Health impact assessment for air pollution in the presence of regional variation in effect sizes: The implications of using different meta-analytic approaches.
The estimated health effects of air pollution vary between studies, and this variation is caused by factors associated with the study location, hereafter termed regional heterogeneity. This heterogeneity raises a methodological question as to which studies should be used to estimate risks in a specific region in a health impact assessment. Should one use all studies across the world, or only those in the region of interest? The current study provides novel insight into this question in two ways. Firstly, it presents an up-to-date analysis examining the magnitude of continent-level regional heterogeneity in the short-term health effects of air pollution, using a database of studies collected by Orellano et al. (2020). Secondly, it provides in-depth simulation analyses examining whether existing meta-analyses are likely to be underpowered to identify statistically significant regional heterogeneity, as well as evaluating which meta-analytic technique is best for estimating region-specific estimates. The techniques considered include global and continent-specific (sub-group) random effects meta-analysis and meta-regression, with omnibus statistical tests used to quantify regional heterogeneity. We find statistically significant regional heterogeneity for 4 of the 8 pollutant-outcome pairs considered, comprising NO2, O3 and PM2.5 with all-cause mortality, and PM2.5 with cardiovascular mortality. From the simulation analysis statistically significant regional heterogeneity is more likely to be identified as the number of studies increases (between 3 and 30 in each region were considered), between region heterogeneity increases and within region heterogeneity decreases. Finally, while a sub-group analysis using Cochran's Q test has a higher median power (0.71) than a test based on the moderators' coefficients from meta-regression (0.59) to identify regional heterogeneity, it also has an inflated type-1 error leading to more false positives (median errors of 0.15 compared to 0.09).


Adrenomedullin causes coronary vasodilation in humans: effects of inhibition of nitric oxide synthesis.
Experimental studies have shown that adrenomedullin (AM) causes vasodilation, in part, mediated by endothelium-derived nitric oxide (NO). However, it remains to be clarified how NO is involved in AM-induced coronary vasoreactivity in humans. We examined whether NO contributes to the vasodilatory effects of adrenomedullin on human coronary arteries. In 10 patients with angiographically normal coronary arteries, adrenomedullin (low dose: 1 ng/kg/min; high dose: 10 ng/kg/min) was infused into the left coronary ostium before and after an infusion of N-monomethyl-L-arginine (L-NMMA, 40 micromol/min for 5 min), an NO synthase inhibitor. Coronary diameter and coronary blood flow (CBF) were evaluated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to adrenomedullin were expressed as percent changes from baseline values. Adrenomedullin at a high dose dilated coronary arteries (3.7+/-0.5%, P<0.001). Adrenomedullin increased the coronary blood flow at both doses (low: 55.7+/-13.9%, P<0.01; high: 48.8+/-9.8%, P<0.001). After the infusion of L-NMMA, adrenomedullin-induced coronary vasodilation and increase in coronary blood flow were attenuated. These findings suggest that adrenomedullin dilates human coronary arteries through an increase in NO production, at least in part.


Release of calcitonin gene-related peptide like-immunoreactivity induced by electrical field stimulation from rat spinal afferents is mediated by conotoxin-sensitive calcium channels.
Electrical field stimulation (EFS, 10 V, 50 mA/cm2, 5-50 Hz, 1 ms pulse duration, 10 s train every 20 s for 5 min) produced a rapid and reproducible outflow of calcitonin gene-related peptide like-immunoreactivity (CGRP-LI) from superfused slices from the dorsal half of the rat spinal cord which is abolished by tetrodotoxin (TTX, 0.3 microM), in vitro capsaicin desensitization (10 microM for 30 min) and in Ca-free medium. The response was unaffected by ruthenium red (10 microM), indomethacin (10 microM) and nifedipine (1 microM) while it was abolished by omega-conotoxin (omega-CTX, 0.1 microM) and, in a naloxone-sensitive manner, by morphine (3 microM). Since CGRP release from capsaicin-sensitive afferents evoked by EFS in rat peripheral tissues is conotoxin-resistant, these findings provide direct evidence for a qualitative difference between central and peripheral endings of capsaicin-sensitive primary afferents in the mechanisms regulating transmitter release in the same species.


Metabolite profiling of plant tissues by liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry.
Plants accumulate an overwhelming variety of secondary metabolites that play important roles in defense and interaction of the plant with its environment. To investigate the dynamics of plant secondary metabolism, large-scale untargeted metabolite profiling (metabolomics) is mandatory. Here, we describe a detailed protocol for untargeted metabolite profiling in which methanol extracts of jasmonate-treated plant tissues are analyzed by reversed-phase liquid chromatography coupled to negative-ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (MS). By means of dedicated integration and alignment software, the relative abundance of thousands of mass peaks, corresponding to hundreds of compounds, is calculated, and mass peaks of which the area is significantly changed by jasmonate treatment are identified. Subsequently, the metabolites corresponding to the significantly changed peaks are tentatively annotated using the accurate mass prediction of the Fourier transform-MS and the generated MS/MS data. Via this method, compounds of medium polarity, such as glucosinolates, alkaloids, phenylpropanoids, flavonoids, polyamines, and saponins, can be analyzed.


Magnetic susceptibility measurement by NMR: 2. The magnetic susceptibility of NMR solvents and their chemical shifts.
Most routine 1H NMR spectroscopy references the chemical shift of TMS to zero. However, its chemical shift varies with solvent and environmental conditions. Chemical shifts and magnetic susceptibilities of TMS and several NMR solvents are accurately measured over a range of temperatures. Methods for improving the measurements of chemical shifts and magnetic susceptibilities are developed and demonstrated. This makes it possible to compare chemical shifts of compounds between solvents, improving the accuracy of solvent effect measurements. The effects of polarizability and aromaticity on the chemical shift of TMS are shown. The molar magnetic susceptibilities of the deuterated solvents are similar to those of the regular protiated solvents.


Primary care engagement in health system change: a scoping review of common barriers and effective strategies.
The complexity of health systems necessitates coordination between a multitude of stakeholders to enact meaningful change. Primary care physicians are a crucial partner to engage, as their investment and participation are critical to the success of any system-level initiative. The aim of this scoping review is to identify common barriers and effective strategies when engaging primary care physicians in designing and implementing health system change. A scoping review was performed. A literature search was performed in March 2020 using five databases. 668 unique articles were identified and underwent a title and abstract review. 23 articles met criteria for full text review and 10 met final inclusion criteria. A backward citation analysis identified two articles. 12 articles underwent data extraction and thematic analysis. Several barriers to engagement were identified including a lack of trust between primary care physicians and decision-makers, strong professional physician identity, clinically irrelevant and complex proposals, and a lack of capacity and supports. Described strategies to overcome these barriers included building trust and relationships, contextual engagement strategies, working with physician leadership, enabling open and intentional communication channels, designing clinically relevant and straightforward initiatives, and considering financial incentives. Barriers to primary care engagement should be addressed with contextually designed strategies and a focus on relationship building, collaborative efforts, and implementing relevant and feasible initiatives. Further research should explore how to best develop relationships with primary care, working with collective voices of primary care physicians, and to better understanding the impact of financial incentives on engagement.


New observations on the karyotype of the Djungarian hamster, Phodopus sungorus.
In this paper, the C-banding pattern of the karyotype of Phodopus sungorus is presented and polymorphism is taken into consideration.


[Mutation analysis for a pedigree affected with keratitis-ichthyosis-deafness syndrome].
To identify mutation of GJB2 gene and provide genetic counseling for a family affected with keratitis-ichthyosis-deafness (KID) syndrome. Genomic DNA was extracted from peripheral blood samples with a standard phenol-chloroform method. PCR and Sanger sequencing were used to analyze potential mutation in the proband. Suspected mutation was verified with a PCR-high-resolution melting (PCR-HRM) method. T-clone sequencing was applied to determine the parental origin of the mutation. A heterozygous mutation, c.148G>A (p.Asp50Asn), which is located in the exon 1 of the GJB2 gene, was found in the proband. The results was confirmed by HRM analysis. Cloning sequencing suggested that the mutation was derived from the father's germline. The hot-spot mutation c.148G>A (p.Asp50Asn) in the GJB2 gene probably underlies the KID syndrome in this Chinese family. A PCR-HRM method has been established to rapidly detect common mutations associated with this disease.


Simulation of vertical dispersion and pollution impact of artificial light at night in urban environment.
The use of artificial light at night (ALAN) enables social and commercial activities for urban living. However, the excessive usage of lighting causes nuisance and waste of energy. Light is provided to illuminate target areas on the street level where activities take place, yet light can also cause trespass to residents at the floors above. While regulations are beginning to cover light design, simulation tools for the outdoor environment have also become more popular for assessing the design condition. Simulation tools allow visualisation of the impact of the selected light sources on those who are affected. However, this cause-and-effect relationship is not easy to determine in the complex urban environment. The current work offers a simple methodology that takes site survey results and correlates them with the simulation model to determine lighting impact on the investigated area in 3D. Four buildings in two mixed commercial and residential streets in Hong Kong were studied. Data collection from each residential building requires lengthy work and permission from each household. Therefore, a valid lighting simulation model could help determine the light pollution impact in the area. A light model using DIALux is developed and calibrated by correlating the simulated data with the actual measured data. The correlation value R2 achieved ranged from 0.95 to 0.99, verifying the accuracy of this model and matched from 340 lx to 46 lx for the lower to higher floors of one building and 10 lx to 4 lx for floors of another building. This model can also be applied to human health research, by providing light-level data on residential windows in an area or determining the environmental impact of a development project.


Serotonin: a novel bone mass controller may have implications for alveolar bone.
As recent studies highlight the importance of alternative mechanisms in the control of bone turnover, new therapeutic approaches can be envisaged for bone diseases and periodontitis-induced bone loss. Recently, it has been shown that Fluoxetine and Venlafaxine, serotonin re-uptake inhibitors commonly used as antidepressants, can positively or negatively affect bone loss in rat models of induced periodontitis. Serotonin is a neurotransmitter that can be found within specific nuclei of the central nervous system, but can also be produced in the gut and be sequestered inside platelet granules. Although it is known to be mainly involved in the control of mood, sleep, and intestinal physiology, recent evidence has pointed at far reaching effects on bone metabolism, as a mediator of the effects of Lrp5, a membrane receptor commonly associated with Wnt canonical signaling and osteoblast differentiation. Deletion of Lrp5 in mice lead to increased expression of Tryptophan Hydroxylase 1, the gut isoform of the enzyme required for serotonin synthesis, thus increasing serum levels of serotonin. Serotonin, in turn, could bind to HTR1B receptors on osteoblasts and stop their proliferation by activating PKA and CREB.Although different groups have reported controversial results on the existence of an Lrp5-serotonin axis and the action of serotonin in bone remodeling, there is convincing evidence that serotonin modulators such as SSRIs can affect bone turnover. Consequently, the effects of this drug family on periodontal physiology should be thoroughly explored.


Baseline findings from the Anal Cancer Examination (ACE) study: screening using digital ano-rectal examination in HIV-positive men who have sex with men.
Cytological screening for anal cancer precursors is not always possible. We investigated digital ano-rectal examination (DARE) as a means of early anal cancer detection in HIV-positive men who have sex with men (MSM). We recruited 327 HIV-positive MSM aged 35 and over from clinics with HIV physicians in Melbourne, Australia, to receive an annual DARE. We analyzed baseline data from patient questionnaires regarding general, anal and sexual health, adverse effects from the anal examination, cancer worry, and quality of life. The majority of men (82%, 95% CI:78-87) felt relaxed during the DARE, 1% (95% CI:0-3) complained of pain, and 1% (95% CI:0-4) reported bleeding after the examination. Nearly all men (99%, 95% CI:96-100) were willing to continue with an annual DARE. Quality of life was unaffected with utility scores of 0.76 before examination vs. 0.77 two weeks after examination, (p = 0.41). An anal abnormality was detected in 86 men (27%, 95% CI:22-31), with one anal cancer identified. The specialist referral rate following DARE was 5% (95% CI:3-8). Recruitment rates were significantly associated with the clinic setting (sexual health centre 78%, general practice 13%, hospital 14%, p = 0.002) and specialty (sexual health physician 67%, general practitioner 20%, infectious disease physician 14%, p = 0.031). Annual DARE to detect anal cancer in HIV-positive MSM was acceptable for patients, with minimal side effects. Strategies to increase HIV physician's patient recruitment would be needed if DARE were to be implemented in anal cancer screening.


Evaluation of Tissue Doppler Tei index for global left ventricular function in mice after myocardial infarction: comparison with Pulsed Doppler Tei index.
The Pulsed Doppler Tei index is a parameter to evaluate combined systolic and diastolic function in humans. However, one major limitation is that the parameters of Pulsed Doppler Tei index cannot be measured within one cardiac cycle. Therefore, accuracy of the Pulsed Doppler Tei index may be affected by anesthesia induced heart rate variation in mice echocardiography. Tissue Doppler Imaging (TDI) enables us to measure both relaxation and contraction velocities simultaneously. Thus, the aim of our study was to validate TDI and Pulsed Doppler Tei index and their reproducibility in mice after experimental anterior myocardial infarction (MI). Pulsed Doppler Tei index and TDI Tei index were assessed before and 4 weeks after MI. Both parameters increased significantly after MI (Pulsed Doppler: 0.4+/-0.04 to 0.7+/-0.03; P<0.001; TDI: 0.2+/-0.03 to 0.5+/-0.04; P<0.0001). In addition, TDI Tei index showed a good correlation with ejection fraction and fractional shortening, and was indicated by better reproducibility than Pulsed Doppler Tei index. Tissue Doppler Tei index is appropriate to characterize global left ventricular function in mice after MI.


Synthesis and binding of stable bisubstrate ligands for phosphoglycerate kinase.
Stable bisubstrate ligands of phosphoglycerate kinase (PGK) have been synthesized with AMP or ADP conjugated to hydrolytically-stable, symmetrical analogues of 1,3-bisphosphoglycerate and their binding to yeast PGK evaluated. Their Kds decrease with net negative charge, with a penta-anionic analogue 7 showing highest affinity-in accordance with its approximation to the transition state for the reaction catalysed by PGK.


Field transplantation of seagrass (Posidonia oceanica) seedlings: Effects of invasive algae and nutrients.
Seedlings are a key life stage in seagrasses, providing genetic diversity and being a useful tool for restoration. We examined the influence of increased sediment nutrients and the presence of the invasive macroalga Caulerpa cylindracea on the success of in situ transplanting Posidonia oceanica seedlings in a six-month experiment. Our results indicate that one-year old seedlings successfully survive in the field and their survival and growth are positively affected by the presence of C. cylindracea. Furthermore, nutrient addition in the sediment had positive effects on both C. cylindracea (increasing its cover) and seedlings (increasing leaf development), and the increased C. cylindracea cover did not result in detrimental effects on seedlings. Therefore, biological invasions and nutrient addition do not reinforce each other in the short term to negatively impact transplanted seedlings, which highlights facilitative interactions between invasive algae and native seagrass and provides useful information for successful strategies of seagrass restoration.


Proportions in papilla, crestal papilla, and proximal contact area in maxillary anterior teeth: A cross-sectional study.
The regeneration and maintenance of the interdental papilla presents a great challenge to the clinician while smile designing. Proportions of papilla height (PH), crestal PH (CPH), and proximal contact areas (PCA) are more stable parameters. The purpose of the present study was to evaluate and correlate the papilla proportion (PP), crestal PP (CPP), and PCA proportion (PCAP) in periodontally healthy males and females. One hundred and twenty patients in an age group of 20-40 years, divided equally based on gender, were assessed for PH, CPH, and PCA of maxillary anterior teeth. The findings were recorded on study models and radiographs to obtain the PP, CPP, and PCAP on the mesial and distal aspects of respective tooth. The overall comparison of parameters was performed using paired t-test. The mean mesial PP (43.51% ± 3.10% for male and 45.23% ± 2.23% for female) and CPP values (48.36% ± 3.35% for male and 51.16% ± 2.96% for female) were found to be greater of each tooth type and were more pronounced for females. The PCAP values were greater for distal aspects (36.76% ± 7.00% for males and 33.30% ± 6.93% for females). The results of the study indicate that PP and CPP are more pronounced in females, while the PCAP is more marked in males. Furthermore, it appears that the PP and CPP are inversely related to the PCAP in both males and females.


Morphologic characteristics of nonsustained ventricular tachycardia detected during Holter monitoring associated with atherosclerotic coronary artery disease.
Nonsustained ventricular tachycardia (VT) is an important prognostic indicator of outcome in patients with organic heart disease. The morphologic features of nonsustained VT were examined by obtaining a derived 12-lead electrocardiogram (ECGD) from a 24-hour Holter recording in 22 patients with nonsustained VT associated with coronary artery disease. A total of 60 nonsustained VT episodes were recorded. Of these, 20 were uniform and 40 were multiform. The mean rate of uniform episodes was faster (140 +/- 32 vs 124 +/- 16 beats/min; p < 0.01) and the duration longer (5.3 +/- 2.0 vs 4.0 +/- 1.0 beats; p < 0.02) than the multiform episodes. The majority (87%) of multiform episodes had only 2 different QRS configurations on the ECGD. Four distinct patterns of QRS configurations were seen within individual multiform nonsustained VT runs: type I--the initial QRS complex has 1 morphology and all subsequent complexes have another configuration; type II--the initial and terminal QRS complex has similar configuration; type III--the first 2 QRS complexes have similar configuration and all subsequent complexes have another morphology; and type IV--the QRS complexes have alternating morphologic features. These 4 different patterns may be related to the mechanism of nonsustained VT (reentry versus automaticity). Patients with multiple episodes of nonsustained VT frequently had differing patterns and morphologic features between episodes. Further studies are needed to evaluate the clinical importance of these findings.


Managing the column equilibration time in hydrophilic interaction chromatography.
For a wide variety of hydrophilic interaction chromatography stationary phases, a repeatable partial equilibration was demonstrated in gradient elution after purging with as little as 12 column volumes of mobile phase. Relative standard deviations of retention time of on average ~0.15% could be obtained after 1 or 2 conditioning (blank) runs. The equilibration period must be kept strictly constant, otherwise selectivity changes occur, but this is not problematic on modern instruments. Partial equilibration was largely independent of stationary phase or gradient slope. Alternatively, full column equilibration is favoured for stationary phases that do not trap extensive water layers, and for materials with a wider pore size that have a lower surface area. Temperatures somewhat above ambient also shorten the equilibration time. Some stationary phases under optimum conditions can achieve full column equilibration using purging with ~12 column volumes, which is useful for rapid set-up of isocratic separations or for conventional gradient analysis.


Comparison of the efficacy of an oral calcitriol pulse or intravenous 22-oxacalcitriol therapies in chronic hemodialysis patients.
1,25-dihydroxy-22-ovavitamin D(3) (22-oxacalcitriol, OCT) was recently introduced commercially as an analogue of 1,25 (OH)(2) vitamin D(3), but one which has less pronounced calcemic activity. To examine the efficacy and tolerability of OCT, 46 hemodialysis patients with secondary hyperparathyroidism were randomly assigned to receive either intravenous OCT or oral calcitriol pulse therapies. The patients were monitored for serum calcium, phosphate, intact parathyroid hormone (PTH), and bone alkaline phosphatase (BAP) for 24 weeks. The efficacy of intravenous OCT was also examined in 24 additional patients who were refractory to oral calcitriol pulse therapy. In the randomized trial, intact PTH levels were significantly suppressed within 4 weeks after the initiation of each therapy, and this effect was well maintained thereafter in both treatment groups. While intact PTH was significantly lower at 4 weeks in the calcitriol pulse group than in the OCT group (P = 0.02), no statistical differences were observed during later treatment periods. BAP was reduced equally by each treatment. At 4 weeks (P = 0.02) and thereafter (P = 0.06), serum calcium was higher among calcitriol-treated patients than among those who received OCT treatment. Eight of 24 patients who were refractory to oral calcitriol pulse therapy responded to intravenous OCT. The patients who responded tended to have lower serum intact PTH and phosphorus levels and smaller parathyroid glands at the start of OCT treatment than nonresponders. OCT is as effective as oral calcitriol pulse therapy in suppressing intact PTH and BAP in chronic hemodialysis patients. It was confirmed that OCT exhibits less calcemic activity than calcitriol. Moreover, under certain conditions, switching to OCT may help in the treatment of hyperparathyroidism, which is refractory to conventional oral calcitriol pulse therapy.


IL-4-producing CD8(+) T cells may be an immunological hallmark of chronic GVHD.
Chronic graft-versus-host disease (cGVHD) occurs in approximately 60-80% of those who survive over 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the pathophysiology of cGVHD is poorly understood. To gain more insight into the immunological mechanism of cGVHD, we examine cytokine production of peripheral blood T cells from 19 patients in the chronic phase of allo-HSCT. The percentage of IFN-gamma-producing CD8(+) T cells among CD8(+) T cells was significantly higher in patients with or without cGVHD than in normal control subjects (P<0.001). On the other hand, the percentage of IL-4-producing CD8(+) T cells among CD8(+) T cells was significantly higher in patients with cGVHD (mean 3.3%; range 1.3-8.2%) than in patients without cGVHD (mean 1.2%; range 0.8-1.7%) and normal control subjects (mean 1.1%; range 0.1-1.6%) (both P<0.001). By contrast, the percentage of IL-4-producing CD4(+) T cells was not different among patients with and without cGVHD and normal controls. These findings suggest that IL-4-producing CD8(+) T cells may be an immunological marker of cGVHD.


[Problems and Suggested Solutions of Advanced Practice Nursing in Disaster Events].
Nurses constitute the largest component of the healthcare workforce and are often the mainstay of disaster management. The leadership, decision-making, and coordination skills that advanced practice nurses possess are of critical value for disaster precision nursing. However, previous studies mostly focused on disaster specialist nurses and emergency or critical care nurses and little attention was directed at advanced practice nurses. In this paper, we reviewed published research and summarized the current status of advanced practice nursing in disaster events. We identified through our analysis the problems in advanced practice nursing, including poor disaster education, a lack of clearly-defined rescue roles, and difficulty in the implementation of practice reform. We suggested solutions, including developing a whole-process and multi-form disaster curriculum, refining rescue tasks from a team perspective, and establishing a system of quality and safety supervision for advanced practice nursing, aiming to provide new ideas for the development of disaster nursing in China.


Mortality-based definition of renal hyperfiltration in middle-aged men: a 35-year cohort from Finland.
While the impact of low glomerular filtration rate (eGFR) on various outcomes has been extensively studied, the other adverse occurrence, renal hyperfiltration (RHF), remains understudied, poorly defined, and, therefore, its impact on mortality unestablished. Using a population-based subcohort from the Kuopio Ischaemic Disease Risk Factor Study restricted to non-diabetic Finnish men aged 54 or 55 years, we followed up n = 1179 study participants for up to 35 years. We evaluated the hazard of all-cause mortality associated to RHF at different cutoff points defining eGFR. Based on models' accuracy we suggested an optimal eGFR cutoff point for the definition of RHF. We divided the RHF category to three subgroups and evaluated them in terms of baseline characteristics and mortality hazard. The eGFR value of 97 mL/min/1.73 m2 corresponded to the models with the highest accuracy. Overall RHF associated with an increased risk of mortality (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.21 to 1.67). Moderate RHF associated with a decreased HR of mortality when compared to mild (0.64; 95% CI 0.46 to 0.9) or to extreme RHF (0.61; 95% CI 0.43 to 0.85), suggesting a rather U-shaped relationship between RHF's eGFR values and mortality hazard. The burden of increased eGFR within what is still considered normal eGFR category was highly underestimated. RHF's eGFR values had a U-shaped association with the risk of overall mortality. A more uniform consensual definition of RHF is needed, as higher to normal eGFR values that are not without consequences.


Phosphorylation of the N-terminal region of Caenorhabditis elegans paramyosin.
Paramyosin from Caenorhabditis elegans was examined for post-translational modification by phosphorylation. Paramyosin purified from populations of mixed-age animals contained 0.7 to 2.0 moles of phosphate per mole of paramyosin. Paramyosin was also phosphorylated in vitro by an endogenous kinase in the particulate fraction. Analysis of the in vitro phosphorylated paramyosin in comparison with the DNA sequence of the unc-15 paramyosin gene of C. elegans shows that serine residues in the non-alpha-helical N-terminal region are the targets of the kinase. The N-terminal region of paramyosin has significant similarity to the non-helical C-terminal region of the two body wall myosin heavy chains of C. elegans. All three regions contain three copies of a Ser-*-Ser-*-Ala motif, the most likely target for phosphorylation in paramyosin, suggesting that these regions may be modified by the same kinase.


DOACs and Atherosclerotic Cardiovascular Disease Management: Can We Find the Right Balance Between Efficacy and Harm.
The balance between efficacy and harm remains a challenge in the adoption of non-vitamin K antagonist direct oral anticoagulants (DOACs) for secondary atherosclerotic disease prevention. We provide a comprehensive review of the evidence for and against the addition of DOACs to the current management of atherosclerotic cardiovascular disease, including stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD), and percutaneous coronary interventions (PCI). The DOAC class exerts pleiotropic effects on atherosclerotic progression through coagulation and inflammatory pathways. In ACS, low-dose DOAC provides no added efficacy in the setting of dual antiplatelet therapy; however, full-dose DOAC increases bleeding. Efficacy-safety profile favor use of low-dose rivaroxaban in select stable CAD or PAD patients. Atrial fibrillation patients undergoing PCI resort to dual therapy with DOAC due to prohibitory bleeding with triple anti-thrombotic therapy. Evidence favors DOAC use in CAD and PAD; however, careful individual considerations must be undertaken.


Basal Cell Carcinoma After High Dose Rate Brachytherapy: Medium-term Dermoscopic Evaluation of Cancer's Response.
Basal cell carcinoma of the facial region remains a challenge for contemporary oncology due to the presence of aesthetic regions and critical organs. Surgery is not always the optimal solution, and high dose rate (HDR) brachytherapy has emerged as an organ-sparing treatment method whose effectiveness has been proven by a growing number of publications. Dermoscopy is a diagnostic tool that bridges clinical and pathological examination of skin lesions. It is routinely used for diagnosis, monitoring of treatment, and post-treatment evaluation; however, the literature lacks data concerning changes in dermoscopic patterns of skin cancers during and after irradiation. Our team conducted a prospective non-randomized trial of 39 patients with high-risk basal cell carcinomas (BCCs), mostly localized within the high-risk zone (H-zone) of the facial region, and who qualified for HDR brachytherapy. HDR contact brachytherapy with custom-made surface molds was introduced, delivering a dose of 45 Gy in 9 fractions prescribed to the tumor. Every patient was observed clinically and dermoscopically at three observational points: before treatment, at the end of treatment (3rd week), and 24 weeks after the end of therapy. The evolution of clinical and dermoscopic patterns was observed by two independent dermoscopists using current diagnostic criteria. A database of 12,088 photographic observations was evaluated. Univariate logistic regression proved that brachytherapy decreases the number of clinical and dermoscopic patterns typical for basal cell carcinoma, as well as dermoscopic features not related to BCC, presumably due to the formation of scar tissue. In addition, univariate logistic regression with random effects proved a positive correlation between tumor size and presence of various dermoscopic patterns typical for BCC. Dermoscopy is proven to be easy to perform and an adequate monitoring tool for patients with BCCs undergoing HDR brachytherapy.


Dihydropyrimidine dehydrogenase (DPD) rapidly regenerates after inactivation by eniluracil (GW776C85) in primary and metastatic colorectal cancer.
Catabolism of 5-fluorouracil (5-FU) is primarily regulated by DPD. Inactivation of DPD using eniluracil is advantageous in that it renders 5-FU orally bioavailable with more predictable pharmacokinetics and blocks one of the major potential mechanisms of 5-FU chemoresistance. The purpose of this study was to initially document inactivation of DPD by eniluracil in primary and metastatic colorectal cancer (CRC) and then to assess the time-course of the regeneration of DPD activity in peripheral blood (and where possible, additional tissues). Of 28 patients entered, 23 were randomized to preoperative oral eniluracil (20 mg orally twice daily) or placebo prior to definitive resection of primary or metastatic CRC. Three patients were replaced, two because they had no residual tumor on pathologic evaluation and one for not taking the study drug. Patients received eniluracil 48, 36, 24 and approximately 12 h prior to surgical resection. In a second part of the study to document tissue regeneration of DPD, the additional five patients received eniluracil 144, 132, 120 and 108 h prior to surgical resection. DPD activity was measured in normal tissues, tumors and peripheral blood mononuclear cells (PBMC). Serum eniluracil and plasma uracil concentrations were determined before and through 28 days after eniluracil dosing. Data are presented as means+/-SEM, and significance defined as P<0.05. Eniluracil inactivated DPD below the level of detection in primary and metastatic CRC as well as in normal tissues (0.0 pmol/min per mg protein) compared to primary tumor, metastatic tumor, PBMC, normal mucosa, and normal liver of patients receiving placebo (57+/-12, 119+/-19, 157+/-22, 77+/-12, 243+/-24 pmol/min/mg protein, respectively; P<0.05). At the time of surgery, serum eniluracil and uracil concentrations were 207+/-36 ng/ml and 2700+/-170 ng/ml in drug-treated patients. Within 6 days following treatment with eniluracil, serum eniluracil and uracil concentrations were undetectable, while DPD activity in PBMC had returned to baseline. The second group of patients (n=5) were given eniluracil 8 and 7 days prior to surgery to evaluate DPD regeneration in normal tissues and primary CRC tissue. In samples of these tissues, collected 6 days after the last eniluracil dose, DPD activity approached baseline in normal mucosa, normal liver and primary tumor (28+/-12, 94+/-23 and 20+/-8 pmol/min per mg protein, respectively). These results demonstrate that oral administration of eniluracil inactivated DPD below the level of detection in normal tissues as well as in primary and metastatic CRC. After discontinuation of eniluracil, DPD rapidly returned toward baseline within 6 days in PBMC, normal intestinal mucosa and normal liver.


The influence of tobacco smoking on dental periapical condition in a sample of an adult population of the Łódź region, Poland.
Epidemiological studies show that apical periodontitis (AP), alongside tooth decay, is the most common oral disease. The aim of the study was to evaluate the influence of smoking on the prevalence of AP in the population of the Łódź region, Poland. The study involved 815 first-time, randomly selected patients reporting to the Central Teaching Hospital of the Medical University of Lodz. The studied group was a systematic sample of the population admitted for treatment in 2016. The study consisted of a questionnaire and a radiological part. Each patient filled out a questionnaire containing demographic data, and an interview regarding smoking and diabetes. The radiological part of the study included the analysis of panoramic radiographs which showed the periapical status, and the presence and quality of root canal treatment. Teeth with AP were observed more frequently in patients addicted to tobacco either at the time of the study or in the past (group 1) - 7.2% than in people who had never smoked (group 2) - 5.2% (p < 0.0005). In the teeth without root canal treatment, AP was observed more frequently in group 1 - 3.5% than in group 2 - 1.9% (p < 0.0005). A statistically significant difference was found in the percentage of endodontically treated teeth between group 1 and group 2 (10.7% vs. 9.6%) (p = 0.017). However, no difference was observed in the frequency of AP in the endodontically treated teeth in both groups (37.6% vs. 35.8%) (p = 0.451). Smokers are a group facing an increased risk of AP and, therefore, there is a need for an early detection and treatment of caries and its complications in this group of patients. The multifactorial etiology of AP indicates the necessity to undertake further studies on the effect of smoking on the periapical status. Int J Occup Med Environ Health. 2020;33(1):45-57.


Highly variable rate of orthodontic tooth movement measured by a novel 3D method correlates with gingival inflammation.
Individual orthodontic treatment duration is hard to predict. Individual biological factors are amongst factors influencing individual rate of orthodontically induced tooth movement (OTM). The study aim is to determine the rate of OTM by a novel 3D method and investigate parameters that may predict the rate of tooth movement. In this prospective cohort study, rate of OTM was determined from 90 three-dimensional intra-oral scans in 15 patients (aged 12-15) undergoing orthodontic treatment. For each patient, intra-oral scans were taken every week for up to 6 weeks (T0-T5). The teeth were segmented from the scans and the scans were superimposed on the palatal rugae. The rate of OTM was calculated for each tooth. Other parameters were gingival inflammation, contact-point displacement and the biological markers, matrix metalloproteinases (MMP), MMP-9 and MMP-2 in gingival crevicular fluid (GCF). Our study showed a high variation in the rate of OTM, varying from 0.15 to 1.24 mm/week. Teeth in the anterior segment tended to move more compared with the posterior segment. The contact point displacement and gingival inflammation varied greatly amongst the patients. The MMPs measured did not correlate with tooth movement. However, the gingival inflammation index showed a significant correlation with OTM. Future studies should include other biological markers related to bone-remodeling. This novel and efficient 3D method is suitable for measuring OTM and showed large individual variation in rate of OTM. Patients show different rates of OTM. The rate of OTM in an individual patient can provide guidance in timing of follow-up appointments.


Expanding telemedicine to reduce the burden on the healthcare systems and poverty in Africa for a post-coronavirus disease 2019 (COVID-19) pandemic reformation.
The coronavirus disease 2019 (COVID-19) global public health emergency, has exposed the fragility of health systems. Access to healthcare became a scarce commodity as healthcare providers and resource-poor populations became victims of the novel corona virus. Therefore, this study focuses on Africa's readiness to integrate telemedicine into the weak health systems and its adoption may help alleviate poor healthcare and poverty after COVID-19. We conducted a narrative review through different search strategies in Scopus on January 20, 2021, to identify available literature reporting implementation of various telemedicine modes in Africa from January 1, 2011 to December 31, 2020. We summarized 54 studies according to geographies, field, and implementation methods. The results show a willingness to adopt telemedicine in the resource-poor settings and hard-to-reach populations, which will bring relief to the inadequate healthcare systems and alleviate poverty of those who feel the burden of healthcare cost the most. With adequate government financing, telemedicine promises to enhance the treating of communicable and non-communicable diseases as well as support health infrastructure. It can also alleviate poverty among vulnerable groups and hard-to-reach communities in Africa with adequate government financing. However, given the lack of funding in Africa, the challenges in implementing telemedicine require global and national strategies before it can yield promising results. This is especially true in regards to alleviating the multidimensionality of poverty in post-COVID-19 Africa.


A population-based study on the risk of cervical cancer and cervical intraepithelial neoplasia among grand multiparous women in Finland.
Previous studies suggest that high parity increases the risk of cervical cancer. We studied the risk of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN3) in a Finnish cohort of grand multiparous (GM) women (at least five children) with low prevalence of sexually transmitted infections (STI). The Finnish Cancer Registry data revealed 220 CC and 178 CIN3 cases among 86 978 GM women. Standardised incidence ratios (SIR) were calculated from the numbers of observed and expected cases. Interval analyses by parity, age at first birth and average birth interval were done using multivariate Poisson regression. Seroprevalence of human papillomavirus (HPV) 16 and Chlamydia trachomatis was tested among 561 GM women and 5703 women with 2-4 pregnancies. The incidence among GM women was slightly above the national average for squamous cell carcinoma of cervix uteri (SIR 1.21, 95% CI 1.05-1.40) and CIN3 (1.37, 95% CI 1.17-1.58), but lower for adenocarcinoma (SIR 0.77, 95% CI 0.52-1.10). The seroprevalence of HPV16 and Chlamydia trachomatis among GM women was lower than in the reference population, except among those women who had their child under age 19. Age under 20 years at first birth increased the risk of CC and CIN3 especially in premenopausal GM women, while increasing parity had no effect. The small relative risks of CC and CIN3 among GM women in our study as compared to studies from other countries can be explained by the exceptionally low prevalence of STIs in Finnish GM women. The observed SIRs between 1.2 and 1.4 should be interpreted to represent increased risk attributable to grand multiparity. The increased incidence of CC and CIN3 among young GM women suggests causal association to HPV 16 and Chlamydia trachomatis infections.


Engineering novel Lec1 glycosylation mutants in CHO-DUKX cells: molecular insights and effector modulation of N-acetylglucosaminyltransferase I.
Many secreted or cell surface proteins are post-translationally modified by carbohydrate chains which are a primary source of heterogeneity. The Lec1 mutant, which is defective in Golgi N-acetylglucosaminyltransferase I (GnTI) activity, produces relatively homogeneous Man(5) GlcNAc(2) glycan modifications, and is widely used for various applications. To facilitate the investigation of GnTI, its Man5 glycan endproduct, and the impact of Man5 on effector function, the present study has established several novel Lec1 mutants in dhfr(-) CHO-DUKX cells through chemical mutagenesis and lectin selection. A total of nine clonal lines exhibiting the Lec1-phenotype are characterized, six of which harbor non-sense mutations leading to a truncated GnTI, and three (R415K, D291N, and P138L) of which are novel loss-of-function sense mutations. Analysis of the rabbit GnTI structure (Unligil et al., 2000) indicates that D291 is the proposed catalytic base and R415 is a crucial residue in forming the substrate binding pocket, whereas P138 is key to maintaining two β strands in proximity to the substrate binding pocket. Computational modeling reveals that the oligomannose glycan backbone of a glycoprotein (the acceptor substrate) fits nicely into the unoccupied channel of the substrate binding pocket partly through hydrogen bonding with R415 and D291. This finding is consistent with the ordered sequential Bi Bi kinetic mechanism suggested for GnTI, in which binding of UDP-GlcNAc (the donor substrate)/Mn(2+) induces conformational changes that promote acceptor binding. When an anti-human CD20 antibody protein is stably expressed in one CHO-DUKX-Lec1 line, it is confirmed that N-glycans are predominantly Man(5) GlcNAc(2) and they do not contain an α1,6-fucose linked to the innermost GlcNAc. Furthermore, this Man(5) GlcNAc(2) modified antibody exhibits a significantly increased ADCC activity than the wild-type protein, while displaying a lower CDC activity. The data support the hypothesis that modulating GnTI activity can influence antibody effector functions for proteins with an IgG1 immunoglobulin Fc domain.


The frequency of non-motor symptoms in SCA3 and their association with disease severity and lifestyle factors.
Non-motor symptoms (NMS) are a substantial burden for patients with SCA3. There are limited data on their frequency, and their relation with disease severity and activities of daily living is not clear. In addition, lifestyle may either influence or be affected by the occurrence of NMS. To characterize NMS in SCA3 and investigate possible associations with disease severity and lifestyle factors. In a prospective cohort study, we performed a cross-sectional analysis of NMS in 227 SCA3 patients, 42 pre-ataxic mutation carriers, and 112 controls and tested for associations with SARA score, activities of daily living, and the lifestyle factors alcohol consumption, smoking and physical activity. Sleep disturbance, restless legs syndrome, mild cognitive impairment, depression, bladder dysfunction and pallhypesthesia were frequent among SCA3 patients, while mainly absent in pre-ataxic mutation carriers. Except for restless legs syndrome, NMS correlated significantly with disease severity and activities of daily living. Alcohol abstinence was associated with bladder dysfunction. Patients with higher physical activity showed less cognitive impairment and fewer depressive symptoms, but these differences were not significant. This study revealed a clear association between disease severity and NMS, likely driven by the progression of the widespread neurodegenerative process. Associations between lifestyle and NMS can probably be attributed to the influence of NMS on lifestyle.


Remnant volume of anterior cruciate ligament correlates preoperative patients' status and postoperative outcome.
A cohort study was conducted to evaluate the correlation of anterior cruciate ligament (ACL) remnant volume with preoperative status and postoperative outcome of the patients after a remnant-preserving double-bundle (DB) ACL reconstruction. Eighty-eight patients of 105 unilateral DB anatomic ACL reconstructions performed between 2006 and 2008 were followed up for 24 months or more. They were evaluated with regard to preoperative knee laxity data under anaesthesia. Postoperative outcome was evaluated based on knee extension and flexion strength, manual laxity tests, KT measurements, etc. Overall knee condition and sports performance were evaluated with Lysholm knee score and subjective rating scale. Overall correlation of the remnant volume with the preoperative and postoperative evaluation was assessed. Then, the patients were divided into three subgroups based on the remnant volume (remnant volume: ≤ 30, 35-55 and ≤ 60 %). The evaluation was performed and analysed statistically among the three subgroups. Generally, preoperative laxity tests showed a weak correlation with the ACL remnant volume. Postoperative knee stability also indicated a weak correlation with the ACL remnant volume. Statistical analyses revealed that there were significant differences among the three groups regarding age at surgery, preoperative period, number of giving-way and preoperative KT measurements. Postoperatively, there were significant differences in Lachman test, KT measurements, Lysholm knee scale, subjective and sports performance recovery scores. As the clinical relevance, the study suggests that the remnant volume will be important as a background of preoperative condition and a predictor of operative outcome for each patient and that a remnant preserving surgery may not be simply better than a non-preserving technique with regard to subjective evaluation and sports performance recovery. The preoperative condition of patients with ACL injury was different depending upon the remnant volume. The remnant volume was also weakly correlated with the postoperative outcome regarding objective stability and subjective recovery.


A signal detection procedure eliminates priming biases in dichotic listening.
Dichotic digit names were presented to normal right-handed adults in two experiments, the first of which used a standard free report procedure and the second of which used a signal detection procedure. Prior to each test, a priming bias was generated by having subjects monitor either the left or right ear for 30 selective listening trials. The expected priming effect was found in Experiment 1: ear asymmetry and order of report were altered according to the ear previously monitored. In contrast, no priming effect was observed with the signal detection procedure used in Experiment 2. There was a right-ear advantage in sensitivity irrespective of the ear previously monitored. The findings suggest that priming biases act by altering the order in which multiple stimuli are processed and reported.


The treatment of facial haemangioma by percutaneous injections of sodium tetradecyl sulfate.
Sotradecol--sodium tetradecyl sulfate--is a sclerosing agent which has been used for years in the treatment of varicose veins, haemorrhoids and haemangiomata. Two cases of large haemangioma of the cheek are presented. Because surgical treatment posed many difficulties we decided to treat with sodium tetradecyl sulfate. Treatment was successful.


Association between season of first detection of breast cancer and disease progression.
The season of recurrence of tumour was investigated by follow-up of 1324 patients with breast cancer and compared with the season of initial tumour detection. Unlike primary tumours, where an increased incidence of detection has previously been observed in late spring and early summer, there was no significant seasonal variation in the time of recurrence. However, women with oestrogen receptor positive or progesterone receptor negative primary tumours recurred significantly more frequently in the same season that their primary cancer was initially detected. Overall there was an increased frequency of recurrence one year from diagnosis. Women less than age 50 who initially found their tumour in winter or autumn had a significantly shorter disease-free interval before recurrence than those first detecting their tumour in summer or spring. This relationship was independent of nodal status and tumour size. Tumours initially detected in winter or autumn thus appeared to follow a more aggressive growth profile. This study indicates that the season of first detection of a breast cancer relates significantly to aspects of the future biologic behaviour of the tumour.


Superior sagittal sinus thrombosis in neonates.
Three neonatal patients with superior sagittal sinus thrombosis are reported. The neurologic signs were bulging of the anterior fontanel and clonic hemi-convulsions. Neonatal polycythemia was believed to be an etiologic factor in two patients. Computed tomography revealed massive edema with slit-like ventricles in two patients. Increased density of the torcular Herophili and straight sinus also were demonstrated in two patients. The diagnosis of superior sagittal sinus thrombosis was confirmed by cerebral angiography in one patient and by digital subtraction angiography in the other two patients. Digital subtraction angiography appears to offer a definite advantage in the diagnosis of cerebral sinus thrombosis in the neonatal period.


Association between deprescribing from polypharmacy and functional recovery and home discharge among older patients with sarcopenia after stroke.
Evidence regarding the association between deprescribing from polypharmacy and outcomes in the convalescent rehabilitation setting is rare. The aim of this study was to assess the association between deprescribing from polypharmacy and functional recovery and home discharge in older patients with sarcopenia after stroke. This retrospective cohort study was conducted at a convalescent rehabilitation hospital from January 2015 to December 2021. Among newly admitted patients in the convalescent rehabilitation ward who had experienced a stroke, patients aged ≥65 y with sarcopenia at admission and who were using at least five medications were included. Sarcopenia was diagnosed according to hand-grip strength and skeletal muscle mass index following the criteria of the Asian Working Group for Sarcopenia 2019. The primary outcome measures were functional independence-measured motor activity (FIM-motor) at discharge and home discharge. Multiple regression analysis was used to determine whether deprescribing from polypharmacy at admission was independently associated with rehabilitation outcomes. Among the 264 patients with polypharmacy, 153 patients (mean age, 81.1 y; 46.4% males) were diagnosed with sarcopenia and included in the analysis. Of them, 56 (36.6%) were deprescribed from polypharmacy. Deprescribing from polypharmacy was independently associated with FIM-motor at discharge (β, 0.137; P = 0.017) and home discharge (odds ratio, 1.393; P = 0.002). Because no effective pharmacotherapy for sarcopenia has been established, the novel findings of this study may be useful in the pharmacotherapy for older patients with sarcopenia after stroke. Deprescribing from polypharmacy on admission was positively associated with functional status at discharge and home discharge in older patients with sarcopenia after stroke.


Genetic variations for the eggshell crystal structure revealed by genome-wide association study in chickens.
Eggshell is a bio-ceramic material comprising columnar calcite (CaCO3) crystals and organic proteinaceous matrix. The size, shape and orientation of the CaCO3 crystals influence the microstructural properties of chicken eggshells. However, the genetic architecture underlying eggshell crystal polymorphism remains to be elucidated. The integral intensity of the nine major diffraction peaks, total integral intensity and degree of orientation of the crystals were measured followed by a genome-wide association study in 839 F2 hens. The results showed that the total integral intensity was positively correlated with the eggshell strength, eggshell thickness, eggshell weight, mammillary layer thickness and effective layer thickness. The SNP-based heritabilities of total integral intensity and degree of orientation were 0.23 and 0.06, respectively. The 621 SNPs located in the range from 55.6 to 69.1 Mb in GGA1 were significantly associated with TA. PLCZ1, ABCC9, ITPR2, KCNJ8, CACNA1C and IAPP, which are involved in the biological process of regulating cytosolic calcium ion concentration, can be suggested as key genes regulating the total integral intensity. The findings greatly advance the understanding of the genetic basis underlying the crystal ultrastructure of eggshell quality and thus will have practical significance in breeding programs for improving eggshell quality.


Pharmacokinetics, safety, and efficacy of lenalidomide plus dexamethasone in patients with multiple myeloma and renal impairment.
Renal impairment (RI) is a common comorbidity in multiple myeloma (MM). Current dose adjustments recommended for renally excreted lenalidomide are based on data from noncancer patients. This study evaluated the pharmacokinetics, safety, efficacy, and exposure-response for lenalidomide plus dexamethasone in patients with relapsed/refractory MM and stable RI using the recommended dose adjustments. This phase 2 multicenter, open-label study stratified patients into 5 groups based on creatinine clearance (CrCl) calculated by Cockcroft-Gault equation: normal renal function (CrCl > 80 mL/min), mild RI (50 ≤ CrCl ≤ 80 mL/min), moderate RI (30 ≤ CrCl < 50 mL/min), severe RI (CrCl < 30 mL/min), and end-stage renal disease requiring hemodialysis. Dosing was based on the lenalidomide label. Among 38 patients, the median age was 68 (range 62-74) years, and poorer renal function was associated with older age, more advanced disease, and more lines of prior therapy. Lenalidomide clearance declined with decreased CrCl. Mean lenalidomide area under plasma concentration-time curve (AUC) was within ±25 % of the target AUC in each group. Overall response was 76 %, and safety profiles were similar across groups, with no exposure-dependent trend in efficacy or toxicity. Estimated glomerular filtration rates calculated using the simplified Modification of Diet in Renal Disease equation highly correlated with lenalidomide clearance and, in 87 % of patients, would lead to assigning the same starting dose of lenalidomide as CrCl. In patients with stable renal function, the recommended dose adjustments achieved proper plasma exposure and similar safety and efficacy across renal groups.


Blended Oncology Nursing Training: A Quality Initiative in East Africa.
Lack of education and awareness about cancer treatment may result in suboptimal care of patients with cancer. Unlike high-income countries, resource-limited countries lack the standardized training and scope of practice in oncology nursing. This quality improvement project was conducted to assess nurses' knowledge gain, retention of knowledge and clinical skill set, and feasibility of a blended learning approach in the care of adult oncology patients across four hospitals in Kenya and Tanzania. We used a combination of computer-led eLearning sessions and face-to-face interactions over 12 months for cancer education to oncology nurses. Pre- and posttests with each training session were combined with face-to-face clinical skills training at beginning and completion of the course. A comprehensive postassessment was conducted immediately after the training, and at 6, 9, and 12 months to evaluate knowledge gain and retention. Of 21 participants across four sites, there was a statistically significant improvement in knowledge scores for 12 participants (P value < .05). The mean pre- and posttest results found significant differences across 10 sessions individually and cumulatively (P value < .01). Results from a one-way repeated measures analysis of variance (ANOVA) test on comprehensive test results suggested that there was no significant difference in knowledge retention across 9 months (F(2, 30) = 1.648412, P > .05). Blended learning is an effective tool in improving knowledge, skills, and self-efficacy for clinicians practicing in resource-limited countries. Developing a structured oncology training program has implications for bridging knowledge gaps among clinicians in resource-limited countries and promoting international knowledge exchange.


Nitroxides inhibit peroxyl radical-mediated DNA scission and enzyme inactivation.
Nitroxides are cell-permeable stable radicals that protect biomolecules from oxidative damage in several ways. The mechanisms of protection studied to date include removal of superoxide radicals as SOD-mimics, oxidation of transition metal ions to preempt the Fenton reaction, and scavenging carbon-centered radicals. However, there is no agreement regarding the reaction of piperidine nitroxides with peroxyl radicals. The question of whether they can protect by scavenging peroxyl radicals is important because these radicals are formed in the presence of oxygen abundant in biological tissues. To further our understanding of the antioxidative behavior of piperidine nitroxides, we studied their effect on biochemical systems exposed to the water soluble radical initiator 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH). AAPH thermally decomposes to yield tert-amidinopropane radicals (t-AP(*)) that readily react with oxygen to form peroxyl radicals (t-APOO(*)). It has recently been reported that piperidine nitroxides protect plasmid DNA from t-AP(*) though not from t-APOO(*). The present study was directed at the question of whether these nitroxides can protect biological systems from damage inflicted by peroxyl radicals. The reaction of nitroxides with AAPH-derived radicals was followed by cyclic voltammetry and electron paramagnetic resonance spectroscopy, whereas the accumulation of peroxide was iodometrically assayed. Assaying DNA damage in vitro, we demonstrate that piperidine nitroxides protect from both t-AP(*) and t-APOO(*). Similarly, nitroxides inhibit AAPH-induced enzyme inactivation. The results indicate that piperidine nitroxides protect the target molecule by reacting with and detoxifying peroxyl radicals.


Lidocaine Reversible Inactivation of the Central Nucleus of Amygdala Impairs Acquisition, Consolidation, and Retrieval of Morphine State-Dependent Learning in Rat.
Morphine causes state-dependent learning that its mechanism and brain-related structures are not fully understood. This study aimed to determine whether lidocaine reversible inactivation of the central nucleus of the amygdala (CeA) could affect acquisition, consolidation, and retrieval of morphine state-dependent learning. One hundred twenty male Wistar rats were allocated into 15 experimental groups. Subcutaneous administration of morphine (5 mg/kg) induced morphine state-dependent learning. Intra-CeA injection of Lidocaine hydrochloride was performed 5 min before each morphine session for transient inactivation of the CeA. The step-through latency and the time spent in the dark compartment were measured using passive avoidance learning task. Our results showed that pretraining, posttraining, and pretest inhibition of the CeA severely impaired acquisition, consolidation, and retrieval of morphine state-dependent learning. These data revealed the involvement of the CeA in different stages of memory and morphine state-dependent learning.


Specific affinity and relative abundance of methanogens in acclimated anaerobic sludge treating low-strength wastewater.
Kinetic parameters affecting effluent water quality including half saturation constant (Ks), maximum specific growth rate (μmax), and specific affinity ([Formula: see text], defined as μmax/Ks) were investigated using three types of anaerobic sludge (raw anaerobic digestion sludge referred to as unacclimated sludge, unacclimated sludge after endogenous decay, and sludge acclimated to low-strength wastewater in an anaerobic membrane bioreactor (AnMBR) for 360 days). Long-term acclimation to low-strength wastewater resulted in sludge with high specific affinity (1.6 × 10-3 L/mg COD/day for acclimated sludge compared to 4.1 × 10-4 L/mg COD/day for unacclimated sludge). The μmax values for unacclimated sludge and acclimated sludge were 0.08 and 0.07 day-1, respectively. The Ks values for unacclimated sludge and acclimated sludge were 194 ± 81 mg COD/L and 45 ± 13 mg COD/L, respectively. Although the Ks of unacclimated sludge after endogenous decay increased to 772 ± 74 mg COD/L, μmax increased to 0.35 day-1 as well, resulting in no statistically significant difference of [Formula: see text] between the two types of unacclimated sludge. Overall, [Formula: see text] is a better indicator than μmax or Ks alone for determining effluent water quality, as effluent substrate concentration is approximately inversely proportional to the specific affinity. 16S rRNA sequencing data analysis indicated a high abundance (85.8% of total archaea) of Methanosaeta in the microbial community after long-term acclimation. High [Formula: see text] associated with the enrichment of Methanosaeta appears to ensure successful anaerobic treatment of low-strength wastewater.


Preclinical assessment of the distribution, metabolism, and excretion of S-propargyl-cysteine, a novel H2S donor, in Sprague-Dawley rats.
To study the distribution, metabolism and excretion of S-propargyl-cysteine (SPRC), a novel hydrogen sulfide (H2S) donor, after oral administration in rats. Adult Sprague-Dawley rats were used. The tissue distribution of [(35)S] SPRC-derived radioactivity was measured using a liquid scintillation counter. The plasma protein binding of SPRC was examined using 96-well equilibrium dialysis. The excretion of SPRC in urine, bile and feces was analyzed using the LC-MS/MS method. The major metabolites in rat biomatrices were identified using MRM information-dependent, acquisition-enhanced product ion (MRM-IDA-EPI) scans on API 4000QTrap system. After oral administration of [(35)S]-SPRC at a dose of 75 mg/kg, [(35)S] SPRC-derived radioactivity displayed broad biological distribution in various tissues of rats, including its target organs (heart and brain) with the highest in kidney. On the other hand, the binding of SPRC to human, rat and dog plasma protein was low. Only 2.18% ± 0.61% and 0.77% ± 0.61% of the total SPRC administered was excreted unchanged in the bile and urine. However, neither intact SPRC nor its metabolites were detected in rat feces. The major metabolic pathway in vivo (rat bile, urine, and plasma) was N-acetylation. The preliminary results suggest that SPRC possesses acceptable pharmacokinetic properties in rats.


First-line nurse leaders' health-care change management initiatives.
To examine nurse leaders' change management projects within British Columbia, Canada. British Columbia Nursing Leadership Institute 2007-10 attendees worked on year-long change management initiatives/projects of importance to their respective health-care institutions. Most leaders were in first-line positions with <3 years' experience. Consenting leaders' project reports (N = 133) were content analysed for specific themes: types of projects; scope of projects (e.g. unit or local level, departmental, institutional); influence targets or key stakeholder groups targeted by the projects; leadership successes and challenges. Of study participants, 77% successfully completed their projects. Staff tool and resource development and existing services improvement were major project types. Care delivery teams were the major influence targets. Only 25% of projects were at the unit level. Many projects had broader scopes, such as institutional levels. Participants cited multiple leadership successes, including enhanced leadership styles and organizational skills. First-line nurse leaders were able to successfully manage projects beyond their traditional scope of responsibilities. The majority of projects dealt with staff needs and healthcare restructuring initiatives. Constant change is a global reality. Change management, a universal competency, must be included in leadership development programmes.


Influence of serum high-molecular-weight and total adiponectin on arteriosclerosis in IgA nephropathy patients.
Adiponectin has attracted a great deal of attention because of its antiatherogenic properties. Previous studies have reported that high-molecular-weight (HMW) adiponectin may be the active form of this protein, but there have been no reports on the relationship between serum adiponectin and arteriosclerosis. The aim of our study was to determine whether HMW or total adiponectin levels are associated with arteriosclerosis in patients with IgA nephropathy. We enrolled 72 patients aged 34.3 +/- 12.7 years, from whom interlobular arteries were obtained by renal biopsy in our hospital between 2003 and 2006 and who were confirmed to have IgA nephropathy. We assessed them in relation to age, gender, body mass index, presence of hypertension, serum total cholesterol, triglyceride, uric acid, high-sensitive C-reactive protein and HMW adiponectin and total adiponectin levels, creatinine clearance, and urinary protein excretion. The severity of arteriosclerosis was semiquantitatively evaluated and classified into the following four grades: 0 = none; 1 = mild; 2 = moderate, and 3 = severe. Multiple stepwise regression analysis showed associations between arteriosclerosis grade and age [standard regression coefficient (st beta) = 0.560, p < 0.001], total adiponectin (st beta = -0.218, p = 0.026), triglyceride (st beta = 0.222, p = 0.033), and presence of hypertension (yes = 1, no = 0; st beta = 0.182, p = 0.036) in the IgA nephropathy patients as a whole and associations between arteriosclerosis grade and age (st beta = 0.708, p < 0.001), HMW adiponectin (st beta = -0.321, p = 0.035), and triglyceride (st beta = 0.292, p = 0.038) in the male IgA nephropathy patients. Serum total adiponectin levels are an independent determinant of arteriosclerosis in IgA nephropathy patients. It was noteworthy that in males the serum HMW adiponectin levels correlated more strongly with arteriosclerosis grade than the total adiponectin levels did. Adiponectin may prevent renal arteriosclerosis.


Widespread occurrence of power-law distributions in inter-repeat distances shaped by genome dynamics.
Repetitive DNA sequences derived from transposable elements (TE) are distributed in a non-random way, co-clustering with other classes of repeat elements, genes and other genomic components. In a previous work we reported power-law-like size distributions (linearity in log-log scale) in the spatial arrangement of Alu and LINE1 elements in the human genome. Here we investigate the large-scale features of the spatial arrangement of all principal classes of TEs in 14 genomes from phylogenetically distant organisms by studying the size distribution of inter-repeat distances. Power-law-like size distributions are found to be widespread, extending up to several orders of magnitude. In order to understand the emergence of this distributional pattern, we introduce an evolutionary scenario, which includes (i) Insertions of DNA segments (e.g., more recent repeats) into the considered sequence and (ii) Eliminations of members of the studied TE family. In the proposed model we also incorporate the potential for transposition events (characteristic of the DNA transposons' life-cycle) and segmental duplications. Simulations reproduce the main features of the observed size distributions. Furthermore, we investigate the effects of various genomic features on the presence and extent of power-law size distributions including TE class and age, mode of parental TE transmission, GC content, deletion and recombination rates in the studied genomic region, etc. Our observations corroborate the hypothesis that insertions of genomic material and eliminations of repeats are at the basis of power-laws in inter-repeat distances. The existence of these power-laws could facilitate the formation of the recently proposed "fractal globule" for the confined chromatin organization.


Protective effect of cultured bear bile powder against dimethylnitrosamine-induced hepatic fibrosis in rats.
Natural bear bile has been used for liver disease in East Asia for thousands of years. However, its use has restrictions. In the current study, the therapeutic effects and potential mechanisms of cultured bear bile powder (CBBP) against hepatic fibrosis were evaluated in a dimethylnitrosamine (DMN)-induced rat model. CBBP treatment significantly improved DMN-induced hepatic necrosis and inflammatory infiltration. Additionally, CBBP remarkably alleviated the increased hepatic collagen content and expression of alpha-smooth muscle actin. Serum metabolomics revealed that 14 serum metabolites, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were decreased in DMN-treated rats, which was reversed by CBBP. Pathway analyses revealed that the main metabolic pathways affected by CBBP were related to fatty acid biosynthesis and metabolism, and biosynthesis of unsaturated fatty acids. EPA and DHA are ligands of peroxisome proliferator activated receptors (PPARs). CBBP treatment significantly stimulated liver mRNA and protein expression of PPARα and PPARγ. CBBP also markedly increased liver expression of PPARα target genes, which are involved in fatty acid β-oxidation, and down-regulated IL-6, a downstream inflammatory gene of PPARγ. In conclusion, CBBP has the potential to attenuate liver fibrosis and its mechanism involves the promotion of the liver expression of PPARα and PPARγ. Our results may help in the development of a novel substitute for bear bile and therapeutic strategies for fibrotic liver diseases.


In vitro infectivity of oncolytic Newcastle Disease Virus: Correlation between plaque and fluorescent focus assays.
Newcastle Disease Virus (NDV) is an avian paramyxovirus that has no significant pathogenicity in humans. Cancer cells with impaired immune defense mechanisms are susceptible to infection and lysis by NDV. A recombinant construct of a lentogenic form of NDV (rNDV) containing an insertion of granulocyte macrophage colony stimulating factor (GMCSF) transgene was earlier reported and shown to have acceptably low avian pathogenicity as well as oncolytic potential. Reliable measurement of infectious titer is key to determining the effectiveness of virus preparations to infect and lyse cells. We report here a comparative evaluation of two infectious titer assays as applied to rNDV: plaque assay and fluorescent focus assay (FFA). Optimization of assay conditions for both titer methods has produced concordant results spanning several orders of magnitude. While plaque formation is the gold standard measure of virus titer, FFA provides higher throughput and faster turn-around. FFA has been further evaluated on two different instrument platforms, for automated versus manual foci recognition and counting, with equivalent results. These results point to amenability of FFA to transfer between different laboratories and analysts, without introducing significant subjectivity in data analysis.


Sources and distribution of aliphatic and polyaromatic hydrocarbons in sediments of Jiaozhou Bay, Qingdao, China.
The composition and distribution of aliphatic (n-alkanes) and polyaromatic hydrocarbons (PAHs) were measured for the surface sediments collected at 25 sites from Jiaozhou Bay, Qingdao, China. Total n-alkanes and PAH concentrations ranged from 0.5 to 8.2 microg/gdw and 0.02 to 2.2 microg/gdw, respectively, and the distribution of both n-alkanes and PAHs showed large spatial variations in the bay. The distribution of PAHs in the sediments was predominated by the three or more ring compounds. High hydrocarbon levels were generally found in the areas associated with high anthropogenic impact and port activities in the bay. The calculated hydrocarbon indexes suggest that petroleum contamination was the main source of n-alkanes, while both pyrolytic and petrogenic sources contributed PAHs to the surface sediments of Jiaozhou Bay. In comparison to other polluted coastal sediments, the level of contamination from both aliphatic hydrocarbons and PAHs in Jiaozhou Bay sediments is relatively low at the present time.


Risk factors for concomitant peripheral arterial occlusive disease in patients with coronary artery disease: is there a difference between diabetic and non-diabetic patients?
The aim of the present study was investigation of cardiovascular risk factors for concomitant Peripheral Arterial Occlusive Disease (PAOD) in diabetic vs. non-diabetic patients with coronary artery disease (CAD). This study included 302 patients (229 men) with a mean age of 62.2 +/- 11.5 years and angiographically documented CAD. These were divided into Group A comprising 116 diabetic patients (79 men) and Group B comprising 186 non-diabetic patients (150 men). Peripheral Arterial Occlusive Disease (PAOD) was diagnosed using a Doppler apparatus. Cardiovascular risk factors that were investigated included age, history of myocardial infarction, smoking, Body-Mass Index, Waist-Hip-Ratio, hypertension and serum lipids. PAOD was diagnosed in 49 patients of Group A (42.4%) and 20 patients of Group B (10.8%). In Group A concomitant PAOD was associated with significantly (p = 0.0001) longer diabetes duration and significantly (p = 0.0001) higher frequency of insulin treatment, as well as significantly (p = 0.02) higher triglycerides and significantly (p = 0.039) lower HDL-Cholesterol. In Group B patients with PAOD had significantly (p = 0.0001) higher age and significantly higher (p = 0.041) LDL-Cholesterol levels than those without PAOD. No association was found between PAOD and presence of remaining risk factors in either group. In multiple regression analysis, concomitant PAOD was associated with diabetes duration (p = 0.0026) and insulin treatment (p = 0.0004) in Group A, while it was associated with age (p = 0.01) in Group B. The associations with serum lipids were no longer significant. Among non-diabetic patients with CAD, those who have concomitant PAOD are significantly older. Among diabetic patients with CAD, those who have concomitant PAOD show significantly longer diabetes duration and significantly higher frequency of insulin treatment.


Ex vivo hemolysis: Three cases demonstrating mechanically-induced hemolysis from the extracorporeal circuit during hemodialysis.
Sporadic mechanically-induced hemolysis associated with kinks in extracorporeal blood circuits during hemodialysis is a rare but potentially serious complication that exhibits laboratory features consistent with both in vivo and in vitro hemolysis. Misclassification of clinically significant hemolysis as in vitro can lead to inappropriate test cancellation and delayed medical interventions. Here, we report three cases of hemolysis attributed to kinked hemodialysis blood lines, which we have defined as "ex vivo" hemolysis. All three cases demonstrated an initial mixed picture of laboratory features consistent with both classifications of hemolysis. Specifically, absent features of in vivo hemolysis on blood film smear despite normal potassium led to the misclassification of these samples as in vitro hemolysis and their cancellation. A proposed mechanism for these overlapping laboratory features is the recirculation of damaged red blood cells from the kinked or pinched hemodialysis line back into the patient circulation producing an "ex vivo" hemolysis presentation. In two of the three cases, the patients developed acute pancreatitis as a result of hemolysis and required urgent medical follow up. We developed a decision pathway to help laboratories in identifying and handling these samples by recognizing that in vitro and in vivo hemolysis have overlapping laboratory features. These cases highlight the need for laboratorians and the clinical care team to be vigilant about mechanically-induced hemolysis from the extracorporeal circuit during hemodialysis. Communication is critical to identify the cause of hemolysis in these patients and prevent unnecessary delays in result reporting.


Specific regression of human cancer cells by ribozyme-mediated targeted replacement of tumor-specific transcript.
In this study, we describe a novel approach to human cancer therapy that is based upon trans-splicing ribozyme-mediated replacement of cancer-specific RNAs with new transcripts that exert therapeutic activities. We have developed a specific ribozyme that can reprogram human telomerase reverse transcriptase (hTERT) RNA to induce transgene activity selectively in cancer cells that express the RNA. The ribozyme-mediated triggering of the transgene expression was accomplished via a high-fidelity trans-splicing reaction with the targeted residue in the hTERT-expressing cells. The ribozyme also induced cytotoxic activity in various hTERT-expressing cancer cells, hence selectively retarding the growth of those cells. Efficient and specific cell regression was also detected with ganciclovir (GCV) treatment only in hTERT-positive cancer cells, which were established to express stably the specific ribozyme that contains the herpes simplex virus thymidine kinase (HSV-tk) gene. Tissue-specific expression of the ribozyme could further augment the target specificity of the ribozyme. Importantly, we observed efficient regression of tumors with GCV treatment in mice that had been inoculated subcutaneously with hTERT-positive cancer cells that stably expressed the specific ribozyme that contains HSV-tk. These results suggest that the hTERT RNA-targeting trans-splicing ribozyme could be a powerful agent for tumor-targeted specific gene therapy.


Degradation of chlorobenzenes by a strain of Acidovorax avenae isolated from a polluted aquifer.
A subsurface microbial community was isolated from a polluted site of Suquía River (Córdoba-Argentina), acclimated during 15 days in aerobic conditions using 1,2-dichlorobenzene (1,2-DCB) as the sole carbon source. From this acclimated community, we isolated and identified by 16S rDNA analysis a strain of Acidovorax avenae, which was able to perform the complete biodegradation of 1,2-DCB in two days affording stoichiometric amounts of chloride. This pure strain was also tested for biodegradation of chlorobenzene (CB); 1,3-DCB and 1,4-DCB, giving similar results to the experiments using 1,2-DCB. The aromatic-ring-hydroxylating dioxygenase (ARHDO) alpha-subunit gene core, encoding the catalytic site of the large subunit of chlorobenzene dioxygenase, was detected by PCR amplification and confirmed by DNA sequencing. These results suggest that the isolated strain of A. avenae could use a catabolic pathway, via ARHDO system, leading to the formation of chlorocatecols during the first steps of biodegradation, with further chloride release and subsequent paths that showed complete substrate consumption.


Ultraviolet photoproducts at the ochre suppressor mutation site in the glnU gene of Escherichia coli: relevance to "mutation frequency decline".
Ochre suppressor mutations induced by UV in the Escherichia coli glnU tRNA gene are CG to TA transitions at the first letter of the anticodon-encoding triplet, CAA. Premutational UV photoproducts at this site have long been known to exhibit an excision repair anomaly ("mutation frequency decline" or MFD), whereby postirradiation inhibition of protein synthesis enhances their excision and reduces suppressor mutation yields ten-fold. We sought to clarify the basis of this unique repair response by determining the spectrum of UV photoproducts on both strands of a 36 bp region of glnU which includes the anticodon-encoding triplet. We found that four different photolesions are produced within the 3 bp sequence corresponding to the tRNA anticodon: (i) on the transcribed strand, TC (6-4) photoproducts and TC cyclobutane dimers are formed in equal numbers at the site of the C to T transition, indicating that this site is a hotspot for the usually less frequent (6-4) photoproduct; (ii) on the nontranscribed strand, TT dimers are found opposite the second and third letters of the anticodon-encoding triplet, adjacent to the mutation site; and (iii) on the nontranscribed strand, an alkali-sensitive lesion other than a (6-4) photoproduct is formed, apparently at the G in the mutation site. We suggest that mutation frequency decline may reflect excision repair activity at closely spaced UV lesions on opposite strands, resulting in double-strand breaks and the death of potential mutants.


Use of new beta-lactam antibiotics for surgical infections.
The availability of beta-lactam antibiotics with extended spectra of activity against organisms commonly seen in surgical infections suggests that aminoglycoside-based therapy is no longer needed for most such community-acquired infections. The primary problems with specific beta-lactams are lack of activity against Bacteroides species and variable activity against Pseudomonas aeruginosa and enterococci. The pharmacokinetic properties of the newer beta-lactams vary considerably. This variation suggests specific settings in which these properties may be taken advantage of to improve clinical outcome.


A calorimetric comparison of the interaction of sodium dodecyl sulfate with cytochrome c and erythrocyte glycoproteins.
The interactions of sodium dodecyl sulfate with cytochrome c and erythrocyte glycoproteins have been studied by the method of titration calorimetry. It was found that the initial addition of sodium dodecyl sulfate to cytochrome c caused an endothermic unfolding of the protein, detectable by circular dichroism (CD). This was followed by the exothermic binding of sodium dodecyl sulfate to the protein, without further CD-detectable conformational changes. In contrast, sodium dodecyl sulfate bound directly to the erythrocyte glycoproteins in an exothermic reaction without any accompanying CD-detectable conformation changes. This indicates that the glycoproteins solubilized in aqueous media have exposed hydrophobic regions which can interact directly with this detergent. The enthalpy changes and stoichiometries of binding are reported.


Brief report: Parent-guided movements during play with children with autism spectrum disorder.
Children with autism spectrum disorder (ASD) demonstrate social and communication impairments from an early age. While researchers have long investigated parenting behaviors in relation to children's social and communication development, fewer studies have examined the relevance of movement-based parenting behaviors to facilitating communication and social engagement with young children. The present study aimed to investigate: (1) parent-guided movements (PGMs) within dyads of parents and typically developing (TD) children and children with ASD; and (2) children's ASD diagnostic and receptive language scores as predictors of PGM frequency. Video-recorded play interactions of 33 TD dyads (mean age: 20.4 months) and 31 dyads with ASD (mean age: 32.6 months) were matched on child's expressive language. Data were obtained from a longitudinal study on developmental language trajectories in ASD and coded for PGMs. Overall, parents of children with ASD initiated PGMs more frequently than parents of TD children during play (U = 269.00, z = - 3.58, p < 0.001). PGM frequency was predicted by children's ADOS scores (X 2 = 5.46, p = 0.02, OR = 1.26, 95% CI [1.04, 1.54]) and receptive language (X 2 = 4.15, p = 0.04, OR = 5.43, 95% CI [1.10, 27.67]). Findings suggest that parents of children with ASD and low receptive language may utilize more movement-based strategies to compensate for their children's impaired social engagement and verbal comprehension. This study offers insight on a particular movement-based modality characterizing ASD dyads that can be used as a measure in parent-mediated interventions.


Recovery of precious metals by an electrochemical deposition method.
Conversion of soluble precious metals into a solid form for further reuse was studied by using an electrochemical deposition approach. It was found that the metal recovery followed a first-order reaction kinetics. The distance between the electrodes had no much impact on the recovery, while higher mixing led to faster kinetics. The presence of humic acid (HA) with lower concentration (<20mg l (-1)) did not have impact on the recovery. When its concentration was increased to 50 mg l (-1), it decreased the metal reduction. Presence of ethylene diamine tetraacetic acid (EDTA) and ionic strength slightly reduced the copper recovery rate. Around 50% removal of for HA and EDTA was achieved. In the competing environment, metal recovery was in the following order: silver>lead>copper. X-ray photoelectron spectroscopic and scanning electronic microscopic analysis of the reduced metals demonstrated that the depositions were composed of mainly elemental metals together with their oxides which were due to the oxidation.


[Intrauterine intraperitoneal transfusion controlled by ultrasound. A case report].
Two intrauterine transfusions in one fetus have been performed utilizing continuous ultrasound supervision by Sonolayer SSA-90 A in the 31st and 33rd gestational week.


Familial Aggregation and Co-Aggregation of Essential Tremor and Parkinson's Disease.
Current data suggest that the 2 common tremor disorders, essential tremor (ET) and Parkinson's disease (PD), may be associated with one another. Familial aggregation studies allow one to further explore their relatedness. Probands with ET (n = 110), PD (n = 130) or both ET and PD (n = 27) and control probands (n = 177) reported whether they had relatives with these diseases or with non-specific tremor. A greater proportion of ET probands than control probands reported relatives with ET (30.0 vs. 2.8%, p < 0.001), non-specific tremor (38.2 vs. 13.6%, p < 0.001) and both ET and PD in different relatives (6.4 vs. 0.6%, p = 0.004). A greater proportion of PD probands than control probands reported relatives with PD (20.0 vs. 8.5%, p = 0.003), ET (11.5 vs. 2.8%, p = 0.002) and both ET and PD in different relatives (6.9 vs. 0.6%, p = 0.002). This study provides evidence for the aggregation of ET in ET families and PD in PD families, and the familial co-aggregation of ET and PD.


Flight muscle differentiation in nymphs of a dragonfly Anax imperator.
Flight muscle fibers of Anax imperator nymphs, in different developmental stages are analyzed for several morphological features, such as the arragnement and numerical ratio of actin and myosin filaments, the pattern of the T system and sarcoplasmic reticulum, the number of microtubules and the fractional volume of mitochondria in each fiber. The T system is initially represented by longitudinal grooves on the cell surface, joined with vesicles of the sarcoplasmic reticulum; this pattern rapidly changes and the grooves start to break up into longitudinal segments. The thin to thick filament ratio is at first quite high (about 4-4.5:1) but rapidly falls to the final (3:1) when the myofibrils are well developed at the fiber periphery. Statistical analyses show that the measured values are significantly different in the various stages of development, also indicating a progressive reduction of the ratio variability. The reduction of thin to thick filament ratio and the variance decrease fit quite well with the hypothesis that the synthesis of actin and myosin depends on independently regulated messenger RNA molecules.


Facile synthesis of silicon nanoparticles inserted into graphene sheets as improved anode materials for lithium-ion batteries.
Silicon nanoparticles have been successfully inserted into graphene sheets via a novel method combining freeze-drying and thermal reduction. The as-obtained Si/graphene nanocomposite exhibits remarkably enhanced cycling performance and rate performance compared with bare Si nanoparticles for lithium-ion batteries.


Temporal changes in the current practice of primary angioplasty: a real life experience of a single high-volume center.
In the last years, new techniques, drugs and devices have been introduced in the current practice of primary angioplasty (PPCI) and validated by pivotal studies The objective of our study was to evaluate if these studies have led to significant changes on the current practice of primary PCI in our center. From March 2003 to December 2013 1980 patients with ST-segment elevation myocardial infarction underwent PPCI within 12-hours of onset of symptoms. We considered 2 periods of our activity: from 2003 to 2009 (P1) with 1078 patients and from 2010 to 2013 (P2) with 902 patients, and compared them in terms of pharmacological and arterial access strategies and of devices utilization. In P2 there was a significant increase of radial access (34.1% vs. 1.5, p<0.001), as well as of the use of bivalirudin (22.7% vs. 0.5%, p<0.001) and of new antiplatelet drugs (prasugrel or ticagrelor) (18.3% vs. 0%, p<0.001) whereas the use of GP IIb-IIIa and of intraaortic balloon pump significantly decreased (from 82.3% to 52%, p<0.001 and from 17% to 7.5%, p<0.001 respectively). In the P2 there was a significant increase of the procedural efficacy (97.2% vs. 95.1%, p=0.01) that persisted after the logistic regression adjustment (OR 2.09, CI 95%, 1.04-4.21). Our study shows that in the last years, in a high-PCI center, after the publication of pivotal randomized trial and nationwide registries, there were significant changes in the PPCI current practice that could have had an impact on procedural efficacy.


Thrombotic risk correlates with mutational status in true essential thrombocythemia.
True essential thrombocythemia (ET) may carry one of the known driver mutations (JAK2, MPL and CALR) or none of them [in triple-negative (3NEG) cases]. The patients' mutational status seems to delineate the clinical manifestations of ET. We report the data of 183 patients diagnosed with ET strictly according to the WHO 2008 criteria and with a full molecular diagnosis, including the following: 114 patients (62·3%) with JAK2V617F; 25 (13·7%) with CALR type 1 and 19 (10·4%) with CALR type 2; 3 (1·6%) with MPL; 22 (12%) who were 3NEG. Thrombotic risk was assessed by means of the IPSET-thrombosis score (IPSET-T). CALR and 3NEG patients had lower haemoglobin levels and leucocyte count than JAK2 patients. CALR patients, and those with type 2 in particular, had higher mean platelet counts and had extreme thrombocytosis more often than any of the other groups. Based on their IPSET-T stratification, 3NEG- and CALR-mutated patients belonged more frequently to the low-risk group and had a significant more favourable thrombosis-free survival rate than those with JAK2 mutation. These findings indicate that the three different molecular markers have a significant impact on the clinical course of true ET, giving rise to different phenotypes of the same disease.


Neuromagnetic responses to tactile stimulation of the fingers: Evidence for reduced cortical inhibition for children with Autism Spectrum Disorder and children with epilepsy.
The purpose of this study was to compare somatosensory responses from a group of children with epilepsy and a group of children with autism spectrum disorder (ASD), with age matched TD controls. We hypothesized that the magnitude of the tactile "P50m" somatosensory response would be reduced in both patient groups, possibly due to reduced GABAergic signaling as has been implicated in a variety of previous animal models and in vivo human MRS studies. We observed significant (~ 25%) decreases in tactile P50m dipole moment values from the source localized tactile P50m response, both for children with epilepsy and for children with ASD. In addition, the latency of the tactile P50m peak was observed to be equivalent between TD and ASD groups but was significantly delayed in children with epilepsy by ~ 6 ms. Our data support the hypothesis of impaired GABAergic signaling in both children with ASD and children with epilepsy. Further work is needed to replicate these findings and directly relate them to both in vivo measures of GABA via e.g. magnetic resonance spectroscopy and psychophysical assessments of somatosensory function, and behavioral indices.


Generalized tetanus in a landscaper without obvious wounds.
Tetanus is rare and potentially fatal infection in the US. Its incidence has declined dramatically over the years in developed countries due to robust immunization programs. We describe a case of generalized tetanus in a 66-year-old inadequately vaccinated landscaper who presented with classical symptoms but did not have any open wounds leading to delay in initial diagnosis but was successfully managed once the diagnosis was established.


Isolation and partial characterization of poly (A)-containing 7.5S messenger RNA from rat liver mitochondria.
Poly(A)-containing low molecular weight (7.5S) messenger RNA was isolated in a highly purified form from both polyribosomes and post-polysomal supernatant of rat liver mitochondria. Both mRNA's contain rather short poly(A) tracts (40-70 mononucleotides) according to a profile of their elution from poly(U)-Sepharose column with a gradient of formamide concentration. Both mRNA's when added to a preincubated mitochondrial lysate programmed the synthesis of a hydrophobic polypeptide of a molecular weight about 9000 daltons which was soluble in the neutral chloroform-methanol mixture.


Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture.
A family of oligonucleotides and phosphorothioate oligonucleotide analogues was synthesized with a cholesteryl group tethered at the 3'-terminal internucleoside link. This modification, introduced to enhance interaction of the polyanions with cell membranes, significantly increases the antiviral activity of the oligomers, as judged by inhibition of syncytia formation and expression of viral proteins p17, p24, and reverse transcriptase for human immunodeficiency virus 1 in Molt-3 cells. In the most favorable case, with a 20-mer cholesteryl-phosphorothioate derivative, complete inhibition by all assays was obtained with an oligomer concentration of 0.2 microM. Even decamers were active, and some antiviral activity was observed for a heptanucleotide cholesteryl-phosphorothioate derivative, which binds very poorly to complementary oligonucleotides. These facts, and the finding that the activity of the phosphorothioate decamers does not correlate with a specific sequence, suggests that a mechanism other than "antisense inhibition" may be operative in these systems.