Treatment Planning Study for Microbeam Radiotherapy Using Clinical Patient Data.
Microbeam radiotherapy (MRT) is a novel, still preclinical dose delivery technique. MRT has shown reduced normal tissue effects at equal tumor control rates compared to conventional radiotherapy. Treatment planning studies are required to permit clinical application. The aim of this study was to establish a dose comparison between MRT and conventional radiotherapy and to identify suitable clinical scenarios for future applications of MRT. We simulated MRT treatment scenarios for clinical patient data using an inhouse developed planning algorithm based on a hybrid Monte Carlo dose calculation and implemented the concept of equivalent uniform dose (EUD) for MRT dose evaluation. The investigated clinical scenarios comprised fractionated radiotherapy of a glioblastoma resection cavity, a lung stereotactic body radiotherapy (SBRT), palliative bone metastasis irradiation, brain metastasis radiosurgery and hypofractionated breast cancer radiotherapy. Clinically acceptable treatment plans were achieved for most analyzed parameters. Lung SBRT seemed the most challenging treatment scenario. Major limitations comprised treatment plan optimization and dose calculation considering the tissue microstructure. This study presents an important step of the development towards clinical MRT. For clinical treatment scenarios using a sophisticated dose comparison concept based on EUD and EQD2, we demonstrated the capability of MRT to achieve clinically acceptable dose distributions.


Associations of surgical and nonsurgical weight loss with knee musculature: a cohort study of obese adults.
Marked weight loss reduces lean body mass and quadriceps thickness. It is unclear whether muscle loss varies according to the method of weight loss. This study compared the association of surgical versus nonsurgical weight loss with change in vastus medialis (VM) properties in obese adults. Twenty obese patients (body mass index ≥ 30 kg/m(2)) who lost weight via laparoscopic gastric banding were matched for weight loss with obese patients who lost weight nonsurgically. The thickness and fat infiltration of VM were assessed at baseline and a mean of 2.4 years later. After adjusting for confounders, the annual change in VM thickness was -2.9% in the surgical group and -.5% for the nonsurgical group (P = .02). There was also a tendency toward an increased risk for VM fat infiltration to be reduced when weight loss occurred nonsurgically (OR 5.1, 95% CI .8-32.8; P = .09). Compared with nonsurgical weight loss, laparoscopic gastric banding was associated with greater VM muscle thickness loss. Relative to laparoscopic gastric banding, there was also a tendency toward an increased risk for VM fat infiltration to be reduced with nonsurgical weight loss. Close attention to preserving muscle properties at the knee when significant amounts of weight loss have occurred is required. Physical therapy may be important in the management of patients after laparoscopic gastric banding in an attempt to preserve skeletal muscle mass.


Using Patient-reported Outcomes Measurement Information System Measures to Understand the Relationship Between Improvement in Physical Function and Depressive Symptoms.
This investigation determined whether improved physical function and decreased pain would reduce depressive symptoms using the Patient-reported Outcomes Measurement Information System (PROMIS). This cohort study analyzed PROMIS Depression, Physical Function, and Pain Interference CAT scores from 3,339 patients presenting to a tertiary orthopaedic center. Patients demonstrating at least a-five point (effect size, 0.5) improvement in PROMIS Physical Function between consecutive visits were eligible for inclusion. Patients presented, on average, with Physical Function and Pain Interference scores nearly one SD worse than population averages and Depression scores that approximated the normal population. Improved Physical Function and Pain Interference scores demonstrated no correlation with change in Depression scores (r = -0.13; r = 0.25). Substantial early improvement in PROMIS Physical Function scores is not associated with change in PROMIS Depression scores. PROMIS Depression scores likely reflect underlying mental health rather than situational depressive symptoms. Prognostic, level III.


12,15-Dimethyl-8-oxa-tetra-cyclo-[8.8.0.02,7.011,16]octa-deca-1(18),2,4,6,11(16),12,14-heptaen-10-ol.
In the title compound, C19H18O2, the pyran ring is in a half-chair conformation. The fused ring system comprising the benzene and cyclo-hexene rings is essentially planar (r.m.s. deviation = 0.053 Å) and forms a dihedral angle of 27.95 (6)° with the other benzene ring. In the crystal, O-H⋯O hydrogen bonds connect the mol-ecules into chains propagating along [001].


New polyunsaturated fatty acid amides isolated from the seeds of Zanthoxylum piperitum.
Five linear fatty acid amides (1-5) of the sandshool class, including two new compounds, were isolated from Zanthoxylum piperitum seeds. Based on combined spectral analyses, the structures of new compounds 4 and 5 were determined to be 2',3'-dihydroxy-alpha-sanshool and 2',3'-dihydroxy-beta-sanshool, respectively. These compounds exhibited weak cytotoxicity in the A-549 (human lung cancer) cell line.


Early Changes in Physical Activity and Quality of Life With Thoracic Radiation Therapy in Breast Cancer, Lung Cancer, and Lymphoma.
The effects of thoracic radiation therapy (RT) on physical functioning and quality of life (QoL) are incompletely defined. We determined the associations between thoracic RT dose volume metrics, physical activity, and QoL in patients with cancer. Participants with breast cancer, lung cancer, or mediastinal lymphoma treated with radiation with or without chemotherapy were enrolled in a prospective, longitudinal cohort study. Data were collected pre-RT, immediately post-RT, and 5 to 9 months post-RT. At each timepoint, self-reported physical activity was assessed via the Godin-Shephard Leisure-Time Physical Activity Questionnaire, and QoL metrics were assessed via Functional Assessment of Chronic Illness Therapy Fatigue and Dyspnea Scales. Multivariable adjusted linear regression models were stratified by breast cancer alone and lung cancer and lymphoma combined. One hundred thirty participants were included in the study. In breast cancer (n = 80), each 1-Gy increase in mean heart dose was associated with worse Functional Assessment of Chronic Illness Therapy Fatigue scores (-1.0; 95% confidence interval [CI], -1.9 to -0.2; P = .021); similar associations were observed between V5 and fatigue (-2.5; 95% CI, -4.4 to -0.6; P = .010 for each 10% increase in V5). In lung cancer and lymphoma (n = 50), each 10% increase in V5 was associated with decreased physical activity (Godin-Shephard Leisure-Time Physical Activity Questionnaire score -2.3; 95% CI, -4.3 to -0.4; P = .017). Although the associations between baseline levels of physical activity and fatigue and dyspnea were of borderline significance in breast cancer alone (P < .10), increased physical activity over time was associated with improvements in fatigue and dyspnea across all cancer types (P < .05 for all). Higher cardiac RT dose was associated with worse fatigue and physical activity across breast cancer, lung cancer, and mediastinal lymphoma. Longitudinal increases in physical activity were associated with concurrent improvements in QoL measures. Strategies to increase physical activity and decrease cardiac RT dose may improve physical functioning and QoL for patients with cancer.


Influenza vaccination and the elderly: pandemic preparedness.
Seasonal influenza causes significant morbidity and mortality in the elderly, the very young and those with chronic illness, despite the availability of effective vaccines. The mortality and morbidity attributed annually to seasonal influenza are small in comparison to the potential mortality and morbidity of a novel highly pathogenic human influenza A virus strain. The current influenza A/H5N1 virus that has caused epidemics in poultry and is evolving to find new niches needs only to become more efficiently transmitted from human to human to cause the next pandemic. Vaccination is the intervention with the potential to save the most lives when a pandemic occurs. Pandemic awareness and preparedness are essential to decrease the predicted chaos, death and illness arising from the next influenza pandemic.


Outcome of percutaneous tibial nerve stimulation (PTNS) for fecal incontinence: a prospective cohort study.
The aim of this study was to assess the long-term efficacy of percutaneous tibial nerve stimulation (PTNS) in fecal incontinence (FI). There is extensive evidence regarding the efficacy of PTNS in urinary incontinence. Data on the efficacy of PTNS for FI are limited to a few small case series with relatively short-follow up. A prospective cohort of patients with FI was studied. Incontinence scores were measured using a validated questionnaire (Cleveland Clinic Florida-FI score) at specific time points: before treatment, after completion of a treatment course (12 PTNS sessions), and before the last maintenance ("top-up") therapy. Deferment time and average number of weekly incontinence episodes were also estimated from a prospective bowel dairy kept by the patient at these time points. Quality of life was assessed with the Rockwood Fecal Incontinence Quality of Life questionnaire. A total of 150 patients were recruited to the study between January 2008 and June 2012. Analysis was performed on 115 patients who continued to receive PTNS after a median follow-up of 26 (range, 12-42) months. The baseline Cleveland Clinic Florida-FI score ±SD (12.0 ± 3.9) improved after 12 PTNS sessions (9.4 ± 4.6, P < 0.0001) and after "top-up" treatments (10.0 ± 4.3, P < 0.0001). The increase in the Cleveland Clinic Florida-FI score between the end of the 12th session and the last "top-up" therapy was also significant (P = 0.04). A similar pattern was seen for the deferment time and the quality of life scores. The median time between "top-up" sessions was 12 months (range, 1-40 months), significantly longer than the recommended interval of 6 months. PTNS is a well-tolerated treatment with high acceptability in the majority of patients. It provides a sustained improvement in FI up to 42 months in a relatively noninvasive manner. The effect of PTNS diminishes with time and additional therapy sessions at 6 monthly intervals may result in greater improvements. PTNS ought to be considered as the first step in all patients with FI refractory to maximum conservative therapies.


Reduced inequality in ambient and household PM2.5 exposure in China.
The society has high concerns on the inequality that people are disproportionately exposed to ambient air pollution, but with more time spent indoors, the disparity in the total exposure considering both indoor and outdoor exposure has not been explored; and with the socioeconomical development and efforts in fighting against air pollution, it is unknown how the exposure inequality changed over time. Based on the city-level panel data, this study revealed the Concentration Index (C) in ambient PM2.5 exposure inequality was positive, indicating the low-income group exposed to lower ambient PM2.5; however, the total PM2.5 exposure was negatively correlated with the income, showing a negative C value. The low-income population exposed to high PM2.5 associated with larger contributions of indoor exposure from the residential emissions. The total PM2.5 exposure caused 1.13 (0.63-1.73) million premature deaths in 2019, with only 14 % were high-income population. The toughest-ever air pollution countermeasures have reduced ambient PM2.5 exposures effectively that, however, benefited the rich population more than the others. The transition to clean household energy sources significantly affected on indoor air quality improvements, as well as alleviation of ambient air pollution, resulting in notable reductions of the total PM2.5 exposure and especially benefiting the low-income groups. The negative C values decreased from 2000 to 2019, indicating a significantly reducing trend in the total PM2.5 exposure inequality over time.


The clinical experience of macitentan in pulmonary hypertension in Indian cohort: 12-month follow-up.
The effectiveness and safety of macitentan, an endothelin-receptor antagonist (ERA) in the treatment of pulmonary arterial hypertension (PAH), has been demonstrated in numerous randomized clinical trials including SERAPHIN, focused on the reduction of morbidity and mortality. Our aim was to demonstrate the clinical and echocardiographic progression using macitentan in Indian patients with PAH. It was a retrospective study of 20 patients with multiple etiologies of PAH who had begun macitentan in routine clinical practice from a single center. There were 55% of patients with existing PAH therapies. The World Health Organization functional class (WHO-FC), 6-min walking distance, N-terminal prohormone of brain natriuretic peptide level (NT-pro-BNP), and echocardiographic data such as tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (sPAP), and the occurrence of pericardial effusion were collected at baseline and 12-month follow-up. The statistical analysis was performed using SPSS software. Of the 20 PAH patients, 70% were women. The majority were in WHO FC II (50%), while 35% were in FC III and 15% were in FC IV. The mean age was 43.4 years at the start of the therapy with macitentan. After 6 months of macitentan therapy, 85% showed substantial improvement in their FC, each increased its 6-min walking distance test (P < 0.0001), and there was a significant reduction in plasma levels of NT-pro BNP (P < 0.0001). There has also been an improvement in echocardiographic parameters such as TAPSE and sPAP (P < 0.0001). Our findings indicate that macitentan has been well tolerated and beneficial in Indian patients with PAH and further, future research is required to verify these results.


Short Text Messages (SMS) as an Additional Tool for Notifying Medical Staff in Case of a Hospital Mass Casualty Incident.
The aim of the study was to verify the effectiveness of short text messages (short message service, or SMS) as an additional notification tool in case of fire or a mass casualty incident in a hospital. A total of 2242 SMS text messages were sent to 59 hospital workers divided into 3 groups (n=21, n=19, n=19). Messages were sent from a Samsung GT-S8500 Wave cell phone and Orange Poland was chosen as the telecommunication provider. During a 3-month trial period, messages were sent between 3:35 PM and midnight with no regular pattern. Employees were asked to respond by telling how much time it would take them to reach the hospital in case of a mass casualty incident. The mean reaction time (SMS reply) was 36.41 minutes. The mean declared time of arrival to the hospital was 100.5 minutes. After excluding 10% of extreme values for declared arrival time, the mean arrival time was estimated as 38.35 minutes. Short text messages (SMS) can be considered an additional tool for notifying medical staff in case of a mass casualty incident.


Antral Helicobacter pylori infection, hypergastrinemia and peptic ulcers: effect of eradicating the organism.
A randomized prospective study on the response of fasting serum gastrin concentrations in peptic ulcer patients was performed in order to test the hypothesis that H. pylori infection in the gastric antrum increases gastrin release, and to examine whether the high fasting serum gastrin concentrations respond to treatment that eradicates H. pylori. One hundred and twenty-seven patients with gastric or duodenal ulcer were included in this study. Patients were divided into three groups on the basis of antral H. pylori status and therapeutic modalities. The first group, 58 patients infected by H. pylori, was treated with metronidazole and tripotassium dicitrato bismuthate combined with ranitidine and mylanta. The second group, 40 patients also infected by H. Pylori, was treated with ranitidine and mylanta. The third group, 29 patients, free of H. pylori infection, was designed to evaluate the influence of H2-receptor antagonist on the change of gastrin. When ulcers were completely healed, changes of gastrin concentrations and H. pylori status were re-examined. H. pylori was eradicated in all patients who have received antibacterial therapy in 4 weeks, and serum gastrin concentrations were significantly decreased after eradication of the organism both in gastric and in duodenal ulcer diseases. (Gastric ulcer: 129.3 +/- 47.0 pg/ml before and 63.7 +/- 21.6 pg/ml after treatment. Duodenal ulcer: 108.3 +/- 35.0 pg/ml and 66.5 +/- 21.9 pg/ml, respectively. Total: 112.7 +/- 38.2 pg/ml vs 66.0 +/- 21.6 pg/ml) (p < 0.01). In contrast, H. pylori-positive patients who have not received antibacterial therapy were still infected at the completion of the study, and serum gastrin concentrations increased even though the difference was not significant. (Gastric ulcer: 118.4 +/- 51.2 pg/ml vs 124.0 +/- 56.5 pg/ml. Duodenal ulcer: 85.4 +/- 35.1 pg/ml vs 104.6 +/- 43.5. Total: 99.5 +/- 45.3 vs 112.9 +/- 48.7 pg/ml.) (p > 0.05). None of the patients who were initially H. pylori-negative has been reinfected during the period of the study, and their serum gastrin concentrations were not changed. (Gastric ulcer: 69.8 +/- 38.0 pg/ml. Total: 63.2 +/- 31.1 pg/ml. Duodenal ulcer: 55.1 +/- 17.6 pg/ml vs 55.8 +/- 13.8 pg/ml. Total: 63.2 +/- 31.1 pg/ml vs 63.4 +/- 30.0 pg/ml). Four- to six-week therapy of H2-receptor antagonist and antacid had no influence on serum gastrin concentrations. On the basis of the above results, we confirmed that the chronic infection of H. pylori of gastric antrum in peptic ulcer patients causes increased release of serum gastrin, and eradication of the organism results in a significant fall in serum gastrin concentrations.


The effects of 1-methyl-3-isobutylxanthine on insulin-sensitive 2-deoxyglucose transport.
The effect of 1-methyl-3-isobutylxanthine on insulin-sensitive 2-deoxyglucose uptake in rat adipocytes was studied. 1-Methyl-3-isobutylxanthine inhibited 2-deoxyglucose uptake rate substantially in both the absence and presence of insulin. The lag-time for the effect of insulin on 2-deoxyglucose uptake was prolonged. At the same time 1-methyl-3-isobutylxanthine caused a decrease in ATP levels. From experiments with isolated rat liver mitochondria it appeared that 1-methyl-3-isobutylxanthine inhibits glutamate plus malate oxidation in State 3.


Postoperative Bleeding Two Weeks After Longitudinal Vaginal Septum Resection with the LigaSure Device: A Case Report.
A longitudinal vaginal septum (LVS) is a rare congenital anomaly often identified during adolescence. Surgical removal is a mainstay in treatment of symptomatic cases; however, there is variation in the techniques used. Little is known about the risk for postoperative complications associated with novel methods. We present the cases of 2 adolescent females, ages 15 and 22, diagnosed with an LVS who elected to undergo surgical removal. A LigaSure device was used for resection, and both individuals experienced significant postoperative bleeding almost 2 weeks following resection. This report outlines two occurrences of postoperative bleeding after LVS resection, which may suggest inadequate surgical site hemostasis with use of the LigaSure apparatus. Further research on outcomes related to this technique is needed.


Amino Acid Polymorphisms in Hla Class II Differentiate Between Thyroid and Polyglandular Autoimmunity.
The structure of the human leucocyte antigen (HLA) peptide-binding clefts strongly contributes to monoglandular and polyglandular autoimmunity (AP). To investigate the impact of amino acid polymorphisms on the peptide-binding interactions within HLA class II and its association with AP. Immunogenetic study. Tertiary referral center for autoimmune endocrine diseases. 587 subjects with AP, autoimmune thyroid disease (AITD), type 1 diabetes (T1D), and healthy unrelated controls were typed for HLA class II. Amino acids within the peptide binding cleft that are encoded by HLA class II exon 2 were listed for all codon positions in all subjects. Overall comparisons between disease and control groups with respect to allele distribution at a given locus were performed by assembling rare alleles applying an exact Freeman Halton contingency table test with Monte-Carlo P values based on 150 000 samples. The Monte Carlo exact Fisher test demonstrated marked differences in all 3 loci, DQA1, DQB1, and DRB1 (P < .0001) between AP and both AITD and controls, as well as between AP type II (Addison's disease as a major endocrine component) and AP type III (T1D + AITD). Differences were also noted between AP and T1D pertaining to the DRB1 allele (P < .041). Seven amino acid positions, DRB1-13, DRB1-26, DRB1-71, DRB1-74, DQA1-47, DQA1-56, and DQB1-57, significantly contributed to AP. Five positions in DQA1 (11, 47, 50, 56, and 69) completely correlated (P < .0001). Amino acid polymorphisms within HLA class II exon 2 mediate the AP risk and differentiate between thyroid and polyglandular autoimmunity.


[Current characteristics of methods for determining cardiac troponins and their diagnostic value: a mini-review]
The expansion and discovery of new diagnostic possibilities for the use of many biomarkers of cardiovascular diseases (CVDs), including cardiospecific troponin isoforms (cTnI, cTnT), is due to improved laboratory methods for their determination. Throughout a long history of the creation and improvement of immunochemical methods for the determination of cTnI and cTnT, significant changes were observed in the concept of biology and its diagnostic value as CVD biomarkers. The obsolete methods of detection of cTnI, cTnT, named low sensitivity and moderate, were distinguished by a relatively low sensitivity, which led to the confirmation late in the diagnosis of acute myocardial infarction (AMI) and, therefore, such methods were gradually replaced by new methods of high and moderate sensitivity, such as definitions of methods, ultra-sensitive (hs-cTnI, hs-cTnT). With the introduction of hs-cTnI and hs-cTnT in clinical practice, the possibility of early diagnosis and exclusion of AMI through the evaluation of the kinetics of the concentration of hs-cTnI and hs-cTnT in the first hours (0-1 hour, 0-2 hours, 0-3 hours) from the moment the patient enters the emergency room. In addition, some of our ideas about the biology of cardiac troponins have changed, and promising new opportunities for their use in medicine have emerged. This manuscript analyzes the key analytical characteristics of hs-cTnI and hs-cTnT detection methods compared to moderately sensitive methods, and reports on new biological data and some new diagnostic possibilities for the use of hs-cTnI and hs-cTnT in modern clinical practice.


Remembering future life goals: Retrospective future thinking affects life goal qualities.
Personal goals are important for the construction and organization of episodic future thought. This study examines the impact of two future thinking perspectives on qualities of mental goal representations. Here, 142 participants (Mage = 21.9 years) reported on the content and characteristics of five life goals either retrospectively, imagining goals from the perspective of their 100-year-old self, or prospectively from the perspective of their current self. Results indicate that retrospectively reported life goals relied more on schematized knowledge, were dated to occur later in life, and were perceived as more self-concordant with increasing distance from the present. Independent of condition, more distant goals were rated as more difficult, less likely to occur, and were associated with lower self-efficacy. This study provides the first evidence that the point in life from which you consider your own future affects the qualities of mental goal representations, suggesting that retrospective future thinking serves as a form of psychological distancing.


The role of CT perfusion imaging in acute stroke diagnosis: a large single-center experience.
The objective of this study was to determine the utility of computed tomography perfusion (CTP) scans in diagnosing acute ischemic stroke (AIS). CTP abnormalities in two contiguous supratentorial levels were correlated with diffusion weighted image (DWI) abnormalities on magnetic resonance imaging (the standard for stroke diagnosis) performed within 1 week in 422 suspected acute ischemic strokes. Of 157 AIS confirmed by DWI, 78 showed CTP abnormalities (sensitivity 49.7%). All of these examinations were performed with a mean of 35 min from the initial emergency department neurological examination. Excluding small non-vascular territory strokes left 77 AIS with a total volume of infarcted tissue of more than 5 cc by DWI. Of these, 71 showed CTP abnormalities (sensitivity 92.2%). Of the 265 patients without AIS, none showed CTP abnormalities (specificity 100%). CTP is a rapid, readily available and effective method of diagnosing AIS in clinical practice, particularly the major intracranial vessel strokes that result in a more devastating outcome.


Involvement of insulin in the acute thermogenic responses to food and nonmetabolizable substances.
Gastric intubation with 40 kJ of a carbohydrate slurry (4 mL) produced increases in resting oxygen consumption (VO2) of 15% to 22% in control, cold-adapted, and hyperthyroid rats, but the absolute rise in metabolic rate after food was greater in the latter group. Tube-feeding methyl cellulose (4 mL, 7% wt/vol) evoked similar increases in VO2 to carbohydrate (15% to 23%), but all of these responses were inhibited by beta-adrenergic blockade with propranolol. In cold-adapted animals, fat (40 kJ, 1.2 mL) produced a greater thermic effect than carbohydrate or methyl cellulose, and water (4 mL) also induced a small (8%), significant increase in VO2. Treatment with diazoxide shortly before the meal, to inhibit insulin release, almost completely inhibited the thermic responses to carbohydrate and methyl cellulose in all groups, but did not alter the effects of fat or water. Ingestion of a nonmetabolizable substance (methyl cellulose), would appear to stimulate metabolic rate to a similar extent to carbohydrate, possibly by causing gastric distention. Thermic effects of both these substances appear to involve insulin release and activation of the sympathetic nervous system. The thermic response to fat can also be inhibited by beta-adrenergic blockade, but apparently does not involve insulin release.


Market structure and hospital-insurer bargaining in the Netherlands.
In 2005, competition was introduced in part of the hospital market in the Netherlands. Using a unique dataset of transactions and list prices between hospitals and insurers in the years 2005 and 2006, we estimate the influence of buyer and seller concentration on the negotiated prices. First, we use a traditional structure-conduct-performance model (SCP-model) along the lines of Melnick et al. (J Health Econ 11(3): 217-233, 1992) to estimate the effects of buyer and seller concentration on price-cost margins. Second, we model the interaction between hospitals and insurers in the context of a generalized bargaining model similar to Brooks et al. (J Health Econ 16: 417-434, 1997). In the SCP-model, we find that the market shares of hospitals (insurers) have a significantly positive (negative) impact on the hospital price-cost margin. In the bargaining model, we find a significant negative effect of insurer concentration, but no significant effect of hospital concentration. In both models, we find a significant impact of idiosyncratic effects on the market outcomes. This is consistent with the fact that the Dutch hospital sector is not yet in a long-run equilibrium.


Microvascular Decompression for Hemimasticatory Spasm: A Case Report and Review of the Literature.
Hemimasticatory spasm is a rare clinical entity characterized by involuntary and paroxysmal contractions of the jaw-closing muscles on 1 side of the face. Although its cause is not fully known, vascular compression of the trigeminal nerve has been speculated. Here, we report 1 case of hemimasticatory spasm that was cured by microvascular decompression of the motor branch of the trigeminal nerve; a relevant literature review was also performed. Hemimasticatory spasm is a rare disease that may be recalcitrant to conservative medical therapy, and vascular decompression of the trigeminal nerve may be required to relieve the spasm.


Ex vivo detection of myelin basic protein-reactive T cells in multiple sclerosis and controls using specific TCR oligonucleotide probes.
T cell reactivity to candidate myelin autoantigens, such as myelin basic protein (MBP), may play an important role in the pathogenesis of multiple sclerosis (MS). Although MBP-reactive T cells have been found to undergo in vivo activation in patients with MS, their true precursor frequency in MS is unknown as current frequency analysis is commonly based on the T cell functional responses to MBP. In this study, we developed a TCR sequence-based ex vivo detection system using colony hybridization with oligonucleotide probes specific for CDR3 of selected T cell clones for the analysis of true T cell precursor frequency in PBMC. The results revealed that the precursor frequency of five independent T cell clones recognizing the immunodominant MBP(83-99) region was found to be in the range of 1.6 x 10(-4) in total T cells in three HLA-DR2 patients with MS compared to that of 0.25 x 10(-4) in HLA-DR2 healthy individuals. The observed frequency of MBP(83-99)-reactive T cells in MS patients was considerably higher than those measured in parallel by cell culture-based analysis (2.3 x 10(-6)) or by enzyme-linked immunospot assay (3.9 x 10(-5)) in the same peripheral blood mononuclear cell specimens. Furthermore, the study showed that MBP(83-99)-reactive T cells detected ex vivo belonged to CD45RA+, CD25+ and CD95- T cell subsets as evidenced by preferential expression of specific TCR transcripts in these cell fractions.


Ciprofloxacin and norfloxacin for selective decontamination in patients with severe granulocytopenia.
In a randomized multicenter study, ciprofloxacin and norfloxacin, each in two different dose regimens and in combination with non-absorbable antimycotics, were administered to 51 patients with acute leukaemia undergoing aggressive remission induction chemotherapy for infection prevention. Both drugs showed an effective elimination of gram-negative potential pathogens and Staphylococcus aureus not affecting the anaerobic flora of the gastrointestinal tract. A low incidence of side effects and a satisfactory patient compliance could be observed. A daily dosage of 1,000 mg ciprofloxacin or 800 mg norfloxacin is recommended for infection prevention in severely granulocytopenic patients.


Quantifying Polarized Extracellular Matrix Secretion in Cultured Endothelial Cells.
In endothelial cells (ECs), the onset of apicobasal polarity is primarily regulated by the interaction of integrins with the surrounding extracellular matrix (ECM). ECs secrete and polymerize fibronectin (FN), a unique, permissive substrate that allows for vascular morphogenesis and lumen formation. We previously identified a signaling pathway that, under the control of the adhesion site adaptor protein PPFIA1, integrates the polarized secretion of freshly synthesized FN with the recycling of conformationally active α5β1 integrin, the main FN receptor in ECs. To characterize the functional role of PPFIA1-dependent signaling in ECs, we set up a Transwell-based assay to quantify the polarized secretion of ECM proteins. To this aim, we allowed ECs to form a confluent monolayer on the Transwell membrane and checked its integrity by measuring transendothelial electric resistance and controlling the stability of tight junctions over time by fluorescent confocal microscope analysis. Finally, we quantified apical and basolateral FN secretion in control and PPFIA1-silenced EC culture medium by western blot analysis coupled to spike-in normalization.


Sanguinarine: a positive inotropic alkaloid which inhibits cardiac Na+,K+-ATPase.
In isolated, isometrically contracting left guinea pig atria, sanguinarine, a benzophenanthridine alkaloid from the papaveracea Sanguinaria canadensis, produced a concentration-dependent positive inotropic effect. Between 2.3 x 10(-6) M and 6.5 x 10(-5) M, sanguinarine increased contractility by 108% which was comparable to the maximal inotropic effect of ouabain. Within the same concentration range, sanguinarine caused inhibition of Na+,K+-ATPase isolated from guinea pig myocardium. 100% inhibition of Na+,K+,ATPase activity occurred at 1 x 10(-4) M sanguinarine. The I50 for enzyme inhibition and the ED50 for the inotropic action of sanguinarine were the same (6-6.5 x 10(-6) M) indicating that both effects may be causally related.


Nuclear localisation of the transcription factor Stat5b is associated with ovine milk protein gene expression during lactation but not during late pregnancy or forced weaning.
Localisation patterns of the transcription factor Stat5b in the udders from pregnant, lactating and involuting ewes were compared with the expression patterns of two major milk protein genes alpha-lactalbumin and alphaS1 casein. Stat5b was detected in the cytoplasm and nuclei of epithelial cells at all stages of mammary gland development. A consistent positive relationship between the nuclear localisation of Stat5b in lactating mammary alveolar epithelial cells, and the presence of milk protein gene mRNA was apparent during lactation and early involution. Conversely, there was little evidence of nuclear localisation of Stat5b in non-lactating mammary alveolar epithelial cells during lactation and early involution. This supports the observation that during lactation, Stat5b may play a role in milk protein gene expression. However, during pregnancy and later involution, while Stat5b was observed to be present in mammary epithelial cell nuclei and cytoplasm, no relationship between this and the presence of milk protein gene mRNA was apparent. This suggests that during late pregnancy and in later involution, Stat5b may be involved in processes other than initiation of milk protein gene transcription.


A Modified Maze Versus Cut-and-Sew Maze for Long-Standing Persistent Atrial Fibrillation Concomitant with Mitral Valve Surgery: A Propensity Score-Matched Cohort Study.
The cut-and-sew maze (CSM) procedure has an excellent efficacy for the elimination of long-standing persistent atrial fibrillation (AF) concomitant with mitral valve surgery. Because of the complexity and prolongation of cardiopulmonary bypass, CSM has not been widely used. The aim of this study was to examine a modified maze procedure that preserves the "cut-and-sew" procedure in the left atrium and uses cryoablation in the right atrium along with cavotricuspid isthmus. From December 2013 to December 2018, 229 patients underwent CSM, and 43 underwent the modified maze procedure during mitral valve surgery. Propensity score matching analysis was used to perform selective 1:2 ratio matching of the 43 patients undergoing the modified maze procedure with 86 patients undergoing CSM. Early operative outcomes were analysed for differences. The absence of AF recurrence without the use of anti-arrhythmic drugs was calculated at 2 years by a generalised linear model analysis. One (1.1%) early death occurred in the CSM group, and no deaths occurred in the modified maze group (p=0.722). The aortic cross-clamp durations were 76.30±8.86 minutes for the modified maze and 92.38±10.88 for the CSM procedure (p<0.001). There were no late strokes or deaths during the 2-year follow-up. The modified maze group showed similar rates of absence of AF without the use of anti-arrhythmic drugs as the CSM group within the 2 years (p=0.332). This modified maze simplifies the "cut-and-sew" procedure and reduces operating time while retaining the efficacy of CSM.


Seven-Year Approach Evolution of the Aortoiliac Occlusive Disease Endovascular Treatment.
Endovascular treatment is now considered the first-line therapy for the aortoiliac occlusive disease (AIOD). We report our experience with the total endovascular treatment of infrarenal and pararenal aortoiliac occlusions and the 7-year approach evolution. A total of 22 patients underwent total endovascular treatment of AIOD from January 2008 to September 2014. Bare metal stents in kissing configuration were deployed in 9 cases, covered stents in kissing configuration in 9 patients and the aortic bifurcation reconstruction with the Y-guidewire configuration technique was performed in the last 4 patients. Technical success was 100%. Perioperative mortality rate was 4.5%. ankle-brachial index improved from 0.49 ± 0.19 to 0.96 ± 0.05 at the right side and from 0.53 ± 0.17 0.98 ± 0.04 at the left side (P < 0.01). Mean follow-up was 39.5 months (range, 5-80 months). The primary patency rate was 95.2% at 1 year and 90.5% at 3 years, and the secondary patency rate was 95.2% at 1 year and 100% at 3 years. Different stent types and configurations used for the aortoiliac endovascular treatment offer all the benefits of these materials for treatment on a case-by-case basis. The Y-guidewire configuration technique for the aortic bifurcation reconstruction may render the procedure more feasible. More cases and longer follow-up are necessary before the widespread use of this technique.


Amino acid variation in cellular processes in 108 bacterial proteomes.
We have analysed 108 bacterial proteomes in the KEGG database to explore the variation of amino acid composition with respect to protein function. The ratio between the observed amino acid composition and that predicted based on mononucleotide composition was calculated for each functional category. This indicated whether the compositional variation arose from mutation or selection pressure. The results showed that charged amino acids (Lys, Arg and Glu), were found more frequently than expected in proteins involved in genetic information processing (i.e. transcription, translation, etc.) Similarly, in the proteins involved in processing environmental information (e.g. signal transduction), the hydrophobic amino acid Leu was found in excess of values expected from the base composition in the genes.


Maternal diet of polyunsaturated fatty acid influence the physical and neurobehaviour of rat offspring.
Polyunsaturated fatty acids (PUFAs) are normal components of growth and development and its derivatives especially n-3 PUFAs have an influence on the development and maturation of nervous system. The purpose of our present study was to investigate the effect of maternal n-3 PUFAs dietary on physical maturation and the neurobiological development of the rat offspring. According to the content of n-3 PUFAs in their diets, female dams were randomly divided into three treatment groups (n = 6-7): deficiency, control and supplementation. The physical parameters and neurobehavioral tests were measured in the rats' offspring. There were no significant differences in litter size and sex ratio between three groups. However, the ratio of brain/body weight was higher in the deficiency pups than the control. As to the body weight, the deficiency pups were heavier than the control pups on postnatal day (PND) 1, PND7, PND14, and PND21, while supplementation pups were lower than the control pups on PND1. There are no significant differences in the physical parameters of incisor eruption and fur appearance between three groups. However, deficiency pups had earlier eye opening than the control pups. Unfortunately, there were no significant differences in surface righting reflex, cliff avoidance, forelimb grip and air righting reflex. Whereas, supplementation pups required less time to complete negative geotaxis than the control pups on PND17. This study suggests that the consumption of adequate n-3 PUFAs is benefit for the optimal growth and development of rat offspring. The n-3 PUFAs supplementation is beneficial to population that did not have sufficient provision of n-3 PUFAs in the diet during gestation and lactation.


Comparison of diode laser-assisted surgery and conventional surgery in the management of hereditary ankyloglossia in siblings: a case report with scientific review.
Laser-assisted surgery is common nowadays and most of the oral soft tissue surgical procedures are done with lasers. Among the commonly available lasers today, the diode laser is the one frequently used one in dentistry. Bleeding control, visibility, and better tissue manipulation are some of the advantages of the laser. This article addresses the management of hereditary ankyloglossia using the diode laser and conventional surgery in siblings.


Time-between control charts for monitoring asthma attacks.
The monitoring of peak expiratory flow rate (PEFR) is crucial for effective management of asthma. Daily PEFR monitoring is recommended, yet the data are rarely used by patients to help them understand their progress or by clinicians to modify treatment plans. Time-between control charts, which have been shown to be specially suited for monitoring rare events, can be used to monitor asthma attacks. Each patient is asked to record his or her PEFR value once a day, and these data are used to construct the control chart. PEFR data for three previously reported cases are presented and used to illustrate the control chart methodology. If duration of consecutive attacks is plotted and the observed duration exceeds the upper control limit (UCL), the patient is getting worse. If length of consecutive symptom-free days is plotted and the observed duration exceeds the UCL, the patient is getting better. In both circumstances, the clinician and the patient explore what brought about the prolonged recovery or periods of deterioration. The object is to increase time until the next attack. Using time-between control charts in monitoring asthma attacks has the advantage of providing a visual display of data that, unlike eyeballing of trends, clarifies when patients should seek additional clinical advice. The control limit allows clinicians and patients to ignore random variations and focus on real changes in underlying patterns of asthma attacks.


Visualizing Metal Distribution in Plants Using Synchrotron X-Ray Fluorescence Microscopy Techniques.
Recent improvements in synchrotron-based X-ray fluorescence (SXRF) microscopy established it as an advanced analytical tool for analyzing 2D- and 3D distribution of mineral elements in plants. Among existing imaging techniques, SXRF microscopy offers several unique capabilities, including in situ metal quantification in plant tissues and high sensitivity, as low as 1 mg kg-1, at the nanoscale spatial resolution. SXRF is increasingly utilized in different plant science disciplines to provide a fundamental understanding of metal homeostasis, and the function of trace elements in plant metabolism and development. Here, we describe methods for SXRF imaging, including sample preparation, the optimization of conventional SXRF for analyzing trace elements, and the development of confocal SXRF (C-SXRF).


Early diagnosis in glaucoma.
This chapter reviews the evidence for the clinical application of vision function tests and imaging devices to identify early glaucoma, and sets out a scheme for the appropriate use and interpretation of test results in screening/case-finding and clinic settings. In early glaucoma, signs may be equivocal and the diagnosis is often uncertain. Either structural damage or vision function loss may be the first sign of glaucoma; neither one is consistently apparent before the other. Quantitative tests of visual function and measurements of optic-nerve head and retinal nerve fiber layer anatomy are useful to either raise or lower the probability that glaucoma is present. The posttest probability for glaucoma may be calculated from the pretest probability and the likelihood ratio of the diagnostic criterion, and the output of several diagnostic devices may be combined to achieve a final probability. However, clinicians need to understand how these diagnostic devices make their measurements, so that the validity of each test result can be adequately assessed. Only then should the result be used, together with the patient history and clinical examination, to derive a diagnosis.


Molecular detection of respiratory pathogens in community-acquired pneumonia involving adults.
Community-acquired pneumonia (CAP) causes substantial morbidity and mortality in adults worldwide. The etiology of CAP often remains uncertain, and therapy is empirical. Thus, there is still room for improvement in the diagnosis of pneumonia. Adults aged >20 years who presented at the outpatient or emergency departments of Linkou and Keelung Chang Gung Memorial Hospital with CAP were prospectively included between November 2016 and December 2018. We collected respiratory specimens for culture and molecular testing and calculated the incidence rates of CAP according to pathogens. Of 212 hospitalized adult patients with CAP, 69.3% were male, and the median age of the patients was 67.8 years. Bacterial pathogens were detected in 106 (50%) patients, viruses in 77 (36.3%), and fungal pathogens in 1 patient (0.5%). The overall detection rate (culture and molecular testing method) was 70.7% (n = 150). Traditional microbial culture yielded positive results in 36.7% (n = 78), molecular testing in 61.3% (n = 130). The most common pathogens were influenza (16.1%), followed by Klebsiella pneumoniae (14.1%), Pseudomonas aeruginosa (13.6%), human rhinovirus (11.8%), and Streptococcus pneumoniae (9.9%). Multiple pathogen co-infections accounted for 28.7% (n = 61), of which co-infection with K. pneumoniae and human rhinovirus comprised the largest proportion. Molecular diagnostic testing could detect 23.6% more pathogens than traditional culture techniques. However, despite the current diagnostic tests, there is still the possibility that no pathogen was detected.


Interlaboratory study to improve the quality of trace element determinations in rainwater.
This is the first publication which describes the development of a reference material (RM) for the determination of 11 trace elements (Cu, Pb, Mn, Ni, Zn, Fe, Cd, Co, V, As and Al) in rainwater at microgram per liter concentrations. An interlaboratory comparison study for the determination of trace elements in rainwater was carried out for material performance studies to establish analyte concentrations with a stated uncertainty. Fifteen reputed laboratories from Asia, Europe and North America participated in the study. These laboratories used their regular in-house methods to analyze the rainwater samples. The aim of this study is to establish concentration levels of trace elements in rainwater based on interlaboratory study results. Details of the production, homogeneity and stability of the reference sample are given in this article. The organization of the study and the quality assurance measures undertaken at the organizer's laboratory are described. The analytical results obtained from individual laboratories and the analytical methods used for the determination of trace elements in rainwater are discussed. Based on the results obtained from the intercomparison study, certified values as well as informative values are assigned to the 11 trace elements in rainwater.


Integrated electrical activity and number of zero crossings during a gradual increase in muscle force in patients with neuromuscular diseases.
In the brachial biceps muscle of 17 patients with myopathy and of 14 patients with neurogenic disorders the integrated electrical activity and number of zero crossings per unit time were analysed in 3 sites of each muscle every 100 msec during a gradual increase in force from zero to maximum within 10 sec. The analysis of integrated electrical activity could not discriminate between patients with myopathy and patients with neurogenic disorders. The slope of the linear relation between the square root of integrated electrical activity and force expressed in kilograms was increased in 44% of the patients with myopathy and in 64% of the patients with neurogenic disorders. The increase in slope may be due to increase in the ratio of electrical activity and force of individual motor units. The integrated electrical activity related to a force of 40% of maximum was decreased in about two-thirds of patients with myopathy and in about half of the patients with neurogenic disorders. This decrease in integrated electrical activity may be due to random loss of muscle fibres or to loss of whole motor units respectively. The integrated electrical activity was linearly related to mean amplitude between potential reversals per unit time (turns). The number of zero crossings was increased in 29% of the patients with myopathy and decreased in 70% of the patients with neurogenic disorders at a force of 30% of maximum. The number of zero crossings was linearly related to turns.(ABSTRACT TRUNCATED AT 250 WORDS)


Spatial ability, handedness, and human sexual orientation.
We investigated the relations among mental rotations and spatial perception abilities, handedness, and sexual orientation in both men and women. The present study included a relatively large sample and attempted to control statistically for important covariates such as general intelligence. Significant sex differences were obtained for mental rotations and spatial perception, but not for handedness. None of these measures was significantly related to sexual orientation within either sex.


Disseminated Mycobacterium chelonae ssp. abscessus in an immunocompetent host and with a known portal of entry.
A unique case is presented in which disseminated Mycobacterium chelonae ssp. abscessus was found in a normal immunocompetent host after a traumatic injury. Although disseminated disease is known to occur in immunocompromised and postsurgical patients, this case is unusual in that it occurred in a patient with no evidence of immunodeficiency and with a known portal of entry.


Sagittal patellar flexion angle measurement determines greater incidence of patella alta in patellar tendinopathy patients.
The objective of this study was to compare patellar height and patella alta between a control cohort and patients with patellar tendinopathy by the sagittal patellar flexion angle (SPFA) measurement. Magnetic resonance imaging (MRI) scans of the knee were obtained from a sports imaging facility and screened to select patients with anterior knee pain. This symptomatic group was divided into two patient cohorts: those with and without MRI features of patellar tendinopathy. Lateral knee radiographs were reviewed and SPFA, knee flexion angle and Insall-Salvati ratio (IS) were measured from the radiographs by two independent reviewers. A total of 99 patients consisting of 48 patellar tendinopathy patients and 51 control patients were included. There was a significantly higher mean patellar height (p = 0.002, d = 0.639) and a greater patella alta incidence in the patellar tendinopathy cohort (25.0%) compared to the controls (3.9%) (p = 0.022, d = 0.312). Insall-Salvati ratio measurements showed no difference in patella alta incidence between tendinopathy and control cohorts. There was excellent inter- and intra-observer reliability of SPFA measurements (ICC 0.99). This is the first study to demonstrate a greater incidence of patella alta in patellar tendinopathy patients compared to controls. A greater patella alta incidence amongst patellar tendinopathy patients as defined by SPFA was found to be clinically relevant, as it suggests these patients may comprise the recalcitrant patient subgroup who do not improve with current surgical intervention and may therefore benefit from a biomechanical surgical solution. III.


Carbon dioxide at an unpolluted site analysed with the smoothing kernel method and skewed distributions.
CO₂ concentrations recorded for two years using a Picarro G1301 analyser at a rural site were studied applying two procedures. Firstly, the smoothing kernel method, which to date has been used with one linear and another circular variable, was used with pairs of circular variables: wind direction, time of day, and time of year, providing that the daily cycle was the prevailing cyclical evolution and that the highest concentrations were justified by the influence of one nearby city source, which was only revealed by directional analysis. Secondly, histograms were obtained, and these revealed most observations to be located between 380 and 410 ppm, and that there was a sharp contrast during the year. Finally, histograms were fitted to 14 distributions, the best known using analytical procedures, and the remainder using numerical procedures. RMSE was used as the goodness of fit indicator to compare and select distributions. Most functions provided similar RMSE values. However, the best fits were obtained using numerical procedures due to their greater flexibility, the triangular distribution being the simplest function of this kind. This distribution allowed us to identify directions and months of noticeable CO₂ input (SSE and April-May, respectively) as well as the daily cycle of the distribution symmetry. Among the functions whose parameters were calculated using an analytical expression, Erlang distributions provided satisfactory fits for monthly analysis, and gamma for the rest. By contrast, the Rayleigh and Weibull distributions gave the worst RMSE values.


The susceptibility of sea-island cotton recombinant inbred lines to Fusarium oxysporum f. sp. vasinfectum infection is characterized by altered expression of long noncoding RNAs.
Disease resistance is one of the most complicated yet important plant traits. The potential functions of long noncoding RNAs (lncRNAs) in response to pathogenic fungi remain unclear. In this study, we sequenced the transcriptomes of four different sea-island cotton (Gossypium barbadense) recombinant inbred lines (RILs) with susceptible, highly susceptible, highly resistant, or super highly resistant phenotypes and compared their responses to Fusarium oxysporum f. sp. vasinfectum (Fov) infection with those of their susceptible and resistant parents. Infection-induced protein coding genes were highly enriched in similar disease resistance-related pathways regardless of fungal susceptibility. In contrast, we found that the expression of a large number of Fov infection-induced lncRNAs was positively correlated with plant susceptibility. Bioinformatics analysis of potential target mRNAs of lncRNAs with both trans-acting and cis-acting mechanisms showed that mRNAs co-expressed or co-located with Fov-regulated lncRNAs were highly enriched in disease resistance-related pathways, including glutathione metabolism, glycolysis, plant hormone signal transduction, anthocyanin biosynthesis, and butanoate metabolism. Together these results suggest that lncRNAs could play a significant role in the response to pathogenic fungal infection and the establishment of disease resistance. The transcriptional regulation of these infection-susceptible lncRNAs could be coordinated with infection-susceptible mRNAs and integrated into a regulatory network to modulate plant-pathogen interactions and disease resistance. Fov-susceptible lncRNAs represent a novel class of molecular markers for breeding of Fov-resistant cotton cultivars.


Ten year comparative analysis of sleeve gastrectomy, Roux-en-Y gastric bypass, and biliopancreatic diversion with duodenal switch in patients with BMI ≥ 50 kg/m2.
Bariatric surgery is the most effective modality to stably reduce weight and related comorbidities in patients suffering from class II and III obesity. Data comparing long-term safety and efficacy of the three most effective bariatric operations are limited in patients with BMI ≥ 50 kg/m2, which complicate shared surgeon-patient decision making regarding optimal procedure selection. A retrospective analysis was performed on all patients with BMI ≥ 50 kg/m2 who underwent biliopancreatic diversion with duodenal switch (BPD/DS), Roux-en-Y gastric bypass (RYGB), or sleeve gastrectomy (SG) at our institution between 2009 and 2019. Data collected from patients' electronic medical records included operative details as well as BMI and presence and resolution of obesity-related comorbidities at 0, 6, 12, 24, 48, and 60 months post-operatively. Among 537 patients with BMI ≥ 50 kg/m2 who had a primary bariatric procedure, 93 patients underwent BPD/DS (17.3%), 341 patients underwent RYGB (63.5%), and 103 patients underwent SG (19.2%). BMI decreased by 23.7 kg/m2 in BPD/DS, 14.7 kg/m2 in RYGB, and 13.6 kg/m2 in SG cohorts at 60 months post-operatively (p < 0.0001). The greatest %TWL occurred in BPD/DS cohort (38.4%) followed by the RYGB (26.3%) and SG (23.6%) cohorts (p < 0.0001). The thirty-day complication rate was 12.9% for BPD/DS, 4.7% for RYGB, and 8.7% for SG (p = 0.015). Our study demonstrated that the BPD/DS is the most effective operation at long-term reduction of BMI and achieved highest %TWL while SG and RYGB had similar results at 60 months post-op. BPD/DS is associated with increased early and late surgical complications compared to RYGB and SG.


Parameterization of individual-based models: comparisons with deterministic mean-field models.
The relating of deterministic, mean-field models into network models, where epidemic spread occurs between interconnected susceptible and infectious individuals or populations, requires careful consideration. Here, we discuss models that consider differently the manner in which contact rate and infectiousness change over time, with different algorithms suitable for different underlying processes. Though these models give coincidental results to the mean-field in the case of large, highly connected networks, the results when sparsely connected networks are considered may differ. Different subsets of the parameters from the mean-field epidemic (R(0), generation time, infectiousness, etc.) are preserved in each case. Despite these differences, simulated epidemics generated under some model architectures are insensitive to the average degree of contact amongst nodes, k. Model-based estimates of k may be model dependent, and must therefore be viewed with caution.


Endovascular therapy for cardiocerebral infarction associated with atrial fibrillation: A case report and literature review.
Cardiocerebral infarction (CCI) is a rare entity that refers to the simultaneous occurrence of acute myocardial infarction and acute ischemic stroke. The management of CCI patients remains unclear. An 86-year-old woman with a medical history of paroxysmal atrial fibrillation presented with a sudden onset of consciousness disturbance and right hemiplegia. Computed tomography of the head revealed no intracranial hemorrhage but the left hyperdense middle cerebral artery sign, associated with ST-segment elevation in II, III, and aVF noted on a routine 12-lead electrocardiogram at admission. The patient was immediately brought to the catheterization laboratory and percutaneous coronary intervention (PCI) was performed first, followed by mechanical thrombectomy, resulting in successful revascularization of the both diseases. Although the treatment strategy of CCI may depend on the condition of coronary and cerebral ischemia, it may be appropriate to prioritize coronary angiography and PCI if not acute ischemic stroke is critical.


Medullary projections to the vagus nerve and posterolateral hypothalamus.
Vagal visceromotor reflexes are dependent upon reciprocal neural connections existing between the medulla and the hypothalamus. Medullohypothalamic neurons may provide feedback cues to the hypothalamus regarding the activity of vagal motor neurons. As yet, however, studies investigating the spatial relationships between medullohypothalamic neurons and vagal motor neurons have not been performed. A variety of retrogradely transported tracers were used for the purpose of mapping the relative locations of medullovagal and medullohypothalamic neurons. Tracers were injected into the cervical vagus nerve and/or the posterolateral hypothalamus, and subsequently the retrogradely labeled medullary neurons were plotted. Labeling of the two neuronal populations was primarily observed within the ventrolateral and dorsomedial medulla. Within the ventrolateral medulla, medullovagal neurons were found within the retrofacial nucleus and nucleus retroambiguus, whereas medullohypothalamic neurons were located subjacent to these nuclei. Within the dorsomedial medulla, labeling of the two neuronal populations was primarily limited to the vagal-solitary complex. At this location medullovagal neurons were found within the dorsal vagal nucleus, whereas medullohypothalamic neurons were largely confined to the caudal aspect of the solitary nucleus. Because of the spatial proximity existing between medullovagal and medullohypothalamic neurons, it is suggested that functional interrelationships may exist between these two neuronal populations. Specifically, it is suggested that the medullohypothalamic neurons identified in this study may support vagal-related functions by providing feedback cues to the posterolateral hypothalamus.


Phylogenetic Analysis of Bird-Virulent West Nile Virus Strain, Greece.
We report the full polyprotein genomic sequence of a West Nile virus strain isolated from Eurasian magpies dying with neurologic signs in Greece. Our findings demonstrate the local genetic evolution of the West Nile virus strain responsible for a human disease outbreak in the country that began in 2010.


Influence of Dietary Copper on Serum Growth-Related Hormone Levels and Growth Performance of Weanling Pigs.
To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300 mg/kg copper sulfate for 80 days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20 days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300 mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250 mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P < 0.01), and the levels of GH, INS, IGF-1, and IGFBP-3 in serum were elevated significantly from the 20th to the 40th day of the experiment (P < 0.01). It is concluded that effects of copper supplemented in the diet on the growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs.


Reproducible and sensitive determination of charged oligosaccharides from haptoglobin by PNGase F digestion and HPAEC/PAD analysis: glycan composition varies with disease.
Many studies have reported changes in the carbohydrate structure of serum glycoproteins in disease, but this information is often of limited value for understanding disease mechanisms because it is obtained with simple and/or indirect methodologies that determine only one structural feature. On the other hand, more detailed carbohydrate methodologies are time-consuming and require a lot of purified material. Using haptoglobin (Hp) as a model protein, a new procedure was devised that determined the oligosaccharide composition of very small amounts of Hp in a relatively short time. The Hp was purified by batch affinity-chromatography, oligosaccharides were removed with PNGase F, and the oligosaccharide composition of charged species was determined using HPAEC/PAD (Dionex carbohydrate analyser). The method was applied to the analysis of Hp from eight healthy individuals and 37 patients with different inflammatory diseases or cancers. Twenty-seven oligosaccharides were consistently detected, but the majority could not be identified. However, by calculating retention times relative to the sialylated biantennary peak (Neu5Ac(alpha)2-3/6Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-6(Neu 5Ac(alpha)2-3/6Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-3)Man(beta)1-4G lcNAc(beta)1-4GlcNAc) it was possible to compare profiles quantitatively. Although no peak was identified as disease-specific, characteristic and reproducible profiles were obtained. Particularly striking were reductions in the major peaks in Crohn's disease, rheumatoid arthritis, stomach cancer, accompanied by increases in unidentified peaks. Previous studies suggested that many of the unknown peaks were due to increased sialylation and fucosylation. Only small changes in patterns were observed for breast and ovarian cancer. The new procedure will be very useful in the characterization of oligosaccharide composition of glycoproteins in clinical specimens.


ClinPred: Prediction Tool to Identify Disease-Relevant Nonsynonymous Single-Nucleotide Variants.
Advances in high-throughput DNA sequencing have revolutionized the discovery of variants in the human genome; however, interpreting the phenotypic effects of those variants is still a challenge. While several computational approaches to predict variant impact are available, their accuracy is limited and further improvement is needed. Here, we introduce ClinPred, an efficient tool for identifying disease-relevant nonsynonymous variants. Our predictor incorporates two machine learning algorithms that use existing pathogenicity scores and, notably, benefits from inclusion of normal population allele frequency from the gnomAD database as an input feature. Another major strength of our approach is the use of ClinVar-a rapidly growing database that allows selection of confidently annotated disease-causing variants-as a training set. Compared to other methods, ClinPred showed superior accuracy for predicting pathogenicity, achieving the highest area under the curve (AUC) score and increasing both the specificity and sensitivity in different test datasets. It also obtained the best performance according to various other metrics. Moreover, ClinPred performance remained robust with respect to disease type (cancer or rare disease) and mechanism (gain or loss of function). Importantly, we observed that adding allele frequency as a predictive feature-as opposed to setting fixed allele frequency cutoffs-boosts the performance of prediction. We provide pre-computed ClinPred scores for all possible human missense variants in the exome to facilitate its use by the community.


Organization of rapid responses to postural and locomotor-like perturbations of standing man.
This study has described the organization of EMG activities among the muscles of a standing subject's legs during rapid postural adjustments (95--120 ms latencies). Adjustments were elicited by the horizontal translation of both feet (causing antero-posterior sway), by the synchronous vertical displacement of both feet (causing changes in height) and by the reciprocal vertical displacement of the feet (causing changes in height) and by the reciprocal vertical displacement of the feet (causing a locomotor-like motion of the legs and lateral sway of the body). The resulting patterns of EMG activity were highly specific for each kind of displacement, and all subjects completely reorganized the pattern of activity from one form to another within the first trials, even immediately following unexpected stimulus changes. The organization of EMG activities during reciprocal vertical displacements was qualitatively quite similar to those observed during the comparable swing and stance phases of the locomotor step cycle; flexor muscles of the ankle and knee (those being shortened by the displacement) contracted in the upwardly displaced leg while extensor muscles were active in the downwardly displaced leg. This pattern was in marked contrast to the activation of lengthening muscles during synchronous vertical and antero-posterior sway displacements. Finally, electrical cutaneous stimulation of the dorsum of one foot during reciprocal vertical displacements always enhanced the EMG activity of the agonist leg muscles, in-phase with the vertical movement.


Modified split tendon transfer of posterior tibialis muscle in the treatment of spastic equinovarus foot deformity: long-term results and comparison with the standard procedure.
Split tendon transfer of tibialis posterior (SPOTT) is a treatment option for the hindfoot varus deformity in patients with cerebral palsy (CP). The purpose of this study was to present the long-term results of the newly modified SPOTT procedure developed by our senior author and compare it with the standard SPOTT technique in equinovarus foot deformity due to CP. Our retrospective cohort study included patients with spastic foot deformity due to CP treated with the standard or modified SPOTT technique. Patients' age at the time of the surgery was ≥ five years with follow-up period of at least four years. Surgical outcomes were evaluated using Kling's criteria during the patient's last follow-up visit. The analysis included 124 patients (146 feet), where 105 feet were treated by the standard SPOTT technique and 41 feet by the modified SPOTT technique. Patients' median age at the time of the surgery was 11 years. Patients were followed-up for a median period of eight years during which the modified SPOTT technique showed significantly better surgical outcomes compared with the standard group (excellent/good results in 38 feet, 92.7%, vs. 79 feet, 75.2%, p = 0.02). Two groups of patients did not significantly differ in GMFCS level, age at the time of the surgery, or patient gender. There was similar distribution in CP patterns in the standard and modified groups; spastic hemiplegia was the most prevalent form, followed by spastic diplegia and spastic paraplegia. Overall, better surgical success was achieved in patients with GMFCS levels I-III (100%, 94.8%, and 69.8%, respectively). SPOTT procedure failure was frequently noticed in patients with GMFCS level IV (90.9%). The modified SPOTT procedure demonstrated efficiency and safety in patients with equinovarus foot deformity due to CP during the long-term follow-up. Compared with the standard procedure, the newly modified SPOTT technique showed significantly better surgical outcome, irrespective of the patients' gender, age, initial GMFCS level, and CP type.


Sources and monthly and seasonal concentration variation study of atmospheric particulates and particles-bound PAEs.
The main goal of this study is to measure the ambient air of total suspended particulates at a mixed (traffic, residential and commercial) sampling site. And the concentrations of phthalate acid ester (PAE) which attached on total suspended particles were also analyzed. In addition, the possible sources of PAEs were also analyzed by the method of back trajectories. Finally, appropriate statistical methods were also used to test monthly and seasonal mean pollutants' (particulates, PAEs) concentration differences at this sampling site. The results indicated that the monthly concentration variation trends were similar for DEHP and total PAEs with the results as followed: November > October > July > December > September. In addition, back trajectories results also indicated that the main pollutant parcels were came from the east side of Taiwan in July. And the pollutant parcels were came from the north side of Taiwan during the month of September, October, November and December in this study. Moreover, the results also showed that the DEHP, DNOP, total PAEs' concentrations with TSP and meteorological conditions were not significantly different. But the relationship among DEHP, DNOP and total PAEs was significantly different; particularly, the relationship between DEHP and total PAEs was highly correlated in this study (R2 = 0.994). Finally, the statistical analysis of total PAEs T test statistic for mean monthly concentrations results suggested that the sample population means were not differed significantly. In other words, there were not any mean monthly concentration differences for PAEs at this sampling site. The only exception was occurred in the month of September versus November. The results showed that there is a statistically significant PAEs' concentration difference between the input groups (September vs. November).


Terahertz radiation driven by two-color laser pulses at near-relativistic intensities: Competition between photoionization and wakefield effects.
We numerically investigate terahertz (THz) pulse generation by linearly-polarized, two-color femtosecond laser pulses in highly-ionized argon. Major processes consist of tunneling photoionization and ponderomotive forces associated with transverse and longitudinal field excitations. By means of two-dimensional particle-in-cell (PIC) simulations, we reveal the importance of photocurrent mechanisms besides transverse and longitudinal plasma waves for laser intensities >10(15) W/cm(2). We demonstrate the following. (i) With two-color pulses, photoionization prevails in the generation of GV/m THz fields up to 10(17) W/cm(2) laser intensities and suddenly loses efficiency near the relativistic threshold, as the outermost electron shell of ionized Ar atoms has been fully depleted. (ii) PIC results can be explained by a one-dimensional Maxwell-fluid model and its semi-analytical solutions, offering the first unified description of the main THz sources created in plasmas. (iii) The THz power emitted outside the plasma channel mostly originates from the transverse currents.


An Efficient Blue-Emission Crystalline Thin-Film OLED Sensitized by "Hot Exciton" Fluorescent Dopant.
Crystalline thin-film organic light-emitting diodes (C-OLEDs) can achieve a large light emission and a low Joule-heat loss under low driving voltage due to the high carrier mobility of the crystalline thin films. However, it is urgent for the C-OLEDs to improve their external quantum efficiency (EQE). Here, a novel strategy is proposed using a doped "hot exciton" material to sensitize a high PLQY blue emitter in C-OLEDs. Benefiting from the capability of the "hot exciton" material harnessing triplet/singlet excitons, the C-OLED exhibits an efficiency breakthrough with a maximum EQE of 6.2%, a much enhanced blue photon output with pure blue emission Commission International de L'Eclairage (CIE) (0.14, 0.15), a low turn-on/operation voltage of 2.6 V(@1 cd m-2 )/3.8 V (@1000 cd m-2 ), and a maximum power efficiency (PE) of 9.4 lm W-1 . This work unlocks the potential of C-OLEDs for achieving high photon output with high EQE.


Bibliometric analysis of the use of artificial intelligence in COVID-19 based on scientific studies.
One such strategy is citation analysis used by researchers for research planning an article referred to by another article receives a "citation." By using bibliometric analysis, the development of research areas and authors' influence can be investigated. The current study aimed to identify and analyze the characteristics of 100 highly cited articles on the use of artificial intelligence concerning COVID-19. On July 27, 2022, this database was searched using the keywords "artificial intelligence" and "COVID-19" in the topic. After extensive searching, all retrieved articles were sorted by the number of citations, and 100 highly cited articles were included based on the number of citations. The following data were extracted: year of publication, type of study, name of journal, country, number of citations, language, and keywords. The average number of citations for 100 highly cited articles was 138.54. The top three cited articles with 745, 596, and 549 citations. The top 100 articles were all in English and were published in 2020 and 2021. China was the most prolific country with 19 articles, followed by the United States with 15 articles and India with 10 articles. The current bibliometric analysis demonstrated the significant growth of the use of artificial intelligence for COVID-19. Using these results, research priorities are more clearly defined, and researchers can focus on hot topics.


Case report: Brown-Séquard syndrome resulting from a ski injury in a 7-year-old male.
Cervical spine and spinal cord injuries are rare in pediatric trauma victims. The majority result from blunt trauma. Spinal cord injury without radiographic abnormality has been reported to be more common among young children than adults. The Brown-Séquard syndrome is rarely seen as the result of blunt trauma. We present the case of young boy who suffered spinal cord injury without radiographic abnormality resulting in the Brown-Séquard syndrome and review the controversy surrounding the use of high-dose corticosteroids in the treatment of pediatric spinal cord injury. Current data do not support the use of corticosteroids as 'standard of care' for this population.


A Seasonal Change of Active Ingredients and Mineral Elements in Root of Astragalus membranaceus in the Qinghai-Tibet Plateau.
Astragalus membranaceus is an important traditional Chinese herb whose roots have been used for medicinal purposes for more than 2000 years. Because of excessive exploitation, the wild resources are currently almost exhausted, and therefore, artificial planting of Astragalus membranaceus has been increasingly important. But to date, few studies have focused on the active ingredients and mineral element of Astragalus membranaceus in the Qinghai-Tibet Plateau.In this study, five density gradients (M1: 10 cm × 25 cm, M2: 15 cm × 25 cm, M3: 20 cm × 25 cm, M4: 25 cm × 25 cm and M5: 30 cm × 25 cm) were assessed to evaluate the effects of various planting densities on the mineral element and secondary metabolite content of Astragalus membranaceus roots in different months. It was found that the content of calycosin-7-O-β-D-glucoside and astragaloside IV reached its highest in October. Ononin content increased month by month, while formononetin content decreased during months. Calycosin content did not show significant changes during seasons. Taken together, these results suggest that the optimal planting density is 15 cm × 25 cm (D2) and the optimal harvest period is October. According to the results, the Cu content in all samples did not exceed the limit (20 mg/kg). Principal component analysis (PCA) revealed that Na, P, K Al, Ba, Ca, Fe, Li, and Mn were selected as characteristic elements of Astragalus membranaceus. The results also showed a high correlation between elements and active ingredients. Ba and Co had extremely significant associations with astragaloside IV.


Ultrasound-guided mechanical fragmentation of sialoliths (sonoguide forceps).
Little data about the efficacy and limitations of ultrasound-guided mechanical intraductal stone fragmentation and removal of sialoliths (Sonoguide Forceps) exist. This was a chart review of patients treated within the last 4 years at 2 tertiary care centers. Sonoguide Forceps were used as a second-line treatment in 22 patients with sialolithiasis. Ten patients were free of stones and symptoms afterwards (7 of 17 submandibular, 2 of 4 parotid, 1 of 1 sublingual). Six patients were primarily treated for parotid sialolithiasis, 4 with successful stone retrieval. The reasons for failure were a lack of accessibility to the stone by the forceps (n = 9), the impossibility of grasping the stone (n = 5), and/or the concomitant grabbing of soft tissue together with the stone (n = 3). The efficacy of Sonoguide Forceps as both a secondary and primary treatment modality makes it an interesting, simple, and inexpensive therapeutic alternative. Relevant parameters for treatment success include the size and position of the stones.


Proteins and acids from petroleum.
The wax distillate fraction (boiling range 300 up to 400 degrees C) from the crude oil "El-Alameen" was found to be a good substrate for the biosynthesis of proteins and/or amino acids by bacteria under special culture conditions. The fermentation processes were accompanied by a refining effect to the oil fraction, elevating its refraction index and lowering its melting point, giving dewaxing effect to the oil fraction.


C-Glycoside metabolism in the gut and in nature: Identification, characterization, structural analyses and distribution of C-C bond-cleaving enzymes.
C-Glycosides, in which a sugar moiety is linked via a carbon-carbon (C-C) bond to a non-sugar moiety (aglycone), are found in our food and medicine. The C-C bond is cleaved by intestinal microbes and the resulting aglycones exert various bioactivities. Although the enzymes responsible for the reactions have been identified, their catalytic mechanisms and the generality of the reactions in nature remain to be explored. Here, we present the identification and structural basis for the activation of xenobiotic C-glycosides by heterocomplex C-deglycosylation enzymes from intestinal and soil bacteria. They are found to be metal-dependent enzymes exhibiting broad substrate specificity toward C-glycosides. X-ray crystallographic and cryo-electron microscopic analyses, as well as structure-based mutagenesis, reveal the structural details of these enzymes and the detailed catalytic mechanisms of their remarkable C-C bond cleavage reactions. Furthermore, bioinformatic and biochemical analyses suggest that the C-deglycosylation enzymes are widely distributed in the gut, soil, and marine bacteria.


An unusual cause of vomiting in an infant of 3 months of age.
This is a 3-month-old infant with a diagnosis of acute cholecystitis presenting with projectile vomiting and no fever and no abdominal pain.


Batch and fixed-bed column studies for biosorption of Zn(II) ions onto pongamia oil cake (Pongamia pinnata) from biodiesel oil extraction.
The present work, analyzes the potential of defatted pongamia oil cake (DPOC) for the biosorption of Zn(II) ions from aqueous solutions in the both batch and column mode. Batch experiments were conducted to evaluate the optimal pH, effect of adsorbent dosage, initial Zn(II) ions concentration and contact time. The biosorption equilibrium and kinetics data for Zn(II) ions onto the DPOC were studied in detail, using several models, among all it was found to be that, Freundlich and the second-order model explained the equilibrium data well. The calculated thermodynamic parameters had shown that the biosorption of Zn(II) ions was exothermic and spontaneous in nature. Batch desorption studies showed that the maximum Zn(II) recovery occurred, using 0.1 M EDTA. The Bed Depth Service Time (BDST) and the Thomas model was successfully employed to evaluate the model parameters in the column mode. The results indicated that the DPOC can be applied as an effective and eco-friendly biosorbent for the removal of Zn(II) ions in polluted wastewater.


[Cell cycle analysis and P53 gene mutation detection of fibroblasts derived from the surrounding skin of keloids].
To investigate whether there are abnormal fibroblasts in the surrounding skin of keloids for better understanding of the etiological feature of keloids. Fresh samples were used for cell culture. Flow cytometry was used for analyzing cell cycles of fibroblasts derived from keloids and the surrounding skin. Proliferative cell proportions were compared between every two groups. P53 exon 4, 5 and 6 were amplified by PCR. DNA was sequenced to examine the structure of the destination gene. The proliferative cell proportion of the fibroblasts derived from the surrounding skin is not so high as that from the verge of keloids, but is higher than the normal skin fibroblasts derived from other part of the keloid patients or persons without keloids (P < 0.05). Mutations (point and frameshift mutations) of P53 exon 4 (6/6) and exon 5(2/6) in fibroblasts derived from the surrounding skin of keloids were identified. Fibroblasts derived from keloids have the same mutations as its surrounding skin. There are abnormal fibroblasts in the surrounding skin of keloids. It may be the consequence of keloid infiltrative growth and a reason of easy recurrence of keloid after therapy.


Analytical methods for trace levels of reactive carbonyl compounds formed in lipid peroxidation systems.
Analysis of trace levels of reactive carbonyl compounds (RCCs), including formaldehyde, acetaldehyde, acrolein, malonaldehyde, glyoxal, and methyl glyoxal, is extremely difficult because they are highly reactive, water soluble, and volatile. Determination of these RCCs in trace levels is important because they are major products of lipid peroxidation, which is strongly associated with various diseases such as cancer, Alzheimer's disease, aging, and atherosclerosis. This review covers the development and application of various derivatives for RCC analysis. Among the many derivatives which have been prepared, cysteamine derivatives for formaldehyde and acetaldehyde; N-hydrazine derivatives for acrolein, 4-hydroxy-2-nonenal, and malonaldeyde; and o-phenylene diamine derivatives for glyoxal and methyl glyoxal were selected for extended discussion. The application of advanced instruments, including gas chromatograph with nitrogen-phosphorus detector (GC/NPD), mass spectrometer (MS), high performance liquid chromatograph (HPLC), GC/MS, and LC/MS, to the determination of trace RCCs in various oxidized lipid samples, including fatty acids, skin lipids, beef fats, blood plasma, whole blood, and liver homogenates, is also discussed.


Computing a family of skeletons of volumetric models for shape description.
Skeletons are important shape descriptors in object representation and recognition. Typically, skeletons of volumetric models are computed using iterative thinning. However, traditional thinning methods often generate skeletons with complex structures that are unsuitable for shape description, and appropriate pruning methods are lacking. In this paper, we present a new method for computing skeletons of volumetric models by alternating thinning and a novel skeleton pruning routine. Our method creates a family of skeletons parameterized by two user-specified numbers that determine respectively the size of curve and surface features on the skeleton. As demonstrated on both real-world models and protein images in bio-medical research, our method generates skeletons with simple and meaningful structures that are particularly suitable for describing cylindrical and plate-like shapes.


Aortic regurgitation in patients with a left ventricular assist device: A contemporary review.
Aortic regurgitation (AR) developing while using a continuous-flow left ventricular assist device (CF-LVAD) affects 25% to 30% of patients within the first year of implantation and is increasingly being recognized as a cause of recurrence of symptomatic heart failure (HF). The underlying mechanisms are likely multifactorial, including changes in the leaflets of the aortic valve (AV), altered root biomechanics, and excessive left ventricular (LV) unloading, together promoting cusp remodeling and commissural fusion. Known risk factors for the development of AR while under support include advanced age, lower body surface area, systemic hypertension, large aortic root diameter, permanently closed AV, and duration of support. Further, variants in the anastomotic angle between the outflow graft and the ascending aorta have recently been recognized to induce structural changes in the aortic wall, contributing to the development and progression of AV disease. Nevertheless, it remains controversial as to whether AR on LVAD has an independent impact on prognosis, and no clear recommendation exists regarding its optimal diagnosis criteria and treatment. Herein we briefly review the literature and focus on the latest results regarding development of AR in patients supported with CF-LVADs. We also provide a structured echocardiographic approach for an accurate assessment of AV dysfunction in this challenging situation.


Design, parametrization, and pole placement of stabilizing output feedback compensators via injective cogenerator quotient signal modules.
Control design belongs to the most important and difficult tasks of control engineering and has therefore been treated by many prominent researchers and in many textbooks, the systems being generally described by their transfer matrices or by Rosenbrock equations and more recently also as behaviors. Our approach to controller design uses, in addition to the ideas of our predecessors on coprime factorizations of transfer matrices and on the parametrization of stabilizing compensators, a new mathematical technique which enables simpler design and also new theorems in spite of the many outstanding results of the literature: (1) We use an injective cogenerator signal module ℱ over the polynomial algebra [Formula: see text] (F an infinite field), a saturated multiplicatively closed set T of stable polynomials and its quotient ring [Formula: see text] of stable rational functions. This enables the simultaneous treatment of continuous and discrete systems and of all notions of stability, called T-stability. We investigate stabilizing control design by output feedback of input/output (IO) behaviors and study the full feedback IO behavior, especially its autonomous part and not only its transfer matrix. (2) The new technique is characterized by the permanent application of the injective cogenerator quotient signal module [Formula: see text] and of quotient behaviors [Formula: see text] of [Formula: see text]-behaviors B. (3) For the control tasks of tracking, disturbance rejection, model matching, and decoupling and not necessarily proper plants we derive necessary and sufficient conditions for the existence of proper stabilizing compensators with proper and stable closed loop behaviors, parametrize all such compensators as IO behaviors and not only their transfer matrices and give new algorithms for their construction. Moreover we solve the problem of pole placement or spectral assignability for the complete feedback behavior. The properness of the full feedback behavior ensures the absence of impulsive solutions in the continuous case, and that of the compensator enables its realization by Kalman state space equations or elementary building blocks. We note that every behavior admits an IO decomposition with proper transfer matrix, but that most of these decompositions do not have this property, and therefore we do not assume the properness of the plant. (4) The new technique can also be applied to more general control interconnections according to Willems, in particular to two-parameter feedback compensators and to the recent tracking framework of Fiaz/Takaba/Trentelman. In contrast to these authors, however, we pay special attention to the properness of all constructed transfer matrices which requires more subtle algorithms.


Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure.
Glyceryl trinitrate (GTN) ointment (0 small middle dot2 per cent) has an efficacy of up to 68 per cent in healing chronic anal fissure, but with headache as a major side-effect. Diltiazem hydrochloride (DTZ) cream (2 per cent) is expected to have fewer side-effects. A prospective double-blind randomized two-centre trial requiring at least 26 patients in each group (alpha = 0.05, beta = 0.9) was instituted after approval of the local ethics committee, to compare the incidence of side-effects (primary endpoint) with 0.2 per cent GTN ointment and 2 per cent DTZ cream in the treatment of chronic anal fissure. Treatments were applied perianally, twice daily for 6-8 weeks. All patients gave written informed consent. Both groups were comparable in patient demographics and clinical characteristics. Twelve patients violated the protocol, withdrew or did not attend follow-up. There were more side-effects with GTN (21 of 29 patients) than with DTZ (13 of 31) (relative risk (RR) 1.84 (95 per cent confidence interval (c.i.) 1.11 to 3.04), P = 0.01). In particular, more headaches occurred with GTN (17 of 29 patients) than with DTZ (eight of 31) (RR 2.06 (95 per cent c.i. 1.18 to 3.59), P = 0.01). There were no significant differences in healing and symptomatic improvement rates between patients receiving GTN (25 of 29) and DTZ (24 of 31). DTZ cream caused substantially fewer headaches than GTN ointment. There was no significant difference in the healing or improvement of chronic anal fissure between the treatments. DTZ may be the preferred first-line treatment for chronic anal fissure.


Rationale and Design of the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure Study.
Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively. The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N-terminal pro-B-type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization. The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.


Aspiration thrombectomy prior to percutaneous coronary intervention in ST-elevation myocardial infarction: a systematic review and meta-analysis.
Trials of aspiration thrombectomy (AT) prior to primary percutaneous intervention (PCI) in patients with ST-segment elevation MI (STEMI) have shown apparently inconsistent results and therefore generated uncertainty and controversy. To summarize the effects of AT prior to PCI versus conventional PCI in STEMI patients. Searches of MEDLINE, EMBASE and CENTRAL to June 2015 and review of reference lists of previous reviews. We included randomized controlled trials (RCTs) comparing AT prior to PCI with conventional PCI alone. Pairs of reviewers independently screened eligible articles; extracted data; and assessed risk of bias. We used the GRADE approach to rate overall certainty of the evidence. Among 73 potential articles identified, 20 trials including 21,660 patients were eligible; data were complete for 20,866 patients. Moderate-certainty evidence suggested a non statistically significant decrease in overall mortality (risk ratio (RR) 0.89, 95 % confidence interval, 0.78 to 1.01, risk difference (RD) 4/1,000 over 6 months), no impact on recurrent MI (RR 0.94, 95 % CI, 0.79 to 1.12) or major bleeding (RR 1.02, 95 % CI, 0.78 to 1.35), and an increase in stroke (RR 1.56, 95 % CI, 1.09 to 2.24, RD 3/1,000 over 6 months). Moderate certainty evidence suggests aspiration thrombectomy is associated with a possible small decrease in mortality (4 less deaths/1000 over 6 months) and a small increase in stroke (3 more strokes/1000 over 6 months). Because absolute effects are very small and closely balanced, thrombectomy prior to primary PCI should not be used as a routine strategy.


Strong correlations elucidate the electronic structure and phase diagram of LaAlO3/SrTiO3 interface.
The interface between the two band insulators SrTiO3 and LaAlO3 has the unexpected properties of a two-dimensional electron gas. It is even superconducting with a transition temperature, T(c), that can be tuned using gate bias V(g), which controls the number of electrons added or removed from the interface. The gate bias-temperature (V(g), T) phase diagram is characterized by a dome-shaped region where superconductivity occurs, that is, T(c) has a non-monotonic dependence on V(g), similar to many unconventional superconductors. Here, we report, the frequency of the quantum resistance-oscillations versus inverse magnetic field for various V(g). This frequency follows the same non-monotonic behaviour as T(c); a similar trend is seen in the low field limit of the Hall coefficient. We theoretically show that electronic correlations result in a non-monotonic population of the mobile band, which can account for the experimental behaviour of the normal transport properties and the superconducting dome.