Risk of bias tools in systematic reviews of health interventions: an analysis of PROSPERO-registered protocols.
Systematic reviews of health interventions are increasingly incorporating evidence outside of randomized controlled trials (RCT). While non-randomized study (NRS) types may be more prone to bias compared to RCT, the tools used to evaluate risk of bias (RoB) in NRS are less straightforward and no gold standard tool exists. The objective of this study was to evaluate the planned use of RoB tools in systematic reviews of health interventions, specifically for reviews that planned to incorporate evidence from RCT and/or NRS. We evaluated a random sample of non-Cochrane protocols for systematic reviews of interventions registered in PROSPERO between January 1 and October 12, 2018. For each protocol, we extracted data on the types of studies to be included (RCT and/or NRS) as well as the name and number of RoB tools planned to be used according to study design. We then conducted a longitudinal analysis of the most commonly reported tools in the random sample. Using keywords and name variants for each tool, we searched PROSPERO records by year since the inception of the database (2011 to December 7, 2018), restricting the keyword search to the "Risk of bias (quality) assessment" field. In total, 471 randomly sampled PROSPERO protocols from 2018 were included in the analysis. About two-thirds (63%) of these planned to include NRS, while 37% restricted study design to RCT or quasi-RCT. Over half of the protocols that planned to include NRS listed only a single RoB tool, most frequently the Cochrane RoB Tool. The Newcastle-Ottawa Scale and ROBINS-I were the most commonly reported tools for NRS (39% and 33% respectively) for systematic reviews that planned to use multiple RoB tools. Looking at trends over time, the planned use of the Cochrane RoB Tool and ROBINS-I seems to be increasing. While RoB tool selection for RCT was consistent, with the Cochrane RoB Tool being the most frequently reported in PROSPERO protocols, RoB tools for NRS varied widely. Results suggest a need for more education and awareness on the appropriate use of RoB tools for NRS. Given the heterogeneity of study designs comprising NRS, multiple RoB tools tailored to specific designs may be required.


Cytoplasmic control of intranuclear polarity by human cytomegalovirus.
Despite its size and rigidity, the cell nucleus can be moved or reorganized by cytoskeletal filaments under various conditions (for example, during viral infection)1-11. Moreover, whereas chromatin organizes into non-random domains12, extensive heterogeneity at the single-cell level13 means that precisely how and why nuclei reorganize remains an area of intense investigation. Here we describe convolutional neural network-based automated cell classification and analysis pipelines, which revealed the extent to which human cytomegalovirus generates nuclear polarity through a virus-assembled microtubule-organizing centre. Acetylation of tubulin enables microtubules emanating from this centre to rotate the nucleus by engaging cytoplasmically exposed dynein-binding domains in the outer nuclear membrane protein nesprin-2G, which polarizes the inner nuclear membrane protein SUN1. This in turn creates intranuclear polarity in emerin, and thereby controls nuclear actin filaments that spatially segregate viral DNA from inactive histones and host DNA, maximizing virus replication. Our findings demonstrate the extent to which viruses can control the nucleus from the cytoplasm.


Sexual function in young women with spontaneous 46,XX primary ovarian insufficiency.
To assess sexual function in women with spontaneous 46,XX primary ovarian insufficiency after at least 3 months of a standardized hormone replacement regimen. Cross-sectional cohort, controlled. National Institutes of Health Clinical Research Center. Women with primary ovarian insufficiency (n = 143) and regularly menstruating controls (n = 70). Self-administered questionnaires, 100 microg/day E(2) patch, oral medroxyprogesterone acetate 10 mg for 12 days each month for patients. Derogatis Interview for Sexual Function Self-Report (DISF-SR). Women with primary ovarian insufficiency had significantly lower DISF-SR composite scores compared with control women. Their serum total testosterone levels were significantly correlated with DISF-SR composite score, although this accounted for only 4% of the variance in this measure. Patients with testosterone levels below normal tended to have lower DISF-SR composite scores. Of patients with primary ovarian insufficiency, 9 of 127 (7%) scored below the second percentile on the composite sexual function score, compared with 1 of 49 control women (2%). As assessed by the DISF-SR, sexual function is in the normal range for most young women with 46,XX spontaneous primary ovarian insufficiency who are receiving physiologic E(2) replacement. However, as a group, these young women score significantly lower on this sexual function scale than control women.


ERK1 plays a critical protective role against N-methyl-D-aspartate-induced retinal injury.
Excitotoxicity has been implicated in several ischemic diseases of the retina, including retinal vessel occlusion and diabetic retinopathy. Glutamate signaling mediated through the N-methyl-D-aspartate (NMDA) receptor contributes to ischemic cell death. The NMDA receptor antagonists MK-801 and memantine have substantial neuroprotective effects in experimental retinal disease models, but the mechanisms by which NMDA receptor activity leads to cell death is not clear. Here we describe a previously unknown role for retinal glial cells in NMDA-induced retinal injury that involves the activation of ERK1/2. Within 1 hr after injecting NMDA intravitreally, activation of ERK1/2 and c-Fos induction were observed in retinal Müller cells. The roles of activated ERK1/2 in neuronal damage were examined using ERK1 gene deficient mice (homozygous ERK1(-/-) mice). NMDA-induced ERK1/2 activation in retina was significantly suppressed in ERK1(-/-) mice, and these mice had significantly higher numbers of TUNEL-positive retinal cells than wild-type mice 24 hr after NMDA injection. These data suggest that, during NMDA injury, Müller cells are activated and play a protective role against NMDA-induced retinal cell death. ERK1 appears to play a major role in this process. These new findings on retinal glial cell response during NMDA injury offer an important new therapeutic target for preventing many retinal disorders associated with excitotoxicity.


Improved survival associated with neoadjuvant chemoradiation in patients with clinical stage IIIA(N2) non-small-cell lung cancer.
Optimal management of clinical stage IIIA-N2 non-small-cell lung cancer (NSCLC) is controversial. This study examines whether neoadjuvant chemoradiation plus surgery improves survival rates when compared with other recommended treatment strategies. Adult patients from the National Cancer Database, with clinical stage IIIA-N2 disease definitively treated between 1998 and 2004 at American College of Surgeons Commission on Cancer accredited facilities, were included in the study. Treatment was defined as neoadjuvant chemoradiation plus either lobectomy (NeoCRT+L) or pneumonectomy (NeoCRT+P), lobectomy plus adjuvant therapy (L+AT), pneumonectomy plus adjuvant therapy (P+AT), and concurrent chemoradiation (CRT). Median follow-up and overall survival (OS) were defined from date of diagnosis to last contact. Five-year OS was estimated using Kaplan-Meier methods. Cox proportional hazard regression was used to estimate hazard ratios and 95% confidence intervals (CIs), adjusting for sociodemographic, clinical, and facility characteristics. Median follow-up was 11.8 months for 11,242 eligible patients. Five-year OS was 33.5%, 20.7%, 20.3%, 13.35%, and 10.9% for NeoCRT+L, NeoCRT+P, L+AT, P+AT, and CRT, respectively (p < 0.0001). On multivariable analysis, the estimated hazard ratio was 0.51 (CI: 0.45-0.58) for NeoCRT+L; 0.77 (0.63-0.95) for NeoCRT+P; 0.66 (0.59-0.75) for L+AT; 0.69 (0.54-0.88) for P+AT; and 1.0 (reference) for the CRT group. Comorbidity did not attenuate the relationship between treatment and survival. This large study demonstrates that patients with clinical stage IIIA-N2 NSCLC, who underwent neoadjuvant chemoradiation followed by lobectomy, were associated with an improved survival.


Ex vivo repair of a large renal artery aneurysm and associated arteriovenous fistula.
The development of a renal artery to vein arteriovenous fistula due to a large extraparenchymal renal artery aneurysm is uncommon. Previous surgical experience with this entity is limited. Based on the existing surgical literature, nephrectomy has been the treatment of choice. We report preservation of the kidney by surgical correction of this entity using ex vivo "bench" repair in a middle-aged female with fibromuscular dysplasia of the renal artery. The technique, results, and recommendations for surgical management are discussed.


Detecting prolonged sitting bouts with the ActiGraph GT3X.
The ActiGraph has a high ability to measure physical activity; however, it lacks an accurate posture classification to measure sedentary behavior. The aim of the present study was to develop an ActiGraph (waist-worn, 30 Hz) posture classification to detect prolonged sitting bouts, and to compare the classification to proprietary ActiGraph data. The activPAL, a highly valid posture classification device, served as reference criterion. Both sensors were worn by 38 office workers over a median duration of 9 days. An automated feature selection extracted the relevant signal information for a minute-based posture classification. The machine learning algorithm with optimal feature number to predict the time in prolonged sitting bouts (≥5 and ≥10 minutes) was searched and compared to the activPAL using Bland-Altman statistics. The comparison included optimized and frequently used cut-points (100 and 150 counts per minute (cpm), with and without low-frequency-extension (LFE) filtering). The new algorithm predicted the time in prolonged sitting bouts most accurate (bias ≤ 7 minutes/d). Of all proprietary ActiGraph methods, only 150 cpm without LFE predicted the time in prolonged sitting bouts non-significantly different from the activPAL (bias ≤ 18 minutes/d). However, the frequently used 100 cpm with LFE accurately predicted total sitting time (bias ≤ 7 minutes/d). To study the health effects of ActiGraph measured prolonged sitting, we recommend using the new algorithm. In case a cut-point is used, we recommend 150 cpm without LFE to measure prolonged sitting and 100 cpm with LFE to measure total sitting time. However, both cpm cut-points are not recommended for a detailed bout analysis.


Lack of suppression of IgE production by recombinant interferon gamma: a controlled trial in patients with allergic rhinitis.
Recent evidence suggests that interferon-gamma (IFN-gamma) is a potent inhibitor of IgE synthesis in rodents. We conducted a randomized, placebo-controlled, two-period clinical trial of human recombinant IFN-gamma in the treatment of allergic rhinitis. Forty-five adults with well-documented ragweed-allergic rhinitis were randomized into three groups of 15 adults each and received subcutaneous injections three times weekly. The first treatment period (4 weeks during the off season) began on April 18, 1988; the second treatment period (6 weeks during ragweed pollination) began on August 15, 1988. All subjects received the same treatment in both periods. Group 1 received 0.2 mg per injection of IFN, group 2 received 0.02 mg of IFN, and group 3 received placebo. One subject in group 1 and three subjects in group 2 withdrew because of adverse reactions, and three subjects withdrew for personal reasons. There were no significant differences in mean weekly symptom scores or supplemental medication scores among the three groups in either treatment period. Furthermore, there were no significant differences in the changes of serum IgE antibody to crude ragweed extract or in serum total IgE among the three groups during or before the ragweed-pollination season. These results indicate that this treatment regimen with IFN-gamma does not alter IgE production in patients with ragweed hay fever and indicate the need for further clinical research of lymphokine modulation of IgE production.


Novel two-tiered developmental screening programme for Singaporean toddlers: a quality improvement report.
Early identification of developmental delays with timely intervention, especially before the age of 3 years, can improve child development. In Singapore, however, diagnosis and intervention for developmental delays occur at a median age of 44 months. As early detection and intervention depends on an effective developmental screening programme, we aimed to improve the detection of developmental delays before the age of 3 years in a primary care setting. We did this by implementing a novel two-tiered screening programme which uses three standardised screening tools (Parents' Evaluation of Developmental Status, PEDS-Developmental Milestones and Ages and Stages Questionnaire-3). We used quality improvement methods to integrate and optimise this two-tiered programme into the existing 9-month and 18-month screening schedule, with an additional screening at 30 months to replace the pre-existing 36-month screening of the National Child Health Surveillance Programme. A total of three Plan-Do-Study-Act cycles were performed to ensure programme feasibility and sustainability. They focused on adequately training the primary care nurses, targeting an 80% screening rate and aiming for 20 min screening tool administration time per child. We assessed the proportion of children referred to the child development units after positive screening for developmental concerns under the new programme, with a pre-post and with-without intervention comparison, and reviewed the screening rates and screening tool administration time. The proportion of 18-month old children referred for developmental concerns improved from 3.5%-7.1% over a 6-month period. For those who received further assessment by developmental specialists after the two-tiered screening, 100% received a definitive diagnosis of developmental delays, similar to the situation before programme introduction. Our quality improvement efforts facilitated successful integration of the two-tiered programme into the pre-existing screening schedule with minimal impact to the clinic workflow. While we highlight challenges in implementation that need to be addressed, our findings support a potential nationwide adoption of the two-tiered programme.


Whole-body magnetic resonance imaging for staging Langerhans cell histiocytosis in children and young adults.
Radiographic skeletal survey (R-SS) is the standard imaging technique for the initial staging of Langerhans cell histiocytosis (LCH). Whole-body magnetic resonance imaging (WB-MRI) has been proposed as an effective, radiation-free alternative. We prospectively assessed patients with LCH followed at three tertiary centers in Italy and Austria. Two national study protocols were independently designed, and data were then pooled to increase the power of their findings. R-SS and WB-MRI were performed at diagnosis and repeated at the follow-up to confirm the nature of the identified lesions and to study their evolution. Data from 67 patients were analyzed (52 from Italy and 15 from Austria). Compared to R-SS, WB-MRI identified 29 additional skeletal lesions in 14 patients (including two false-positive lesions). Two skeletal lesions were detected at R-SS and missed at WB-MRI (false negative). Per-lesion sensitivity rates were 78.6% (95% CI: 71.0-85.9) for R-SS and 98.4% (95% CI: 94.4-99.8) for WB-MRI, respectively. Based on WB-MRI findings, six patients would have been upstaged to a higher risk class than staging with R-SS. WB-MRI had a significantly higher detection rate for skeletal lesions compared to R-SS. Clinical and radiology expertise is required to avoid upstaging and overtreatment.


Rapid and reliable re-design of miniaturized microwave passives by means of concurrent parameter scaling and intermittent local tuning.
Re-design of microwave passive components for the assumed operating frequencies or substrate parameters is an important yet a tedious process. It requires simultaneous tuning of relevant circuit variables, often over broad ranges thereof, to ensure satisfactory performance of the system. If the operating conditions at the available design are distant from the intended ones, local optimization is typically insufficient, whereas global search entails excessive computational expenses. The problem is aggravated for miniaturized components, typically featuring large numbers of geometry parameters. Furthermore, owing to their tightly-arranged layouts, compact structures exhibit considerable cross-coupling effects. In order to reliably evaluate electrical characteristics under such conditions full-wave electromagnetic (EM) analysis is mandatory. Needless to say, EM-driven design over broad ranges of operating frequencies is an arduous and costly endeavor. In this paper, we introduce a novel procedure for rapid and reliable re-design of microwave passives. Our methodology involves concurrent scaling of geometry parameters interleaved with local (gradient-based) tuning. The scaling stage allows for low-cost relocation of the operating frequencies of the circuit, whereas the optimization stage ensures continuous (iteration-wise) alignment of the performance figures with their target values. The presented framework is validated using several miniaturized microstrip couplers, re-designed over extended ranges of the center frequencies. For all considered structures, satisfactory designs are successfully identified despite the initial designs being distant from the targets, whereas local tuning turns out to be demonstrably inferior. Apart from its efficacy, one of the most important advantages of the proposed framework is its simplicity, and the lack of problem-dependent control parameters.


New therapeutic approaches for ANCA-associated vasculitides.
For many years, despite severe side effects, vasculitides have been managed with high doses of corticosteroids and long-lasting intensive immunosuppression. Recent, innovative approaches have improved our knowledge of the disease pathophysiologies leading to novel treatments that are transforming the standard of care, at least for antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs) and again providing new elements to further understanding of the disease mechanisms. Although this could seem to be a virtuous circle of enhanced comprehension and innovation, many questions regarding patient care remain unsolved and a closer look at the past could temper this exciting race to new drug discovery. In this review, we describe the different evidence-based medicine strategies, the drugs that are being tested in AAV patients and novel strategies that should improve AAV treatment. However, the costs and benefits of the development of new treatment strategies are also considered in light of 20 years of clinical trial experience in the field of AAVs.


Parents' information needs and preferences related to bronchiolitis: a qualitative study.
Bronchiolitis affects more than one-third of children less than age 2 years and can cause substantial anxiety for parents, leading them to seek information on how to care for their sick child. The aim of our qualitative study was to explore the information needs and preferences of parents caring for a child with bronchiolitis. We used a qualitative descriptive approach. Participants were recruited by means of purposive sampling from Oct. 1, 2017, to Mar. 15, 2018 from the Stollery Children's Hospital emergency department, a specialized pediatric emergency department in Edmonton. Individual semistructured interviews were conducted. Fifty-three parents were recruited to participate, of whom 30 could not be reached after 4 contact attempts and 8 refused. Thus, 15 parents participated (16 children). Three major themes were identified: 1) parents' information needs about bronchiolitis, 2) parents' preferred information sources and 3) parents' preferred information delivery formats. Participants indicated that they want and require credible, easy-to-understand information about bronchiolitis in a variety of formats, and especially valued information obtained directly from a health care professional or an evidence-based website. This study provides important information about parents' information needs concerning bronchiolitis in children. Identifying the information that parents want and value in relation to acute pediatric illnesses is imperative to developing innovative educational approaches for parents that reflect patient-centred care.


Measurement of bending and torsion with and without an intramedullary nail implanted in sheep tibia in vivo.
This report concerns the analysis of the dynamic measurements of torque and bending on nailed tibiae, using two sheep walking at different speeds on a treadmill, both before and after nailing. The amplitude and the period of the measured values are reported and discussed in relationship to the speed and duration of the experiment.


Infrainguinal endovascular and bypass surgery for critical leg ischemia in patients on long-term dialysis.
Lower limb revascularization has been shown to be worthwhile for treatment of critical leg ischemia in uremic patients, but poor results are expected in patients on long-term dialysis. We have retrospectively evaluated the results of a series of 21 consecutive patients on long-term dialysis who underwent 20 infrainguinal bypass graft and 5 endovascular procedures for critical leg ischemia to identify factors contraindicating any infrainguinal revascularization attempt in this patient population. At 2-year follow-up, the patency rate was 74%, leg salvage rate was 85%, and survival rate was 23%, whereas 23% of patients were alive with salvaged leg. Patients on hemodialysis achieved better survival outcome than patients on peritoneal dialysis (p = 0.02). Multivariate analysis showed that low serum level of albumin (p = 0.009; p = 0.005) and coronary artery disease (p = 0.0002; p = 0.001) had an adverse effect on the survival rate and on the rate of patients alive with salvaged leg, respectively. Patients without coronary artery disease achieved an alive-with-salvaged-leg rate at 1- and 2-year follow-up of 68% and 41%, respectively, whereas 12% of patients with coronary artery disease survived with salvaged leg after 1 year, but none of them survived with salvaged leg at 2-year follow-up (p = 0.003). In conclusion, infrainguinal revascularization for lower extremity ischemia in dialysis patients is hardly indicated in the presence of coronary artery disease and severe hypoalbuminemia.


Study of coal and graphite specimens by means of Raman and cathodoluminescence.
The weak luminescence shown by coals has been attributed to accessorial minerals and poly-nuclear aromatic hydrocarbons, such as exinite, vitrinite or inertinite, while the luminescence quenching has been found in asphaltenes produced by coal hydrogenation or in pyridine extracts. Nowadays, the spatial resolution and the improved luminescence efficiency of the modern spectrometers allow some details of the luminescent emission centers to be explained. We have selected museum historical coal specimens with different rank, i.e., peat, lignite, sub-bituminous, bituminous, and anthracite to be analyzed by their spectra from cathodoluminescence probe (CL) of an environmental scanning electron microscopy (ESEM), with an energy dispersive spectrometry analyzer (EDS). Additional analytical controls were also performed by X-ray diffraction (XRD), X-ray fluorescence (XRF) and Raman spectrometries. We conclude that coals may display different luminescence emission features coming from several different sources, as follows: (i) broadband of intense luminescence from polynuclear aromatic hydrocarbons, (ii) weakly visible broadband luminescence attributed to band-tail states caused by variations in the energy gap of individual sp(2) carbon clusters, which are different in size and/or shape, (iii) silicate impurities causing the common luminescence peak at 325 nm observed in coals. This peak is due to non-bridging oxygen hole centres (≡Si-O·) probably generated by precursor Si-O-C species formed by ≡Si-O· defects and carbon atoms; (iv) a 710 nm CL emission commonly detected also in wood and ivory, which has been correlated with hydrocarbon groups of chlorophyll or lignine. Coals are very complex rocks, composed by both organic and inorganic phases with variable and complex spectra. More analyses are necessary and carbonaceous standards of graphite, silicon carbide, stuffed carbon silica and diamond at variable experimental conditions have to be developed.


[Role of the orthodontist in surgical-orthodontic treatment: total osteotomies].
The total osteotomies of the upper and lower jaw are considered with particular reference to the orthodontic treatment before, during and after surgery. Several clinical cases are presented.


Does forceps training on a birth simulator allow obstetricians to improve forceps blade placement?
The aim of this study was to evaluate whether forceps training on a birth simulator allows obstetricians to improve forceps blade placement. Analysis was based on 600 forceps blade placements performed by ten trainees on a simulator. The trajectories used by the trainees were assessed using reference spheres that reflected an optimal bimalar placement. Three definitions of success were used: small-sphere success, medium-sphere success and large-sphere success were respectively defined by the forceps blade tip being within 5, 10 or 15mm of the center of the sphere (the small-sphere being nested within the medium-sphere and the small and medium being nested within the large-sphere). Wilcoxon paired analysis was performed to compare the first (50 trajectories) and final (50 trajectories) sets of five forceps placements. Graphical representation and linear regression were used to visualize the learning process. 596 trajectories were available for analysis. During the last set of five forceps the success rate was respectively 28%, 72% and 86% for small-sphere, medium-sphere and large-sphere success with the right blade and 8%, 32% and 70% for the left blade. Wilcoxon analysis showed a highly significant improvement for all kinds of success in the right blade and for large-sphere success in the left blade. Linear regression slopes were significant. Using a projection, the theoretical numbers of placements needed to achieve a 100% success rate for small-sphere, medium-sphere and large-sphere were respectively 80, 45 and 35. These results strongly suggest that performing forceps blade placement on birth simulator allows obstetricians to improve their skills.


Doppler echocardiography in diastology: 35 years of Japanese contribution to its advancement and utility.
Echocardiography is one of the most important and clinically useful techniques in the assessment of diastolic function. Because of the prevalence of this technique, "diastology" and even the concept of diastolic heart failure have become familiar to researchers and physicians. We believe the first description by Kitabatake and his colleagues in 1982 of the use of Doppler technique to assess the transmitral flow velocity pattern in various cardiac diseases was the beginning of this development. Since then, a number of excellent works regarding echocardiographic assessment of diastolic function have emerged from Japan. Here, we review the Japanese contributions to the development of the use of Doppler echocardiography in diastology.


Distribution patterns of octylphenol and nonylphenol in the aquatic system at mai po marshes nature reserve, a subtropical estuarine wetland in Hong Kong.
Spatial and temporal distribution of octylphenol (OP) and nonylphenol (NP) in Mai Po Marshes, a subtropical estuarine wetland in Hong Kong, were investigated. Surface water samples were collected every month from 11 sites during the period of September-December 2004. Concentrations of OP and NP ranged from 11.3 to 348 ng/L and from 29 to 2591 ng/L, respectively. The high levels of NP and OP were found in November and December than in September and October. The levels of OP and NP have no significant spatial differences except September. Total organic matter in the sediments appeared to be an important factor in controlling the fate of these compounds in the aquatic environment.


Isolation of a cellulotytic Bacteroides sp. from human feces.
An anaerobic cellulolytic bacterium, identified as a Bacteroides sp., was present in 10(-8) g of feces from only one of five human subjects.


A prospective, controlled study of SNS01 (ectoine nasal spray) compared to BNO-101 (phytotherapeutic dragées) in patients with acute rhinosinusitis.
In this observational study, data on the efficacy, effects on quality of life and tolerability of the topical formulation SNS01 (Ectoin Rhinitis nasal spray) were compared to those of BNO-101 (Sinupret forte dragées) in patients with acute rhinosinusitis in the ear, nose, and throat (ENT) clinical setting. Patients with the diagnosis of acute rhinosinusitis were included in this non-interventional study with a treatment duration of 14-16 days. They received either a herbal phytotherapeutic dragée (control) or an ectoine-based nasal spray (investigational product), each to be taken according to the instructions for use (IFU) and summary of product characteristics (SPC). At each visit, the physician performed a nasal endoscopy, recorded the Sinusitis Symptom Score and checked for adverse events. During the entire treatment period, patients recorded the Sinusitis Symptom Score in patient diaries. In addition, patients receiving the nasal spray filled out a questionnaire to assess the tolerability of the treatment. To investigate effects on quality of life patients were asked to fill out the German version of a sinusitis-specific HRQL (health related quality of life) questionnaire. NCT01684540. Patient diary entries, the assessment of the Sinusitis Symptom Score and the HRQL questionnaire demonstrated that the ectoine nasal spray was as effective as the phytotherapeutic dragées in treating acute rhinosinusitis. After two weeks of treatment, the assessments of both the patients' diaries and physicians' record forms indicated statistically significant improvement (p ≤ 0.001) in the symptom scores of the two groups (57.8% improvement for ectoine and 49.3% improvement for the phytotherapeutic dragées compared to baseline). Also, overall scores of 80 in the sensory questionnaire confirmed the good tolerability of the nasal spray. Correspondingly, HRQL improved significantly over the course of the treatment in both groups. SNS01 and BNO-101 demonstrated comparable effects in the treatment of acute rhinosinusitis. Following German regulations, this trial was set up as an observational 'non-interventional' study, which does not allow for a placebo group or randomization of patients. Although the grade of evidence delivered by the study data is thus reduced from Ib to IIa, it does, however, reflect a realistic view of the most common clinical practice.


Auditory syntactic comprehension in nine aphasia groups (with CT scans) and children: differences in degree but not order of difficulty observed.
Auditory syntactic comprehension was examined in nine groups of aphasics (60 stroke cases) and 3 and 6 year old children. Ten syntactic contrast pairs were studied. Differences in degree but not order of difficulty were observed. The 5 easier pairs were Gender; On/Under; Negative/Affirmative; Object-number; Subject-number; the 5 more difficult pairs were Past/Present; Subject/Object Reversible; Is/Are; Relative Clause; and Future/Present. The "marked" half-pair was significantly more difficult--i.e., Negative vs. Affirmative; Plural vs. Singular Subject; Future or Past vs. Present. Performance on the test was significantly correlated with the BDAE Auditory Comprehension z-score and Token Test. The 3 year old children most closely resembled the Severe Wernicke's (but were better than the Globals), and the 6 year old children were similar to aphasia cases with mild comprehension deficits and frontal or parietal perisylvian lesions which spared most of Wernicke's area. Wernicke's area (posterior two-thirds superior temporal gyrus area) appears to be the area most sensitive to auditory syntactic comprehension. However, the surrounding perisylvian areas including frontal and parietal lobes are also areas sensitive to syntactic comprehension.


Left-sided Breast Cancer Irradiation With Deep Inspiration Breath-hold: Changes in Heart and Lung Dose in Two Periods.
Post-operative radiotherapy for breast cancer can increase cardiac disease in a dose-dependent manner. In this study we show the reduction of dose to heart and left anterior descending artery (LAD) which can be achieved by using "Deep inspiration breath-hold" (DIBH) technique. Tangential 3D-planned radiation was delivered to 357 patients with left-sided breast cancer, 159 of them with the DIBH technique. A distinction was made according to fractionation scheme. The mean heart dose was significantly reduced by DIBH from 2.64 Gy to 1.39 Gy (p<0.001). The mean dose to the LAD was significantly reduced from 5.68 Gy to 3.88 Gy (p<0.001). Mean dose and volume receiving 5, 10 and 15 Gy of ipsilateral lung were higher with both hypofractionated schedule and conventional fractionation in the DIBH group. DIBH in left-sided breast irradiation is an effective method of reducing the radiogenic heart dose.


Purification and Characterization of an Extracellular Cholesterol Oxidase of Bacillus subtilis Isolated from Tiger Excreta.
A mesophilic Bacillus sp. initially isolated from tiger excreta and later identified as a Bacillus subtilis strain was used to produce an extracellular cholesterol oxidase (COX) in cholesterol-enriched broth. This bacterial isolate was studied for the production of COX by manipulation of various physicochemical parameters. The extracellular COX was successfully purified from the cell-free culture broth of B. subtilis by successive salting out with ammonium sulfate, dialysis, and riboflavin-affinity chromatography. The purified COX was characterized for its molecular mass/structure and stability. The enzyme possessed some interesting properties such as high native Mr (105 kDa), multimeric (pentamer of ∼21 kDa protein) nature, organic solvent compatibility, and a half-life of ∼2 h at 37 °C. The bacterial COX exhibited ∼22 % higher activity in potassium phosphate buffer (pH 7.5) in the presence of a nonionic detergent Triton X-100 at 0.05 % (v/v). The K m and V max value of COX of B. subtilis COX were found to be 3.25 mM and 2.17 μmol min ml(-1), respectively. The purified COX showed very little cytotoxicity associated with it.


A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains.
Malaria vaccines are being developed against different stages in the parasite's life cycle, each increasing the opportunity to control malaria in its diverse settings. Sporozoite vaccines are designed to prevent mosquito-induced infection; first generation recombinant or synthetic peptide vaccines have been tested in humans. Asexual erythrocytic stage vaccines, developed to prevent or reduce the severity of disease, have been tested in animals and in humans. A third strategy is to produce sexual stage vaccines that would induce antibodies which would prevent infection of mosquitoes when ingested in a bloodmeal containing sexual stage parasites. Although not directly protective, the sexual stage vaccine combined with a sporozoite or asexual stage vaccine (protective component) could prolong the useful life of the protective component by reducing transmission of resistant vaccine-induced mutants. In areas of low endemnicity, the sexual stage vaccine could reduce transmission below the critical threshold required to maintain the infected population, thereby assisting in the control or eradication of malaria. Transmission of Plasmodium falciparum, the major human malaria, can be blocked by monoclonal antibodies against three sexual stage-specific antigens. We have cloned the gene encoding the surface protein of relative molecular mass Mr 25,000 (25K; Pfs25), expressed on zygotes and ookinetes of P. falciparum. The deduced amino-acid sequence consists of a signal sequence, a hydrophobic C-terminus, and four tandem epidermal growth factor EGF-like domains.


Pediatric penetrating thoracic trauma: Examining the impact of trauma center designation and penetrating trauma volume on outcomes.
We analyzed the impact of treating center designation and case volume of penetrating trauma on outcomes after pediatric penetrating thoracic injuries (PTI). PTI patients <18 years were identified from the National Trauma Data Bank (2013-2016). Centers were categorized by type (Pediatric or Adult) and designation status (Level I, Level II, and other). Performance was calculated as the difference between observed and expected mortality and standardized using the total penetrating trauma volume per center. Expected mortality was calculated using the Trauma Mortality Prediction Model. Pearson correlation and linear mixed-effects models evaluated the association between variables and performance. We identified 4,134 PTI patients treated at 596 trauma centers: 879 (21%) at Adult Level I, 608 (15%) at Adult Level II, 531 (13%) at Pediatric Level I, 320 (8%) at Pediatric Level II, and 1,796 (43%) at other centers. Primary injury mechanisms were firearm-related (58%) and cut/piercing (42%). Overall mortality was 16% and median predicted mortality was 3.6% (IQR: 1.5% - 11.2%). Among patients with thoracic firearm-related injuries, centers with lower penetrating case volume and total trauma care demonstrated significantly worse outcomes. Multivariable analysis revealed Adult Level I centers had superior outcomes compared with all other non-Level I centers. There was no difference in mortality between Pediatric and Adult Level I centers. Adult Level I trauma center designation and annual case volume of penetrating thoracic trauma are associated with improved mortality after pediatric firearm-related thoracic injuries. Further study is needed to identify factors in higher volume centers that improve outcomes. Level III.


Vesicoureteral Injury during Benign Hysterectomy: Minimally Invasive Laparoscopic Surgery versus Laparotomy.
The findings of previous studies have been inconsistent as to whether benign hysterectomy via minimally invasive laparoscopic surgery increases the risk of vesicoureteral injury when compared with laparotomy. The objectives of our study were to (1) examine the rate of vesicoureteral injury on benign hysterectomy by the surgical approach and (2) compare the risk of vesicoureteral injury specifically between minimally invasive laparoscopic and abdominal hysterectomy on a populational level. Retrospective population-based observational study. The National Inpatient Sample. A total of 501 110 women who had undergone hysterectomy for benign gynecologic disease between January 2012 and September 2015 were included as follows: total abdominal hysterectomy (TAH, n = 284 365 [56.7%]), total laparoscopic hysterectomy (TLH, n = 60 410 [12.1%]), abdominal supracervical hysterectomy (Abd-SCH, n = 55 655 [11.1%]), laparoscopic-assisted vaginal hysterectomy (LAVH, n = 45 620 [9.1%]), total vaginal hysterectomy (TVH, n = 34 865 [7.0%]), and laparoscopic supracervical hysterectomy (LSC-SCH, n = 20 195 [4.0%]). A comprehensive risk assessment for vesicoureteral injury by hysterectomy mode was performed, adjusting for patient demographics and gynecologic disease types. Propensity score inverse probability of treatment weighing was used to compare (1) TLH versus TAH and (2) LSC-SCH versus Abd-SCH with generalized estimating equations. In a sensitivity analysis, gynecologic disease-specific injury risk and vaginal route-specific injury risk (LAVH vs TVH) were assessed. Vesicoureteral injury was reported in 1045 (0.21%) women overall. LAVH (0.28%) had the highest bladder injury rate, whereas LSC-SCH had the lowest (0.10%) (p <.001). TLH (0.13%) had the highest ureteral injury rate, whereas TAH had the lowest (0.04%) (p <.001). In propensity score inverse probability of treatment weighing models, compared with TAH, TLH was associated with an increased risk of ureteral injury (odds ratio [OR] 3.95, 95% confidence interval [CI] 2.03-7.67, p <.001) but not bladder injury (OR 1.04, 95% CI 0.57-1.90, p = .897). Risk of ureteral injury was particularly high when TLH was performed for endometriosis (OR 6.15, 95% CI 1.18-31.9, p = .031) or for uterine myoma (OR 4.15, 95% CI 2.13-8.11, p <.001). In contrast, for supracervical or vaginal hysterectomy, minimally invasive laparoscopic approaches were not associated with an increased risk of vesicoureteral injury (LSC-SCH vs Abd-SCH: OR 0.62, 95% CI 0.19-1.98, p = .419; LAVH vs TVH: OR 1.21, 95% CI 0.63-2.33, p = .564). The risk of vesicoureteral injury on benign hysterectomy is low overall regardless of hysterotomy modalities but varies widely with the surgical approach. Compared with TAH, TLH may be associated with an increased risk of ureteral injury.


Comparing Xe+ pFIB and Ga+ FIB for TEM sample preparation of Al alloys: Minimising FIB-induced artefacts.
Recently, the dual beam Xe+ plasma focused ion beam (Xe+ pFIB) instrument has attracted increasing interest for site-specific transmission electron microscopy (TEM) sample preparation for a local region of interest as it shows several potential benefits compared to conventional Ga+ FIB milling. Nevertheless, challenges and questions remain especially in terms of FIB-induced artefacts, which hinder reliable S/TEM microstructural and compositional analysis. Here we examine the efficacy of using Xe+ pFIB as compared with conventional Ga+ FIB for TEM sample preparation of Al alloys. Three potential source of specimen preparation artefacts were examined, namely: (1) implantation-induced defects such as amophisation, dislocations, or 'bubble' formation in the near-surface region resulting from ion bombardment of the sample by the incident beam; (2) compositional artefacts due to implantation of the source ions and (3) material redeposition due to the milling process. It is shown that Xe+ pFIB milling is able to produce improved STEM/TEM samples compared to those produced by Ga+ milling, and is therefore the preferred specimen preparation route. Strategies for minimising the artefacts induced by Xe+ pFIB and Ga+ FIB are also proposed. LAY DESCRIPTION: FIB (focused ion beam) instruments have become one of the most important systems in the preparation of site-specific TEM specimens, which are typically 50-100 nm in thickness. TEM specimen preparation of Al alloys is particularly challenging, as convention Ga-ion FIB produces artefacts in these materials that make microstructural analysis difficult or impossible. Recently, the use of noble gas ion sources, such as Xe, has markedly improved milling speeds and is being used for the preparation of various materials. Hence, it is necessary to investigate the structural defects formed during FIB milling and assess the ion-induced chemical contamination in these TEM samples. Here we explore the feasibility and efficiency of using Xe+ PFIB as a TEM sample preparation route for Al alloys in comparison with the conventional Ga+FIB.


Human cardiac myosin light chains: sequence comparisons between myosin LC1 and LC2 from normal and idiopathic dilated cardiomyopathic hearts.
The primary structures of light chains isolated from the human myocardium with idiopathic dilated cardiomyopathy (IDC) were determined and compared with the sequence structures of myosin light chains obtained from control human heart myosin. Sequences were determined by chemical analysis and the identity of N-terminal residues established by mass spectrometry. The N-terminal residues in essential (ELC) and regulatory (RLC) light chains were blocked and were identified to be trimethyl alanine. The amino acid sequences of ELC and RLC from control human myosin revealed a high degree of homology with those purified from rat and chicken cardiac myosin. Comparison with a published partial chemical sequence of the human heart myosin light chains revealed significant variations. However, there was very good agreement with published sequences obtained by molecular biological techniques. Sequences of the light chains from cardiomyopathic myosin revealed no difference in the primary structures when compared with control human heart myosin light chains indicating IDC had no influence on, nor was caused by, altered myosin light chain gene expression.


Construction and characterization of cDNA clones encoding the 5' end of the chicken pro alpha 1(I) collagen mRNA.
As a first step in isolating the 5' end of the chicken pro alpha 1(I) collagen gene, we constructed cDNA clones complementary to the 5' end of the pro alpha 1(I) mRNA using synthetic oligodeoxynucleotides complementary to a conserved region within the N-terminal telopeptide as primers. cDNA clones corresponding to the 5'-untranslated region, signal peptide, N-propeptide and telopeptide were identified based on homology with the human pro alpha 1(I) collagen protein sequence, and on hybridization to pro alpha 1(I) mRNA on Northern blots. A comparison of the nucleotide sequence of these clones with the sequence of the 5' end of the pro alpha 2(I) collagen mRNA confirms that there is 84% homology in a 49-bp region surrounding the translation start point, and shows that there is 70% homology in the nucleotide sequences encoding the N-propeptide triple helical region of the two type-I collagen chains.


Is bone analysis with μCT useful for short postmortem interval estimation?
The evaluation of the postmortem interval (PMI) is an important consideration in forensic medicine. The time between death and the discovery thereof is extremely important, not only in terms of the legal process, but also for the course of the investigation. At the time of the discovery of human bones, the evaluation of the PMI is extremely difficult. To date, there is no really effective tool for this evaluation. The objective of our study is to characterize the architectural modifications of human bones using micro-tomography (μCT) in the postmortem period. Ten bone samples were extracted from a single fresh human cranial vault (no freezing, no embalming) from a body donation. The samples were conserved in a controlled environment (a laboratory hood at 20 °C with 60% humidity) for 10 weeks. Every 2 weeks after the death and the sample extraction from the vault, the samples were analyzed with μCT (resolution 10 μm, Bruker HR1172 ®). The 3D analysis focused on general 3D data related to the trabeculae: the total volume (TV), the bone volume (BV), and the bone surface (BS), as well as specific trabeculae data; namely: the number of trabeculae (TbN), trabecular thickness (TbTh), the average distance between the trabeculae (TbSp), and the trabecular pattern factor (TbPf). Each sample was observed separately and compared to itself over time; no comparisons among samples were made. We used a linear mixed model for repeated measures (an unstructured covariance pattern model) and post hoc comparisons between each consecutive time using linear contrast with an SAS software package, release 9.3 (SAS Institute, Cary, NC). We showed a statistical difference for BS/BV (p = 0.046) over time, with a significant decrease during the first 2 weeks (p = 0.003; mean decrease, - 0.99, 95% CI [- 1.61; - 0.36]), while TbSp (p < 0.0001) showed a significant increase during the first 2 weeks (p < 0.0001; mean increase, 0.022, 95% CI, [- 0.016; - 0.028]).Our study highlighted architectural trabecular modifications on postmortem bones using the μCT. These modifications occurred at an early stage, during the first 2 weeks of conservation. Complementary work will need to be performed to allow for better understanding of the biological phenomena observed and to create databases of osseous taphonomy, starting with various individuals, mediums of conservation, types of bone, and with varying techniques for analysis.


Peroxisomal oxidases in various tissues of diabetic rats.
The effect of diabetes mellitus induced by streptozotocin on the activities of peroxisomal oxidases and H2O2-metabolizing enzymes, and lipid peroxidation in various rat tissues were investigated. Peroxisomal acyl-CoA oxidase, D-amino acid oxidase and L-alpha-hydroxyacid oxidase were measured by a sensitive spectrophotometric method using dichlorofluorescein/peroxidase as the detector of H2O2. Acyl-CoA oxidase activity was increased most markedly in the heart of diabetic rats, less markedly in the liver, and tended to be increased in the kidneys. The activities of other peroxisomal oxidases were much lower than that of acyl-CoA oxidase in the liver and kidneys, and were undetectable in the heart. Catalase activity was decreased in the liver and kidneys of diabetics, and was increased in the heart. Glutathione peroxidase activity was increased more markedly in the kidneys of the diabetics, and less markedly in the heart than in the liver. Lipid peroxide level was higher in the kidneys of the diabetics than in the controls, unchanged in the heart, and was lower in the liver of the diabetics than in the controls. Thus, peroxisomal beta-oxidation and the H2O2 production coupled with that, were activated in various tissues of diabetic rats, presumably as a part of the overall increase in lipid oxidation. However, they did not appear to contribute to the enhanced oxidative stress induced by diabetes mellitus.


Surgical plans generated from telemedicine visits are rarely changed after in-person evaluation in spine patients.
The role of telemedicine within the realm of spine surgery is evolving, catalyzed by the recent pandemic. Specifically, the capability of this technology to provide high-quality, cost-effective care without an in-person interaction and physical examination remains poorly defined. To characterize the impact of telemedicine on spine surgical planning by assessing whether surgical plans established in virtual visits changed following in-person evaluation. Retrospective cohort study. We evaluated the records of patients who were indicated for surgery with documented specific surgical plans during a virtual encounter (March-July 2020) and underwent subsequent in-person evaluation prior to surgery. We determined whether surgical plans changed between the virtual encounter and the in-person interaction. Secondarily, we reviewed use of the virtual physical examination across surgeons. We reviewed virtual and in-person clinical encounters from a single academic spine division, evaluating those patients who were seen exclusively via telemedicine encounters and indicated for surgery with documented specific surgical plans. These plans were compared to the surgical plan after these same patients underwent in-person evaluation. Demographic data, patient primary complaint, and the type and extent of physical examination performed by the surgeon were recorded. Of the 33 patients included, the surgical plan did not change among 31 individuals (94%) following in-person interaction. For the two patients where surgical plans were modified, multilevel fusions were increased by one level. There was notable inter- and intra-surgeon variability with regard to the use of virtual physical exams. Our findings suggest that telemedicine evaluations are efficient means of preoperative assessment of spine patients and delineation of surgical plans. These results may support innovations that can optimize access to care for patients.


First study of hormesis effect on mushroom cultivation.
The use of fungicides is common in mushroom cultivation, but no study was carried out applying reduced doses of fungicides in order to increase yield, taking account the hormesis effect. The aim of this manuscript was to verify the effects of different concentrations of fungicides to stimulate the productivity of different strains of Agaricus bisporus. Two stages were developed, an in vitro study to define the best concentration to be applied in the second experiment an agronomic study, which consisted of the application of the selected fungicides, in their respective concentrations, in an experiment carried out in the mushroom chamber. Clearly, the result of the hormesis effect on mushroom cultivation can be verified. The results obtained in the 1st stage of the study (in vitro) were not always reproduced in the 2nd stage of the study (in vivo). The kresoxim methyl active ingredient may be an important chemical agent, while strain ABI 15/01 may be an extremely important biological agent to increase yield in the study of hormesis effects.


Cone-Beam Weight-Bearing Computed Tomography of Ankle Arthritis and Total Ankle Arthroplasty.
Weight-bearing computed tomography has multiple advantages in evaluating the hindfoot and ankle. It can assess hindfoot and ankle alignment, pathology in ankle arthritis, and complications related to total ankle replacements. It is an essential tool in ankle osteoarthritis diagnostic, preoperative planning, and total ankle replacement outcomes. It allows for better accuracy and reproducibility of alignment and implant size. In addition, it has the potential to more assertively detect complications related to weight bearing.


Expression of Epithelial Cell Adhesion Molecule (EpCAM) in Tumor Spheroids of Human Colorectal Adenocarcinoma Cells.
We studied the formation of spheroids by Caco-2, SW480, and HCT116 human colorectal adenocarcinoma cell lines under low-adhesion culturing conditions. Of these three cell lines, only HCT116 formed stable tumor spheroids. Flow cytometry analysis of 19 surface markers in monolayer HCT116 culture and spheroids formed by these cells revealed considerable similarity of the expression profiles in these two culturing modes. The only exception was EpCAM molecule: its expression in spheroids was 3-fold higher than in the monolayer culture. Scanning confocal laser microscopy showed equal EpCAM distribution in the inner mass of the spheroids.


Applications of diffusion-weighted MRI in thoracic spinal cord injury without radiographic abnormality.
Diffusion-weighted MRI (DWI) has been proposed as a method to evaluate the integrity of white matter tracts in the spinal cord. The integrity of the spinal cord reflects the exact stage of traumatic injury. The purpose of this study was to evaluate the diagnostic value of DWI in SCIWORA in the thoracic spine. A total of five patients with thoracic SCIWORA underwent MRI and DWI within 48 h of injury. DWIs were obtained with a single-shot fast spin-echo (SSFSE) sequence; TI- and T2-weighted images were obtained with spin echo. Consistency among the clinical presentation, outcome, MRI and DWI was analysed. There was complete injury in one patient and partial in four patients. Four patients showed hypointense T1-weighted signal and hyperintense T2-weighted signal, and one patient had no changes on MRI. All patients showed hyperintense signal on DWI. Two patients made good recoveries (ASIA grades D and E), one had a moderate recovery (ASIA grade C), and two showed minimal or no improvement (ASIA grade A or B) in neurological function. Patients with no cord changes on MRI showed abnormal signals on DWI. It is likely that in the future DWI may provide important information complimentary to conventional MRI and allow a better prognostic evaluation of recovery from SCIWORA.


Recombinant Expression, Purification and PEGylation of DNA Ligases.
Reagent proteins such as DNA ligases play a central role in the global reagents market. DNA ligases are commonly used and are vital in academic and science research environments. Their major functions include sealing nicks by linking the 5'-phosphorylated end to a 3'-hydroxyl end on the phosphodiester backbone of DNA, utilizing ATP or NADP molecules as an energy source. The current study sought to investigate the role of PEGylation on the biological activity of purified recombinant DNA ligases. We produced two recombinant DNA ligases (Ligsv081 and LigpET30) using E. coli expression system and subsequently purified using affinity chromatography. The produced proteins wereconjugated to site specific PEGylation or non-specific PEGylation. FTIR and UV-VIS spectroscopy were used to analyze secondary structures of the PEG conjugated DNA ligases. Differential scanning fluorimetry was employed to assess the protein stability when subjected to various PEGylation conditions. In this study, both recombinant DNA ligases were successfully expressed and purified as homogenous proteins. Protein PEGylation enhanced ligation activity, increased transformation efficiency by 2-foldfor plasmid ligations and reduced the formation of protein aggregates. Taken together, site-specific PEGylation can potentially be explored to enhance the biological activity and stability of reagent proteins such as ligases.


CO adsorption on copper in alkaline electrolytes: an electrochemical and ellipsometric study.
The influence of CO on the passive behavior of copper was analyzed in the potential region near the rest potential in borax solutions (pH 9.2) by cyclic voltammetry, ellipsometry, and surface charge determination techniques. The oxide formation is explained as a sequence of Cu(2)O growth, cation adsorption, Cu(II), and dissolution steps, similarly to previously reported investigations for the metal in free CO solutions. The CO adsorption hinders the cationic defect in the outer oxide layer and accelerates the Cu(2)O growth both at open circuit and in controlled potential experiments. The isoelectric point, iep, obtained at pH 10.8 for both the metal Cu and CuO particles in KCl solutions shifts to pH 10.1 for copper particles in the presence of CO. The iep indicates a CuO coating on Cu metallic particles in the absence of CO.


The effect of training load stress on salivary cortisol concentrations, health parameters and hematological parameters in horses.
The performance of sport horses is conditioned not only by the quality of its gene pool, but also by a large number of external factors. The most dominant being nutrition, quality of breeding, level of zootechnical care and the quality of the sports rider and coach. Important factor is the process of individuals' adaptation to the training load occurring during the training itself. This study was focused on the analysis of salivary cortisol levels as well as hematological and biochemical blood parameters in relation to load to which the tested horses were subjected. In the study 14 horses of sport breeds were analyzed a all tested horses were in the same (medium) level of training load. Tested horses underwent following stages of workload - transportation, jumping training, parkour competition, treadmill training, riding training, shoeing and lunging of various intensity. Saliva samples were obtained using a tampon on a string which was inserted into horse's oral cavity, chewed by the horse and placed in a sterile tube with a closable lid. Afterwards, the samples were then stored in deep-freezing boxes at temperature of -80 °C. The EIA cortisol kit was used in this study. The absorbance was read at the wavelength of 450 nm against a reference wavelength of 620-630 nm or a blank sample. Blood samples were obtained at the beginning of the experiment, after half a year of running the experiment and at the end of the experiment from v. jugularis. Hematological analysis were carried out using automatic hematologic analyser and multiple parameters were observed. Analysis of biochemical parameters in blood serum were realized using commercial DiaSys kits and semiautomatic biochemical spectrophotometer. Sodium, potassium and chlorides were measured using automatic analyzer EasyLytePlus. In all monitored forms of exercise (transportation, jumping training, parkour competition, treadmill training, riding training, horse shoeing, lunging), an increase in cortisol concentrations immediately after the exercise was recorded, but only spotted statistically significant differences were found during the transportation of monitored horses. The levels of blood parameters were within the reference range during the experiment period. From a comprehensive evaluation of the results, it can be stated that there were no visible health changes to the horses that underwent the experimental load and that manipulation with horses is an important factor that has effect on horses' stress response. In general, the results of this study show no visible impact of training and/or load on the health status of horses over entire 12-month duration of the experiment.


Ultrastructure of rat seminal vesicle epithelium in the acute phase of spinal cord transection.
After a spinal cord injury (SCI), most men experience fertility related problems including poor semen quality in which decreased sperm viability and motility, have been proposed to be related to the accessory sex glands dysfunction. In this study, we investigated the probable effects of SCI on the seminal vesicle epithelium in rat. Spinal cord was injured in adult male rats by surgical transection at the level of T9. Controls received similar surgery without transection. Five days later, animals were killed and the seminal vesicles were removed, subjected to routine procedures for light and transmission electron microscopy respectively. Acute inflammation of the seminal vesicles including vasodilatation and migration of leukocytes to epithelium was observed through the light microscopy. Transmission electron microscopy study revealed significant changes in the experimental epithelium, such as decrease in rough endoplasmic reticulum, secretory granules and Golgi apparatus dimensions, accumulations of fat droplets and lipofuscin in the cytoplasm, euchromatinized and swelled nuclei, decrease in cell diameters, and the presence of macrophages and hollow spaces in the epithelium. The seminal vesicle of sham-operated animals showed normal morphology. Histologic evidence in this study confirms dysfunction of seminal vesicle in the acute phase of SCI. Further works are needed to follow up the reversibility of such lesions.


Effects of alcohol feeding on androgen receptors in the rat pituitary gland.
Specific binding of testosterone-1 beta, 2 beta-3H by cytosol from anterior pituitary gland of alcohol-fed, isocaloric control, and castrated control and alcohol-fed rats with or without testosterone treatment has been investigated by charcoal assay. The number of androgen binding sites was significantly reduced in alcohol-fed rats (8 +/- 1.0 fmoles/mg cytosol protein), when compared to the isocaloric control value (13.2 +/- 2.1 fmoles/mg protein), with no significant change in Kd (0.7 +/- 0.14 nM). Castration significantly increased the number of receptor sites in control rats and when castrated control animals were treated with testosterone the binding sites were decreased to the intact control level. In contrast, castration or testosterone given to castrated alcohol-fed rats did not alter alcohol-induced reduction of the receptor sites. The binding affinity (Kd) is identical in all groups. The concentration of serum luteinizing hormone (LH) was significantly lower in alcohol-fed rats when compared to that of normal controls. An increased serum LH level with a decreased testosterone level was noted in castrated control rats. However, castration of alcohol-fed rats had little or no effects on the concentrations of LH and testosterone. Administration of testosterone suppressed castration-induced high LH in control rats but alcohol-induced reduction of LH level was not altered by this treatment. These findings indicate that alcohol exerts a suppressive effect on the content of androgen receptors and secretory functions of gonadotropins in the pituitary gland.


Pathologic left-handedness: does it exist?
The concept of pathologic left-handedness is reviewed, both from a historical and an empirical point of view. It is suggested that there is no adequate evidence to justify its continued use. The fact that the concept is still much used may be the result of a desire to restore to the brain its lost symmetry, by allowing Dax's Law once more to be true.


[Prognostic value of cardiac rhythm in acute myocardial infarction].
A computer-assisted special calculating complex to analyze a dynamic series of 128 successive R-R ECG intervals in 42 patients with acute myocardial infarction is described. It was established that statistical indices of the rhythm allow to evaluate the degree of severity of the disease, the reserve of adaptation possibilities of the body and predict the course of the disease.


QSTR with extended topochemical atom (ETA) indices. 16. Development of predictive classification and regression models for toxicity of ionic liquids towards Daphnia magna.
Ionic liquids have been judged much with respect to their wide applicability than their considerable harmful effects towards the living ecosystem which has been observed in many instances. Hence, toxicological introspection of these chemicals by the development of predictive mathematical models can be of good help. This study presents an attempt to develop predictive classification and regression models correlating the structurally derived chemical information of a group of 62 diverse ionic liquids with their toxicity towards Daphnia magna and their interpretation. We have principally used the extended topochemical atom (ETA) indices along with various topological non-ETA and thermodynamic parameters as independent variables. The developed quantitative models have been subjected to extensive statistical tests employing multiple validation strategies from which acceptable results have been reported. The best models obtained from classification and regression studies captured necessary structural information on lipophilicity, branching pattern, electronegativity and chain length of the cationic substituents for explaining ecotoxicity of ionic liquids towards D. magna. The derived information can be successfully used to design better ionic liquid analogues acquiring the qualities of a true eco-friendly green chemical.


The role of interstitial brachytherapy using template in locally advanced gynecological malignancies.
Brachytherapy plays a major role in the treatment of patients with carcinoma of the cervix. However, routine intracavitary brachytherapy may not be feasible or adequate to treat locally advanced disease. The purpose of this prospective study was to assess treatment outcome for patients with locally advanced gynecological malignancies treated with interstitial brachytherapy using Martinez Universal Perineal Interstitial Template (MUPIT) and to study the acute and late sequelae after treatment by this technique. Thirty previously untreated patients with histologically confirmed carcinoma of the cervix (20 patients), vault (7 patients), and vagina (3 patients) were treated by a combination of external beam radiotherapy using megavoltage irradiation to the pelvis to a dose of 4000 to 5000 cGy followed by interstitial brachytherapy using MUPIT between June 2000 to August 2001 at Gujarat Cancer and Research Institute, Ahmedabad. Only those patients who were found unsuitable for conventional brachytherapy or in whom intracavitary radiotherapy was found to be unlikely to encompass the tumor volume were treated with interstitial template brachytherapy using MUPIT applicator and were enrolled for this study. Criteria for inclusion in this study were as follows: Hemoglobin--minimum 10 gm%; Performance Status--70% or more (Karnofsky Scale); Histopathological confirmation; FIGO Stage--IIb-IIIb (excluding frozen pelvis). Among the 30 patients studied, 4 lost to follow-up and they were excluded from the study. With a median follow up of 9 months, local control was achieved in (20/26) 76.92% patients. The local control was better for nonbulky tumors compared to bulky tumors irrespective of stage of disease. Local control rate was better in patients with good regression of disease after EBRT. The time gap between EBRT and implant also had an impact on the outcome. Interstitial template brachytherapy by MUPIT is a good alternative to deliver high-dose radiation in locally advanced gynecological malignancies where conventional brachytherapy application is either not feasible or unlikely to encompass tumor volume adequately. The locoregional control obtained is definitely better than external beam therapy alone and within the accepted range of complications. However, long-term follow-up is needed to comment on late morbidities.


General construction pattern of histamine H3-receptor antagonists: change of a paradigm.
Novel omega-phenyl substituted and unsubstituted alkyl and alkenyl imidazole derivatives were prepared and tested for their antagonist activity in vitro and in vivo at histamine H3-receptors. Some compounds showed high in vitro and in vivo H3-receptor activity despite their structure bearing no polar moiety in the centre of the molecule which is a common structural feature of all other antagonists known. Quite probably there are further in vivo effects for some compounds resulting from other receptor interactions.


The effects of saturated fat and n-6 polyunsaturated fat on postprandial lipemia and hemostatic activity.
The effect of different fat loads on postprandial lipemia and hemostatic activity was examined in 10 middle-aged men using 3 different meals. One meal was rich in saturated fatty acids (cream), the other rich in n-6 polyunsaturated fatty acids (sunflower oil) and the third was fat-free containing only carbohydrates. Lipoprotein lipids and hemostatic parameters were measured during fasting and 2, 4, 6 and 8 h after the test meal. In fasting samples, several hemostatic parameters were significantly associated with lipoprotein lipids. Most notable were the strong associations of fibrinolysis parameters tissue plasminogen activator antigen and plasminogen activator inhibitor activity (PAI-1) with total and very low density lipoprotein (VLDL) triglycerides. During lipemia, the associations were approximately similar or slightly weaker than in the fasting state. Both fat loads resulted in similar postprandial lipid responses: VLDL and high density lipoprotein (HDL) triglycerides reached maximum at 4 h after the meal. VLDL cholesterol also increased 4 and 6 h after the fat loads. HDL3 cholesterol declined after the fatty meals but no change was observed in the HDL2 fraction. The fat-free meal gave no significant lipid changes during the time course studied. Factor VII activity (F VII:C) increased 6 and 8 h after the fatty meals, whereas a decrease was observed after the fat-free meal. The changes (+/- S.D.) at 8 h after cream, sunflower oil and fat-free meal were 5.2 +/- 3.3, 3.3 +/- 4.2 and -5.8 +/- 7.9 percentage points, respectively, and the effect of the meal on the changes was statistically significant (F (8,99) = 2.99, P = 0.0048). F VII antigen (F VII:Ag) tended to decline during the day but there was no difference between the meals. Factor VIII activity (F VIII:C) was highest after the polyunsaturated fat meal and lowest after the fat-free meal. PAI-1 declined during the day and the decline tended to be steepest after the fat-free morning meal. The effect of the meal on the changes in lipoprotein lipids and hemostatic factors varied significantly between individuals. In conclusion, postprandial lipemia after a single fatty meal was associated with procoagulatory change in F VII:C but there was no difference between saturated fat and n-6 polyunsaturated fat.


Simultaneous voltammetric detection of ascorbic acid, dopamine and uric acid using a pyrolytic graphite electrode modified into dopamine solution.
Pyrolytic graphite electrodes (PGE) were modified into dopamine solutions using phosphate buffer solutions, pH 10 and 6.5, as supporting electrolyte. The modification process involved a previous anodization of the working electrode at +1.5 V into 0.1 mol L(-1) NaOH followed by other anodization step, in the same experimental conditions, into dopamine (DA) solutions. pH of the supporting electrolyte performed an important role in the production of a superficial melanin polymeric film, which permitted the simultaneous detection of ascorbic acid (AA), (DA) and uric acid (UA), DeltaE(AA-DA)=222 mV; DeltaE(AA-UA)=360 mV and DeltaE(DA-UA)=138 mV, avoiding the superficial poisoning effects. The calculated detection limits were: 1.4x10(-6) mol L(-1) for uric acid, 1.3x10(-5)molL(-1) for ascorbic acid and 1.1x10(-7) mol L(-1) for dopamine, with sensitivities of (7.7+/-0.5), (0.061+/-0.001) and (9.5+/-0.05) A mol(-1) cm(-2), respectively, with no mutual interference. Uric acid was determined in urine, blood and serum human samples after dilution in phosphate buffer and no additional sample pre-treatment was necessary. The concentration of uric acid in urine was higher than the values found in blood and serum and the recovery tests (92-102%) indicated that no matrix effects were observed.


Determination of nanostructure of liposomes containing two model drugs by X-ray scattering from a synchrotron source.
Small-angle X-ray scattering has been employed to study how the introduction of paracetamol and acetylsalicylic acid into a liposome bilayer system affects the system's nanostructure. An X-ray scattering model, developed for multilamellar liposome systems [Pabst et al. (2000), Phys. Rev. E, 62, 4000-4009], has been used to fit the experimental data and to extract information on how structural parameters, such as the number and thickness of the bilayers of the liposomes, thickness of the water layer in between the bilayers, size and volume of the head and tail groups, are affected by the drugs and their concentration. Even though the experimental data reveal a complicated picture of the drug-bilayer interaction, they clearly show a correlation between nanostructure, drug and concentration in some aspects. The localization of the drugs in the bilayers is discussed.


Measuring transcription dynamics in living cells using fluctuation analysis.
Single-cell studies of gene regulation suggest that transcription dynamics play a fundamental role in determining expression heterogeneity within a population. In addition, the three-dimensional organization of the nucleus seems to both reflect and influence expression patterns in the cell. Therefore, to gain a holistic understanding of transcriptional regulation, it is necessary to develop methods for studying transcription of single genes in living cells with high spatial and temporal resolution. In this chapter, we describe a recently developed approach for visualizing and quantifying pre-mRNA synthesis at a single active gene in the nucleus. The approach is based on the high-affinity interaction between MS2/PP7 bacteriophage coat proteins and RNA hairpins which are transcribed by the gene of interest. The MS2/PP7 coat protein is fused to a fluorescent protein and binds the nascent mRNA, allowing for detection of single transcription events in the fluorescence microscope. By time-lapse fluorescence imaging and quantitative image analysis, one can generate a time trace of fluorescence intensity at the site of transcription. By temporal autocorrelation analysis, one can determine enzymatic activities of RNAP such as initiation rate and elongation rate. In this protocol, we summarize the experimental concept, design, and execution for real-time observation of transcription in living cells.


Excretion in feces and mucosal persistence of Salmonella ser. Typhimurium in pigs subclinically infected with Oesophagostomum spp.
To determine interactions between Oesophagostomum spp and Salmonella ser. Typhimurium in pigs. 30 healthy 5- to 6-week-old pigs. Pigs were allotted to 3 groups (n = 10 pigs/group) and treated as follows: group A was given Oesophagostomum dentatum and O quadrispinulatum; group B was given O dentatum, O quadrispinulatum, and S Typhimurium; and group C was given S Typhimurium only. Pigs in groups A and B were trickle infected with Oesophagostomum spp 3 times weekly throughout the study. After 19 days, groups B and C were inoculated once with S Typhimurium. One pig from each group was euthanatized on the day of Salmonella exposure and 2 and 4 days after Salmonella exposure. The remaining pigs were euthanatized on days 16 and 17 after Salmonella exposure. Pigs with dual infections of nematodes and bacteria (group B) excreted significantly higher amounts of S Typhimurium in feces, compared with nematode-free pigs (group C). In addition, group-B pigs excreted S Typhimurium on more days than pigs in group C. Salmonella Typhimurium was detected in the cecum and colon in the majority of pigs in group B, whereas S Typhimurium was only detected in the colon in pigs in group C. Immunohistochemical examination detected S Typhimurium in 7 of 9 pigs in group B but only 2 of 9 pigs in group C. Interactions between intestinal nematodes and bacteria may play an important role in the dynamics of S Typhimurium infections.


Metabolic adaptation of Lactococcus lactis in the digestive tract: the example of response to lactose.
Lactococcus lactis is a model of food-grade lactic acid bacterium, which can durably colonize the digestive tract of germ-free mice. To study in vivo the bacterial adaptation to a novel nutritional resource brought by alimentation, the lactose-catabolizing strain IL2661 of L. lactis was established in monoxeny in mice. Half of the mice then received a lactose-rich diet. The mouse has no efficient intestinal lactase and is well adapted to a follow-up of the metabolic activity of microbial origin. The analysis of lactose and lactate in the feces suggested that L. lactis was able to use lactose in vivo. We developed a proteomic approach to evaluate in deeper details the metabolic response of the bacterium. We observed that L. lactis switched its metabolism to use the novel carbon source and reduced the level of proteins involved in an alternative mode of ATP production. In parallel, we also found that the amount of proteins involved in transcriptional regulation, transport and catabolism decreased in the presence of lactose. The proteome analysis informed us about the resources used by the bacteria in absence of lactose. In competition experiments, we found that the metabolic adaptation gives a strong ecological advantage to the bacteria able to efficiently utilize lactose.


[Treatment strategies in diabetic nephropathy - Update 2022].
A new classification of patients with diabetes mellitus into so-called clusters can be used to assess the risk of developing diabetic nephropathy. Up to date treatment of patients with diabetic nephropathy includes not only glycemic control, but focuses on a holistic approach with prevention of (progression of) secondary diabetic complications and reduction of the patient's cardiovascular mortality. To achieve this treatment goals, it requires comprehensive management of the patient to implement lifestyle interventions (regarding diet, physical activity, weight loss, smoking cessation) and selection of the medication with the greatest individual benefit. Part of lifestyle intervention is adherence to a dietary regimen that has again been shown in recent studies to be relevant in inhibiting progression of chronic kidney disease and reducing cardiovascular risk. In particular, this includes protein restriction with preference for plant sources of protein, and salt restriction. Adjustment of drug therapy is no longer based on antihyperglycemic effects alone, but takes into account inhibition of progression of nephropathy and cardiac risk, as well as support of body weight control. For this purpose, in addition to RAAS inhibitors from the field of antihypertensives, the antidiabetic classes of SGLT2 inhibitors and GLP-1 receptor agonists as well as the non-steroidal aldosterone antagonist finerenone are now available.


Inhibitory effects of magnolol on voltage-gated Na+ and K+ channels of NG108-15 cells.
Magnolol, a polyphenolic compound isolated from Houpu, a Chinese herb from the bark of Magnolia officinalis, has been reported to have in vitro and in vivo neuroprotective effects. In spite of these reported beneficial effects, studies on the direct impact of magnolol on neuronal ion channels have been scarce. Whether magnolol affects voltage-gated Na(+) channels (VGSC) and voltage-gated K(+) (Kv) channels is unknown. Using the whole-cell voltage-clamp method, we studied the effects of magnolol on voltage-gated ion channels in neuronal NG108-15 cells. Magnolol inhibited VGSC channels with mild state-dependence (IC(50) of 15 and 30 μM, at holding potentials of -70 and -100 mV, respectively). No frequency-dependence was observed in magnolol block. Magnolol caused a left-shift of 18 mV in the steady-state inactivation curve but did not affect the voltage-dependence of activation. Magnolol inhibited Kv channels with an IC(50) of 21 μM, and it caused a 20-mV left-shift in the steady-state inactivation curve without affecting the voltage-dependence of activation. In conclusion, magnolol is an inhibitor of both VGSC and Kv channels and these inhibitory effects may in part contribute to some of the reported neuroprotective effects of magnolol.


Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with Nivolumab.
Nivolumab has shown promising effects in patients with non-small-cell lung cancer (NSCLC) as a second- or later-line treatment. This study aimed to identify patients who would not experience any benefit from nivolumab treatment. In this study, data for 201 patients treated with nivolumab during 17 December 2015 to 31 July 2016 at three respiratory medical centers in Japan were retrospectively reviewed. We collected clinical data at the time of nivolumab treatment commencement. We investigated the relationship between progression-free survival (PFS) and patient characteristics. In both univariate and multivariate analysis, performance status (PS) score ≥2, steroid use at baseline and lactate dehydrogenase (LDH) level >240 IU/l were significantly associated with poor PFS (all p<0.05). PS score ≥2, steroid use at baseline and a high LDH level were predictive of poor PFS in patients with NSCLC treated with nivolumab. Careful monitoring is recommended for treating such patients with nivolumab (UMIN-ID: UMIN000025908).


A technique for the detection, decomposition and analysis of the EMG signal.
In the present paper we have described a system for acquiring, processing and decomposing EMG signals for the purpose of extracting as many motor unit action potential trains as possible with the greatest level of accuracy. This system consists of 4 main sections. The first section consists of methodologies for signal acquisition and quality verification. Three channels of EMG signals are acquired using a quadripolar needle electrode designed to enhance discrimination among different MUAPs. An automated experiment control system is devised to free the experimenter from the burden of experiment detailed surveillance and bookkeeping; and to allow on-line assessment of the EMG signal quality in terms of decomposition suitability. The second section consists of methodologies for signal sampling and conditioning. The EMG signal is bandpass filtered (between 1 kHz and 10 kHz), sampled and compressed by eliminating parts of the signal under a preset threshold level. The third section consists of a signal decomposition technique where motor unit action potential trains are extracted from the EMG signal using a highly computer assisted interactive algorithm. The algorithm uses a continuously updated template matching routine and firing statistics to identify MUAPs in the EMG signal. The templates of the MUAPs are continuously updated to enable the algorithm to function even when the shape of a specific MUAP undergoes slow variations. The fourth section deals with ways in which to analyze and display the results. The more frequently used representation formats are: (1) display of MUAP wave shapes; (2) impulse trains representing motor unit firings; (3) IPI plots where time interval between successive firings of the same motor unit is plotted vs. time of the muscle contraction; (4) firing rate plots where the estimated time-varying mean firing rate of the detected motor units is plotted vs. time of the muscle contraction. The performance of the system has been tested in terms of: (1) consistency among results obtained by different operators; (2) accuracy evaluated on synthetic EMG signal; (3) indirect measure of accuracy on real EMG signal by comparing results pertaining the same motor unit action potential trains derived by two EMG signals, independently and simultaneously recorded from two different electrodes.


Ultrastructural acute features of active remodeling after chemical pleurodesis induced by silver nitrate or talc.
This study evaluated submicroscopic features of active pleural remodeling associated with chemical pleurodesis. Twenty seven rabbits received intrapleural injection of 0.5% silver nitrate (SN; N = 9) or 400 mg/kg talc slurry (N = 9) in 2 ml of saline solution; control rabbits (N = 9) received 2 ml of saline alone. The rabbits were sacrificed 15 minutes, 24 hours, or 7 days postinjection, and specimens of visceral pleura were obtained, fixed, and photographed for submicroscopic analysis. After 15 minutes of talc or SN exposure, prominent injury to the mesothelial cells and mesothelial cell-mesothelial basement membrane (MC-MBM) union was visible. There was focal remesothelialization of the denuded area through mesothelial cell migration, proliferation, and differentiation. After 24 hours, early wound healing, characterized by a superficial exudate, was evident where myofibroblasts had proliferated through a gap in the MC-MBM. After 7 days, proliferation of highly active myofibroblasts was observed; these cells produced abundant extracellular matrix components in a more organized distribution paralleling the surface. This third stage of remodeling was more evident with SN than talc-induced chemical pleurodesis. Our results suggest that ideal chemical pleurodesis results from injury to the MC-MBM union and abnormal wound healing, involving three essential steps: remesothelialization, fibroblastic proliferation, and extracellular matrix accumulation and remodeling.


Machine learning classification of plant genotypes grown under different light conditions through the integration of multi-scale time-series data.
In order to mitigate the effects of a changing climate, agriculture requires more effective evaluation, selection, and production of crop cultivars in order to accelerate genotype-to-phenotype connections and the selection of beneficial traits. Critically, plant growth and development are highly dependent on sunlight, with light energy providing plants with the energy required to photosynthesize as well as a means to directly intersect with the environment in order to develop. In plant analyses, machine learning and deep learning techniques have a proven ability to learn plant growth patterns, including detection of disease, plant stress, and growth using a variety of image data. To date, however, studies have not assessed machine learning and deep learning algorithms for their ability to differentiate a large cohort of genotypes grown under several growth conditions using time-series data automatically acquired across multiple scales (daily and developmentally). Here, we extensively evaluate a wide range of machine learning and deep learning algorithms for their ability to differentiate 17 well-characterized photoreceptor deficient genotypes differing in their light detection capabilities grown under several different light conditions. Using algorithm performance measurements of precision, recall, F1-Score, and accuracy, we find that Suport Vector Machine (SVM) maintains the greatest classification accuracy, while a combined ConvLSTM2D deep learning model produces the best genotype classification results across the different growth conditions. Our successful integration of time-series growth data across multiple scales, genotypes and growth conditions sets a new foundational baseline from which more complex plant science traits can be assessed for genotype-to-phenotype connections.


A Mixed Methods Approach to Equity and Justice Research: Insights from Research on Children's Reasoning About Economic Inequality.
Mixed methods research approaches are gaining traction across various social science disciplines, including among developmental scientists. In this chapter, we discuss the utility of a mixed methods research approach in examining issues related to equity and justice. We incorporate a brief overview of quantitative and qualitative monomethod research approaches in our larger discussion of the advantages, procedures, and considerations of employing a mixed methods design to advance developmental science from an equity and justice perspective. To better illustrate the theoretical and practical significance of a mixed methods research approach, we include examples of research conducted on children and adolescents' conceptions of economic inequality as one example of developmental science research with an equity and justice frame.


Role of tau deposition in early cognitive decline in Down syndrome.
Drawing on the amyloid/tau/neurodegeneration (AT[N]) model, the study examined whether the tau positron emission tomography (PET) biomarker [18F]AV-1451 was associated with episodic memory problems beyond what was predicted by the amyloid beta (Aβ) PET in Down syndrome (DS). Data from 123 non-demented adults with DS (M = 47 years, standard deviation = 6.34) were analyzed. The Cued Recall Test assessed episodic memory. Tau PET standardized update value ratio (SUVR) was assessed across Braak regions as continuous and binary (high tau [TH] vs. low tau [TL]) variable. Global PET Aβ SUVR was assessed as binary variable (Aβ- vs. Aβ+). In models adjusting for controls, tau SUVR was negatively associated with episodic memory performance in the Aβ+ but not Aβ- group. The Aβ+/TH group evidenced significantly worse episodic memory than the Aβ+/TL group. Similar to late-onset and autosomal dominant Alzheimer's disease (AD), high tau was an indicator of early prodromal AD in DS.


Breathing during exercise: demands, regulation, limitations.
In humans alveolar ventilation (VA) is adjusted almost perfectly to the metabolic demands of mild and moderate exercise. For example, in exercise transitions and in the steady state, PaCO2 rarely deviates by more than 1 to 3 mmHg from the value at rest. This near-homeostasis contrasts to most other mammalian species; equines for example, demonstrate a progressive hypocapnia and alkalosis as exercise intensity is increased to moderate levels. In equines, the control systems seem programmed for a specific hyperventilation that contributes to maintenance of PaO2 homeostasis. Generally, during heavy exercise all species hyperventilate creating hypocapnia, increased PAO2, widened A-a O2 gradient, and PaO2 homeostasis. The origin of the metabolic ventilatory stimulus remains controversial. Evidence exists for: a) "neural" mediation, either central command or peripheral afferent in nature; and b) "humoral" mediation with an intra-thoracic metabolite receptor being a possibility. The mechanism of the species differences in hyperventilation during exercise does not appear to be due to species variation in chemoreceptor "fine tuning". Contrary to traditional thinking, recent findings suggest that the hyperventilation during heavy exercise might not be mediated by lactacidosis stimulation of chemoreceptors. The increase in VA during exercise is achieved efficiently in that airway diameter is modulated and the pattern of breathing and the recruitment of respiratory muscles are set to minimize the O2 cost of breathing. It has been postulated that mechanoreceptors in airways, lung parenchyma and the chest wall are important to efficient breathing. Their role and contribution to the exercise hyperpnea has been shown by reductions in respiratory neural output within breath when respiratory impedance is reduced via helium breathing. Hilar nerve afferents do not appear to be critical to this response. However, carotid chemoreceptors appear essential for "fine tuning" of VA when respiratory impedance is reduced. In most healthy exercising mammals, the efficiency component of the exercise stimulus does not compromise VA. There are two known major exceptions. One is the extremely fit human athlete during very high workloads when atypically there is minimal or no hyperventilation resulting in arterial hypoxemia. That indeed the high O2 cost of breathing compromises VA is indicated by hyperventilation and alleviation of hypoxemia with resistance unloading through helium breathing. A second example of a compromise of VA is that of a galloping racehorse at very high workloads.(ABSTRACT TRUNCATED AT 400 WORDS)


Molluscan ligand-gated ion-channel receptors.
In this chapter we introduce the reader to the structures of the different types of ligand-gated ion-channel receptor, and the numerous receptor subtypes that have recently been revealed to exist, in both invertebrate and vertebrate species, by the application of molecular biological methods. We then review some of the data in support of the existence, in molluscs, of such receptor/channel complexes for gamma-aminobutyric acid, glutamate and acetylcholine. Finally, recent results from our laboratory on the cloning and expression of complementary DNAs, from the pond-snail Lymnaea stagnalis, that encode GABA(A) and glutamate receptor subunits will be described.


Systematization of Nursing Care: how did the concept mature?
to analyze the Systematization of Nursing Care conceptual maturation from the perspective of pragmatic utility. a concept analysis study. The stages were: select the concept; elaborate analytical questions; comprehensively review the literature; and determine concept structural components. Sixty-one documents were analyzed after a search carried out until October 2019. four temporal periods of contextual changes have occurred since the emergence of ideas of a systematization in the 1960s. This first lasted until 1990. It was followed by those from 1990 to 2002, from 2002 to 2009 and from 2009 onwards. Partial conceptual maturity was identified, operationalization over the years, based on multiple definitions, and, currently, a concept of Systematization of Nursing Care with managerial and organizational attributes. the concept of Systematization of Nursing Care is partially mature, presents multiple definitions, being operationalized in uncertain connections with other concepts.


Transforming growth factor-beta1 affects interleukin-10 production in the bone marrow of patients with chronic idiopathic neutropenia.
Chronic idiopathic neutropenia (CIN) is a bone marrow (BM) failure syndrome characterized by accelerated apoptosis of myeloid progenitor cells because of a local imbalance between pro-inflammatory and anti-inflammatory cytokines. In this study, we investigated the interplay among transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and soluble flt-3 ligand (sFL) within the BM of CIN patients and probed the role of these cytokines in the pathophysiology of CIN. We used long-term BM cultures (LTBMC) to evaluate TGF-beta1, IL-10, and sFL levels in CIN patients (n = 70) and healthy subjects (n = 35). Cytokine levels in LTBMC supernatants were correlated with the number of circulating neutrophils and the proportion of BM CD34+/CD33+ myeloid progenitor cells. CIN patients had increased TGF-beta1 and sFL levels in LTBMCs compared with controls and individual cytokine values were found to be correlated inversely with the number of neutrophils and the proportion of CD34+/CD33+ cells. Patients displayed low supernatant IL-10 levels compared with controls and cytokine values were found to be correlated positively with the number of neutrophils and the proportion of CD34+/CD33+ cells. The levels of TGF-beta1 were found to be inversely correlated with IL-10 and positively with sFL values in LTBMC, supernatants suggesting a possible interplay among these cytokines in CIN BM. Neutralization of TGF-beta1 in LTBMCs increased IL-10 levels significantly in patients but not in controls, while neutralization had no effect on sFL levels. Excessive production of TGF-beta1 within the BM microenvironment of CIN patients results in downregulation of IL-10 and reduction of myeloid progenitor cells. Overexpression of sFL probably represents a compensatory mechanism to the low myeloid progenitor cells.


Preliminary investigation of 48V-labeled VO(acac)2 for cancer imaging: An initial proof-of-concept study.
In this preliminary study, a procedure for synthesizing novel PET radiotracer vanadium-48-labeled-vanadyl acetylacetonate was developed, including radioisotope production via cyclotron, separation of 48V, chelation as 48VO(acac)2, and assessment through in vitro cellular studies. We employed the beam-stop setup in a cyclotron as the target holder to irradiate titanium foils in the reaction of natTi (p,n)48V. The radioisotope production rate was 4.84 ± 0.67 μCi/μA-h. Overall radiochemical yield was 12.86 ± 0.51% with gamma-ray spectroscopy showing no detectable contaminant peaks. HPLC of 48VO(acac)2 showed a retention time (1:48) corresponding closely to that (1:50) of commercial VO(acac)2, verifying the successful synthesis of 48VO(acac)2. In vitro cellular studies demonstrated radiotracer uptake and saturation around 0.48 nM. These studies pave the way for improving methodologies and in vivo experiments, including imaging studies, in future investigations.