Middle-distance Front Crawl Determinants When Using a Wetsuit.
Our aim was to establish the determinants explaining the wetsuit advantages in middle-distance swimming efforts. Thirty-one triathletes and open water swimmers performed two 400 m front crawl bouts in a 25 m swimming pool with swim and wetsuits (with 48 h rest in-between). Anthropometric, kinematic and physiological variables were measured and Pearson correlation coefficients and stepwise linear regression analysis were used to determine their relationships. Associations observed in the 400 m front crawl included time improved using wetsuit with swimmers age (r=0.38; p=0.017), cross-sectional area (r=0.33; p=0.034), wetsuit upper limbs thickness (r=-0.49; p=0.010), ΔInternational Swimming Federation Points (r=-0.39;p=0.016), Δstroke rate (SR, r=0.48; p=0.003), Δstroke length (SL, r=-0.39; p=0.015), Δpropelling efficiency (r=-0.37; p=0.019) and Δblood lactate concentrations (r=0.30; p=0.048) in the total sample. In females, associations were found between the time improved and wetsuit upper and lower limbs thickness (both r=-0.78; p=0.011), and in males associations were found between time improved and age (r=0.43; p=0.030), ΔSR (r=0.56; p=0.005) and ΔSL (r=-0.44; p=0.026). Furthermore, 48% of the 400 m front crawl time improved was explained by wetsuit upper limbs thickness and SR changes (total sample), 62% explained by the wetsuit lower limbs thickness (females) and 48% of this enhancement was related to age and SR changes (males). Therefore, faster upper and lower limbs actions and wetsuit upper and lower limbs thickness are beneficial for 400 m front crawl performance improvement.


Direct Write Assembly of Graphene/Poly(ε-Caprolactone) Composite Scaffolds and Evaluation of Their Biological Performance Using Mouse Bone Marrow Mesenchymal Stem Cells.
Scaffold and mesenchymal stem cell-based cartilage tissue engineering offers a favorable way for the repair and regeneration of injured cartilage. In this study, poly (ε-caprolactone) PCL scaffolds with grid-like structure having periodic lattice was manufactured by robocasting method in the presence of graphene nanoplatelets for cartilage tissue engineering applications. For this purpose, a PCL solution (20 wt%) containing pristine graphene nanopowders in the form of platelets was prepared as printing ink and it was dispensed through a nozzle at room temperature to an ethanol bath at 4 °C. The construction of porous scaffolds was made by a layer-by-layer assembly. Results revealed that graphene additions were not detrimental to deposition process and the structure of the resultant scaffolds. In vitro cell tests indicated that the prepared grid-like graphene/PCL composite scaffolds have good cytocompatibility and non-toxicity for mouse bone marrow mesenchymal stem cells. The stem cells attached and proliferated well on the scaffolds and they also demonstrated a chondrogenic differentiation in the absence of transforming growth factors.


Hemispheric asymmetry of processing temporal aspects of repetitive movement in two patients with infarction involving the corpus callosum.
Two right-handed patients with infarction involving the forebrain commissural fibres produced irregular but rapid repetitive movements with their left hands while producing normal movements with their right hands as well as having normal oral expression. The abnormality was more conspicuous when producing slow tapping patterns. When required to reproduce rapid tapping patterns of around 5 beats/sec, one of the patients produced a comparatively regular tapping pattern. Thus, we believe that both hemispheres are equipped with the faculty to produce rapid repetitive patterns and that only the left hemisphere is responsible for the temporal processes involved in producing required repetitive patterns.


Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.
The NLRP3 inflammasome has been implicated in the development and progression of heart failure. The aim of this study was to determine the safety of an oral inhibitor of the NLRP3 inflammasome, dapansutrile (OLT1177), in patients with heart failure and reduced ejection fraction (HFrEF). This was a phase 1B, randomized, double-blind, dose escalation, single-center, repeat dose safety and pharmacodynamics study of dapansutrile in stable patients with HFrEF (New York Heart Association Class II-III). Subjects were randomized to treatment with dapansutrile for up to 14 days at a ratio of 4:1 into 1 of 3 sequential ascending dose cohorts (500, 1000, or 2000 mg) each including 10 patients. Subjects underwent clinical assessment, biomarker determination, transthoracic echocardiogram, and maximal cardiopulmonary exercise testing at baseline, day 14, and day 28 to ascertain changes in clinical status. Placebo cases (N = 2 per cohort) were used as a decoy to reduce bias and not for statistical comparisons. Thirty participants (20 men) were treated for 13 (12-14) days. No serious adverse events during the study were recorded. All clinical or laboratory parameters at day 14 compared with baseline suggested clinical stability without significant within-group differences in the dapansutrile-pooled group or the 3 dapansutrile cohorts. Improvements in left ventricular EF [from 31.5% (27.5-39) to 36.5% (27.5-45), P = 0.039] and in exercise time [from 570 (399.5-627) to 616 (446.5-688) seconds, P = 0.039] were seen in the dapansutrile 2000 mg cohort. Treatment with dapansutrile for 14 days was safe and well tolerated in patients with stable HFrEF.


Inhibitors of angiotensin converting enzyme decrease early atherosclerosis in hyperlipidemic hamsters. Fosinopril reduces plasma cholesterol and captopril inhibits macrophage-foam cell accumulation independently of blood pressure and plasma lipids.
The effect of two angiotensin converting enzyme (ACE) inhibitors on the development of atherosclerosis was determined in hyperlipidemic hamsters. Preliminary studies indicated that only fosinopril (50 mg/kg) temporarily decreased mean arterial pressure, while after chronic dosing fosinopril and captopril (50 mg/kg) were ineffective. The same dose of fosinopril and captopril inhibited the angiotensin I pressor response, indicating these agents suppressed ACE activity in vivo. In the 3 week atherosclerosis experiment, all hamsters were fed chow supplemented with 0.05% cholesterol and 10% coconut oil. Control hamsters were compared with those receiving either 50 mg/kg per day of fosinopril or 50 mg/kg per day of captopril. After 3 weeks, fosinopril reduced plasma total cholesterol, low density lipoprotein (LDL) plus very low density lipoprotein cholesterol and total triglycerides by 17%, 27% and 45%, respectively. Captopril only reduced high density lipoprotein cholesterol by 20%. Neither fosinopril or captopril altered blood pressure at 3 weeks. Atherosclerosis was quantified from en face preparations of the lesion-prone aortic arch that were stained with oil red O (for cholesteryl ester and triglycerides). In control hamsters, oil red O labeled numerous subendothelial macrophage-foam cells located along the inner curvature of the aortic arch. Compared with controls, fosinopril reduced the number of intimal macrophage-foam cells/mm2, foam cell size and the fatty streak area by 85%, 38% and 90%, respectively. Captopril decreased these parameters by 44%, 16% and 53%. Thus captopril decreased early atherosclerosis without affecting plasma LDL cholesterol or blood pressure, which suggested that inhibiting ACE (or kininase II) directly impeded the accumulation and formation of macrophage-foam cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Intracellular glutathione levels determine cell sensitivity to apoptosis induced by the antineoplasic agent N-(4-hydroxyphenyl) retinamide.
We have previously demonstrated that the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) induces the overproduction of reactive oxygen species (ROS) in human leukemia cells, which in turn triggers the intrinsic (mitochondrial) apoptotic pathway. In order to study the role of glutathione in 4-HPR-induced apoptosis, the levels of this antioxidant were analyzed in cell lines which are sensitive and resistant to the effects of 4-HPR, and the effect of the modulation of glutathione levels on 4-HPR cytotoxicity was characterized. Mitochondrial membrane potential (deltaPsim) and the levels of glutathione were measured by flow cytometry. A fluorometric assay was used to measure intracellular ROS generation and Western blot was employed to analyze tissue transglutaminase expression. 4-HPR generated large quantities of ROS in cell lines which expressed low glutathione levels, these cells being the most sensitive to the retinoid. The sensitivity of leukemia cells to 4-HPR could be modulated, either by increasing intracellular glutathione contents using all-trans retinoic acid (ATRA), or by decreasing it using DL-buthionine-S,R-sulfoximine (BSO). ATRA increased the level of expression of tissue transglutaminase, whereas inhibition of this enzyme led to enhanced apoptosis. Our findings indicate that the glutathione content contributes to determining the sensitivity of cells to 4-HPR and points to the potential application of glutathione-inhibiting agents as enhancers in 4-HPR-based therapies.


Down-regulation of miR-214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist.
miRNAs play an important role in many human diseases, including cancer metastasis. However, the mechanisms by which miRNAs regulate intrahepatic cholangiocarcinoma metastasis remain poorly understood. In the present study, we assayed the expression level of miR-214 in intrahepatic cholangiocarcinoma tissues by real-time PCR, and defined the target gene and biological function by luciferase reporter assay and Western blot analysis. We found that the miR-214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non-metastatic tissues. Inhibition of miR-214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cell. We further demonstrated that down-regulation of miR-214 increased the transcript levels of the epithelial-mesenchymal transition-associated gene Twist, and then decreased E-cadherin levels. We confirmed that down-regulation of miR-214 promoted the epithelial-mesenchymal transition by directly targeting the Twist gene. These results suggest an important role for miR-214 in regulating metastasis of intrahepatic cholangiocarcinoma, and potential application of miR-214 in intrahepatic cholangiocarcinoma therapy.


Arthroscopic débridement for primary osteoarthritis of the elbow: analysis of preoperative factors affecting outcome.
The purposes of this study were to evaluate the clinical results of arthroscopic débridement and to identify preoperative factors that influence the outcome. Forty-three elbows with primary osteoarthritis in 43 patients treated with arthroscopic débridement were retrospectively evaluated. At a mean follow-up of 38 months (range, 18-77 months), the visual analog scale (VAS) score for pain, the arc of elbow motion, and the Mayo Elbow Performance Index (MEPI) score were assessed. The relationships between postoperative MEPI score and postoperative motion arc and preoperative factors including age, sex, involvement of the dominant arm, duration of symptoms, demand of elbow activity, VAS score, previous history of failed surgery, and arc of elbow motion were statistically evaluated. The mean VAS score for pain, the mean arc of flexion-extension, and the mean MEPI score significantly improved after the operation (all P values < .001). Multivariate regression analysis revealed that among preoperative variables, arc of motion was found to be the only independent prognostic factor that affected both postoperative elbow function (P = .024) and final arc of motion (P < .001). The cutoff value of preoperative arc of motion for the final arc of motion was determined to be 80° (P < .001). Involvement of the dominant arm was found to be another independent factor that affected postoperative MEPI scores (P = .016). Arthroscopic débridement for elbow osteoarthritis provides satisfactory pain relief, improvement of elbow motion, and good functional outcome. Based on the fact that preoperative motion arc is the independent factor that can predict clinical outcome, arthroscopic treatment is highly recommended for patients who have a motion arc of 80° or more as it yields reliable results.


Hypertonicity-induced cation channels rescue cells from staurosporine-elicited apoptosis.
Cell shrinkage is one of the earliest events during apoptosis. Cell shrinkage also occurs upon hypertonic stress, and previous work has shown that hypertonicity-induced cation channels (HICCs) underlie a highly efficient mechanism of recovery from cell shrinkage, called the regulatory volume increase (RVI), in many cell types. Here, the effects of HICC activation on staurosporine-induced apoptotic volume decrease (AVD) and apoptosis were studied in HeLa cells by means of electronic cell sizing and whole-cell patch-clamp recording. It was found that hypertonic stress reduces staurosporine-induced AVD and cell death (associated with caspase-3/7 activation and DNA fragmentation), and that this effect was actually due to activation of the HICC. On the other hand, staurosporine was found to significantly reduce osmotic HICC activation. It is concluded that AVD and RVI reflect two fundamentally distinct functional modes in terms of the activity and role of the HICC, in a shrunken cell. Our results also demonstrate, for the first time, the ability of the HICC to rescue cells from the process of programmed cell death.


Aqueous enzymatic extraction of Moringa oleifera oil.
This paper reports on the extraction of Moringa oleifera (MO) oil by using aqueous enzymatic extraction (AEE) method. The effect of different process parameters on the oil recovery was discovered by using statistical optimization, besides the effect of selected parameters on the formation of its oil-in-water cream emulsions. Within the pre-determined ranges, the use of pH 4.5, moisture/kernel ratio of 8:1 (w/w), and 300stroke/min shaking speed at 40°C for 1h incubation time resulted in highest oil recovery of approximately 70% (goil/g solvent-extracted oil). These optimized parameters also result in a very thin emulsion layer, indicating minute amount of emulsion formed. Zero oil recovery with thick emulsion were observed when the used aqueous phase was re-utilized for another AEE process. The findings suggest that the critical selection of AEE parameters is key to high oil recovery with minimum emulsion formation thereby lowering the load on the de-emulsification step.


The Relation Between the Presence of Aspiration or Penetration and the Clinical Indicators of Dysphagia in Poststroke Survivors.
To examine the relation between the presence of penetration or aspiration and the occurrence of the clinical indicators of dysphagia. The presence of penetration or aspiration is closely related to the clinical indicators of dysphagia. It is essential to understand these relationships in order to implement proper diagnosis and treatment of dysphagia. Fifty-eight poststroke survivors were divided into two groups: patients with or without penetration or aspiration. Medical records and videofluoroscopic swallowing examinations were reviewed. The occurrence of clinical indicators of dysphagia between two groups was analyzed with Cross Tabulation and the Pearson chi-square test (p<0.05). Poststroke survivors with penetration or aspiration had significantly high occurrences of delayed initiation of the swallow (p=0.04) and reduced hyolaryngeal elevation (p<0.01) than those without penetration or aspiration. The results of this study indicate that delayed initiation of the swallow is a strong physiological indicator of penetration or aspiration during the oral stage of swallowing in poststroke survivors. For the pharyngeal stage of swallowing, hyoid and laryngeal elevation is a key event related to occurrence of penetration or aspiration. Clinical indicators should be investigated further to allow appropriate implementation of treatment strategies for stroke survivors.


Practical challenges to the clinical implementation of saliva for SARS-CoV-2 detection.
Due to global shortages of flocked nasopharyngeal swabs and appropriate viral transport media during the COVID-19 pandemic, alternate diagnostic specimens for SARS-CoV-2 detection are sought. The accuracy and feasibility of saliva samples collected and transported without specialized collection devices or media were evaluated. Saliva demonstrated good concordance with paired nasopharyngeal swabs for SARS-CoV-2 detection in 67/74 cases (90.5%), though barriers to saliva collection were observed in long-term care residents and outbreak settings. SARS-CoV-2 RNA was stable in human saliva at room temperature for up to 48 h after initial specimen collection, informing appropriate transport time and conditions.


Immunophenotyping of acute myeloid leukaemia: relevance of analysing different lineage-associated markers.
The immunophenotype of 135 previously untreated patients with FAB defined acute myeloid leukaemia (AML) was studied at diagnosis. The panel of reagents included monoclonal antibodies (MoAb) recognising myeloid-associated determinants (CD11, CD13, CD14, CD33 and others) as well as MoAb directed towards lymphoid antigens (CD7, CD10, CD19) and TdT. The results indicate that CD13 and/or CD33 are consistently expressed in AML and only rarely in ALL blasts (131/135 + ve cases, versus 4/130 in ALL). Lymphoid antigen expression was rarely detected when CD10 and CD19 were investigated in AML (0.9% and 2% + ve cases, respectively), whereas significant positivities were found for TdT and CD7 (20% and 10% respectively). Concerning FAB subtypes, two new MoAb (LAM3 and LAM7) proved very useful in the specific recognition of AML with monocytic features. The phenotype CD13+ and/or CD33+, CD9+, HLA-DR- was found to be almost exclusive for M3 AML. The response to induction chemotherapy was analysed in CD7+ and in TdT+ patients. In the latter group a statistically significant lower response rate was found with respect to TdT-ve-AML patients.


Development of a quantitative assay to measure expression of transforming growth factor β (TGF-β) in Lost River sucker (Deltistes luxatus) and shortnose sucker (Chasmistes brevirostris) and evaluation of potential pitfalls in use with field-collected samples.
The Nature Conservancy is in the process of restoring the Williamson River Delta in an attempt to recreate important juvenile habitat for the endangered shortnose sucker Chasmistes brevirostris and the endangered Lost River sucker Deltistes luxatus. Measurement of TGF-β mRNA expression level was one of the indicators chosen to evaluate juvenile sucker health during the restoration process. TGF-β mRNA expression level has been correlated with disease status in several laboratory studies and TGF-β mRNA expression level has been used as a species-specific indicator of immune status in field-based fish health assessments. We describe here the identification of TGF-β and a possible splice variant from shortnose sucker and from Lost River sucker. The performance of a quantitative RT-PCR assay to measure TGF-β mRNA expression level was evaluated in field-collected spleen and kidney tissue samples. The quality of extracted RNA was higher in tissues harvested in September compared to July and higher in tissues harvested at lower temperature compared to higher temperature. In addition, the expression level of both TGF-β and 18S as assessed by qRT-PCR was higher in samples with higher quality RNA. TGF-β mRNA expression was lower in kidney than in spleen in both Lost River sucker and shortnose sucker.


[Special aspects of retroperitoneal trauma in children (author's transl)].
During childhood, the retroperitoneal trauma resulting from birth has some specific aspects. Besides the rupture of the parenchymatous organs, in particular bleeding of the suprarenal glands occurs. The indication for surgical intervention must be based on the general condition of the child. Substitution of hypoprothrombinemia will be necesary in most cases. Intramural duodenal hematoma and rupture of the ureter in the immediate vicinity of the pelvoureteral connection, are observed especially in childhood. Retropneumooperitoneum following the increasingly popular method of intermittent respiration by above atmospheric pressure respiration of the newborn is now more frequently observed, as is necrosis of the wall of the bladder by instillation of medication and catheters in the arteries of the navel.


Development of a Deep Learning Model for Retinal Hemorrhage Detection on Head Computed Tomography in Young Children.
Abusive head trauma (AHT) in children is often missed in medical encounters, and retinal hemorrhage (RH) is considered strong evidence for AHT. Although head computed tomography (CT) is obtained routinely, all but exceptionally large RHs are undetectable on CT images in children. To examine whether deep learning-based image analysis can detect RH on pediatric head CT. This diagnostic study included 301 patients diagnosed with AHT who underwent head CT and dilated fundoscopic examinations at a quaternary care children's hospital. The study assessed a deep learning model using axial slices from 218 segmented globes with RH and 384 globes without RH between May 1, 2007, and March 31, 2021. Two additional light gradient boosting machine (GBM) models were assessed: one that used demographic characteristics and common brain findings in AHT and another that combined the deep learning model's risk prediction plus the same demographic characteristics and brain findings. Sensitivity (recall), specificity, precision, accuracy, F1 score, and area under the curve (AUC) for each model predicting the presence or absence of RH in globes were assessed. Globe regions that influenced the deep learning model predictions were visualized in saliency maps. The contributions of demographic and standard CT features were assessed by Shapley additive explanation. The final study population included 301 patients (187 [62.1%] male; median [range] age, 4.6 [0.1-35.8] months). A total of 120 patients (39.9%) had RH on fundoscopic examinations. The deep learning model performed as follows: sensitivity, 79.6%; specificity, 79.2%; positive predictive value (precision), 68.6%; negative predictive value, 87.1%; accuracy, 79.3%; F1 score, 73.7%; and AUC, 0.83 (95% CI, 0.75-0.91). The AUCs were 0.80 (95% CI, 0.69-0.91) for the general light GBM model and 0.86 (95% CI, 0.79-0.93) for the combined light GBM model. Sensitivities of all models were similar, whereas the specificities of the deep learning and combined light GBM models were higher than those of the light GBM model. The findings of this diagnostic study indicate that a deep learning-based image analysis of globes on pediatric head CTs can predict the presence of RH. After prospective external validation, a deep learning model incorporated into CT image analysis software could calibrate clinical suspicion for AHT and provide decision support for which patients urgently need fundoscopic examinations.


Removal of methylene blue using MnO2@rGO nanocomposite from textile wastewater: Isotherms, kinetics and thermodynamics studies.
In this study, the adsorptive removal of methylene blue dye, which is commonly used in textile industries, was investigated using the MnO2@reduced graphene oxide (rGO) adsorbent. The sonication-assisted synthesis from rGO nanosheets and MnO2 nanoparticles resulted to the MnO2@rGO nanocomposite with improved physicochemical properties. The characterization results showed the improved surface area, porous structure and adsorption sites from the nitrogen adsorption-desorption studies, improved morphology from the Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) and the improved crystal structure from X-ray powder diffraction (XRD). The improved physicochemical properties on the MnO2@rGO nanocomposite played a significant role in enhancing the dye removal in textile wastewater. The equilibrium experimental data was best described by the Langmuir isotherm model with a maximum adsorption capacity of 156 mg g-1, suggesting a monolayer adsorption. The kinetic data best fitted the pseudo-second order kinetic model, suggesting a chemisorption adsorption process. The thermodynamic data (ΔG°, ΔH° and ΔS°) confirmed the feasibility, randomness and spontaneous nature of the adsorption process. The mechanism of adsorption involved the hydrogen bonding, π-π interactions and electrostatic interactions. The removal of methylene blue using MnO2@rGO nanocomposite in spiked textile wastewater yielded a 98-99% removal. The method demonstrated competitiveness when compared with literature reported results, paving way for further investigations towards industrial scale applications.


Phylogenetic relationships among Hoplobatrachus rugulosus in Thailand as inferred from mitochondrial DNA sequences of the cytochrome-b gene (Amphibia, Anura, Dicroglossidae).
A fragment (564 bp) of the mitochondrial cytochrome-b (Cyt-b) gene was studied for 73 individual rice field frogs (Hoplobatrachus rugulosus) from 18 geographical locations (populations) within Thailand. Sequence analysis revealed the presence of 12 haplotypes, with five haplotypes being represented in two or more populations, and the other seven being population-distinct haplotypes. Phylogenetic analysis by maximum parsimony, maximum likelihood, and neighbor joining analyses all placed the 12 haplotypes into two distinct and well-separated clades with high bootstrap support, reflecting the high sequence divergences between the clades (25.3-32.3%). The mountain ranges and the Isthmus of Kra are likely to have played important roles in hindering gene flow among H. rugulosus populations in Thailand. From the sequence divergence values, the two clades of H. rugulosus can be classified into two distinct species, and therefore, the strains of H. rugulosus bred in farm stocks should be restricted to a population of one clade so as to avoid cross breeding between the two clades.


Root proteomics reveals cucumber 24-epibrassinolide responses under Ca(NO3)2 stress.
The application of exogenous 24-epibrassinolide promotes Brassinosteroids intracellular signalling in cucumber, which leads to differentially expressed proteins that participate in different life process to relieve Ca(NO 3 ) 2 damage. NO3 (-) and Ca(2+) are the main anion and cation of soil secondary salinization during greenhouse cultivation. Brassinosteroids (BRs), steroidal phytohormones, regulate various important physiological and developmental processes and are used against abiotic stress. A two-dimensional electrophoresis gel coupled with MALDI-TOF/TOF MS was performed to investigate the effects of exogenous 24-epibrassinolide (EBL) on proteomic changes in cucumber seedling roots under Ca(NO3)2 stress. A total of 80 differentially accumulated protein spots in response to stress and/or exogenous EBL were identified and grouped into different categories of biological processes according to Gene Ontology. Under Ca(NO3)2 stress, proteins related to nitrogen metabolism and lignin biosynthesis were induced, while those related to cytoskeleton organization and cell-wall neutral sugar metabolism were inhibited. However, the accumulation of abundant proteins involved in protein modification and degradation, defence mechanisms against antioxidation and detoxification and lignin biosynthesis by exogenous EBL might play important roles in salt tolerance. Real-time quantitative PCR was performed to investigate BR signalling. BR signalling was induced intracellularly under Ca(NO3)2 stress. Exogenous EBL can alleviate the root indices, effectively reduce the Ca(2+) content and increase the K(+) content in cucumber roots under Ca(NO3)2 stress. This study revealed the differentially expressed proteins and BR signalling-associated mRNAs induced by EBL in cucumber seedling roots under Ca(NO3)2 stress, providing a better understanding of EBL-induced salt resistance in cucumber seedlings. The mechanism for alleviation provides valuable insight into improving Ca(NO3)2 stress tolerance of other horticultural plants.


Feeding: what it means to patients and caregivers and how these views influence Singaporean Chinese caregivers' decisions to continue feeding at the end of life.
The decision-making process underlying caregivers' choice to continue feeding at the end of life is not well understood. To provide a better understanding of the complex interplay of factors that influence the decision by caregivers to continue feeding. Palliative care patients and their main caregiver recruited at National Cancer Centre Singapore between May and July 2011 were included. Data were collected using an interviewer-administered questionnaire. One hundred respondents were included. Three major prevailing themes were identified: filial piety, source of hope, and expression of affection. Nonparametric statistical testing showed that patients and caregivers shared similar views about feeding at the end of life. The major themes identified above undergird the caregiver's decision to continue feeding at the end of life.


Targeted disruption of SHIP leads to Steel factor-induced degranulation of mast cells.
To investigate the role of the src homology 2 (SH2)-containing inositol 5' phosphatase (SHIP) in growth factor-mediated signalling, we compared Steel factor (SF)-induced events in bone marrow-derived mast cells (BMMCs) from SHIP-/- and SHIP+/+ littermates. We found SF alone stimulated massive degranulation from SHIP-/- but none from SHIP+/+ BMMCs. This SF-induced degranulation, which was not due to higher c-kit levels in SHIP-/- cells, correlated with higher intracellular calcium than that in SHIP+/+ cells and was dependent on the influx of extracellular calcium. Both this influx and subsequent degranulation were completely inhibited by PI-3-kinase inhibitors, indicating that SF-induced activation of PI-3-kinase was upstream of extracellular calcium entry. A comparison of phosphatidylinositol-3,4,5-trisphosphate (PIP3) levels following SF stimulation of SHIP+/+ and SHIP-/- BMMCs suggested that SHIP restricted this entry by hydrolyzing PIP3. Although PI-3-kinase inhibitors blocked the release of intracellular calcium, implicating PIP3, and PLCgamma-2 was slightly more tyrosine phosphorylated in SHIP-/- cells, the increase in inositol-1,4,5-trisphosphate (IP3) and intracellular calcium levels were identical in SHIP-/- and SHIP+/+ BMMCs. These results suggest that SHIP prevents SF from triggering degranulation of normal BMMCs, and does so by hydrolyzing PIP3, which in turn limits extracellular calcium entry at a step after the release of intracellular calcium.


Use of herbal extract from Artemisia herba-alba (Shih) in pharmaceutical preparations for dental hygiene.
Antibiotic resistance in bacterial species is opening new avenues to search for alternative modes of antimicrobial treatment, medicinal plant extracts being one among them. The aim of this study was to access the possibility of medicinal plant extract from Shih in the manufacture of pharmaceutical preparations for oral hygiene specifically for the prevention and treatment of dental caries due to Streptococcus mutans. Antimicrobial effects of crude organic extract of Shih on S. mutans isolated from the saliva were examined by taking S. mutans with culture media only (-ve control); S. mutans treated with the antibiotic gentamicin (+ve control) and S. mutans treated with Shih. Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were Determination by Iodonitrotetrazolium chloride (INT) colorimetric assay Time-kill dynamic assay was performed using broth microdilution method. The metabolic reason behind the bacteriostatic and bactericidal effect were studied by measuring the glucose utilization by the microbes, pH as a measure of acid production, nucleic acids quantitation to check the DNA status and inhibition of water-insoluble glucan synthesis were undertaken. Shih MIC for S. mutans was at 2.5 mg/ml and MBC was 4 mg/ml. S. mutans bacterial population started reclining within 60 min of incubation with Shih at MBC. Utilization of added glucose was very high at MIC due to bacteria overcoming the stress, whereas at MBC its utilization was less. Accordingly pH also became acidic to 2.9 with MIC and 4.03 with MBC. There was a great degree of inhibition in the formation of nucleic acids indicating this crude extract interferes with DNA replication. Inhibition of glucan synthesis was to the tune of 45% as compared to control. Thus we conclude that Shih has potentially effective antibacterial activity hence it can be proposed as a potentially effective antiplaque and anticariogenic agent in the form of mouth wash or gum paint. However, the cytotoxicity of the extract needs to be evaluated in in-vitro and in-vivo conditions before it is considered as a safe antiplaque and anticariogenic agent.


A practical radiographic comparison of short board technique and Kendrick Extrication Device.
Cervical spine immobilization is necessary during the prehospital care of most trauma patients. Earlier studies performed in controlled, indoor settings suggested short board technique (SBT) was the standard against which other methods of cervical stabilization should be measured. Our study approximated the prehospital setting by comparing the use of tape, SBT, and Philadelphia collar (PC) with tape, the Kendrick Extrication Device (KED), and PC after immobilization in and extrication from a compact car. Seven men were immobilized with KED and SBT in addition to PCs and tape. These subjects were extricated and then taken by ambulance stretcher across a 50-yd length of concrete to the radiology suite. Flexion, extension, lateral bending, and rotation were measured. KED-PC (16 degrees +/- 8 degrees) was statistically superior to SBT-PC (41 degrees +/- 5 degrees) in limiting rotation (P less than .001). KED-PC and SBT-PC were similar in their abilities to limit extension (8 degrees +/- 4 degrees vs 6 degrees +/- 5 degrees), flexion (4 degrees +/- 2 degrees vs 4 degrees +/- 4 degrees), and lateral bending (13 degrees +/- 5 degrees vs 17 degrees +/- 6 degrees). In an approximation of the prehospital setting, tape, a PC, and either KED or SBT substantially limit extension, flexion, and lateral bending of the normal cervical spine. KED-PC is more beneficial in rotation.


Studies of the capacity of factor Xa to protect factor Va from inactivation by activated protein C.
Blood coagulation Factor Xa and activated protein C are both serine proteases derived from circulating, vitamin K-dependent precursors. They express, respectively, procoagulant and anticoagulant properties through Ca2+ and phospholipid-dependent interactions with coagulation Factor Va. The present studies were undertaken to determine whether Factor Xa and activated protein C interact independently or competitively with Factor Va. The interactions were assessed by examining the activated protein C-catalyzed inactivation of Factor Va in the absence and presence of Factor Xa at various concentrations. The results indicated that the two proteins compete for Factor Va and that Factor Xa protects Factor Va from inactivation by activated protein C. The ability of Factor Xa to protect Factor Va was observed either in the absence of a Factor Xa substrate or under conditions in which the complex of Factor Va and Factor Xa was engaged in the conversion of substrate (prethrombin 1) to thrombin.


Generation of corticosteroid binder IB from binder II by a sulfhydryl dependent renal cytosolic factor.
It has long been debated whether binder IB represents a unique form of the glucocorticoid receptor or is derived from the larger molecular weight form, binder II, by limited proteolysis. Transformed glucocorticoid receptors in kidney, liver and mixed kidney/liver cytosols were examined using anion exchange and gel filtration chromatography. The transformed receptor in liver cytosols chromatographs as binder II on DEAE-Sephadex A-50 anion exchange columns and has a Stokes radius of approx 6.0 nm. The transformed receptor in kidney cytosols chromatographs as binder IB on DEAE-Sephadex A-50 anion exchange columns and has a Stokes radius of 3.0-4.0 nm (3.2 nm on agarose; 3.0-4.0 nm on Sephadex G-100). Using cytosols prepared from mixed homogenates (2 g kidney plus 8 g liver tissue), our experiments show that binder II is converted to a lower molecular weight form (Rs = 3.2 nm on agarose; Rx = 3.9 nm on Sephadex G-100) that is identical to binder IB in its elution position from DEAE-Sephadex anion exchange resin. Identical results are obtained using kidney/liver/cytosols mixed in vitro in which only the hepatic receptor, binder II, is labelled with [3H]TA. These results support the hypothesis that the renal receptor, binder IB, is a proteolytic fragment of binder II and does not represent a polymorphic form of the glucocorticoid receptor. The renal converting activity is dependent on free-SH for full activity but is insensitive to the protease inhibitors leupeptin, antipain, and PMSF. The conversion of hepatic binder II to binder IB in in vitro mixing experiments can be prevented if kidney cytosol is gel filtered on Sephadex G-25 and the eluted macromolecular fraction is adjusted to 10 mM EGTA (or EDTA) prior to mixing with the [3H]TA labelled hepatic cytosol.


The genetics of alcoholisms and related disorders.
The inheritance of alcohol abuse and other psychopathology in 862 men and 913 women adopted by non-relatives, was studied. Both male and female adoptees were at greater risk to develop alcohol abuse if their biological, but not their adoptive, parents were alcoholic. Three types of families with alcoholism were distinguished that differed in frequency of alcohol abuse, somatoform disorders in women and in relation to antisocial behaviour in male adoptees. The combination of both genetic and environmental risk factors was necessary for the development of alcoholism in the most common, milieu-limited type of alcoholism. In families with a less common, male-limited, type of vulnerability, alcohol abuse was highly heritable in men, but women had multiple somatic complaints and seldom abuse. In a third type of family the common vulnerability was expressed as antisocial behavior with violent criminality and recurrent alcohol abuse in males, but as high frequency somatization in female relatives.


Interdisciplinary medication review to improve pharmacotherapy for patients with intellectual disabilities.
Background Patients with intellectual disabilities is an underserved patient group that have poor abilities to express their health complaints. Objective The aim of this study was to improve pharmacotherapy in patients with intellectual disability, by the use of medication reviews and interdisciplinary case conferences. Setting Patients with intellectual disabilities receiving home care services in Oslo, Norway. Method Patients receiving home care services were recruited by a nurse. A clinical pharmacist conducted medication reviews, and thereafter, the patients' general practitioner, nurse/social educator and clinical pharmacist discussed the pharmacotherapy at an interdisciplinary case conference. Patient demographics, prescribed drugs (strength, dose, indication) and drug-related problems (DRPs) were recorded. Main outcome measure Patient outcomes and actions taken to resolve DRPs 6 weeks after the case conference. Results Forty patients (34-77 years) with intellectual disabilities consented to medication reviews. They used on average 12 different drugs (range 5-23). The most commonly prescribed drugs were CNS-active drugs: analgesics (25 patients), antiepileptics (23 patients) and anxiolytics (21 patients). In total, 27 patients used between 3 and 7 different CNS-active drugs. The clinical pharmacist identified 178 DRPs in 39/40 patients (average 4.5 DRPs, range 0-13). DRPs for 30% of all prescribed drugs were resolved (145/481). Overall, 11% of drugs were deprescribed, 8% required therapeutic monitoring/follow-up, and either the dosage, formulation or route of administration were changed for 7% of the drugs. Conclusions Patients with intellectual disabilities receiving home care services were prescribed many unnecessary drugs and needed adjustment of pharmacotherapy for about one third of their prescribed drugs. The interdisciplinary case conferences improved pharmacotherapy for this vulnerable patient group.


Effect of through-plane and twisting motion on left ventricular strain calculation: direct comparison between two-dimensional and three-dimensional speckle-tracking echocardiography.
The aim of this study was to investigate the effect of out-of-plane motion on discrepancies in strain measurements between two-dimensional (2D) and three-dimensional (3D) echocardiography. Two-dimensional and 3D data sets were acquired in 54 patients. Using 2D and 3D speckle-tracking software, global circumferential strain (CS) and longitudinal strain (LS) as well as CS and LS at three left ventricular (LV) levels was measured. The effect of through-plane motion was assessed by mitral annular displacement. Although a good correlation of global CS was noted between the two methods (r = 0.80, P < .01), mean values of global CS were significantly higher on 3D compared with 2D echocardiography. Correlations of CS and their mean differences were 0.65 and -4.61 at the basal level, 0.76 and -4.17 at the midventricular level, and 0.60 and -2.23 at the apical level, respectively. Correlation of global CS between the two methods was higher in patients who showed mitral annular displacement < 9.4 mm (r = 0.81) compared with those with mitral annular displacement ≥ 9.4 mm (r = 0.61). A good correlation of global LS (r = 0.89, P < .01) was noted, with no significant bias. Correlations of LS and their mean differences were 0.52 and 1.59 at the basal level, 0.89 and -1.17 at the midventricular level, and 0.73 and 1.46 at the apical level, respectively. Correlation of LS between the two methods was higher in patients who showed LV twist < 12.2° (r = 0.94) compared with patients with LV twist ≥ 12.2° (r = 0.68). Through-plane motion produced discrepancies in CS measurements, especially at the LV basal level. Larger bias of LS at the basal and apical LV levels compared with the midventricular level between the two methods suggests that LV twisting also affects the calculation of 2D LS.


[Determination of superoxide dismutase (sod) in erythrocytes in glucose-6-phosphate dehydrogenase deficiency (G6PD-deficiency)].
Determining SOD in red blood cells was made in 26 carriers of G6PD defect 9 haemicygotic mark carriers and 16 heterocytic mark carriers had a diminished SOD enzyme activity. This is probably due to an inactivation of SOD by diminished reductive equivalents in the metabolism of defect cells. In this way, more oxidatively effective radicals will appear, even OH. among them. The latter may render the enzyme ineffective by binding it to the imidazol group in the catabolic centre. Consequently, an accumulation of the substrate O2-. may lead to a further cell damage, thus causing an increased haemolysis.


Molecular cloning, sequence analysis and expression in Escherichia coli of Camelus dromedarius glucose-6-phosphate dehydrogenase cDNA.
This study determined the full length sequence of glucose-6-phosphate dehydrogenase cDNA (G6PD) from the Arabian camel Camelus dromedarius using reverse transcription polymerase chain reaction. The C. dromedarius G6PD has an open reading frame of 1545 bp, and the cDNA encodes a protein of 515 amino acid residues with a molecular weight of 59.0 KDa. The amino acid sequence showed the highest identity with Equus caballus (92%) and Homo sapiens (92%). The G6PD cDNA was cloned and expressed into Escherichia coli as a fusion protein and was purified in a single chromatographic step using nickel affinity gel column. The purity and the molecular weight of the enzyme were checked on SDS-PAGE and the purified enzyme showed a single band on the gel with a molecular weight of 63.0 KDa. The specific activity of G6PD was determined to be 289.6 EU/mg protein with a fold purification of 95.45 and yield of 56.8%.


Hospitalization rates of generic metoprolol compared with the original beta-blocker in an epidemiological database study.
A less favourable galenic profile of generic formulations of the beta-blocker metoprolol raised the concern of a higher risk for serious cardiovascular (CV) events. We assessed hospital admission rates for CV diseases and prescription prevalences of various drugs using claims data of statutory health insurances (SHIs) to compare the incidence of serious CV events among users of original and generic metoprolol. Index events included hospitalization due to myocardial infarction, hypertensive crisis and stroke. Data files of three SHIs were linked with dispensing data of drug prescriptions from each pharmacy's electronic data processing centre on an individual basis. Incidences of hospital admissions among patients receiving original metoprolol and among patients treated with the generic equivalent were compared by logistic regression, stratified for Bremen and the rest of Northern Germany. Risk estimates and confidence intervals were adjusted for confounders. A total of 49,673 patients receiving metoprolol were identified within a cohort of 3,649,285 insurance members. While the crude analysis revealed a higher risk for index events in patients receiving the generic drug (Bremen: RR 1.45; Northern Germany: RR 1.14), no elevated risk remained after confounder adjustment (Bremen: OR 1.06; Northern Germany: OR 1.04). Among co-morbid conditions considered as confounders, a previous CV event and an elevated thromboembolic risk exerted the strongest effect on index events. SHI data are a valuable source for pharmacoepidemiology and health services research in Germany. Incidence rates of serious CV events did not reveal any noticeable differences between the original and the generic group after confounder adjustment.


The localization of memory.
MRI showed severe lesions, thought to be specific for the Wernicke-Korsakoff syndrome, in an alcohol dependent patient with an excellent memory. The morphological abnormalities thought to be typical of Wernicke-Korsakoff syndrome might be features of chronic alcoholism and malnutrition. This contention has important implications for the localization of memory functions. Recent literature on the anatomical basis and mechanism of memory is reviewed. Memory probably resides in multifocal neural networks rather than in specific anatomical sites.


Rethinking Immunological Risk: A Retrospective Cohort Study of Severe SARS-Cov-2 Infections in Individuals With Congenital Immunodeficiencies.
Debates on the allocation of medical resources during the coronavirus disease 2019 (COVID-19) pandemic revealed the need for a better understanding of immunological risk. Studies highlighted variable clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in individuals with defects in both adaptive and innate immunity, suggesting additional contributions from other factors. Notably, none of these studies controlled for variables linked with social determinants of health. To determine the contributions of determinants of health to risk of hospitalization for SARS-CoV-2 infection among individuals with inborn errors of immunodeficiencies. This is a retrospective, single-center cohort study of 166 individuals with inborn errors of immunity, aged 2 months through 69 years, who developed SARS-CoV-2 infections from March 1, 2020, through March 31, 2022. Risks of hospitalization were assessed using a multivariable logistic regression analysis. The risk of SARS-CoV-2-related hospitalization was associated with underrepresented racial and ethnic populations (odds ratio [OR] 4.50; 95% confidence interval [95% CI] 1.57-13.4), a diagnosis of any genetically defined immunodeficiency (OR 3.32; 95% CI 1.24-9.43), obesity (OR 4.24; 95% CI 1.38-13.3), and neurological disease (OR 4.47; 95% CI 1.44-14.3). The COVID-19 vaccination was associated with reduced hospitalization risk (OR 0.52; 95% CI 0.31-0.81). Defects in T cell and innate immune function, immune-mediated organ dysfunction, and social vulnerability were not associated with increased risk of hospitalization after controlling for covariates. The associations between race, ethnicity, and obesity with increased risk of hospitalization for SARS-CoV-2 infection indicate the importance of variables linked with social determinants of health as immunological risk factors for individuals with inborn errors of immunity.


Statistical study of the relationship between free chlorine levels and bacteriological checks on systems in the Paris area.
The majority of French cities are supplied with treated surface water. The primary factor in determining the quality of this water concerns disinfection to ensure that the system is not contaminated with parasites, coliforms and streptococci; some of these organisms, especially coliforms, are capable of multiplying within the system. The presence of bacteria indicative of faecal contamination in water samples, which contains a significant amount of free chlorine, has revealed a possible link between the two. Based upon sampling points of the Parisian system (and in the suburbs for purposes of comparison), we show the existence of a linear relationship between the results of analyses for coliforms on a given day, D, and the content of free chlorine in the water on days D-2 and D-3. Subsequent ground tests confirm the explanations proposed regarding these phenomena.


Back pain among health care workers in Pennsylvania 2002-2006.
While back pain is common among health care workers in the United States, the epidemiology of back pain is unclear. The purpose of this study was to estimate the incidence and trend of back pain from work-related injuries among health care workers. Data from the Pennsylvania Work Injuries and Illnesses Reports from 2002 to 2006 were analyzed. Estimated back injuries account for 24.6% of all reported injuries in healthcare workers in Pennsylvania. From 2002 to 2006, there was a 22.5% increase in the incidence of reported back pain in this population. Due to a lack of detailed reports regarding the incidence of back pain among Pennsylvania healthcare workers, it is recommended that a survey of healthcare workers who perform patient handling be completed.


Effects of bone morphogenetic protein 4, gremlin, and connective tissue growth factor on estradiol and progesterone production by bovine granulosa cells.
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β family of proteins that have been implicated in the paracrine regulation of granulosa cell (GC) function, but whether responses to BMPs change with follicular size or interact with connective tissue growth factor (CTGF) or BMP antagonists (e.g., gremlin [GREM]) to directly affect GC function of cattle is unknown. Therefore, to determine the effects of BMP4 on proliferation and steroidogenesis of GCs and its interaction with GREM or CTGF, experiments were conducted using bovine GC cultures. In vitro, BMP4 (30 ng/mL) inhibited (P < 0.05) follicle-stimulating hormone (FSH) plus insulin-like growth factor 1 (IGF1)-induced progesterone and estradiol production by large- and small-follicle GCs, but the inhibitory effect of BMP4 on estradiol production was much more pronounced in large-follicle GCs. In small-follicle GCs, BMP4 had no effect (P > 0.10) on IGF1-induced proliferation, but GREM inhibited (P < 0.05) cell proliferation and estradiol and progesterone production in IGF1 plus FSH-treated GCs. In large-follicle GCs, BMP4 (10 to 30 ng/mL) increased (P < 0.05) GC numbers and GREM (100 ng/mL) blocked this effect. In large-follicle GCs, CTGF inhibited (P < 0.05) FSH plus IGF1-induced progesterone and estradiol production, and CTGF blocked the stimulatory effect of BMP4 on GC proliferation. These results indicate that BMP4, GREM, and CTGF inhibit GC aromatase activity and progesterone production. Also, the stimulatory effect of BMP4 on GC proliferation and the inhibitory effects of BMP4 on GC steroidogenesis are more pronounced in large vs. small follicles.


Robotic-assisted surgery for prostatectomy - does the diffusion of robotic systems contribute to treatment centralization and influence patients' hospital choice?
Between 2008 and 2018, the share of robotic-assisted surgeries (RAS) for radical prostatectomies (RPEs) has increased from 3 to 46% in Germany. Firstly, we investigate if this diffusion of RAS has contributed to RPE treatment centralization. Secondly, we analyze if a hospital's use of an RAS system influenced patients' hospital choice. To analyze RPE treatment centralization, we use (bi-) annual hospital data from 2006 to 2018 for all German hospitals in a panel-data fixed effect model. For investigating RAS systems' influence on patients' hospital choice, we use patient level data of 4614 RPE patients treated in 2015. Employing a random utility choice model, we estimate the influence of RAS as well as specialization and quality on patients' marginal utilities and their according willingness to travel. Despite a slight decrease in RPEs between 2006 and 2018, hospitals that invested in an RAS system could increase their case volumes significantly (+ 82% compared to hospitals that did not invest) contributing to treatment centralization. Moreover, patients are willing to travel longer for hospitals offering RAS (+ 22% than average travel time) and for specialization (+ 13% for certified prostate cancer treatment centers, + 9% for higher procedure volume). The influence of outcome quality and service quality on patients' hospital choice is insignificant or negligible. In conclusion, centralization is partly driven by (very) high-volume hospitals' investment in RAS systems and patient preferences. While outcome quality might improve due to centralization and according specialization, evidence for a direct positive influence of RAS on RPE outcomes still is ambiguous. Patients have been voting with their feet, but research yet has to catch up.


Acrodermatitis enteropathica.
A case of acrodermatitis enteropathica belatedly recognized in a pregnant 23-year-old woman is reported. The condition was not specifically diagnosed during childhood. It cleared at puberty but recurred during two of three pregnancies in the form of pustular, vesiculobullous, and psoriasiform lesions. There were no associated signs or symptoms in other organs. Initial diagnoses upon the recurrence during the third pregnancy were herpes gestationis and impetigo herpetiformis. A markedly decreased serum zinc level (18 micrograms/dl) was found. Treatment with zinc sulfate was instituted, and within 3 days the cutaneous lesions began to clear. Two months after the birth of a healthy child, and without further therapy, all lesions had resolved and the serum zinc level was nearly normal. Acrodermatitis enteropathica should be considered in the differential diagnosis of unresponsive bullous dermatoses occurring during pregnancy.


Determination of correction factors in small MLC-defined fields for the Razor and microSilicon diode detectors and evaluation of the suitability of the IAEA TRS-483 protocol for multiple detectors.
Small field output factors for Multileaf collimator (MLC)-defined field sizes between 0.5 × 0.5 cm2 and 3 × 3 cm2 were measured with six different detectors for a Varian TrueBeam in 6-MV, 6-FFF, 10-MV, and 10-FFF photon beams. Correction factors k Q clin , Q ref f clin , f ref $k_{{Q_{{\rm{clin}}}},{Q_{{\rm{ref}}}}}^{{f_{{\rm{clin}}}},{f_{{\rm{ref}}}}}$ from the IAEA publication TRS-483 were used to correct the measured output factors. The corrected output factors from the six detectors were used to calculate correction factors for the PTW microSilicon T60023 (PTW, Freiburg, Germany) and IBA Razor (IBA Dosimetry, Schwarzenbruck, Germany) detectors. The uncertainty of the output and correction factors in this study was calculated and the calculations presented in detail. The application of the TRS-483 correction factors significantly reduced the variation in output factors between the various detectors, with the exception of the PTW 60016 diode in 6-MV and 6-FFF beams, and the IBA PFD in 10-MV and 10-FFF beams. Correction factors calculated for the Razor agreed within 2.9% of existing literature for all energies, while the microSilicon correction factors agreed within 1.6% to the literature for 6-MV beams. The uncertainty in the microSilicon and Razor correction factors was calculated to be less than 0.9% (k = 1). This study shows that TRS-483 correction factors reduce the variation in output factors between the detectors used in this study and presents a suitable method for determining correction factors for detectors with unpublished values.


Compensation of the natural magnetic field does not alter N-acetyltransferase activity and melatonin content of rat pineal gland.
The aim of this study was to investigate if compensation of the natural magnetic field (NMF) influences pineal melatonin production. Rats were exposed to an artificial magnetic field (AMF) that compensated the NMF during the night for 30 min. In another experiment rats were treated with the beta-adrenergic agonist isoproterenol prior to treatment with the same AMF during the day. Pineal N-acetyltransferase activity was determined by a radioenzymatic assay and melatonin content was measured by radioimmunoassay. No statistically significant differences in these parameters were found in rats treated with this AMF when compared to control animals.


Evaluation of 3-Day Course of Doxycycline for the Treatment of Uncomplicated Chlamydia trachomatis Cervicitis.
The purpose of this study was to compare the efficacy of a 3-day course of doxycycline to a standard 7-day course for treating uncomplicated chlamydia cervicitis. During an 18-month period, 77 women with uncomplicated chlamydia cervicitis were randomized to receive either a 3-day or a 7-day course of doxycycline (100 mg twice daily). Tests of cure were performed 3 weeks after completion of therapy with the Amplicor polymerase chain reaction (PCR) assay (Roche Molecular Systems, Branchburg, NJ). Demographics, therapeutic results, and side effects for the two groups were compared. Seventy-three patients completed the study: 35 in the 3-day group and 38 in the 7-day group. There were no significant differences in age, gravidity, or parity between the groups. There was a 94% (33/35) cure rate in the 3-day group and a 95% (36/38) cure rate in the 7-day group (P = 1.0). Thirty-four percent and 32% of the patients in the 3- and 7-day groups reported side effects, respectively; there was no significant differences between the 3- and 7-day groups in regard to population demographics, patient compliance, therapeutic outcome, or side effects. A 3-day course of doxycycline appears to be as effective as a 7-day course of doxycycline for the treatment of uncomplicated chlamydia cervicitis.


Orbital floor fractures in young children.
Isolated orbital floor fractures in children before the end of the 7th year of life are said to seldom occur. This is thought to be due to differences in anatomy from adults in that the maxillary sinus is developing and the orbit is still increasing in size. Two cases of isolated orbital floor fractures in children aged less than 8 years are reported, their management discussed, and the literature reviewed.


Laparoscopic sphincter-preserving total mesorectal excision with colonic J-pouch reconstruction: five-year results.
To prospectively evaluate the oncologic and functional outcomes of laparoscopic total mesorectal excision (TME) with colonic J-pouch reconstruction. TME is considered the established gold standard in rectal cancer surgery. However, data on laparoscopic sphincter-preserving TME are limited. Patients with mid or low rectal cancer underwent laparoscopic TME with colonic J-pouch reconstruction by a single surgical team. Clinical and oncologic data were prospectively recorded and analyzed. From March 1999 to September 2004, 105 patients underwent laparoscopic TME with colonic J-pouch reconstruction. The mean operating time was 170.4 minutes and mean blood loss was 91.5 mL. The mean anastomotic distance from the anal verge was 3.9 cm. Conversion was required in 2 cases. The mean circumferential and distal margins were 17.1 mm and 3.4 cm, respectively. There was 1 case of microscopic circumferential margin involvement and 1 case of microscopic distal margin involvement. There was no 30-day mortality, and 6 patients underwent reoperation for major complications. There was no port-site metastasis. The mean follow-up time was 26.9 months (range, 1.3-65.6 months). The actuarial 5-year cancer-specific survival and local recurrence rates were 81.3% and 8.9%, respectively. Erectile dysfunction occurred in 13.6% of males, while 2 patients developed incomplete bladder denervation. Bowel function after ileostomy closure was satisfactory, with an average bowel motion of less than 3 times per day at 2 years after ileostomy closure. Laparoscopic TME with colonic J-pouch reconstruction is a safe procedure with reasonable operating time and does not appear to pose any threat to the oncologic and functional outcomes.


A low-dose comprehensive cardiac CT protocol assessing anatomy, function, perfusion, and viability.
Radiation exposure in cardiac imaging is a major healthcare concern and low-dose cardiac imaging has important implications for patients. We describe the application of a low-dose comprehensive cardiac computed tomography protocol that assesses anatomy, function, perfusion and viability with correlations to invasive coronary angiography and magnetic resonance imaging.


Appetitive olfactory conditioning in the neonatal male rat facilitates subsequent sexual partner preference.
Pairing a neutral odor with a male rat's initial sexual experiences to ejaculation produces a subsequent conditioned ejaculatory preference (CEP) in which males ejaculate preferentially with receptive females that bear the odor relative to unscented receptive females. In 1986, Fillion and Blass reported that neonatal male rats exposed to a neutral lemon odor (citral) painted on their mother's ventrum while nursing ejaculated faster as adults with sexually receptive, citral-scented females compared to unscented receptive females. The present study examined whether the same odor paired with tactile reward in neonatal male rats would alter the subsequent expression of a CEP. Newborn Long-Evans male rats were separated from their mothers each day beginning on Postnatal Day 1 and placed into a Plexiglas cage that contained either unscented or citral-scented bedding (N = 8/group). During each trial, rats were stroked from head to toe with a soft, narrow paintbrush, after which they were returned to their mothers. Males were weaned at 21 days of age and housed in same-treatment pairs for an intervening 50 days. Following habituation to a large open field, males were presented with two sexually receptive Long-Evans females, one scented with citral, and the other unscented, for a 30-min test of copulation. Males in the Paired group copulated and ejaculated preferentially with the scented female whereas males in the Unpaired group showed no preference. Pairing a neutral odor with a reward state in infancy generates a preference in male rats to ejaculate with sexually receptive females bearing the same odor in adulthood.


Peripartum cardiomyopathy--report of 16 cases.
To analyze the clinical characteristics of peripartum cardiomyopathy and to evaluate the different factors that influence the prognosis of the peripartum cardiomyopathy. A retrospective review was undertaken on records of women who were diagnosed with peripartum cardiomyopathy at Peking Union Medical College Hospital between Jan. 1983 and May 1999. During the research period, only 16 pregnant women were documented as peripartum cardiomyopathy. Some of the women undertook ultrasonic cardiographic (UCG) examination that showed decreased systolic function. Seven women were complicated with pregnancy induced hypertension. Three died of disseminated intravascular coagulation, embolism and cardiogenic shock respectively. Early diagnosis of the peripartum cardiomyopathy is extremely important. The UCG can provide helpful information on disease progression or regression.


A solvable selfreproductive hypercycle model for the selection of biological molecules.
By introducing a modified enzyme coupling in Eigen's hypercycle equations we have produced an exactly solvable selfreproductive hypercycle model. The model shows explicitly how collections of different macromolecular information carriers may coexist, through internal couplings, in the presence of constraints. We show how the "selective value" concept is manifested in the model and give simple criteria for selection among competing hypercycles.


Indicators to assess the quality of programs to prevent occupational risk for tuberculosis: are they feasible?
to analyze the feasibility of quality indicators for evaluation of hospital programs for preventing occupational tuberculosis. a descriptive cross-sectional study. We tested indicators for evaluating occupational tuberculosis prevention programs in six hospitals. The criterion to define feasibility was the time spent to calculate the indicators. time spent to evaluate the indicators ranged from 2h 52min to 15h11min 24sec. The indicator for structure evaluation required less time; the longest time was spent on process indicators, including the observation of healthcare workers' practices in relation to the use of N95 masks. There was an hindrance to test one of the indicators for tuberculosis outcomes in five situations, due to the lack of use of tuberculin skin test in these facilities. The time requires to calculate indicators in regarding to the outcomes for occupational tuberculosis largely depends upon the level of organizational administrative structure for gathering data.


Clinical features and treatment outcomes of peripheral T-cell lymphoma in children. A current data report from Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG).
Peripheral T-cell lymphomas (PTCL) are lymphoproliferative disorders derived from post-thymic cells, that occur extremely rarely in children. The optimal treatment of pediatric PTCL remains still unclear. Ten children with PTCL from 3 up to 18 years of age registered by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) were retrospectively analyzed. All patients were treated with different regimens including protocols: for lymphoblastic lymphoma in 7 cases, for anaplastic large cell lymphoma in 1, CHOP in 1. Five of the 10 patients with PTCL were classified as stage II; 4 as stage III and 1 as stage IV due to extralymphatic organs (bone marrow) involvement. Four histological subtypes of PTCL were recognized: extranodal NK/T-cell lymphoma, nasal type (ENTNT), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), subcutaneous panniculitis-like T-cell lymphoma (SPL), Sezary syndrome (SS). After first-line therapy 9 patients initially achieved complete remission, 4 relapsed, 5 died. One patient achieved remission spontaneously. Three children (1 with stage IV and 2 in relapse) underwent high-dose chemotherapy with allogeneic bone marrow stem cell transplantation and all of them are alive and in CR. The cumulative probability of 5-year overall survival (OS) for our whole group was 63.9% (95%CI: 35.2-88.2%) with a median follow-up time of 48.4 months (range 24-90+ months). The 5-year event free survival (EFS) was 81%. PTCLs are a heterogeneous and rare group of childhood NHLs. According to our experience the standard chemotherapy for precursor lymphomas seems to be a beneficial treatment option for children with PTCL. Allogeneic stem cell transplantation may improve the outcome in selected patients.


Concomitant expression of inhibitory molecules for T cell activation predicts poor survival in patients with esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is a major subtype of esophageal cancers. The Five-year survival rate of ESCC is low and molecular targets for ESCC treatment and prognosis assessment are very limited. T cells are critical for clearance of cancer cells and blockade of co-inhibitory molecules for T cell activation has emerged as a promising therapy to treat cancer patients. However, in ESCC patients such co-inhibitory molecules regulating T cell activation is poorly documented. We aim to evaluate how the presence of inhibitory check-point molecules in T cells could impact survival of patients. We performed follow-up study of 161 patients undergoing resection of esophageal carcinoma from February 2014 to December 2015, by immunohistochemical staining of six co-inhibitory molecules for T cell activation, namely PD-1, CTLA-4, TIM-3, LAG-3, BTLA and A2AR. Expression of each of the six co-inhibitory molecules was analyzed for its correlation with patient survival by Kaplan-Meier survival analysis. We also applied Kaplan-Meier analyses to evaluate concomitant expression of co-inhibitory molecules and their correlation with patient survival. We found that levels of PD-1, TIM-3 and BTLA can be used as independent prognostic factors for overall survival of patients with ESCC. More importantly, our study found that the co-expression of PD-1 and TIM-3, PD-1 and BTLA, TIM-3 and BTLA significantly reduced the survival of patients with ESCC (P<0.05). Therefore, our results suggest the necessity of evaluating the tumor tissue expression of co-inhibitory molecules and targeting co-expressed molecules in immunotherapies for ESCC patients.


The IgM anti-desmoglein 1 response distinguishes Brazilian pemphigus foliaceus (fogo selvagem) from other forms of pemphigus.
Fogo selvagem (FS) and pemphigus foliaceus (PF) possess pathogenic IgG anti-desmoglein 1-(Dsg1) autoantibodies. Although PF occurs sporadically, FS is endemic in Limao Verde (LV), Brazil (3.4% prevalence). IgM anti-Dsg1 were detected in 58% FS LV patients (n=31), 19% of FS patients from Hospital-Campo Grande (n=57), 19% from Hospital-Goiania (n=42), 12% from Hospital-Sao Paulo (n=56), 10% of PF patients from United States (n=20), and 0% of PF patients from Japan (n=20). Pemphigus vulgaris (n=40, USA and Japan), bullous pemphigoid (n=40, USA), and healthy donors (n=55, USA) showed negligible percentages of positive sera. High percentages of positive IgM anti-Dsg1 were found in healthy donors from four rural Amerindian populations (42% of 243) as compared with urban donors (14% of 81; P<0.001). More than 50% of healthy donors from LV (n=99, age 5-20 years) possess IgM anti-Dsg1 across ages, whereas IgG-anti-Dsg1 was detected in 2.9% (age 5-10 years), 7.3% (age 11-15 years), and 29% of donors above age 16. IgM anti-Dsg1 epitopes are Ca2+ and carbohydrate-independent. We propose that IgM anti-Dsg1 are common in FS patients in their native environment and uncommon in other pemphigus phenotypes and in FS patients who migrate to urban hospitals. Recurrent environmental antigenic exposure may lead to IgM and IgG responses that trigger FS. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub.


Insight into the role of HSPG in the cellular uptake of apolipoprotein E-derived peptide micelles and liposomes.
Liposomes and micellar carriers equipped with targeting and cellular uptake mediating peptides have attracted attention for numerous applications. The optimization of the carrier requires an understanding of how their properties influence target cell recognition and uptake. We developed a dipalmitoylated apolipoprotein E-derived peptide, named P2A2 as promising vector to mediate cellular uptake of potential micellar and liposomal carriers. Confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS) were used to get insight into the internalization mediated by carboxyfluoresceine-labeled P2fA2 and the all-D amino acid analogue P2fa2 into brain capillary endothelial cells. Both peptide micelles and liposomes entered cells via endocytosis. Cell surface heparan sulfate proteoglycans (HSPGs) were involved in the internalization process of peptide-bearing liposomes characterized by a diameter of 100 nm, a low surface density of 100 peptide molecules per vesicle and a helical conformation of the vector. In contrast, peptide micelles characterized by a diameter of about 10 nm, a high peptide density caused by 19 associated molecules and a high conformational flexibility of the vector sequence did not address HSPG. Unspecific interactions between the carriers and membrane constituents predominate the two uptake processes but stereospecific components seem to be involved. Both routes differ with respect to transport efficiency. The results provide a prospective basis to optimize liposomes and micelles as drug delivery systems.


Cost Effects of a Health Coaching in Children and Adolescents With Mental Health and Developmental Disorders.
Health coaching (HC) aims to strengthen the role of primary care pediatricians in the treatment of children and adolescents with mental health and developmental disorders by extending consultation time and using disease-specific manuals. We evaluated the effect of HC on costs of specialized, pediatrician, and overall care. In a retrospective cohort study based on German health insurance claims data, we identified children aged up to 17 years with a newly diagnosed mental health and/or developmental disorder between 2013 and 2015. Patients getting HC were matched to patients receiving usual care. Costs were calculated for 1 year following the start of the treatment and compared by 2-part and gamma models. Absolute costs and cost differences were calculated with bootstrapped 95% confidence intervals (CI). We compared 5597 patients receiving HC with 5597 control patients. The probability of incurring specialized care costs was similar between the groups (0.96, 95% CI: 0.88; 1.05). However, for those who did incur costs, specialized care costs were significantly lower for HC-treated patients (0.77, 95% CI: 0.63; 0.93). Accordingly, specialized care costs were lower by €-94 (95% CI: €-175; €-18), while pediatrician care costs were higher for HC-treated patients by €57 (95% CI: €49; €64). Hence, overall costs did not differ between the groups (€-59, 95% CI: €-191; €71). Provision of HC has the potential to lower the costs of specialized care, while increasing the costs of pediatrician care. Overall costs did not differ, suggesting that the additional costs incurred by the HC were offset.


Regulation of ornithine aminotransferase mRNA levels in rat kidney by estrogen and thyroid hormone.
The regulation of the mitochondrial matrix enzyme, ornithine aminotransferase, by estrogen and triiodothyronine (T3) in rat kidney was examined using a cloned cDNA probe and in vitro translation of poly(A+) RNA. After a single, acute dose of either 17 beta-estradiol or T3, the rate of enzyme synthesis and the levels of translatable and hybridizable ornithine aminotransferase mRNA all increase in parallel. Levels of hybridizable mRNA were estimated by hybridization of randomly 32P-labeled RNA to filter-bound plasmid DNA. Maximal levels of induction by estrogen and T3 were about 15- and 3-fold, respectively. Lag times of at least 5 h and less than 3 h were observed for induction by T3 and estrogen. T3 and estrogen exert a synergistic effect in increasing ornithine aminotransferase mRNA levels. 16 h after T3 administration and 24 h after estrogen administration, a 1.6- and 13-fold increase in mRNA levels were observed. Both of these treatments in combination for the indicated time periods resulted in a 21-fold increase in ornithine aminotransferase mRNA. From the mRNA accumulation curves, half-lives of 10 to 14 h and 12 to 16 h were estimated for the mRNA after estrogen and T3 induction, respectively. These similar half-lives suggest that an increase in the rate of mRNA production is primarily responsible for the induction observed after estrogen administration.


[Y chromosomal factor controls transcription of autosomal fertility genes in Drosophila melanogaster males].
Transposition of the P[1ArB] vector was used to generate three mutations inducing sterility in homozygous males: ms(3)P50, ms(3)P122, and ms(3)P115 located within 67A4-B13, 92A2-14, and 75D regions on the polytene map. Staining for beta-galactosidase synthesized by P[1ArB] allowed us to study enhancer activity of these ms genes in the testicles. Their activity correlated to the presence of the YS arm but was little affected by the presence of YL arm of Y chromosome.


Culture versus Policy: More Global Collaboration to Effectively Combat COVID-19.
The outbreak of COVID-19 seriously challenges every government with regard to capacity and management of public health systems facing the catastrophic emergency. Culture and anti-epidemic policy do not necessarily conflict with each other. All countries and governments should be more tolerant to each other in seeking cultural and political consensus to overcome this historically tragic pandemic together.


Tardive intermittent massive vaginal bleeding from abnormal blood vessels within cesarean scar: Two more new cases should bring our attention to a new entity.
The two cases in this report had intermittent massive vaginal bleeding with a distant history of cesarean delivery. Such severe bleeding was life-threating but was eventually cured by surgical management. To the best of our knowledge, this is the second report of cases of tardive vaginal bleeding caused by abnormal blood vessels embedded within cesarean scars. The two new cases in this report suggest a novel cause of tardive vaginal bleeding, which should bring our special attention to post-cesarean clinical practice.


Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients.
Pediatric acute lymphoblastic leukemia (pALL) patients have better overall survival and methotrexate (MTX) is an effective drug used in their treatment. However, the treatment-related adverse effects (TRAEs) have a bigger impact on the therapy. In this study, we have evaluated the association of polymorphisms in genes encoding proteins engaged in MTX metabolism, and the cytogenetic aberrations with TRAEs. A total of 115 patients between the age of 1 and 18 years (average: 6.6) under maintenance therapy were selected for the study. SLC19A1 (c.80G > A), MTHFR (c.677C > T; c.1298A > C), and TYMS (c.*450_*455del) genotypes were determined using PCR techniques and Sanger sequencing. Cytogenetic and SNP findings were analyzed for any association with the reported toxicities using odds ratio, chi-square test, multifactor dimensionality reduction (MDR) analysis for synergistic effect and, multinomial logistic regression analysis for the likelihood of adverse events. Among the evaluated genetic variations, SLC19A1 (c.80G > A) was significantly associated with TRAEs (OR = 5.71, p = 0.002). Multinomial logistic regression analysis (chi-sq = 16.64, p < 0.001) and MDR analysis (chi-sq = 10.51 p < 0.001) confirmed the finding. On the other hand, no significant association was observed between adverse events and any specific cytogenetic aberration. SLC19A1 facilitates the import of cyclic dinucleotides and reduced folates, evaluating genotypes in this gene can help in better management of patients on methotrexate treatment. Assessing a broader gene panel can help in finding more associated markers and delivering personalized medicine to the patients.


FGFR1/MAPK-directed brachyury activation drives PD-L1-mediated immune evasion to promote lung cancer progression.
Immune checkpoint inhibitors provide promising benefits for patients with cancer. However, efficacy has been encumbered by high resistance rates. It is critical to understand the basic mechanisms of tumor-mediated resistance to this treatment modality. Previous studies have found that the transcription factor brachyury is highly expressed in lung cancer. Here, we show that brachyury activation induces the upregulation of PD-L1 leading to inactivation of T cell proliferation in vitro and inhibited infiltration of CD8+ and CD3+ T cells into tumor in an immunocompetent mouse model. We further demonstrate that FGFR1/MAPK activation regulates brachyury and PD-L1 expressions and promotes immunosuppression. Blocking FGFR1/MAPK suppresses brachyury and PD-L1 expressions, revives immune activity, and reverses the resistance to anti-PD-1 treatment to produce a durable therapeutic response. We also find that lung cancer patients with high activation of the FGFR1-MAPK-brachyury-PD-L1 signature and low expression of CD8A, CD3D, or PDCD1 have worse survival outcomes. These findings elucidate a novel mechanism of immune escape from immune checkpoint therapy and provide an opportunity to enhance its therapeutic efficacy in the treatment of a subset of FGFR1/MAPK/brachyury/PD-L1-driven lung cancer.


Volatilization of in situ generated antimony trichloride using aqua regia vapors for the determination of ultra trace impurities in high-purity antimony using inductively coupled plasma-mass spectrometry.
Volatilization of Sb has been carried out using vapors generated from aqua regia for the determination of non-volatile impurities present in antimony. The antimony trichloride (SbCl3) thus generated was volatilized >99.9% at 250 degrees C in 90 min. Recoveries of spiked impurities Al, Mn, Co, Ni, Cu, Sr, Ag, Cd, Ba, Pb were found to be >90% (47% for Pb) after volatilization of the matrix element. The only reagent used (aqua regia vapors) was generated in situ in a closed environment minimizing the external contamination. The procedure offers experimental blanks and method detection limits at lower ng g(-1) using ICP-MS. The method has been applied for the determination of impurities in two Sb samples of 99.5 and 99.999% (5N) purity. The developed method was validated using bromide volatilization procedure. The results obtained by the present method were also compared with those of Sector Field ICP-MS (SF-ICP-MS).


TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response.
PARP1 is the main sensor of single- and double-strand breaks in DNA and, in building chains of poly(ADP-ribose), promotes the recruitment of many downstream signaling and effector proteins involved in the DNA damage response (DDR). We show a robust physical interaction between PARP1 and the replication fork protein TIMELESS, distinct from the known TIMELESS-TIPIN complex, which activates the intra-S phase checkpoint. TIMELESS recruitment to laser-induced sites of DNA damage is dependent on its binding to PARP1, but not PARP1 activity. We also find that the PARP1-TIMELESS complex contains a number of established PARP1 substrates, and TIMELESS mutants unable to bind PARP1 are impaired in their ability to bind PARP1 substrates. Further, PARP1 binding to certain substrates and their recruitment to DNA damage lesions is impaired by TIMELESS knockdown, and TIMELESS silencing significantly impairs DNA double-strand break repair. We hypothesize that TIMELESS cooperates in the PARP1-mediated DDR.


A Retrospective Comparison of Fitness and Exercise Progression in Patients With Coronary and Peripheral Artery Disease in Cardiac Rehabilitation.
Cardiac rehabilitation (CR) is recommended for patients with coronary (CAD) and peripheral (PAD) artery disease. However, no study has compared changes in cardiorespiratory fitness (VO2peak) or exercise prescription progression among PAD, CAD, and concomitant PAD and CAD (BOTH). The objectives of this study were to 1) compare change in VO2peak among patients with PAD, CAD, and BOTH, and 2) examine progression in exercise prescription parameters in a comprehensive 6-month cardiac rehabilitation (CR) program. A retrospective analysis of patient data recorded from 2006 to 2017 from a large urban hospital was conducted. Patients with PAD (n = 63) and BOTH (n = 164) were included in the analyses. Patients with CAD (n = 63) were matched to PAD by sex (36.5% female), age (69 years), smoking status, diabetes, and year in program. There were significant improvements in VO2peak from baseline to 6 months in all groups (CAD +2.7 ± 3.4 mL⋅kg-1⋅min-1, PAD +2.4 ± 3.8 mL⋅kg-1⋅min-1, BOTH +1.8 ± 3.1 mL⋅kg-1⋅min-1; all P < 0.001). Between-group differences were significant between PAD and CAD as well as between CAD and BOTH (P = 0.001). Walking distance, duration, and pace increased for all groups over 6 months (P < 0.001), with a significant difference in pace between CAD and BOTH (P = 0.006). Patients with PAD, CAD, and BOTH had significant improvements in VO2peak following a 6-month CR program. However, despite similar prescribed walking distance and duration, improvements in VO2peak were mitigated in PAD and BOTH compared with CAD. These results support benefits of CR for patients diagnosed with PAD, but alternate exercise strategies should be explored for patients with PAD.


Neonatal total parenteral nutrition ascites from liver erosion by umbilical vein catheters.
A preterm infant was found to have total parenteral nutrition (TPN) ascites after infusion through a low umbilical vein catheter (UVC). Objective. To evaluate the clinical and imaging findings of neonates with TPN ascites after infusion through UVCs. Eight patients with TPN ascites were identified over three years. Charts were abstracted for clinical data. Plain-film, ultrasound (US), and contrast studies through the UVCs were examined to determine UVC placement, presence of liver injury, and confirmation of intraperitoneal extravasation from the UVC. All eight patients with TPN ascites presented with hypotension and abdominal distension. All had UVCs overlying the liver on plain film. Catheters were in place a mean of 8.9 days prior to TPN extravasation. US in four patients showed hepatic parenchymal damage around the UVC tip. Contrast studies in six patients showed intraperitoneal spill. While low UVC placement may sometimes be clinically unavoidable, TPN administered through abnormally positioned UVCs is not without risk.


A case with acute-on-chronic liver failure receiving liver transplantation during daclatasvir and asunaprevir therapy in chronic hepatitis C patient.
We report a case with hepatitis C virus genotype 1 b liver cirrhosis who received liver transplantation because of acute-on-chronic liver failure during daclatasvir (DSV) and asunaprevir (ASV) combination therapy. To our knowledge, this is the first case received liver transplantation during DSV + ASV therapy. Therefore, clinicians should pay particular attention to the possibility of acute liver failure during DSV and ASV combination therapy.


Factors influencing the relapse risk at steroid dose reduction in myasthenia gravis.
In a selected group of 69 patients with myasthenia gravis treated with prednisone, the factors were studied that might have influenced the reoccurrence or exacerbation of clinical signs after initial improvement in two-thirds of the patients. It was not evident that the speed of dose reduction was responsible for the relapse in most patients. Azathioprine added to the prednisone regimen was found to reduce the relapse rate at steroid reduction. Pure ocular cases and patients who underwent thymectomy without thymoma had a higher chance to remain in remission after prednisone was stopped. Maintenance dose could be determined in 18 patients and was 0.42 mg/kg/2 d., but the difference between patients with or without azathioprine was not significant.


Therapeutic misconception and the appreciation of risks in clinical trials.
Studies repeatedly have shown that clinical research subjects have trouble appreciating the implications for their clinical care of participating in a clinical trial. When this failure is based on a lack of appreciation of the impact on individualized clinical care of elements of the research design, it has been called the "therapeutic misconception". Failure to distinguish the consequences of research participation from receiving ordinary treatment may seriously undermine the informed consent of research subjects. This article reports results concerning appreciation of the risks of trial participation from intensive interviews with 155 subjects from 40 different clinical trials at two different medical centers in the USA. Working from transcripts of the interviews, every statement of a risk or disadvantage of trial participation was identified and coded into one of 5 different categories. Totally, 23.9% of subjects reported no risks or disadvantages in spite of being explicitly asked about them. Another 2.6% reported only incidental disadvantages such as having to drive a long way to get to the experimental site. In all 14.2% reported only disadvantages associated with the standard treatment (usually side effects). Another 45.8% told the interviewer about disadvantages and risks associated with the experimental intervention (usually side effects). Only 13.5% could report any risks or disadvantages resulting from the research design itself, such as randomization, placebos, double-blind designs and restrictive protocols. The results of this research suggest that subjects often sign consents to participate in clinical trials with only the most modest appreciation of the risks and disadvantages of participation.


Column liquid chromatography of methotrexate and its metabolites using a post-column photochemical reactor and fluorescence detection.
On irradiation with short-wavelength UV light in the presence of hydrogen peroxide, methotrexate and its metabolites 7-hydroxymethotrexate and 2,4-diamino-N10-methylpteroic acid are cleaved into highly fluorescent products. This reaction can be used for the sensitive and selective detection of the compounds in biological fluids, following reversed-phase high-performance liquid chromatographic separation. Study of the effect of the mobile phase composition and irradiation time on fluorescence signal intensity showed that a residence time of ca. 3 s in the on-line photochemical reactor was best. The detection limit for methotrexate was 0.4 ng, for 7-hydroxymethotrexate 1.0 ng and for 2,4-diamino-N10-methylpteroic acid 0.6 ng. The addition of dimethylformamide to the mobile phase enhanced the selectivity of separation.


Long noncoding RNA CASC2 suppresses esophageal squamous cell carcinoma progression by increasing SOCS1 expression.
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related deaths worldwide. Emerging evidence suggests the involvement of long noncoding RNAs (lncRNAs) in tumorigenesis. LncRNA Cancer Susceptibility Candidate 2 (CASC2) has been demonstrated to act as a tumor suppressor contributing to the development and progression of several cancers. However, the functional significance and underlying mechanism of CASC2 in ESCC progression has not been well elucidated. The expression levels of CASC2 in ESCC tissues were detected by qRT-PCR. CASC2 overexpression and knockdown models were established and used to investigate the functional role of CASC2 in ESCC cells. RIP, RNA pull-down and dual-luciferase assay was used to detect the association between CASC2 and miR-155. The interaction between CASC2 and Suppressor Of Cytokine Signaling 1 (SOCS1) was assessed by RIP and RNA pull-down assays. In the present study, we found that CASC2 was significantly downregulated in ESCC tissues and positively correlated with overall survival time of patients with ESCC. Functional assays demonstrated that CASC2 suppressed proliferation, migration and invasion, as well as enhanced drug sensitivity in ESCC cells. Mechanistically, CASC2 inhibited ESCC progression by upregulating the expression of SOCS1 via two different ways. CASC2 acted as competing endogenous RNA (ceRNA) for miR-155 to post-transcriptionally increase SOCS1 expression. On the other hand, CASC2 was capable of interacting with SOCS1 protein and suppressing its degradation. Conclusively, these results demonstrated that CASC2 could exert as a tumor suppressive lncRNA in ESCC progression via regulating SOCS1.


Salvage Radiotherapy versus Observation for Biochemical Recurrence following Radical Prostatectomy for Prostate Cancer: A Matched Pair Analysis.
Salvage radiotherapy (SRT) improves oncologic outcomes in prostate cancer (PCa) patients who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, evidence on hard clinical endpoints is scarce. We compare long-term oncologic outcomes of SRT versus no radiotherapy (noRT) in patients with BCR after RP. Within a multi-institutional database, we identified patients with BCR after RP between 1989 and 2016 for PCa. Patients with lymph node invasion, with adjuvant radiotherapy, or with additional androgen deprivation therapy at BCR were excluded. In all patients with SRT, SRT was delivered to the prostatic bed only. Propensity score matching (PSM) was performed to account for differences in pathologic tumor characteristics. Kaplan-Meier analyses and Cox regression models tested the effect of SRT versus no RT on metastasis-free (MFS) and overall survival (OS). Of 1832 patients with BCR, 32.9% (n = 603) received SRT without ADT. The median follow-up was 95.9 months. Median total SRT dose was 70.2 Gy. After 1:1 PSM, at 15 years after RP, MFS and OS rates were 84.3 versus 76.9% (p < 0.001) and 85.3 versus 74.4% (p = 0.04) for SRT and noRT, respectively. In multivariable Cox regression models, SRT was an independent predictor for metastasis (HR: 0.37, p < 0.001) and OS (HR: 0.64, p = 0.03). This is the first matched-pair analysis investigating the impact of SRT versus observation only in post-RP recurrent PCa. After compensating for established risk factors, SRT was associated with better long-term MFS and OS. These results on clinical endpoints underline the curative potential of SRT.


Glowing Sucker Octopus (Stauroteuthis syrtensis)-Inspired Soft Robotic Gripper for Underwater Self-Adaptive Grasping and Sensing.
A soft gripper inspired by the glowing sucker octopus (Stauroteuthis syrtensis)' highly evolved grasping capability enabled by the umbrella-shaped dorsal and ventral membrane between each arm is presented here, comprising of a 3D-printed linkage mechanism used to actuate a modular mold silicone-casting soft suction disc to deform. The soft gripper grasp can lift objects using the suction generated by the pump in the soft disc. Moreover, the protruded funnel-shaped end of the deformed suctorial mouth can adapt to smooth and rough surfaces. Furthermore, when the gripper contacts the submerged target objects in a turbid environment, local suctorial mouth arrays on the suction disc are locked, causing the variable flow inside them, which can be detected as a tactile perception signal to the target objects instead of visual perception. Aided by the 3D-printed linkage mechanism, the soft gripper can grasp objects of different shapes and dimensions, including flat objects, objects beyond the grasping range, irregular objects, scattered objects, and a moving turtle. The results report the soft gripper's versatility and demonstrate the vast application potentials of self-adaptive grasping and sensing in various environments, including but are not limited to underwater, which is always a key challenge of grasping technology.


Oligodipsia and dissociative experiences in borderline personality disorder.
To test the frequency of attenuated fluid intake behavior (oligodipsia) in patients with borderline personality disorder (BPD) and to test if there is an inverse correlation between oligodipsia and the intensity of current dissociative experience in a pilot study. Analyses were based on a sample of 15 BPD patients and 15 healthy controls. Fluid intake per diem and intensity of dissociative experience were measured by standardized self-reports daily for 7 days. The BPD patients ingested a significantly lower fluid volume per diem when compared with healthy controls (P < 0.001). We found a strong correlation between intensity of co-occurring dissociative experience and fluid intake or urine osmolality (r = 0.762 and 0.665), independently of sleep quality and general BPD symptom severity. The results indicate that oligodipsia may constitute a serious problem at least for a subgroup of BPD patients, and may be correlated with some of the most problematic symptoms of BPD.


Omega-3 and omega-6 fatty acids and type 2 diabetes.
Polyunsaturated fatty acids are of particular interest in the nutritional therapy for diabetes, given their potential role in several pathophysiological processes related to cardiovascular disease. Both omega-3 and omega-6 fatty acids are beneficial for improving lipid profiles in healthy individuals and among type 2 diabetic patients: Supplementation with omega-3 fatty acids lowers triglycerides and VLDL-cholesterol. However, they might also increase LDL-cholesterol. Omega-3 fatty acids are, from the latest evidence, not related to mortality and cardiovascular disease. Similarly, glucose control and hypertension, as well as risk of microvascular complications, seem unaffected by omega-3 supplementation. Most studies involved mainly patients with type 2 diabetes, and future research needs to focus on the type 1 diabetic patient. Also, the role of omega-6 fatty acids remains largely unknown.