal half of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid supplemented with increasing concentrations of various adenosine receptor ligands. The data showed that stimulation of adenosine A(1) and (possibly) A(3) receptors, but not A(2A) receptors, exerted an inhibitory influence on the spinal release of CGRP-like material. In contrast, none of the adenosine A(1), A(2A) and A(3) receptor agonists tested within relevant ranges of concentrations significantly affected the release of substance P- and cholecystokinin-like materials. These results support the idea that adenosine-induced antinociception at the spinal level might possibly be caused, at least partly, by the stimulation of inhibitory adenosine A(1) receptors located presynaptically on primary afferent fibres containing CGRP but not substance P.


[Study of specific immunoglobulins (total, IgG, IgM, IgA, IgE) in indirect immunofluorescence and ELISA in 40 patients with trichinosis followed over a 9-month period].
The evolution of the classes of specific immunoglobulins (IgG, IgM, IgA, IgE) of 40 cases of human trichinosis was followed over a nine month period by means of an indirect immunofluorescence test (IF) and ELISA. Specific IgG and IgM appear between 4 and 6 weeks after infection and were still demonstrable after 9 months (respectively in 87.5% and 38.5% of the patients with IF, in 85% and 87.5% with ELISA). Specific IgA were mainly seen on the 2nd month and specific IgE were detected in 37.5% of the patients on the 4th month. In this outbreak, specific antibodies seem to appear later than in a second outbreak observed a few weeks later.


Common ethical dilemmas of family caregivers of palliative patients in Indonesia.
Family caregivers, especially in Asian countries, have a profound role in caring for a sick family member. However, there are wide variations between the Asian and western world in terms of culture and facilities. Therefore, the problems and needs of family caregivers between those two regions may also be distinct, and it is important to explore and elaborate based on our empirical evidence. In Indonesia, motives and values in caregiving and religion become the wheel-power of the family caregivers in providing care. This affects action and consequences for caregivers. This paper attempts to elaborate on common ethical dilemmas that usually face by family caregivers in Indonesia. Unfortunately, family caregivers typically are not prepared to make those challenging decisions. Therefore, we recommend not only that family caregivers need to be involved in the caring process, but also their issues and ethical dilemmas should be assessed and addressed by health care professionals, especially nurses, who have the most frequent contact with patient and family caregiver.


Lesions of the vulva.
Lesions of the vulva are common and are often associated with unnecessary and sometimes harmful delays in diagnosis and definitive therapy. Simple office biopsies, performed prior to treatment, permit histologic classification of the lesion and provide a basis for therapeutic recommendations.


Relation of Length of Stay to Unplanned Readmissions for Patients Who Undergo Elective Percutaneous Coronary Intervention.
The cost of inpatient percutaneous coronary interventions (PCI) procedure is related to length of stay (LOS). It is unknown, how LOS may be associated with readmission rates and costs of index PCI and readmissions in elective PCI. This study aims to evaluate rates, predictors, causes, and costs associated with 30-day unplanned readmissions according to lLOS in patients, who underwent elective PCI. We included patients in the Nationwide Readmission Database, who were admitted to hospital from 2010 to 2014, who underwent uncomplicated elective PCI. LOS was defined as 0, 1, 2, and ≥3 days. A total of 324,345 patients were included in the analysis and the 30-day unplanned readmission was 4.75%, 4.67%, 6.44%, and 9.42% in the LOS groups 0, 1, 2, and ≥3 days, respectively. Prolonged LOS was associated with increased average total 30-day cost (index and readmission cost, 0 days $15,063, 1 day $14,693, 2 days $18,136, and ≥3 days $24,336). Compared with 0 days, the odds of readmissions were greater for 2 days (odds ratio 1.41, 95% confidence interval 1.07 to 1.87, p = 0.016) and ≥3 days (odds ratio 1.70, 95% confidence interval 1.28 to 2.24, p <0.001). Comorbidities were strong predictors of LOS and noncardiac causes, account for more than half of all causes for readmission. Longer LOS was associated with reduced incidence of readmissions for noncardiac causes such as noncardiac chest pain, but a greater rate of readmissions for heart failure. In conclusion, shorter length of stay was associated with reduced healthcare costs in elective PCI.


Estimation of hepatic distributional volumes using non-labeled reference markers.
Hepatic distributional volumes were investigated in the in situ perfused rat liver. Perfusion experiments were conducted using Krebs bicarbonate buffer delivered via the portal vein in single-pass mode at a total flow rate of 15 mL/min. A bolus dose of normal erythrocytes (RBC, vascular marker) and Evans blue (EB, extracellular marker) respectively was administered in the presence and absence of protein. At the end of the experiment, liver total water content was determined by desiccation and freeze-drying methods. Similar moment analysis results and superimposable effluent curves were obtained in the presence (RBC, mean transit time [MTT]: 7.31 +/- 0.45 s and volume of distribution [V]: 0.17 +/- 0.01 mL/g; EB, MTT: 10.9 +/- 0.62 s and V: 0.25 +/- 0.02 mL/g) and in the absence (RBC, MTT: 7.55 +/- 0.84 s and V: 0.18 +/- 0.02 mL/g; EB, MTT: 9.24 +/- 0.77 s and V: 0.20 +/- 0.02 mL/g) of protein, which indicates that the hepatic distribution of RBC and EB within the liver is not influenced by protein. Furthermore, the almost identical results obtained with the desiccation and freeze-drying methods clearly suggest that the freeze-drying method can be used as an alternative to desiccation for the estimation of liver water content.


Effect of liposomal celecoxib on proliferation of colon cancer cell and inhibition of DMBA-induced tumor in rat model.
Celecoxib, a selective cyclooxygenase-2 inhibitor, has shown potential anticancerous activity against majority of solid tumors especially on patients with colon cancer. However, associations of serious side effects limit the usage of celecoxib in colon cancer treatment. To address this issue and provide an alternative strategy to increase the efficacy of celecoxib, liposomal formulation of celecoxib was prepared and characterized. Anticancer activity of liposomal celecoxib on colon cancer cell HCT 15 was evaluated in vitro. Furthermore, tumor inhibition efficiency by liposomal celecoxib was studied on 7,12-dimethyl benz(a)anthracene (DMBA)-induced tumor in rat model. In order to elucidate the antioxidant activity of celecoxib-loaded liposomes, antioxidant superoxide dismutase (SOD) generation and lipid peroxide (LPx) formation in both liver and kidney tissues were examined. Characterization of the formed unilamellar liposomes revealed the formation of homogeneous suspension of neutral (empty) or anionic (celecoxib-loaded) liposomes with a well-defined spherical shape which have a mean size of 103.5 nm (empty liposome) and 169 nm (liposomal celecoxib). High-performance liquid chromatography (HPLC) analysis and hemolytic assay demonstrated 46% of celecoxib entrapment efficiency and significantly low hemolysis, respectively. Liposomal celecoxib exhibited dose-dependent cytotoxicity and apoptotic activity against HCT 15 cells which are comparable to free celecoxib. In vivo study demonstrated inhibition of tumor growth. Biochemical analysis of the liposomal celecoxib-treated group significantly inhibited the LPx formation (oxygen-free radicals) and increased the activity of SOD. Our results present the potential of inhibiting colon cancer in vitro and DMBA-induced tumor in rat model in vivo by liposomal celecoxib.