Major Cardiac Events After Non-cardiac Surgery.
Postoperative cardiovascular complications might be difficult to assess and are known to be associated with longer hospital stay and increased costs as well as higher morbidity and mortality rates. The aim of this study was to evaluate the predictors for major cardiac events (MCE) after non-cardiac surgery. The study included 4398 patients who were admitted to the Surgical Intensive Care Unit between January 1, 2006 and July 19, 2013. Acute physiology and chronic health evaluation II score and simplified acute physiology score (SAPS II) were calculated, and all variables entered as parameters were evaluated independently. Multivariate logistic regression analysis was performed to assess the independent factors for MCE. A total of 107 people experienced MCE. The independent predictors for postoperative MCE were higher fraction of inspired oxygen (FiO2) (odds ratio [OR] 38.97; 95 % confidence interval [CI] 10.81-140.36), history of ischemic heart disease (OR 3.38; 95 % CI 2.12-5.39), history of congestive heart disease (OR 2.39; 95 % CI 1.49-3.85), history of insulin therapy for diabetes (OR 2.93; 95 % CI 1.66-5.19), and increased SAPS II (OR 1.03; 95 % CI 1.01-1.05). Having a MCE was associated with a longer length of stay in the surgical intensive care unit (OR 1.01, 95 % CI 1.00-1.01). FiO2, ischemic heart disease, congestive heart disease, insulin therapy for diabetes, SAPS II, and length of stay in the surgical intensive care unit were independent predictors for MCE.


Pharmacological Therapy Optimization for Heart Failure: A Practical Guide for the Internist.
Heart failure carries significant morbidity and mortality and affects a large population of patients cared for predominantly by primary care physicians. The complexity of managing heart failure patients is increasing as new therapies continue to emerge. This review outlines important clinical pearls and proposes strategies for optimization of medical therapy.


Rural and urban older adults' perspectives of strength in their daily lives.
The purpose of this study was to understand older adults' perspectives of strength in their daily lives. Maintaining strength is important as the population ages and many older adults live into their 80s and 90s. Few studies have explored older adults' views of strength and its management as they age. A qualitative descriptive design was used. The sample consisted of 5 focus groups (n = 41) that participated in semistructured interviews. Transcribed data were analyzed using the constant comparative method. Three themes emerged-the capacity to meet variable demands, changes in strength, and strategies to stay strong. Older adults regard strength as an integration of physical and internal capacities for meeting a range of demands and use physical, mental, and social activities for staying strong. Nurses have an important role in helping older adults focus on strength and their abilities rather than inabilities to enhance healthy aging.


Imidazole-1-sulfonyl azide-based diazo-transfer reaction for the preparation of azido solid supports for solid-phase synthesis.
An efficient, standard, mild, and copper-free imidazole-1-sulfonyl azide hydrochloride-based diazo-transfer method was implemented in a set of four resins that cover a broad range of hydrophobicity. The imidazole-1-sulfonyl azide hydrochloride is easily prepared/commercially available, stable upon storage at 4 °C, and proved to be a suitable alternative to triflyl azide for diazo-transfer reactions in amine functionalized resins. We have successfully applied the azido resins for the conjugation of a TFA-labile Wang-type linker using Click Chemistry.


First-time mothers' perspectives on relationships with and between midwives and doctors: insights from a qualitative study of giving birth in New Zealand.
to explore the experience of giving birth for first-time New Zealand mothers. qualitative methodology was employed to obtain an in-depth insight into the birth experience using semi-structured interviews conducted face-to-face 11 days to 16 weeks (median 13.5 weeks) after giving birth were audio-recorded and transcribed verbatim. the interviews were of a small group of New Zealand mothers. ten first-time mothers aged 24-38 years (median 31.5 years) participated. transcripts were analysed using a phenomenological form of thematic analysis. a core theme was relationship issues. Two subthemes were delineated: lack of relationship between mothers and midwives and doctors; and the conflict between midwives and doctors. personal, caring and co-operative relationships with all maternity care professionals were basic to New Zealand mothers feeling good about their birth experience. relationships, with and between, all maternity care professionals merit further investigation in an effort to optimise birth satisfaction.


Improvement of insulin resistance and early atherosclerosis in patients after gastric banding.
To evaluate the effect of massive weight loss on insulin sensitivity, soluble adhesion molecules, and markers of the insulin resistance syndrome (IRS). Eighteen morbidly obese patients underwent gastric banding and were evaluated before and 6 and 12 months after surgery. Total insulin secretion, hepatic insulin extraction, and insulin sensitivity were analyzed by oral glucose-tolerance test model analysis. In addition, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, leptin, high-sensitivity C-reactive protein, plasminogen activating factor-1 (PAI-1), and tissue plasminogen activator were measured. BMI dropped from 45.22 +/- 5.62 to 36.99 +/- 4.34 kg/m(2) after 6 months and 33.72 +/- 5.55 kg/m(2) after 12 months (both p < 0.0001). This intervention resulted in a significant reduction of blood pressure (p < 0.00001), triglycerides (p < 0.01), fasting blood glucose (p = 0.03), basal insulin (p < 0.001), and basal C-peptide (p = 0.008) levels. Total insulin secretion decreased (p < 0.05), whereas hepatic insulin extraction (p < 0.05) and oral glucose insulin sensitivity index (p < 0.0001) increased compared with baseline. Leptin (p < 0.0001) and E-selectin levels decreased significantly after 6 and 12 months (p = 0.05), whereas significantly lower levels of intercellular adhesion molecule-1 and PAI-1 were only seen after 6 months. Subclinical inflammation, measured by high-sensitivity C-reactive protein, was lowered to normal ranges. No changes were observed in vascular cell adhesion molecule-1 and tissue plasminogen activator levels. Although gastric banding ameliorates several features of the IRS, including 29.05% improvement in insulin sensitivity and blood pressure and reduction of soluble adhesion molecules and PAI-1, considerable weight loss did not normalize all components of the IRS in morbidly obese patients.


Prospective randomized trial of external versus internal transcatheter cardioversion in patients with chronic atrial fibrillation.
To evaluate the safety and long-term efficacy of internal transcatheter cardioversion, forty patients with chronic, lone atrial fibrillation were studied. The patients were randomised to internal transcatheter cardioversion or to conventional external cardioversion. In cases where the procedure was unsuccessful, cross-over to the alternate method was performed. Oral anticoagulation therapy was started three weeks prior to the procedure and was maintained for another three weeks following successful cardioversion. Sinus rhythm was restored in 16/18 patients (88%) in the internal cardioversion group, versus 9/22 patients (40%) in the external cardioversion group (p < 0.01). In addition, 8/13 (61%) patients who were crossed-over to internal cardioversion were successfully cardioverted to sinus rhythm. In contrast, both patients who were crossed-over to external cardioversion remained in atrial fibrillation. During a mean follow-up period of 23 months, 13 (39.3%) patients maintained sinus rhythm. Using the intention to treat principle, the recurrence rate was not statistically different between the two methods. It is concluded that internal cardioversion is more effective in acutely restoring sinus rhythm compared to external cardioversion. However, both methods have similar long-term recurrence rates.


Elective Abdominal Surgery for Inflammatory Bowel Disease.
Elective abdominal surgery for inflammatory bowel disease is common. Surgery for Crohn's disease is not curative, and treatment must be individualized to the disease process. Surgery for ulcerative colitis generally is curative but consideration of patient-specific factors is important for staging of the procedure and determining whether ileal pouch-anal anastomosis is appropriate.


The Regulation of GluN2A by Endogenous and Exogenous Regulators in the Central Nervous System.
The NMDA receptor is the most widely studied ionotropic glutamate receptor, and it is central to many physiological and pathophysiological processes in the central nervous system. GluN2A is one of the two main types of GluN2 NMDA receptor subunits in the forebrain. The proper activity of GluN2A is important to brain function, as the abnormal regulation of GluN2A may induce some neuropsychiatric disorders. This review will examine the regulation of GluN2A by endogenous and exogenous regulators in the central nervous system.


Real-World Persistence and Treatment Interval in Patients with Diabetic Macular Edema Treated with Anti-Vascular Endothelial Growth Factors in the USA.
There is little understanding of long-term treatment persistence in patients receiving anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), particularly relating to treatment intervals. The aim of this study was to investigate the association between treatment interval and discontinuation rate after 24 months of unilateral anti-VEGF treatment in patients with DME under routine clinical care in the USA. This was a non-interventional, retrospective cohort study to review the health insurance claims of adults with DME linked with the IBM MarketScan® Commercial and Medicare Supplemental databases, who were continuously enrolled in a health plan for at least 6 months prior to their first anti-VEGF treatment and for a duration of at least 24 months between July 2011 and June 2017. Patients were grouped on the basis of the injection interval they achieved at 24 months of treatment. Discontinuation rate beyond 24 months and its association with treatment intervals at 24 months was estimated using the Kaplan-Meier method and Cox proportional hazards models. The overall discontinuation rate among the 1702 eligible patients from 24 to 60 months after treatment initiation was 30%. At 60 months, patients were more likely to remain on treatment in shorter (75.3% [4-week interval group]) versus longer treatment interval groups (62.1% [> 12-week interval group], difference = 13.2%, [95% confidence interval (CI) 1.06, 2.06], p = 0.01). Patients on a > 12-week interval were twice as likely to discontinue treatment compared with those on an 8-week interval (hazard ratio = 2.01 [95% CI 1.43, 2.82], p < 0.001). Patients with DME on longer anti-VEGF treatment intervals at 24 months consistently had higher discontinuation rates in the following years than those on shorter treatment intervals.


One-pot production of chitin with high purity from lobster shells using choline chloride-malonic acid deep eutectic solvent.
For the first time in this study, chitin was solely extracted from lobster shells through a fast, easy and eco-friendly method using deep eutectic solvents (DESs), consisting of mixtures of choline chloride-thiourea (CCT), choline chloride-urea (CCU), choline chloride-glycerol (CCG) and choline chloride-malonic acid (CCMA). The physiochemical properties of the isolated chitins were compared with those of the chemically prepared one and commercial one from shrimp shells. Results showed that CCT, CCU and CCG DESs had no important effect on the elimination of proteins and minerals, while chitin obtained by CCMA DES showed a high purity. The yield (20.63±3.30%) of chitin isolated by CCMA DES was higher than that (16.53±2.35%) of the chemically prepared chitin. The chitin obtained by CCMA DES could be divided into two parts with different crystallinity (67.2% and 80.6%), which also had different thermal stability. Chitin from lobster shells showed porous structure, which is expected to be used for adsorption materials and tissue engineering.


Colloids versus crystalloids for emergency patients.
Emergency as well as critical care nurses are often responsible for the administration and regulation of fluid resuscitation for their patients. A serious and potentially fatal decline in vital organ performance can often occur as a result of inappropriate volume management. However, emergency and/or critically ill patients who require fluid resuscitation often receive concurrent therapy and monitoring that may have equal or greater impact on the survival and therapeutic end points than does the type of fluid received. These variables have made historical comparisons of crystalloid versus colloid resuscitation difficult. The purpose of this article is to critique three articles that examine crystalloid and colloid resuscitation for patients with various disease processes.


Comparative Study of Collagen versus Synthetic-Based Meniscal Scaffolds in Treating Meniscal Deficiency in Young Active Population.
The aim of this study was to compare the effectiveness of 2 different meniscal scaffolds in treating patients with irreparable partial medial meniscal tear and patients complaining of pain in the medial compartment of the knee due to a previous partial medial meniscectomy. Based on previous studies, we hypothesized that both the scaffolds are effective in improving clinical outcomes in these patient populations. Twenty-eight patients underwent collagen-based medial meniscus implantation (CMI-Menaflex) and 25 with a second-generation scaffold (Actifit). All patients were assessed with Lysholm, Tegner scale, and MRI evaluation-preoperatively, at 6 months, at 12 moths, and followed-up for a minimum of 2 years. Second look arthroscopy and concomitant biopsy were performed in 7 and 12 patients of CMI and Actifit groups, respectively. The CMI group at final follow-up showed improvement in Lysholm score from 58.4 ± 17.3 to 94.5 ± 6.0, while the Actifit group showed improvement from 67.0 ± 15.7 to 90.3 ± 13.1; the improvement was statistically significant in both the groups but intergroup difference was not statistically significant (P = 0.1061). Tegner Activity Scale score improved in both the groups, but intergroup difference was not statistically significant (P = 0.5918). MRI evaluation showed in situ scaffold and no progression of degenerative arthritis in both the groups at final follow-up. Histological evaluation showed more fibrous tissue with blood vessels in the CMI group and the Actift group showed avascular cartilaginous features. Both the scaffolds are effective in improving patients' symptoms and joint function at short-term follow-up.


Phospholipase C-mediated hydrolysis of phosphatidylcholine is an important step in PDGF-stimulated DNA synthesis.
Recent evidence suggests the involvement of phosphatidylcholine (PC) hydrolysis both in the control of normal cell growth and in transformation. We show here that the simple exogenous addition of Bacillus cereus PC-hydrolyzing phospholipase C (PC-PLC) is sufficient to elicit a potent mitogenic response in Swiss 3T3 fibroblasts by a mechanism that is independent of protein kinase C. Our results on the additivity and synergism between B. cereus PC-PLC, PDGF, and insulin in the mitogenic response indicate that this novel phospholipid degradative pathway may be important in the mitogenic signaling cascade activated by PDGF.


The next generation personalized models to screen hidden layers of breast cancer tumorigenicity.
Breast cancer (BC) is a challenging disease and major cause of death amongst women worldwide who die due to tumor relapse or sidelong diseases. BC main complexity comes from the heterogeneous nature of breast tumors that demands customized treatments in the form of personalized medicine. Spatiotemporally dynamic and heterogeneous nature of BC tumors is shaped by their clonal evolution and sub-clonal selections and shapes resistance to collective or group therapies that drives cancer recurrence and tumor metastasis. Personalized intervention promises to administer medications that selectively target each individual patient tumor and even further each colonized secondary tumor. Such personalized regimens will require creation of in vitro and in vivo models genuinely recapitulating characteristics of each tumor type as initiating platforms for two main purposes: to closely monitor the tumorigenic processes that shape tumor heterogeneity and evolution as the main driving forces behind tumor chemo-resistance and relapse, and subsequently to establish patient-specific preventive and therapeutic measures. While application of tumor modeling for personalized drug screening and design requires a separate review, here we discuss the personalized utilities of xenograft modeling in investigating BC tumor formation and progression toward metastasis. We will further elaborate on the impact of innovative technologies on personalized modeling of BC tumorigenicity at improved resolution. Heterogeneous nature of each BC tumor requires personalized intervention implying that modeling breast tumors is inevitable for better disease understanding, detection and cure. Patient-derived xenografts are just the initiating piece of the puzzle for ideal management of breast cancer. Emerging technologies promise to model BC more personalized than before.


Effect of a Rule-in Biomarker Test on Pulmonary Nodule Management: A Survey of Pulmonologists and Thoracic Surgeons.
The field of biomarker development is evolving to assist in determining benign from malignant pulmonary nodules. Although a prospective clinical utility would best to show how a biomarker affects patient treatment and outcomes, we sought to begin to understand how the results might alter management by determining how physicians would use the results of a rule-in blood test to manage pulmonary nodules. Pulmonologists and thoracic surgeons in the American College of Chest Physicians clinician database were invited to participate in an online survey. The participant demographic data were collected. Four hypothetical clinical vignettes were presented. The participants accessed the pretest probability (probability of cancer [pCA]) for malignancy and chose the management strategies as the case progressed. The management strategies chosen before and after the result of a rule-in biomarker test were compared and assessed for guideline concordance. Of the 455 eligible participants who had opened the survey, 416 (92%) completed it: 332 pulmonologists and 84 thoracic surgeons. Although 91% of the participants were very comfortable managing nodules, depending on the case, 30% to 62% incorrectly assessed the pCA, with 22% to 62% overestimating the risk and 8% to 51% underestimating the risk. After a rule-in blood test result, the clinician change in management moved in the right direction in some cases but, in others, the physicians used the results incorrectly. Pulmonologists and thoracic surgeons differed in the management strategies, with surgeons recommending surgery more often. Although the use of biomarker testing for pulmonary nodule evaluation is promising, without proper physician education, the potential for harm exists. Clinical utility studies are needed to appropriately inform the effect of biomarker use.


No effect of moderate alcohol intake on the detection of concealed identity information in the laboratory.
The Concealed Information Test (CIT) enables the detection of certain (e.g., crime-relevant or personal) information, even if participants aim to conceal their knowledge. The current preregistered study investigated whether previously observed impairing effects of alcohol intoxication on participants' performance in a reaction time CIT (RT CIT) field study also translate to a laboratory environment. In contrast to the previous study of Suchotzki and Gamer (Sci Rep 8:7825, 2018) in which alcohol consumption was voluntary and self-administered, the current study used a randomized assignment of participants to either an alcohol group (n = 88; receiving a drink with 3 cl alcohol) or a sober control group (n = 89; receiving a drink with just some alcohol drops to hide group assignment). After drink administration, participants completed an RT CIT, in which they were instructed to hide knowledge of their own identity. Blood alcohol concentration (BAC) was estimated via breath alcohol ratio. In contrast to the previous field study, results revealed no differences in CIT-performance between intoxicated and sober participants. Aside from questioning the robustness of the result of the previous field study, our results also point to a number of interesting theoretical explanations for the discrepancy between both results, which are elaborated in the discussion.


Association of leg bias with bipedal speed and power in developing soccer players.
The aim of this research was to determine whether there is any association between leg bias and bipedal locomotion in young male soccer players. 227 participants, members of a Polish football club, were tested. Leg dominancy and maximal specific power of each leg were recorded.


Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten cases of an aggressive form of differentiated thyroid carcinoma.
In an attempt to advance and improve the characterization of the so-called diffuse follicular variant of papillary thyroid carcinoma (diffuse FVPTC) we studied a series of 59 thyroid carcinomas consecutively treated in a specialized center. The clinicopathologic and some of the immunohistochemical characteristics (uPA-R, Lewis X, Sialyl Lewis X, and MIB-1) of ten cases of FVPTC displaying a multinodular or diffuse pattern of growth, and histologic features similar to those previously described in diffuse FVPTC, were compared with those of common papillary thyroid carcinoma (PTC, 25 cases) and common FVPTC (8 cases). Cases of diffuse FVPTC differed significantly from common PTC and FVPTC in targeting younger patients and in exhibiting a prevalence of multicentricity, extrathyroid extension, nodal metastasis, and vascular invasion. Immunohistochemically, diffuse FVPTC cases were characterized by the overexpression of uPAR and sialyl Lewis X. No differences were observed regarding MIB 1 immunoreactivity. Regardless of the term used to designate the multicentric, invasive form of FVPTC (diffuse or multinodular FVPTC) it is crucial to acknowledge the existence of cases of FVPTC with a guarded prognosis that should be distinguished from the classic, uninodular form of FVPTC.


Triglyceride composition of bovine milk fat with elevated levels of linoleic acid.
The effect of increasing the linoleic acid (18:2) content of milk fat on the composition and structure of the triglycerides (TG) was investigated. Protected sunflower seed supplement was added to the diet of a cow grazing on pasture, and the structure and composition of the milk fat compared with the milk fat from its monozygous twin which had been fed a control diet. The relative proportions of TG fractions of high, medium, and low molecular weight in the milk fat with elevated levels of 18:2 (15.5% 18:2) were 43.0, 19.5, and 37.5 moles %, respectively, compared with 36.1, 19.7, and 44.2 moles %, respectively in the milk fat from the cow fed the control diet. Separation of these three TG fractions of each milk fat into TG classes with different levels of unsaturation showed that the milk fat with elevated levels of 18:2 contained higher proportions of diene, triene, and tetraene TG and correspondingly lower proportions of saturated and, to a lesser extent, monoene TG. The saturated and monoene TG from the two milk fats had similar fatty acid compositions. However, the diene TG of the 18:2-rich milk fat included high proportions of the combination of 18:2 with two saturated fatty acids (FA) which are minor constituents of normal milk fats. Likewise, the triene TG reflected the presence of 18:2 in combination with 18:1 and a saturated FA.


Base excision repair and cancer.
Base excision repair is the system used from bacteria to man to remove the tens of thousands of endogenous DNA damages produced daily in each human cell. Base excision repair is required for normal mammalian development and defects have been associated with neurological disorders and cancer. In this paper we provide an overview of short patch base excision repair in humans and summarize current knowledge of defects in base excision repair in mouse models and functional studies on short patch base excision repair germ line polymorphisms and their relationship to cancer. The biallelic germ line mutations that result in MUTYH-associated colon cancer are also discussed.


Limited Reliability of the Spot Urine Protein/Creatinine Ratio in the Longitudinal Evaluation of Patients With Lupus Nephritis.
Cross-sectional studies document that the spot protein/creatinine ratio (PCR) is often an inaccurate estimate of proteinuria magnitude compared with the 24-hour PCR, which is the gold standard. However, the extent to which the inaccuracy of the spot PCR varies over time and between individuals has not previously been reported. We address these crucial questions using a unique database, an National Institutes of Health trial in which lupus nephritis (LN) patients (N = 103) provided spot PCR testing each month and 24-hour PCR testing every 3 months for up to 15 months after induction therapy. A gold standard proteinuria trend line was constructed for each patient by joining the points that represented the serial 24-hour PCR values of the patient. The spot PCR values of the patient were then plotted in relationship to the 24-hour PCR trend line. Using our previous work, which estimated the 95% confidence intervals for the 24-hour PCR at specific levels, we determined in each patient whether the spot PCR values were "reliable," "problematic," or "unreliable." The sequential spot PCR of the patients deviated widely and often from the 24-hour PCR trend line, to the extent that, if the spot PCR results were used in real time for clinical decision-making, it was likely management errors would occur. Spot PCRs were reliable in 41%, problematic in 24%, and unreliable in 35% of patients. Those with unreliable spot PCRs could not be predicted and were more likely to respond poorly to treatment. The spot PCR should not be used for management of LN, and perhaps, other glomerulopathies.


Development of a new gas chromatography-mass spectrometry (GC-MS) methodology for the evaluation of 5α-reductase activity.
The androgens testosterone (T) and dihydrotestosterone (DHT) play a key role in the function and integrity of prostate tissue, but are also implicated in prostate cancer and benign prostatic hyperplasia (BPH). The reduction of androgen levels can be achieved by the inhibition of 3-oxo-5α-steroid-4-dehydrogenase (5α-reductase), which is responsible for the irreversible conversion of T into its more active metabolite DHT. In fact, the use of 5α-reductase inhibitors (RIs), like finasteride, can be a valuable strategy for the treatment of BPH and in chemoprevention of prostate tumors. In this work a new method based on a dispersive liquid-liquid microextraction (DLLME) procedure, followed by gas chromatography-mass spectrometry (GC-MS), to evaluate the 5α-reductase activity, by measuring the conversion percentage of T into DHT was optimized and validated. Enzymatic assays were carried out in human prostate microsomes, using T as substrate. T and DHT were extracted by the developed DLLME technique and quantified, after silylation, by GC-MS. Variables affecting the extraction efficiency and derivatization of T and DHT were evaluated. The optimized method showed good linearity (with correlation coefficients over 0.9994 for T and 0.9995 for DHT), good recoveries (higher than 80%), and good intra- and inter-day precision (below 13%, 3 levels, n=6). The detection limits for T and DHT were 0.5 nM and the limits of quantification were 5 nM. The new GC-MS method is a good alternative to the already described methods, to evaluate 5α-reductase activity, since it avoids the use of radioactive compounds and corresponds to a fast and sensitive methodology with a good extraction efficiency, accuracy and high recovery. As this method allows the evaluation of 5α-reductase activity, also permits the study of inhibitory efficacy of new molecules as potential RIs.


Label-free colorimetric detection of cancer related gene based on two-step amplification of molecular machine.
Highly sensitive detection of K-ras gene is of great significance in biomedical research and clinical diagnosis. Here, we developed a colorimetric biosensing system for the detection of proto-oncogene K-ras based on enhanced amplification effect of DNA molecular machine, where dual isothermal circular strand-displacement amplification (D-SDA) occurs on two arms in one-to-one correspondence. Specifically, we designed a primer-locked hairpin probe (HP) and a primer-contained linear polymerization template (PPT). In the presence of target gene, HP can hybridize with PPT, forming a DNA molecular machine with dual functional arms (called DFA-machine). Each of the two probes in this machine is able to be extended by polymerase on its counterpart species. Moreover, with the help of nicking endonuclease, the dual isothermal polymerization is converted into dual circular strand-displacement amplification, generating a large amount of anti-hemin aptamer-contained products. After binding to hemins, the aptamer/hemin duplex, horseradish peroxidase (HRP)-mimicking DNAzyme, was formed and catalyzed the oxidation of colorless ABTS by H2O2, producing a visible green color. The proposed colorimetric assay exhibits a wide linear range from 0.01 to 150nM with a low detection limit of 10pM. More interestingly, the mutations existing in target gene are easily observed by the naked eye. It should be noted that this colorimetric system was proved by the analysis of K-ras gene of SW620 cell lines. The simple and powerful DFA-machine is expected to provide promising potential in the sensitive detection of biomarkers for cancer diagnosis, prognosis and therapy.


Comparison of pulsed and pseudocontinuous arterial spin-labeling for measuring CO2 -induced cerebrovascular reactivity.
To compare the performance of pulsed and pseudocontinuous arterial spin-labeling (PASL and pCASL) methods in measuring CO(2) -induced cerebrovascular reactivity (CVR). Subjects were scanned using both ASL sequences during a controlled hypercapnia procedure and visual stimulation. CVR was computed as the percent CO(2) -induced increase in cerebral blood flow (Δ%CBF) per mmHg increase in end-tidal PCO(2) . Visually evoked responses were expressed as Δ%CBF. Resting CBF and temporal signal-to-noise ratio were also computed. Regionally averaged values for the different quantities were compared in gray matter (GM) and visual cortex (VC) using t-tests. Both PASL and pCASL yielded comparable respective values for resting CBF (56 ± 3 and 56 ± 4 mL/min/100g) and visually evoked responses (75 ± 5% and 81 ± 4%). Values of CVR determined using pCASL (GM 4.4 ± 0.2, VC 8 ± 1 Δ%CBF/mmHg), however, were significantly higher than those measured using PASL (GM 3.0 ± 0.6, VC 5 ± 1 Δ%CBF/mmHg) in both GM and VC. The percentage of GM voxels in which statistically significant hypercapnia responses were detected was also higher for pCASL (27 ± 5% vs. 16 ± 3% for PASL). pCASL may be less prone to underestimation of CO(2) -induced flow changes due to improved label timing control.


Glyph guessing for 'oo' and 'ee': spatial frequency information in sound symbolic matching for ancient and unfamiliar scripts.
In three experiments, we asked whether diverse scripts contain interpretable information about the speech sounds they represent. When presented with a pair of unfamiliar letters, adult readers correctly guess which is /i/ (the 'ee' sound in 'feet'), and which is /u/ (the 'oo' sound in 'shoe') at rates higher than expected by chance, as shown in a large sample of Singaporean university students (Experiment 1) and replicated in a larger sample of international Internet users (Experiment 2). To uncover what properties of the letters contribute to different scripts' 'guessability,' we analysed the visual spatial frequencies in each letter (Experiment 3). We predicted that the lower spectral frequencies in the formants of the vowel /u/ would pattern with lower spatial frequencies in the corresponding letters. Instead, we found that across all spatial frequencies, the letter with more black/white cycles (i.e. more ink) was more likely to be guessed as /u/, and the larger the difference between the glyphs in a pair, the higher the script's guessability. We propose that diverse groups of humans across historical time and geographical space tend to employ similar iconic strategies for representing speech in visual form, and provide norms for letter pairs from 56 diverse scripts.


Linkage analysis of the Rett syndrome using human chromosomal specific probes.
Restriction fragment length polymorphic (RFLP) human DNA probes have been used for linkage analysis in families with the Rett syndrome. A cytogenetic marker could be detected in 6 out of 14 cases of the Rett syndrome in the region of Xp22, and a deletion was seen in one severe case. Informative results were obtained with two of the chromosomal specific DNA probes, 99.6 and D2, in two different families.


Risk factors for anastomotic leakage after laparoscopic low anterior resection: A single-center retrospective study.
Anastomotic leakage (AL) is a serious complication affecting short-term and long-term outcomes in rectal cancer surgery. While laparoscopic low anterior resection is a widespread procedure, the risk factors for AL are not well established. This study aimed to evaluate risk factors for AL after laparoscopic low anterior resection with double stapling technique (DST) anastomosis. We performed a retrospective cohort study of laparoscopic low anterior resection with DST anastomosis for rectal cancer between January 2010 and February 2019. Finally, a total of 1197 patients were eligible for the study. Twenty-five variables were collected for univariate and multivariate analyses. AL occurred in 49 patients (4.1%). In multivariate analysis, blood loss (≥70 mL) and no defunctioning stoma were independent risk factors (odds ratio [OR] 2.23; 95% confidence interval [CI] 1.08-4.34; P = .030 and OR 3.15; 95% CI 1.66-6.37; P = .0003, respectively). In addition, risk factors for AL were analyzed in 601 patients without defunctioning stoma. As a result, AL occurred in 36 patients (6.0%) and multivariate analysis demonstrated that blood loss (≥70 mL) and anastomotic level from anal verge (<5 cm) were independent risk factors (OR 3.11; 95% CI 1.24-7.44; P = .016 and OR 2.33; 95% CI 1.14-4.69; P = .020, respectively). Laparoscopic low anterior resection is feasible and safe with a low AL rate. Important factors associated with AL were blood loss and defunctioning stoma. Without defunctioning stoma, blood loss and distal anastomosis are also important factors.


Staging surgery for intraventricular bilateral giant Rosai-Dorfman disease in children.
Rosai-Dorfman disease (RDD) is an uncommon, benign, and idiopathic histiocytic proliferative disorder. Multiple intracranial RDD is extremely rare and treatment varies. A 9-year-old girl was admitted with 3-month history of blurred vision and facial paralysis, a 2-month history of recurrent giggle, and cognitive impairment. Computed tomography and magnetic resonance imaging scans revealed bilateral ventricular masses based on the dural membrane and the diameters of the masses were 9.1 cm and 9.2 cm, respectively. The lesions were completely removed with staging surgeries. Fifteen months after operation, blurred vision was still present but facial paralysis and giggle and cognitive impairment disappeared. Imaging examinations suggested that there were no new or recurring lesions. For multiple large intracranial masses, surgical treatment is necessary and staged surgery benefits perioperative safety. Active follow-up with magnetic resonance imaging is necessary.


Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: insights from the SOLVD Treatment trial.
Angiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD). In the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤ 35% and serum creatinine level ≤ 2.5mg/dl were randomized to receive either placebo (n=1284) or enalapril (n=1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)). Overall, during 35 months of median follow-up, all-cause mortality occurred in 40% (502/1252) and 35% (440/1250) of placebo and enalapril patients, respectively (hazard ratio {HR}, 0.84; 95% confidence interval {CI}, 0.74-0.95; p=0.007). All-cause mortality occurred in 45% and 42% of patients with CKD (HR, 0.88; 95% CI, 0.73-1.06; p=0.164), and 36% and 31% of non-CKD patients (HR, 0.82; 95% CI, 0.69-0.98; p=0.028) in the placebo and enalapril groups, respectively (p for interaction=0.615). Enalapril reduced cardiovascular hospitalization in those with CKD (HR, 0.77; 95% CI, 0.66-0.90; p<0.001) and without CKD (HR, 0.80; 95% CI, 0.70-0.91; p<0.001). Among patients in the enalapril group, serum creatinine elevation was significantly higher in those without CKD (0.09 versus 0.04 mg/dl in CKD; p=0.003) during first year of follow-up, but there was no differences in changes in systolic blood pressure (mean drop, 7 mm Hg, both) and serum potassium (mean increase, 0. /L, both). Enalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD.


Efficacy of cold plasma in producing Salmonella-free duck eggs: effects on physical characteristics, lipid oxidation, and fatty acid profile.
Concerns related to foodborne pathogens necessitate the decontamination of avian eggs. Conventional decontamination methods, such as egg washing, usually use health-threatening chemicals (e.g. chlorine). Hence, innovative chemical-free decontamination approaches are interesting for the food industry, especially to decontaminate commonly Salmonella infected products such as duck eggs. The present study is the first attempt to evaluate the effectiveness of cold plasma against Salmonella enterica inoculated on the surface of duck eggshell. In this regard, Salmonella-contaminated duck eggs were treated by arc plasma for 10, 20, 30, and 40 s. The bacteria count, eggshell strength, color, pH, Haugh unit, acid value (AV), thiobarbituric acid reactive substances (TBARS), and fatty acid profile of the plasma-treated samples were then compared with those of untreated sample. According to the results, all the plasma treatments significantly decreased the Salmonella population and longer treatment times enhanced the bactericidal effects of plasma. A maximum bacterial reduction of 4.1 log cycle was observed when plasma was applied for 40 s. Furthermore, plasma treatments did not deteriorate the quality parameters of eggs such as eggshell strength, eggshell color, yolk color, Haugh unit, AV, and TBARS. These findings introduced arc plasma as an emerging tool for improving the safety of duck eggs with good potential for industrial application.


Multimodal management of patellar tendinopathy in basketball players: A retrospective chart review pilot study.
The aim of this observational study was to document changes in pain, dysfunction, and fear of movement in basketball players using a multimodal rehabilitation approach for managing patellar tendinopathy. A multimodal treatment approach was utilized with basketball athletes during a competitive season. Numeric pain rating scale (NPRS), Victorian Institute of Sport Assessment Patellar (VISA-P) questionnaire, and a Tampa Scale of Kinesiophobia were used as outcome measures to assess for patellar tendon pain and knee function. A single group, pre-test/post-test, de-identified, retrospective chart review was performed at the end of the season. Nine basketball players were diagnosed and treated for patellar tendinopathy during the course of a single season. VISA-P questionnaire scores were significantly higher at the end of the season, with a mean increase of 30 points (95% CI 22-38 p < 0.05). This magnitude of improvement exceeds the minimum clinically important difference of the VISA-P of 13 points. The NPRS during training over the previous week was significantly improved by 4.6 points (95% CI 2.6-6.6) from the start of treatment to the end of the season. Dry needling, Extracorporeal Shockwave Therapy (ESWT), hands on manual therapy, and corrective exercise may be safe and effective strategies to reduce patellar tendon pain and improve knee function. Future research involving a larger sample size, control group, and randomization is indicated.


Molecular patterning along the sea urchin animal-vegetal axis.
The molecular regulatory mechanisms underlying primary axis formation during sea urchin development have recently been identified. Two opposing maternally inherited systems, one animalizing and one vegetalizing, set up the animal-vegetal (A-V) axis. The vegetal system relies in part on the Wnt-beta-catenin-Tcf/Lef signaling pathway and the animal system is based on a cohort of animalizing transcription factors that includes members of the Ets and Sox classes. The two systems autonomously define three zones of cell-type specification along the A-V axis. The vegetalmost zone gives rise to the skeletogenic mesenchyme lineage; the animalmost zone gives rise to ectoderm; and the zone in which the two systems overlap generates endoderm, secondary mesenchyme, and ectoderm. Patterning along the A-V also depends on cellular interactions involving Wnt, Notch, and BMP signaling. We discuss how these systems impact the formation of the second axis, the oral-aboral axis; how they connect to later developmental events; and how they lead to cell-type-specific gene expression via cis-regulatory networks associated with transcriptional control regions. We also discuss how these systems may confer on the embryo its spectacular regulatory capacity to replace missing parts.


Merkel cell carcinoma: high recurrence rate despite aggressive treatment.
Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine cancer of the skin whose incidence has been increasing. The objective of the study was to evaluate current treatment modalities, including sentinel lymph node (SLN) biopsy and outcomes and identify prognostic factors in patients with MCC. A retrospective chart review of patients with MCC. Clinical, pathologic, treatment characteristics, disease status, and survival were collected. All slides were reviewed by a single pathologist, and additional pathologic elements were evaluated for prognosis. Twenty-six patients were identified in the study period. All patients were Caucasian with an average age of 71.3 y. Twenty-one patients had tumors in sun-exposed locations, and 13 had a prior history of skin cancer. All nonmetastatic patients underwent wide excision. SLN biopsy was successful in 19 patients. The SLN was positive in 21% of patients. Radiation therapy was used in 13 patients. Average follow-up was 26 mo, and median survival was 29 mo. Recurrence occurred in eight patients: four locoregional, two distant, one combined, and one unknown. Recurrence occurred in five patients with stage I disease. Five patients with negative SLN later developed recurrence. The presence of metastasis to the nodes was significant for recurrence. No other pathologic factor was found to have prognostic significance. Despite aggressive surgical and radiation treatment, MCC has a high rate of locoregional recurrence, even in early stage disease. SNLB is useful for the staging and management of patients. Further research is needed to identify better prognostic markers.


A case of solid-pseudopapillary neoplasm, focusing on contrast-enhanced endoscopic ultrasonography.
We used contrast-enhanced endoscopic ultrasonography (CE-EUS) to diagnose a case of solid-pseudopapillary neoplasm (SPN) in an adult man. A 58-year-old man was referred to our hospital because of a pancreatic mass found by positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) during a medical checkup in 2009. Trans-abdominal ultrasonography revealed a 24-mm hypoechoic mass at the pancreatic tail with calcification inside. Multiphasic computed tomography (CT) showed a solid mass with delayed enhancement. EUS revealed a hypoechoic mass without lateral shadowing, and neither a septum nor cystic component was detected. CE-EUS using Sonazoid(®) showed a hypovascular mass compared with the surrounding pancreatic parenchyma, and the inside of the mass was enhanced like an alveolus nest, suggesting pseudopapillary change. Diagnosis of a solid-pseudopapillary neoplasm and a concomitant small neuroendocrine tumor was made by distal pancreatectomy.


Endoscopic management of refractory leak and gastro-cutaneous fistula after laparoscopic sleeve gastrectomy: a randomized controlled trial.
Gastro-cutaneous fistula is a rare complication after laparoscopic sleeve gastrectomy (LSG) with incidence of occurrence 1-2%. Most of gastro-cutaneous fistulae do not respond to conservative management and need intervention either surgically or endoscopically. This prospective randomized clinical study included referred patients who had LSG performed at our department or other centers, and complicated with post-LSG leak or gastro-cutaneous fistula between December/2019 and March/2021. Included patients were ASA Physical status I-II. Primary and secondary outcomes were recurrence of the fistula and mortality in each group after the intervention during the 18 months follow-up period, respectively. Thirty patients were randomized into two groups: Surgery Group (SG, n = 15) and Endoscopy Group (EG, n = 15). Mean age of patients was 42.3 ± 8.7 and 42.6 ± 8.3 years-old in SG and EG, respectively. Females constituted 73.3% and 80% in SG and EG, respectively. Median time-to-gastric leak post LSG was six (range: 4-7) days in both groups. SG patients were surgically managed with primary repair of the gastric fistula and gastrojejunostomy in 13 patients or converting SG into Roux-en-Y gastric bypass in two patients, while EG patients were endoscopically managed with stitching, stenting, stenting and dilation, and clipping and dilation in 5, 4, 4 and 2 patients, respectively. Incidence of recurrent leak during 1st week was significantly higher in SG than EG (p < 0.001). No mortality reported in EG, while 2 patients died in SG (p = 0.48). Endoscopic intervention may offer a successful modality in managing post-LSG gastric leak and gastro-cutaneous fistula that do not respond to conservative measures in stable patients.


Beneficial effects of long-term administration of ONO-3144, a free radical scavenger, on stroke-prone SHR.
To clarify the preventive effects of ONO-3144, a free radical scavenger, on stroke-prone spontaneously hypertensive rats (SHRSP) and free radicals related to the hypertensive disorders. Drugs with powdered chow were administered orally to the rats from 2- to 14-month-old. Body weight, blood pressure, rectal temperature, oxygen consumption rate, thyroid hormones, lipids, platelet number, ocular fundus, autopsy, and life span were investigated. ONO-3144 did not affect the growth, blood pressure, concentrations of thyroid hormones and lipids in the blood, but decreased the rectal temperature and oxygen consumption rate. ONO-3144 also prevented the platelet number decrease, sclerotic change of retinal artery, edematous and hypertrophic changes in parenchymal and circulatory organs. Both the average life-span and the longest life time of SHRSP given 40 mg/kg ONO-3144 were longer than those of normotensive rats and no administration hypertensive rats. The oxidative f ree radicals closely relate to hypertension-induced pathophysiological changes in SHRSP, and ONO-3144 prevents the changes of those disorders, and then brings longevity.


Calcilytics inhibit the proliferation and migration of human prostate cancer PC-3 cells.
The carcinogenesis and development of prostate cancer are mediated by enhanced Ca2+ signaling. In the present study, the pharmacological profile of the Ca2+-sensing receptor (CaSR) antagonists (calcilytics) was examined in human prostate cancer PC-3 cells. NPS2143 and Calhex 231 blocked extracellular Ca2+-induced increases in cytosolic [Ca2+]. NPS2143 and Calhex 231 inhibited cell proliferation (IC50 = 7.4 and 10.3 μM, respectively) and migration. The exposure to NPS2143 or Calhex 231 down-regulated CaSR protein expression. These results demonstrated that calcilytics inhibited cell proliferation/migration and down-regulated CaSR expression in human prostate cancer cells, suggesting their potential as novel therapeutic drugs for prostate cancer.


Experimental investigation on the effect of liquid injection by multiple orifices in the formation of droplets in a Venturi scrubber.
Venturi scrubbers are widely utilized in gas cleaning. The cleansing elements in these scrubbers are droplets formed from the atomization of a liquid into a dust-laden gas. In industrial scrubbers, this liquid is injected through several orifices so that the cloud of droplets can be evenly distributed throughout the duct. The interaction between droplets when injected through many orifices, where opposite clouds of atomized liquid can reach each other, is to be expected. This work presents experimental measurements of droplet size measured in situ and the evidence of cloud interaction within a Venturi scrubber operating with multi-orifice jet injection. The influence of gas velocity, liquid flow rate and droplet size variation in the axial position after the point of the injection of the liquid were also evaluated for the different injection configurations. The experimental results showed that an increase in the liquid flow rate generated greater interaction between jets. The number of orifices had a significant influence on droplet size. In general, the increase in the velocity of the liquid jet and in the gas velocity favored the atomization process by reducing the size of the droplets.


[Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021, interpretation and expectation].
The Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021 (2021 guidelines) was recently released. The guidelines summarized the evidences from literatures up to July 2019, and composed by 6 parts as "screening and early treatment", "infection", "hemodynamic management", "ventilation", "additional therapies" and "long-term outcomes and goals of care" with a total of 93 items and 99 recommendations. Compared with the 2016 guidelines (96 recommendations), although the total number of recommendations in the 2021 guidelines is similar, the number of "strong recommendations (recommend)" in 2021 guidelines has dropped significantly, as the number of "weak recommendations (suggest)" has increased significantly, and the level of the quality of evidence on which the recommendations are based has been significantly lowered. Furthermore, 2021 guidelines have also markedly deleted or simplified the recommendations regarding infection prevention, acute respiratory distress syndrome (ARDS) treatment, nutritional support and so on. While, the most obvious improvement appears in the segment of "long-term outcomes and goals of care", in which the patients and their families could get help in term of determining their physical rehabilitation and discharge follow-up plans and formulating exact goals of care. 2021 guidelines did not adopt new and emerging therapies or treatments, such as metagenomic next-generation sequencing (mNGS), diaphragm protective ventilation, timing of initiating renal replacement therapy for acute kidney injury, early mobility, endotoxin adsorption, tranexamic acid, E-medicine and telemedicine, big data and artificial intelligence and other new therapies. Collectively, it may suggest the 2021 guidelines tend to be conservative and simplified rather than fairly optimized and logicalized, which may arouse controversy in the future and affect clinician compliance.


Negative regulation of multifunctional Ca2+/calmodulin-dependent protein kinases: physiological and pharmacological significance of protein phosphatases.
Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) play pivotal roles in intracellular Ca2+ signaling pathways. There is growing evidence that CaMKs are involved in the pathogenic mechanisms underlying various human diseases. In this review, we begin by briefly summarizing our knowledge of the involvement of CaMKs in the pathogenesis of various diseases suggested to be caused by the dysfunction/dysregulation or aberrant expression of CaMKs. It is widely known that the activities of CaMKs are strictly regulated by protein phosphorylation/dephosphorylation of specific phosphorylation sites. Since phosphorylation status is balanced by protein kinases and protein phosphatases, the mechanism of dephosphorylation/deactivation of CaMKs, corresponding to their 'switching off', is extremely important, as is the mechanism of phosphorylation/activation corresponding to their 'switching on'. Therefore, we focus on the regulation of multifunctional CaMKs by protein phosphatases. We summarize the current understanding of negative regulation of CaMKs by protein phosphatases. We also discuss the biochemical properties and physiological significance of a protein phosphatase that we designated as Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP), and those of its homologue CaMKP-N. Pharmacological applications of CaMKP inhibitors are also discussed. These compounds may be useful not only for exploring the physiological functions of CaMKP/CaMKP-N, but also as novel chemotherapies for various diseases.


Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies.
Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies. Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available. Forty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P = 0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P < 0.01); otherwise, the groups were similar. Time to discontinuation analysis, which accounts for efficacy, safety and tolerability, revealed a lower early pimavanserin discontinuation rate and a higher late pimavanserin discontinuation rate (HR < 1 before day 43, HR > 1 after day 43; P = 0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P = 0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P = 0.001). Accounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term.


Development of human precision grip. IV. Tactile adaptation of isometric finger forces to the frictional condition.
The adaptation of the grip forces to the frictional condition between the digits and an object relies on feedforward sensorimotor mechanisms that use tactile afferent input to intermittently update a sensorimotor memory that controls the force coordination, i.e., the ratio between grip force (normal to the grip surface) and load force (tangential to the grip surface). The present study addressed the development of these mechanisms. Eighty-nine children and 15 adults lifted an instrumented object with exchangeable grip surfaces measuring the grip and load forces. Particularly in trials with high friction (sandpaper), the youngest children used a high grip force to load force ratio. Although this large safety margin against slips indicated an immature capacity to adapt to the frictional condition, higher grip forces were produced for more slippery material (silk versus sandpaper). The safety margin decreased during the first 5 years of age, in parallel with a lower variability in the grip force and a better adaptation to the current frictional condition. The youngest children (18 months) could adapt the grip force to load force ratio to the frictional condition in a series of lifts when the same surface structure was presented in blocks of trials, but failed when the surface structure was unpredictably changed between subsequent lifts. The need for repetitive presentation suggests a poor capacity to form a sensorimotor memory representation of the friction or an immature capacity to control the employed ratio from this representation. The memory effects, reflected by the influences of the frictional condition in the previous trial, gradually increased with age. Older children required a few lifts and adults only one lift to update their force coordination to a new friction. Hence, the present finding suggests that young children use excessive grip force, a strategy to avoid frictional slips, to compensate for an immature tactile control of the precision grip.


Cord blood stem cell-generated KIR+NK cells effectively target leukemia cell lines.
Acute lymphoid (ALL) and myeloid leukemia (AML) are known to be invasive and highly lethal hematological malignancies. Because current treatments are insufficient and have a variety of side effects, researchers are looking for new and more effective therapeutic methods. Interestingly, ongoing efforts to find the best approach to optimize NK cell anti-leukemia potential shed light on the successful treatment of cancer. Mature KIR+NK cells ability to remove HLA Class-I deficient cells has been exploited in cancer immunotherapy. Here, we generated KIR+NK cells from cord blood stem cells using IL-2 and IL-15 cytokines. Our finding underlined the importance of KIR expression in the cytotoxic function of NK cells. Taken together, this study presented an effective in vitro method for the expansion and differentiation of KIR+NK cells using cytokines without any feeder cells. Furthermore, the presented culture condition could be useful for the generation of mature and pure NK cells from limited numbers of CD34+ cord blood cells and might be used as a novel method to improve the current state of cancer therapy.


Quantum capacities of transducers.
High-performance quantum transducers, which faithfully convert quantum information between disparate physical carriers, are essential in quantum science and technology. Different figures of merit, including efficiency, bandwidth, and added noise, are typically used to characterize the transducers' ability to transfer quantum information. Here we utilize quantum capacity, the highest achievable qubit communication rate through a channel, to define a single metric that unifies various criteria of a desirable transducer. Using the continuous-time quantum capacities of bosonic pure-loss channels as benchmarks, we investigate the optimal designs of generic quantum transduction schemes implemented by transmitting external signals through a coupled bosonic chain. With physical constraints on the maximal coupling rate [Formula: see text], the highest continuous-time quantum capacity [Formula: see text] is achieved by transducers with a maximally flat conversion frequency response, analogous to Butterworth electric filters. We further investigate the effect of thermal noise on the performance of transducers.


["Hot-water epilepsy ", "warm-water epilepsy", or bathing epilepsy? Report of three cases and considerations regarding an old theme].
Partial and generalized tonic-clonic reflex seizures related to hot water bathing have been described as temperature-related. We describe three cases of bathing epilepsy: a 28 year-old white male and a 30 year-old white female with spells triggered either by warm or hot water, and a 32 year-old female with spells triggered by hot water. The later two of the three cases presented localized epilepsy and a familial history of epilepsy. A complex tactile stimuli might play the most relevant role on seizure triggering, as well as water temperature with an additive effect over cutaneous stimulation.


Cis-diamminedichloroplatinum II in advanced urothelial cancer.
Thirteen patients with advanced urothelial cancer received a minimum of 2 courses of cis-diamminedichloroplatinum II. Of these patients 6 (46 per cent) achieved a partial response with an average duration of more than 6 months. One patient has received cis-diamminedichloroplatinum for more than 1 year and has no clinical evidence of tumor (complete response in lung metastasis plus excision of local recurrence). The routine administration of intravenous fluids and mannitol immediately before cis-diamminedichloroplatinum prevented the nephrotoxicity associated with this drug. An outpatient setting was well tolerated in most instances. This report confirms the activity of cis-diamminedichloroplatinum in urothelial cancer and suggests its use as an adjuvant to operation and/or radiotherapy in selected cases.


A model of Martian surface chemistry.
Alkaline earth and alkali metal superoxides and peroxides, gamma-Fe2O3 and carbon suboxide polymer are proposed to be constituents of the Martian surface material. These reactive substances explain the water modified reactions and thermal behaviors of the Martian samples demonstrated by all of the Viking Biology Experiments. It is also proposed that the syntheses of these substances result mainly from electrical discharges between wind-mobilized particles at Martian pressures; plasmas are initiated and maintained by these discharges. Active species in the plasma either combine to form or react with inorganic surfaces to create the reactive constitutents.


Experimental immunohistochemical studies on the substance P neuron system in the lateral habenular nucleus of the rat: distribution and origins.
We examined the distribution and afferent projections of substance P-like immunoreactive (SPI) fibers in the lateral habenular nucleus of the rats by using the indirect immunofluorescence method. On the basis of the distribution, a dense plexus of SPI fibers in the lateral habenular nucleus (LHb) could be divided into two parts: medial (mLHb) and lateral (lLHb). The present study demonstrates that SPI fibers in the lLHb originate from SPI cells in the rostral entopeduncular nucleus (rEP) and the adjacent area, while those in the mLHb originate from SPI cells in the medial habenular nucleus. Moreover, we showed that the axons from SPI cells in the rEP reached the lLHB via the "pallidohabenular tract."


Current event-free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia.
Imatinib is an effective tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML) in chronic phase (CP). Although some patients may fail on therapy with imatinib, effective salvage therapy is available with second-generation TKIs. Current measurement of efficacy for each therapy is judged by its individual impact on overall survival and event-free survival (EFS). In total, 586 patients with CML in CP who received imatinib were included in this analysis in 2 cohorts: imatinib as front-line therapy (n = 281) or after failure on interferon-α (IFN-α) (n = 305). By accounting for successful salvage treatment (ie, regain of complete cytogenetic response), the current EFS (CEFS) rate was calculated to obtain a more accurate impression of the outcome of patients with CML who received treatment with sequential TKIs. For patients who received imatinib after failing on IFN-α, the 7-year EFS rate was 61%, whereas the CEFS rate was 69%. The 7-year EFS rate for patients who received imatinib as initial therapy was 81% compared with a 7-year CEFS rate of 88%. CEFS provided a more accurate representation of the outcome of patients with CML in CP. These patients may frequently be treated successfully with subsequent TKIs after experiencing failure on the first TKI.


Selective recruitment of nucleoporins on vaccinia virus factories and the role of Nup358 in viral infection.
Vaccinia virus (VACV), a member of the Poxviridae family, uses cytoplasmic factories for its replication. Recent studies indicated that VACV infection requires a set of nucleoporins. However, how the nucleoporins contribute to viral life cycle remains unclear. Here, we report that the nucleoporins Nup62 and Nup358 localize to the cytoplasmic viral factories (VFs). Nup358 was targeted to the VFs at 6h post-infection (hpi), whereas Nup62, along with the previously reported translation factors such as eIF4E, eIF3η and G3BP1, was recruited to the VFs at 8 hpi. Nup358 depletion led to a decrease in the size and number of viral factories and reduction in viral yield. Further studies showed that Nup358 is involved in recruiting Nup62 and eIF4E to the VFs. Collectively, our results reveal spatio-temporal regulation in the recruitment of nucleoporins and translation factors to VFs, and particularly the importance of Nup358 in VACV infection.


Poly-γ-glutamic acid/chitosan nanogel greatly enhances the efficacy and heterosubtypic cross-reactivity of H1N1 pandemic influenza vaccine.
In 2009, the global outbreak of an influenza pandemic emphasized the need for an effective vaccine adjuvant. In this study, we examined the efficacy of poly-γ-glutamic acid/chitosan (PC) nanogel as an adjuvant for the influenza vaccine. PC nanogel significantly enhanced antigen-specific cross-presentation and cytotoxic T lymphocyte (CTL) activity. Compared with alum, the protective efficacy of the pandemic H1N1 influenza (pH1N1) vaccine was substantially increased by PC nanogel, with increased hemagglutination-inhibition titers, CTL activity, and earlier virus clearance after homologous and heterosubtypic [A/Philippines/2/82 (H3N2)] virus challenges. However, CD8+ T cell-depleted mice displayed no protection against the heterosubtypic virus challenge after immunization with PC nanogel-adjuvanted pH1N1 vaccine. We also observed that using PC nanogel as a vaccine adjuvant had a dose-sparing effect and significantly enhanced the long-lasting protection of the pH1N1 vaccine. Together, these results suggest that PC nanogel is a promising vaccine adjuvant that could broadly prevent influenza virus infection.


Oxidative stress and pathological changes after coronary artery interventions.
Oxidative stress greatly influences the pathogenesis of various cardiovascular disorders. Coronary interventions, including balloon angioplasty and coronary stent implantation, are associated with increased vascular levels of reactive oxygen species in conjunction with altered endothelial cell and smooth muscle cell function. These alterations potentially lead to restenosis, thrombosis, or endothelial dysfunction in the treated artery. Therefore, the understanding of the pathophysiological role of reactive oxygen species (ROS) generated during or after coronary interventions, or both, is essential to improve the success rate of these procedures. Superoxide O2(·-) anions, whether derived from uncoupled endothelial nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, xanthine oxidase, or mitochondria, are among the most harmful ROS. O2(·-) can scavenge nitric oxide, modify proteins and nucleotides, and induce proinflammatory signaling, which may lead to greater ROS production. Current innovations in stent technologies, including biodegradable stents, nitric oxide donor-coated stents, and a new generation of drug-eluting stents, therefore address persistent oxidative stress and reduced nitric oxide bioavailability after percutaneous coronary interventions. This review discusses the molecular mechanisms of ROS generation after coronary interventions, the related pathological events-including restenosis, endothelial dysfunction, and stent thrombosis-and possible therapeutic ways forward.


Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens.
Organophosphate-induced delayed neuropathy (OPIDN) is pathologically characterized by the swollen axon containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles. At present, the exact mechanism of OPIDN is unclear and the effective therapeutic methods is not available to counter this syndrome. Recent studies had shown that the autophagy was involved in OPIDN. The adipocytokine Apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous system. Recent researches illuminated that Apelin was neuroprotective factor and Apelin could regulate the autophagy in vivo and vitro model. So we investigated the effect of Apelin-13 on the OPIDN induced by Tri-ortho-cresyl phosphate (TOCP) in hens and explored the role of autophagy in Apelin-13 preventing OPIDN. Adult Roman hens were given a single dose of 750 mg/kg TOCP by gavage for 21 days to induce OPIDN, and neural dysfunction were detected, and the formation of autophagosomes in spinal cord neurons was observed by transmission electron microscopy, and the molecular markers of autophagy microtubule-associated protein light chain-3 (LC3) and the autophagy substrates p62/SQSTM1 were determined by Western blot analysis. The results demonstrated that the obvious neurological dysfunction such as hindlimb paralysis and paralysis of gait was present, the number of autophagosomes in the neurons of spinal cords was significantly increased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly increased in the OPIDN model group compared with the control group. Compared with the OPIDN model group, the neurological dysfunction of tens was obviously reduced, the clinical signs scores was significantly decreased, the number of autophagosomes in the neurons of hen spinal cords was significantly decreased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly decreased in Apelin-13 treatment group. Our results suggested that Apelin-13 prevented against the OPIDN induced by TOCP in hens, which the mechanism might be associated with regulation autophagy flux by Apelin-13.


Program development for leaders in the post-truth era: Arts-based creative leadership communication program.
Developments in media and communication technologies welcomed a new era, defined as post-truth, implying a general distancing from truth, where fake or speculative messages can be instantly shared by a vast audience. In this era, we need leaders with strong emotional and social skills to create a positive and ethical impact in society. In this study, due to the requirements of the Post-Truth Era which necessitates a new approach to leadership development, an arts-based learning intervention entitled Arts-Based Creative Leadership Communication Program is designed for leaders with three main objectives to increase, firstly, their creative communication skills; secondly, healing effect of arts for their resilience; and, thirdly, their social sensitivity through arts. After the design and implementation of this program, its targeted effects on the participants were analyzed. Results indicated that all of the expected outcomes were achieved successfully. The highest development was seen in the healing effect, while change in social sensitivity appeared as the lowest. Emotional skills as non-verbal communication element was developed more than social skills. Meanwhile, the emergence of the pandemic with its digital transformation process increased the effects of the program. To sum up, the program was found successful for the leaders in the Post-Truth Era.


Effect of Bluetooth headset and mobile phone electromagnetic fields on the human auditory nerve.
The possibility that long-term mobile phone use increases the incidence of astrocytoma, glioma and acoustic neuroma has been investigated in several studies. Recently, our group showed that direct exposure (in a surgical setting) to cell phone electromagnetic fields (EMFs) induces deterioration of auditory evoked cochlear nerve compound action potential (CNAP) in humans. To verify whether the use of Bluetooth devices reduces these effects, we conducted the present study with the same experimental protocol. Randomized trial. Twelve patients underwent retrosigmoid vestibular neurectomy to treat definite unilateral Ménière's disease while being monitored with acoustically evoked CNAPs to assess direct mobile phone exposure or alternatively the EMF effects of Bluetooth headsets. We found no short-term effects of Bluetooth EMFs on the auditory nervous structures, whereas direct mobile phone EMF exposure confirmed a significant decrease in CNAPs amplitude and an increase in latency in all subjects. The outcomes of the present study show that, contrary to the finding that the latency and amplitude of CNAPs are very sensitive to EMFs produced by the tested mobile phone, the EMFs produced by a common Bluetooth device do not induce any significant change in cochlear nerve activity. The conditions of exposure, therefore, differ from those of everyday life, in which various biological tissues may reduce the EMF affecting the cochlear nerve. Nevertheless, these novel findings may have important safety implications.


Behavioral characteristics of SART-stressed mice in the forced swim test and drug action.
SART-stressed (repeated cold-stressed) mice exhibited shortened immobility time in forced swimming tests, and a time-dependent increase in the duration of immobility time of stressed mice was less compared to unstressed mice. These changes were blocked by diazepam and alprazolam without influence on the immobility time of unstressed mice. The shortening of immobility time caused by SART stress was inhibited by repeated pretreatment with imipramine and mianserin, but not by a single dose. In contrast, neither single nor repeated administrations of lithium carbonate had effect on the immobility time of SART-stressed mice. The SART stress technique may be a potential model to investigate the relationship between stress and depression with complex symptoms like excessive emotion- and anxiety-related depression.


Prediction of primary vs secondary hypertension in children.
Despite current guidelines, variability exists in the workup of hypertensive children due to physician preferences. The study evaluates primary vs secondary hypertension diagnosis from investigations routinely performed in hypertensive children. This retrospective study included children 5 to 19 years with primary and secondary hypertension. The proportions of abnormal laboratory and imaging tests were compared between primary and secondary hypertension groups. Risk factors for primary vs secondary hypertension were evaluated by logistic regression and likelihood function analysis. Patients with secondary hypertension were younger (5-12 years) and had a higher proportion of abnormal creatinine, renal ultrasound, and echocardiogram findings. There was no significant difference in abnormal results of thyroid function, urine catecholamines, plasma renin, and aldosterone. Abnormal renal ultrasound findings and age were predictors of secondary hypertension by regression and likelihood function analysis. Children aged 5 to 12 years with abnormal renal ultrasound findings and high diastolic blood pressures are at higher risk for secondary hypertension that requires detailed evaluation.


A systematic survey of face stimuli used in psychological research 2000-2020.
For decades, psychology has relied on highly standardized images to understand how people respond to faces. Many of these stimuli are rigorously generated and supported by excellent normative data; as such, they have played an important role in the development of face science. However, there is now clear evidence that testing with ambient images (i.e., naturalistic images "in the wild") and including expressions that are spontaneous can lead to new and important insights. To precisely quantify the extent to which our current knowledge base has relied on standardized and posed stimuli, we systematically surveyed the face stimuli used in 12 key journals in this field across 2000-2020 (N = 3374 articles). Although a small number of posed expression databases continue to dominate the literature, the use of spontaneous expressions seems to be increasing. However, there has been no increase in the use of ambient or dynamic stimuli over time. The vast majority of articles have used highly standardized and nonmoving pictures of faces. An emerging trend is that virtual faces are being used as stand-ins for human faces in research. Overall, the results of the present survey highlight that there has been a significant imbalance in favor of standardized face stimuli. We argue that psychology would benefit from a more balanced approach because ambient and spontaneous stimuli have much to offer. We advocate a cognitive ethological approach that involves studying face processing in natural settings as well as the lab, incorporating more stimuli from "the wild".


Effect of Dermacentor albipictus (Acari:Ixodidae) on blood composition, weight gain and hair coat of moose, Alces alces.
The physiological effects of the winter tick, Dermacentor albipictus, on moose, Alces alces, were investigated. Blood composition, weight gain, food intake and change in the hair coat of moose calves, four infested with D. albipictus larvae, and eight uninfested, were monitored. Infested moose groomed extensively, apparently in response to feeding nymphal and adult ticks, and developed alopecia. Other clinical signs included: chronic weight loss, anemia, hypoalbuminemia, hypophosphatemia, and transient decreases in serum aspartate transaminase and calcium during the period of nymphal and adult female tick engorgement. Infested animals did not become anorexic. Two moose with severe hair loss had increases in gamma globulin shortly after the onset of female tick engorgement. Results suggest that alopecia is associated with tick resistance. Animals that groom and develop hair loss likely carry fewer ticks and therefore suffer less severely from blood loss.


Prospective Exploratory Study of the Effects of Postoperative Endocrine Medication on the Endometrium in Breast Cancer Patients.
This study aimed to investigate the pathological effects of long-term postoperative endocrine medication on the endometrium in breast cancer patients. Data of 99 patients with primary breast cancer who underwent hysteroscopy and obtained endometrial biopsy from 1 June 2018 to 31 December 2021 at the Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital were prospectively collected. Hysteroscopy was performed followed by endometrial histopathological examination in 99 breast cancer patients, including 44 taking tamoxifen (TAM), 26 taking other endocrine drugs, and 29 not taking endocrine drugs. The endometrial thickness in the TAM group was significantly higher than that in the other endocrine drug groups and the group not taking endocrine drugs (p=0.017). The receiver operating characteristic curves for the abnormal premenopausal endometrial thickening were plotted in this study; an endometrial thickness of 15.5 mm seen on ultrasound could be used as the most accurate ultrasound diagnostic threshold for the diagnosis of abnormal premenopausal endometrial hyperplasia, with an area under the curve of 0.888 (95% CI: 0.716, 1.000), a sensitivity of 100%, and a specificity of 75%, which was consistent with the results of our previous retrospective study. An endometrial thickness of ≥5 mm in postmenopausal women with breast cancer taking TAM was still used as the cut-off value for routine ultrasound diagnosis of abnormal postmenopausal endometrial hyperplasia. An ultrasound endometrial thickness (proliferative phase) of >15 mm in premenopausal patients can be used as the most accurate ultrasound diagnostic threshold for the diagnosis of abnormal endometrial hyperplasia. After menopause, an ultrasound endometrial thickness of ≥5 mm is still used as the criterion for diagnosing abnormal endometrial hyperplasia. Older patients should be monitored for signs of vaginal bleeding and fluid discharge, and hysteroscopy should be performed if necessary to ascertain the endometrial condition.


Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance.
Inactivation of the tumour-suppressor gene p53 has been demonstrated in a variety of human tumours. We extracted DNA from paraffin-embedded tissues of 67 ovarian carcinoma samples (54 primary tumours, seven metastases and six tumours obtained after chemotherapy), and analysed allelic losses and mutations of the p53 gene using single-strand conformation polymorphism (SSCP) analysis of DNA fragments amplified by a polymerase chain reaction (PCR). Allelic loss was observed in 24 of 32 informative cases. The mutation was detected in 14 of 54 primary ovarian carcinomas: eight serous cystadenocarcinomas (SCA), 42%), five endometrioid adenocarcinomas (EA, 42%) and one mucinous cystadenocarcinoma (14%). The incidence of the alteration was higher in SCA and EA than in other histological types, but the difference was not statistically significant. The incidence of p53 gene abnormalities in ovarian carcinomas tended to be increased in patients with disease advanced (over FIGO stage II). Mutations were found in exons 5 and 7 only and consisted mainly of single nucleotide substitutions [9 or 14 (64%) in exon 7; 4 of 14 (29%) in exon 5]. In 13 of 14 cases, p53 gene mutations occurred concomitantly with losses of the normal allele. The status of the p53 gene in metastases and the tumours obtained after chemotherapy was identical to that in the primary tumours. The presence of p53 gene mutation did not correlate with histological grade, response to primary therapy and survival. These findings suggest that mutational alterations of the p53 gene are involved in the development of a significant proportion of some ovarian carcinomas (SCAs or EAs), especially in advanced stages. However, they may not be a marker predicting the biological behaviour or the outcome of the disease.


Preliminary Study on Quantitative Assessment of the Fetal Brain Using MOLLI T1 Mapping Sequence.
Prenatal quantitative evaluation of myelin is important. However, few techniques are suitable for the quantitative evaluation of fetal myelination. To optimize a modified Look-Locker inversion recovery (MOLLI) T1 mapping sequence for fetal brain development study. Prospective observational preliminary cohort study. A total of 71 women with normal fetuses divided into mid-pregnancy (gestational age 24-28 weeks, N = 25) and late pregnancy (gestational age > 28 weeks, N = 46) groups. A 3 T/MOLLI sequence. T1 values were measured in pedunculus cerebri, basal ganglia, thalamus, posterior limb of the internal capsule, temporal white matter, occipital white matter, frontal white matter, and parietal white matter by two radiologists (11 and 16 years of experience, respectively). The Kruskal-Wallis test was used for reginal comparison. For each region of interest (ROI), differences in T1 values between the mid and late pregnancy groups were assessed by the Mann Whitney U test. Pearson correlation coefficients (r) were used to evaluate the correlations between T1 values and gestational age for each ROI. Intraobserver and interobserver agreement was determined by the intraclass correlation coefficient (ICC). A P value <0.05 was considered statistically significant. Interobserver and intraobserver agreements of T1 were good for all ROIs (all ICCs > 0.700). There were significant differences in T1 values between lobal white matter and deep regions, respectively. Significant T1 values differences were found between middle and late pregnancy groups in pedunculus cerebri, basal ganglion, thalamus, posterior limb of the internal capsule, temporal, and occipital white matter. The T1 values showed significantly negative correlations with gestational weeks in pedunculus cerebri (r = -0.80), basal ganglion (r = -0.60), thalamus (r = -0.68), and posterior limb of the internal capsule (r = -0.77). The T1 values of fetal brain may be assessed using the MOLLI sequence and may reflect the myelination. 3 TECHNICAL EFFICACY: Stage 2.


An ultrastructural study of pulmonary capillary vessels in blood volume-overloaded rat.
Blood volume overload to pulmonary capillaries was experimentally induced by arterio-venous fistula between the left common carotid artery and the left external jugular vein in 42 S-D rats. The animals were sacrificed 1,2,4,8 and 24 weeks after the operation. Just after anastomosis, blood flow index of the shunted rats was about 4 times larger than in the controls and the high value was kept throughout the experiment (p less than 0.05). The relative right ventricular weight was about 1.5 times larger than in the controls (p less than 0.05). The capillary endothelium of the alveolar septum showed nuclear enlargement, swelling of the cytoplasm with microvillous projection, and increases of pinocytotic vesicles and microfilaments. In some cases, focal edema was seen accompanied with an increase of immature stromal cells. The basement membrane showed vague in contour in edematous area, especially in the epithelial side of the alveolar septum. These changes appeared most predominantly in 2 weeks and subsided almost completely in 24 weeks. Number of endothelial nucleus of the shunted rats increased significantly in 2 and 4 weeks and was normalized in 24 weeks. The surface area and volume of the capillaries also increased significantly in 2 and 4 weeks of the shunted animals. These findings showed that the capillary endothelium reacted and then was adapted to the blood volume overload.


Serum p53 antibodies detection in oral squamous cell carcinoma, oral potentially malignant disorders and healthy individuals: A multicentre study.
To detect antibodies against p53 in serum of patients of oral squamous cell carcinoma and oral potentially malignant disorders compared to healthy individuals. The descriptive cross-sectional study was conducted at the departments of Oral and Maxillofacial Surgery, Peshawar Dental College, Peshawar, Khyber College of Dentistry, Peshawar, and the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from April, 2016 to March, 2017, and comprised serum of oral squamous cell carcinoma patients in group A, oral potentially malignant disorder patients in group B and healthy individuals in group C. Serum concentrations of anti-p53 antibodies were determined by enzyme-linked immunosorbent assay. Data was analysed using SPSS 20. Of the180 subjects, there were 60(33.3%) in each of the three groups. Circulating serum p53 antibodies were detected in 59(98.3%) cases in group A, 58(96.6%) in group B and in 20(33.3%) individuals in group C (p=0.001). The expression of circulating p53 antibodies in serum samples of squamous cell carcinoma and oral potentially malignant disorders patients indicates the potential to be a probable candidate for being taken as a diagnostic or prognostic biomarker.


Treatment with COLchicine in hospitalized patients affected by COVID-19: The COLVID-19 trial.
To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F<275 mmHg (P=0.005), AST>40 U/L (P<0.001), pre-existent heart (P=0.02), lung (P=0.003), upper-gastrointestinal (P=0.014), lower-gastrointestinal diseases (P=0.009) and cancer (P=0.008) were predictive of achieving the primary outcome. Diarrhoea (9.1% vs 0%, p=0.0031) and increased levels of AST at 6 days (76.9±91.8 vs 33.5±20.7 U/l, P=0.016) were more frequent in the colchicine group. Colchicine did not reduce the rate and the time to the critical stage. Colchicine was relatively safe although adverse hepatic effects require caution. We confirm that older (>60 years) patients with comorbidities are characterized by worse outcome.


Triptonide, a Diterpenoid Displayed Anti-Inflammation, Antinociceptive, and Anti-Asthmatic Efficacy in Ovalbumin-Induced Mouse Model.
The present study was intended to explore the valuable effects of triptonide on inflammation, asthmatic, and nociceptive. Triptonide possesses numerous beneficial effects extensively managed in the treatment of inflammation disease condition. Initially, triptonide showed anti-inflammation properties over lipopolysaccharide-induced RAW 264.7 cells. Hence, the present study was directed to explore the protecting efficacy of triptonide in ovalbumin (OVA)-induced asthma in mice. Asthma was induced intraperitoneally administration (200μL) in female BALB/c mice with suspension which has ovalbumin (100 μg/mL) and aluminum hydroxide (10 mg/mL). Triptonide (30 mg/kg) over OVA-induced experimental animals altered lung mass, nitric oxide, myeloperoxidase, immunoglobulin E status, interleukins (4, 5, and 13) inflammatory cytokines status, and histological modifications. Animals were also managed with the standard drug dexamethasone (50 mg/kg) followed by the asthma induction, which is also efficient over OVA-induced experimental animals. The nociception was provoked in male Swiss mice by various chemicals (acetic acid, capsaicin, and glutamate). The animals were administered with triptonide (5, 10, and 15 mg/kg) and separate standard drugs like diclofenac sodium (10 mg/kg) and morphine (5 mg/kg) over chemical-induced nociceptive animals. The present outcome evidently established that the triptonide considerably reduced the various chemical-induced nociception in mice (Fig. 7A, B, and C). Ultimately, the present work explored the evident powerful anti-inflammation, antinociceptive, and anti-asthma properties of a diterpenoid, triptonide experimental animal models. And it is recommended that triptonide is an excellent compound in the management of asthma and its related diseases.


Bioavailability and biodegradation of nonylphenol in sediment determined with chemical and bioanalysis.
The surfactant nonylphenol (NP) is an endocrine-disrupting compound that is widely spread throughout the environment. Although environmental risk assessments are based on total NP concentrations, only the bioavailable fraction possess an environmental risk. The present study describes the bioavailability and biodegradability of NP over time in contaminated river sediment of a tributary of the Ebro River in Spain. The bioavailable fraction was collected with Tenax TA(R) beads, and biodegradation was determined in aerobic batch experiments. The presence of NP was analyzed chemically using gas chromatography-mass spectrometry and indirectly as estrogenic potency using an in vitro reporter gene assay (ER(alpha)-luc assay). Of the total extractable NP in the sediment, 95%+/-1.5% (mean +/- standard error) desorbed quickly into the water phase. By aerobic biodegradation, the total extractable NP concentration and the estrogenic activity were reduced by 97%+/-0.5% and 94%+/-2%, respectively. The easily biodegradable fraction equals the potential bioavailable fraction. Only 43 to 86% of the estrogenic activity in the total extractable fraction, as detected in the ER(alpha)-luc assay, could be explained by the present NP concentration. This indicates that other estrogenic compounds were present and that their bioavailability and aerobic degradation were similar to that of NP. Therefore, we propose to use NP as an indicator compound to monitor estrogenicity of this Ebro River sediment. To what extent this conclusion holds for other river sediments depends on the composition of the contaminants and/or the nature of these sediments and requires further testing.


A new branch on the tree: next-generation sequencing in the study of cancer evolution.
Cancer is a disease caused by the accumulation of genetic alterations in association with successive waves of clonal expansion. Mapping of the human genome sequence, in conjunction with technical advances in the ability to sequence entire genomes, have provided new insight into the mutational spectra and genetic events associated with clonal evolution of cancer. Moving forward, a clearer understanding of those alterations that undergo positive and negative selection throughout carcinogenesis and leading to metastatic dissemination would provide a boon not only to our understanding of cancer evolution, but to the development of potential targets for therapeutic intervention as well.


The inflammatory circuitry of miR-149 as a pathological mechanism in osteoarthritis.
Osteoarthritis (OA) is a multifactorial degenerative pathology, whose progression is exacerbated by pro-inflammatory cytokines signaling. Among the changes triggered in chondrocytes during inflammation, modified expression of tiny epigenetic regulators as microRNAs was shown having deleterious implications for articular cartilage. Aim of the present study was to identify differentially expressed microRNAs in human OA cartilage and to determine their relevance to pathological progression. An OA model based on inflammatory stimulation of a chondrocytic human cell line was used to analyze microRNAs deregulation, and results revealed miR-149 severely down-regulated by IL1β and TNFα. Real-time PCR analysis of miR-149 was exerted also in human primary chondrocytes isolated from cartilage of OA donors and postmortem from subjects with no known history of OA, confirming down-regulation in osteoarthritis. Moving on a functional study, miR-149 regulatory effect on tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1β) and interleukin 6 (IL6) 3'UTRs was evaluated by luciferase assays, and chondrocytes production of TNFα upon miR-149 transfection was measured by enzyme-linked immuno sorbent assay. We found that miR-149 is down-regulated in OA chondrocytes, and this decrease seems to be correlated to increased expression of pro-inflammatory cytokines such as TNFα, IL1β and IL6. OA is a multifactorial disease and we think that our results give new insights for understanding the complex mechanisms of osteoarthritic pathogenesis.


Efficacy of carboplatin given in a phase II window study to children and adolescents with newly diagnosed metastatic soft tissue sarcoma.
The activity of carboplatin was evaluated in a phase II window study in previously untreated children with metastatic soft tissue sarcoma. Children with poor-risk metastatic disease (over 10 years and/or with bone/bone marrow involvement) treated in the SIOP MMT 98 study were scheduled to receive two courses of intravenous carboplatin (area under curve [AUC] of 10), 21 days apart. Sixteen eligible patients were entered into the rhabdomyosarcoma (RMS) group. Response (complete remission or partial remission) was seen in five children (31%, 95% confidence interval (CI) 14-56%). Ten eligible patients with other soft tissue sarcomas were recruited into the non-RMS group. Two responses (20%, 95% CI 6-51%) were seen. Toxicity in both groups was predictable nausea, vomiting and marrow suppression and there were no toxic deaths. Single-agent carboplatin at AUC of 10 has an acceptable toxicity profile but only moderate efficacy in poor-risk metastatic soft tissue sarcoma.


Effect of plant phenolic compounds on biofilm formation by Pseudomonas aeruginosa.
In the natural environment, bacteria predominantly exist in matrix-enclosed multicellular communities associated with various surfaces, referred to as biofilms. Bacteria in biofilms are extremely resistant to antibacterial agents thus causing serious problems for antimicrobial therapy. In this study, we showed that different plant phenolic compounds, at concentrations that did not or weakly suppressed bacterial growth, increased the capacity of Pseudomonas aeruginosa PAO1 to form biofilms. Biofilm formation of P. aeruginosa PAO1 was enhanced 3- to 7-fold under the action of vanillin and epicatechin, and 2- to 2.5-fold in the presence of 4-hydroxybenzoic, gallic, cinnamic, sinapic, ferulic, and chlorogenic acids. At higher concentrations, these compounds displayed an inhibiting effect. Similar experiments carried out for comparison with Agrobacterium tumefaciens C58 showed the same pattern. Vanillin, 4-hydroxybenzoic, and gallic acids at concentrations within the range of 40 to 400 μg/mL increased the production of N-3-oxo-dodecanoyl-homoserine lactone in P. aeruginosa PAO1 which suggests a possible relationship between stimulation of biofilm formation and Las Quorum Sensing system of this bacterium. Using biosensors to detect N-acyl-homoserine lactones (AHL), we demonstrated that the plant phenolics studied did not mimic AHLs.