Cardiac electrophysiologic testing: its role in the selection of antiarrhythmic drug regimens for supraventricular and ventricular arrhythmias.
Cardiac electrophysiology studies use intracardiac recording and programmed stimulation to define the mechanisms and most appropriate therapy for supraventricular and ventricular arrhythmias. Using these techniques, the majority of clinical tachycardias can be reproducibly initiated and terminated in the electrophysiology laboratory, thereby allowing the most appropriate therapy to be selected. With this approach, antiarrhythmic agents can be tested in a systematic, serialized fashion for efficacy, safety and patient tolerance. With both supraventricular and ventricular tachycardias, suppression of arrhythmia induction predicts freedom from recurrence, whereas inducibility carries a poor prognosis in clinical follow-up. Electrophysiology studies provide a safe and effective approach to the treatment of selected patients with cardiac arrhythmias.


Thorotrast-associated gliosarcoma. Including comments on thorotrast use and review of sequelae with particular reference to lesions of the central nervous system.
The occurrence of a glioblastoma with sarcoma, a gliosarcoma, in the left frontal-temporal area of a 49-year-old woman with a history of Thorotrast exposure, is described. Thorotrast-laden histiocytes and free Thorotrast material were found in both components of the tumor. An overlying, adherent dural cranial lesion was found to contain massive deposits of Thorotrast embedded in a dense fibrotic and sclerotic stroma with focal calcification. These features are typical of "Thorotrastoma." Thorotrast stains greenish-brown with hematoxylin and eosin and appears as refractile granular particles of relatively uniform size either within histiocytes or as free material. The radioactivity of the deposits was confirmed through the use of a scintillation counter, and 232 thorium was definitively identified though the use of scanning electron microscopy with energy-dispersive X-ray analysis. Immunohistochemical studies of the tumor demonstrated glial fibrillary acid protein (GFAP) immunoreactivity in areas of glioma and focal vimentin and actin immunoreactivity in areas of sarcoma. Thorotrast-associated lesions of the central nervous system (CNS) are infrequently reported, and a Thorotrast-associated gliosarcoma has not yet been reported. The use of Thorotrast, its radiobiology, and sequelae are reviewed with particular emphasis on lesions occurring in the CNS.


Cytokine-enhanced expression of glycoprotein Ib alpha in human endothelium.
Platelet glycoprotein Ib is a major platelet membrane protein composed of two disulfide-linked chains, termed the alpha and beta chains. The larger alpha chain (GpIb alpha), a platelet receptor for von Willebrand factor, plays a major role in mediating platelet adhesion to the subendothelium. Our laboratories have previously reported synthesis of a protein in human endothelial cells that is immunoprecipitated with polyclonal and monoclonal antibodies to platelet GpIb alpha. Lopez et al. (Lopez, J. A., Chung, D. W., Fujikawa, K., Hagan, F. S., Papayannopoulou, T., and Roth, G. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5615-5619) have reported the cloning of GpIb alpha from a human erythroleukemia (HEL) cell cDNA library. Using this clone as probe, we have isolated two partial GpIb alpha clones from a human umbilical vein endothelial cell lambda gt11 cDNA library. These clones were localized within HEL-derived GpIb alpha cDNA by sequence and restriction enzyme analysis. Additionally, they detected the same message species in HEL and tonsilar RNA that was detected with the HEL GpIb alpha cDNA. Low level GpIb alpha mRNA expression was detected in cultured human umbilical vein endothelial cells, which was increased by treatment of the cells with tumor necrosis factor-alpha. This effect was enhanced by pretreatment with interferon-gamma. Additionally, localization of GpIb alpha in endothelium of fresh tonsilar tissue was demonstrated by immunohistochemistry and in situ hybridization. GpIb alpha may play a role in mediating platelet or other effector cell adhesion to activated endothelium.


Industrial heat island mitigation in Angul-Talcher region of India: Evaluation using modified WRF-Single Urban Canopy Model.
Linkages of urban and industrial cooling with sustainable development goals and climate change perspectives are well acknowledged, mainly for developing economies in tropical climates. Angul-Talcher region is one of the oldest industrial clusters of India, and the region experiences higher atmospheric heat island intensities with magnitudes of 7 to 9 °C attributed to the Industrial Heat Island (IHI) effect. In the present study, various measures for mitigating heat island effect in the region and assessed their impact using an Improved Weather Research and Forecasting model coupled with the Single-Layer Urban Canopy Model. The improved framework includes the release of industrial emissions at stack height and sector-wise diurnal profiles of anthropogenic heat (AH) released from vehicles, residential, and industry/power. The mitigation measures comprised strategies like alteration in building materials and conversion of landuse-landcover (LULC) of selected grid cells in the model domain to more vegetation or water bodies. It was noted that the cool roofs and walls together reduced IHIs by 0.5 °C, while green roofs and cool pavements achieved a reduction of 0.3 °C and 0.1 °C, respectively. The introduction of water bodies showed maximum reduction in IHIs by 3 to 5 °C during daytime and 1 to 2 °C over mining and industrial stations. During night-time, conversion to mixed forests was more effective (ΔT ≈ 1 °C) than conversion to water bodies. A combination of cool roofs with the introduction of water bodies in the mining areas and mixed forest patches in industry stations was found to be the most effective mitigation strategy for mitigating the industrial heat island effect over the Angul-Talcher region. These mitigation scenarios can/should serve as a theoretical reference for implementing actual mitigation measures, which would require consideration of economic, social, and policy aspects apart from scientific ones for practical application.


Introducing clinical pharmacy services to cardiovascular clinics at a university hospital in Northern Cyprus.
Background Clinical pharmacists are the primary source of scientifically valid information and advice on the safe, rational, and cost-effective use of medications. However, ward-based clinical pharmacy services are not well optimized in Northern Cyprus. Objective Ward based clinical pharmacy services were introduced and evaluated in cardiovascular clinics. Setting Cardiology and cardiovascular surgery departments in a tertiary university hospital. Methods A prospective interventional study introduced and documented clinical pharmacy services for 120 days. Drug-related problems were classified using the Pharmaceutical Care Network Europe PCNE DRP classification tool V6.2. Main outcome measure Interventions proposed and acceptance rate of recommendations. Results A total of 133 patients were reviewed, and, 81 patients had drug-related problems. Only 402 (93.1%) of the 432 suggested interventions were accepted and regarded as clinically relevant. Drug-related problems primarily involved antihypertensive, diuretic, and antithrombotic agents. Treatment effectiveness was the major type of drug-related problems (107; 49.3%) followed by adverse drug reactions (74; 34.1%). Drug dose and selection were the most frequent causes of drug-related problems. Add/change/stop medications were the most common types of intervention at the prescriber level. A total of 171 (78.8%) of the identified 217 drug-related problems were solved, 4 (1.8%) of the problems were partially solved, 32 (14.7%) problems were unsolved, and 10 (4.6%) problems had unknown outcomes. Conclusion Clinical pharmacy services may have optimized therapy effectiveness and prevent adverse effects. The pharmacist interventions were highly accepted by cardiologists; this may indicate the presence of a great opportunity and need to optimize and implement CPS in other hospitals in Northern Cyprus.


The cost-effectiveness of three thyroid function testing strategies for suspicion of hypothyroidism in a primary care-setting.
To determine the sensitivity and specificity of thyroxine (T4) and the cost-effectiveness of three testing strategies in the diagnosis of hypothyroidism in a primary care setting. 1) A retrospective chart review to determine sensitivity and specificity of T4 in diagnosing hypothyroidism; a cost-effectiveness analysis comparing ordering an initial T4 test alone, an initial thyroid-stimulating hormone (TSH) test alone, and T4 and TSH tests together in diagnosing hypothyroidism; a sensitivity analysis was performed on critical assumptions. Primary care adult practice of a health maintenance organization. Eight hundred sixteen consecutive patients suspected of having hypothyroidism who had both T4 and TSH tests performed. None. The sensitivity of a T4 cut-off of 7 micrograms/dl (90.3 nmol/L) in diagnosing primary hypothyroidism was 93% (95% confidence interval = 85-100%) and the specificity was 68% (95% confidence interval = 65-71%). The cost-effectiveness ratios of using an initial T4 or TSH test were about the same across a wide range of test characteristics and disease prevalence estimates. As the ratio of T4 to TSH test charges declines from 0.6 to 0.2, the marginal cost of the TSH-first method increases from $3,500 to $18,000 for each additional hypothyroid patient identified. Ordering both tests together was very costly compared with the single test methods ($125,000 for each additional case diagnosed) and remained so under a wide range of assumptions. When hypothyroidism is suspected, a TSH-first testing approach is generally preferable due to its greater sensitivity and, under most assumptions, only small increment in average or marginal cost per case compared with a T4-first method.


Integration of United States emergency medicine concepts into emergency services in the New Independent States.
At this writing, a collaborative partnership has been in place for 30 months between the Boston University Medical Center, the University of Massachusetts Medical Center, the Armenian Ministry of Health, and the Emergency Hospital of Yerevan, Armenia, to improve emergency and trauma care in that city. Fifty-five individuals have traveled to and from the Emergency Hospital, the partner hospital. The collaboration has led to the creation of the Emergency Medical Services Institute (EMSI) at Emergency Hospital, an 800-bed facility that serves as a trauma center and as base for the Yerevan ambulance system. A curriculum (text and slides) has been developed and translated into Armenian and Russian. To date, the Armenian EMSI has trained nearly 300 emergency medical personnel: physicians, nurses, drivers, and first responders. The Armenian EMSI faculty have received training in directing instruction of emergency care providers. Plans are in place to begin training in Armenian cities outside of Yerevan and in neighboring republics. An emergency medicine residency program received ministry approval and was begun with six resident physicians in January 1995. To date, 45 nurses have graduated from a 400-hour training program. This partnership program chose an education initiative as the vehicle for interaction between the United States and the formerly Soviet-directed Armenian health care system. Officials of the partner hospital requested assistance in upgrading the skills of its abundant emergency care workforce, citing cardiovascular disease, trauma, and accidents as leading causes of death and disability in Armenia.(ABSTRACT TRUNCATED AT 250 WORDS)


Five-Year Cumulative Incidence of Axillary Web Syndrome and Comparison in Upper Extremity Movement, Function, Pain, and Lymphedema in Survivors of Breast Cancer With and Without Axillary Web Syndrome.
To determine the cumulative incidence and natural history of axillary web syndrome (AWS) and its related postoperative risk for physical impairments in a cohort of women followed for 5 years post breast cancer surgery. Prospective, longitudinal study. Academic health center. Women (N=36) with and without AWS after breast cancer surgery with sentinel node biopsy or axillary lymph node dissection. Not applicable. Participants were assessed for AWS, shoulder goniometric flexion and abduction range of motion, function (Disability of the Arm, Shoulder, and Hand), lymphedema (bioimpedance spectroscopy, girth measures, tissue dielectric constant), and pain (visual analog scale) at 2, 4, 12, and 78 weeks and 5 years after breast cancer surgery. Analysis of variance compared range of motion, function, lymphedema, and pain in women identified with AWS with those without AWS across visits. Univariate logistic regression assessed if AWS was a risk factor for physical impairment at 5 years. The cumulative incidence of AWS was 57%. Fifty percent (14/28) of the women who completed all study visits had signs of AWS at 5 years. Abduction active range of motion was significantly lower in women with AWS at 2 and 4 weeks post surgery. AWS was identified as a risk factor for reduced shoulder motion at 5 years. Regardless of AWS, 75% of the women experienced 1 or more upper extremity physical impairments at 5 years, which is an increase from 66% at 78 weeks in the same cohort. AWS is associated with reduced shoulder range of motion in the early postoperative time period, can persist for 5 years after breast cancer surgery, and increases the risk of long-term reduced shoulder range of motion. Long-term physical issues are apparent after breast cancer surgery regardless of AWS.


Radiation dose in paediatric cardiac catheterisation: A systematic literature review.
It is believed that children are more sensitive to ionising radiation than adults. This work reviewed the reported radiation dose estimates for paediatric cardiac catheterisation. A systematic literature review was performed by searching healthcare databases for studies reporting radiation dose using predetermined key words relating to children having cardiac catheterisation. The quality of publications was assessed using relevant Critical Appraisal Skills Programme questions and their reported radiation exposures were evaluated. It is only in recent years that larger cohort observations have been undertaken. Although radiation dose from paediatric cardiac catheterisation has decreased in recent years, the literature indicated that it remains varied and potentially substantial. Standardisation of weight categories and procedure types such as those recommended by the PiDRL project could help compare current and future radiation dose estimates.


Nodal Response to Neoadjuvant Chemotherapy Predicts Receipt of Radiation Therapy After Breast Cancer Diagnosis.
Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved overall survival (OS) in patients with breast cancer, but it is unclear how post-NACT response influences radiation therapy administration in patients presenting with node-positive disease. We sought to determine whether nodal pCR is associated with likelihood of receiving nodal radiation and whether radiation therapy among patients experiencing nodal pCR is associated with improved OS. Clinical N1 (cN1) female breast cancer patients diagnosed during 2010 to 2015 who were ypN0 (ie, nodal pCR; n = 12,341) or ypN1 (ie, residual disease; n = 13,668) after NACT were identified in the National Cancer Database. Multivariate logistic regression was used to identify factors associated with receiving radiation therapy. Cox proportional hazards modeling was used to estimate the association between radiation therapy and adjusted OS. The study included 26,009 patients; 43.9% (n = 5423) of ypN0 and 55.3% (n = 7556) of ypN1 patients received nodal radiation. Rates of nodal radiation remained the same over time among ypN0 patients (trend test, P = .29) but increased among ypN1 patients from 49% in 2010 to 59% in 2015 (trend test, P < .001). After adjusting for covariates, nodal pCR (vs no stage change) was associated with decreased likelihood of nodal radiation after mastectomy (∼20% decrease) and lumpectomy (∼30% decrease; both P < .01). After mastectomy, nodal (vs no) radiation conferred no significant survival benefit in ypN0 patients, but it approached significance for ypN1 patients (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.69-0.99, P = .04; overall P = .11). After lumpectomy, nodal radiation was associated with improved adjusted OS for ypN0 (HR, 0.38; 95% CI, 0.22-0.66) and ypN1 patients (HR, 0.44; 95% CI, 0.30-0.66; both P < .001), but this improvement was not significantly greater than that associated with breast-only radiation. ypN0 patients were less likely to receive nodal radiation than ypN1 patients were, suggesting that selective omission already occurs and, in the context of limited survival data, could potentially be appropriate for select patients.


Simultaneous determination of cyclophosphamide and 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry - application to Chinese systemic lupus erythematosus patients.
A pharmacogenomics study of cyclophosphamide in systemic lupus erythematosus patients is being conducted in our laboratory in which the plasma concentrations of cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide should be assayed rapidly and sensitively. A rapid, stable and sensitive liquid chromato-graphy/electrospray ionization tandem mass spectrometry method was developed to simultaneously determine cyclophosphamide and 4-hydroxycyclophosphamide in human plasma with ifosfomide as an internal standard. After a protein precipitation with cold acetonitrile and stabilization of 4-hydroxycyclophosphamide by ansyldrazine and extraction with ethyl acetate, separation was performed on a C18 3.5 μm 2.1 × 50 mm column with mobile phase of acetonitrile and water (50:50, v/v) with 0.1% formic acid at 200 μL/min. The chromatographic run time was 3 min. The linear calibration curves ranged from 5 to 5000 ng/mL for cyclophosphamide and 5-500 ng/mL for 4-hydroxycyclophosphamide. The recoveries of the liquid extraction were 54.5%-58.5% for cyclophosphamide and 103.5%-105.5% for 4-hydroxycyclophosphamide. The lower limit of quantification was 5 ng/mL for both analytes. The intra- and inter-day precision was <15% for quality control samples at 4000, 500, 50 ng/mL for cyclophosphamide and 4-hydroxycyclophosphamide at 400, 100, 20 ng/mL. The method was applied in this pharmacogenomics study in Chinese systemic lupus erythematosus patients treated with low-dose cyclophosphamide. The method was efficient with shorter running time and lower limit of quantification compared to previous reports and has been successfully applied in this pharmacogenomics study.


[The influence of diazepam (valium) on the effect of phenprocoumon (marcumar) (author's transl)].
In 10 patients who were treated with phenprocoumon (Marcumar) for thrombembolic diseases, we examined the influence of the combined therapy with diacepam (Valium) on the effect of the anticoagulant. After stopping the therapy with diacepam we saw a significant increase of the prothrombinetime (Quick) beyond the therapeutic level of 25%. By increasing the dosis of phenprocoumon the therapeutic level was achieved again not until after 8 days. The dosis needed for maintaining this level was on the average 32% higher than during the time of the therapy in which diacepam was used. Because of the increased thrombembolic risk, when going beyond the therapeutic level of the prothrombinetime, this interaction is of clinical importance.


Tissue immune profiles supporting response to mesenchymal stromal cell therapy in acute graft-versus-host disease-a gut feeling.
Acute graft-versus-host disease (aGvHD), post-allogeneic hematopoietic stem cell transplantation, is associated with high mortality rates in patients not responding to standard line care with steroids. Adoptive mesenchymal stromal cell (MSC) therapy has been established in some countries as a second-line treatment.Limitations in our understanding as to MSC mode of action and what segregates patient responders from non-responders to MSC therapy remain. The principal aim of this study was to evaluate the immune cell profile in gut biopsies of patients diagnosed with aGvHD and establish differences in baseline cellular composition between responders and non-responders to subsequent MSC therapy.Our findings indicate that a pro-inflammatory immune profile within the gut at the point of MSC treatment may impede their therapeutic potential. These findings support the need for further validation in a larger cohort of patients and the development of improved biomarkers in predicting responsiveness to MSC therapy.


Interposition arthroplasty of the elbow with hinged external fixation for post-traumatic arthritis.
This retrospective case series reviewed 9 men and 4 women (mean age, 41 years) with severe post-traumatic elbow arthrosis treated with interposition arthroplasty and temporary hinged external fixation. In 2 patients, treatment was considered to have failed because of early postoperative instability, and their results were classified as poor. The remaining 11 were followed up for a mean of 4 years (range, 1-11 years). The mean arc of flexion improved from 48 degrees before surgery to 110 degrees after surgery. The mean postoperative Broberg-Morrey score was 77 points, reflecting a mean improvement of 41 points (range, 13-68 points) and corresponding with 1 excellent, 4 good, 4 fair, and 4 poor results. Four patients had severe instability associated with bone loss of the distal humerus or trochlear notch. Interposition arthroplasty can improve elbow motion and function but at the expense of elbow stability despite hinged external fixation.


In vivo electrochemical studies of rat striatal dopamine and serotonin release after morphine.
The effect of the reference opiate, morphine (d-morphine-sulfate), on endogenously released striatal dopamine and serotonin was studied in male, adult, anesthetized Sprague-Dawley rats. The intraperitoneal administration of morphine produced a biphasic effect on striatal dopamine release. A significant increase in the dopamine signal was seen in the first hour after drug administration; a significant decrease in the dopamine signal was seen in the second and third hour after drug administration. On the other hand, the effect of morphine on striatal serotonin release was monophasic. Morphine significantly increased serotonin release from rat striatum. The effect lasted three hours after morphine administration, i.e., the effect persisted significantly throughout the study. These data show a simultaneous opiate-dopaminergic and opiate-serotonergic interaction in rat striatum. These data further extend studies which have suggested that the pharmacological mechanism of action of morphine may have its etiology in the concurrent modulation of more than one neurotransmitter.


Liver iron quantification in children and young adults: comparison of a volumetric multi-echo 3-D Dixon sequence with conventional 2-D T2* relaxometry.
Magnetic resonance imaging (MRI)-based liver iron quantification is the standard of care to guide chelation therapy in children at risk of hemochromatosis. T2* relaxometry is the most widely used technique but requires third-party software for post-processing. Vendor-provided three-dimensional (3-D) multi-echo Dixon techniques are now available that allow inline/automated post-processing. The purpose of our study was to evaluate the diagnostic accuracy of a volumetric multi-echo Dixon technique using conventional T2* relaxometry as the reference standard in a pediatric and young adult population. In this retrospective study, we queried the radiology information system to identify all MRIs performed for liver iron quantification from July 2015 to January 2020. All patients had undergone T2* relaxometry on a 1.5-tesla (T) scanner for liver iron concentration (LIC) estimation. In addition, a 3-D multi-echo Dixon was performed using Siemens Healthineers LiverLab (Erlangen, Germany). Two readers independently estimated liver R2* and T2* on the multi-echo Dixon by drawing free-hand regions of interest on the scanner-generated R2* and T2* maps. Conventional T2*-relaxometry-based LIC was the reference standard. We estimated interobserver agreement by concordance correlation coefficient (CCC). We used Bland-Altman analysis and Pearson correlation coefficient (r) to compare LIC by the two methods. Fifty-four MRIs on 38 patients (22 females) were available for analysis. Mean patient age was 11.8 years (standard deviation [SD] 5.3 years). Reference standard LIC ranged 1.1-21.1 (median 6.8) mg/g dry weight of liver. The concordance between readers for T2* estimation using 3-D multi-echo Dixon was substantial (CCC 0.99, confidence interval 0.99-1.00). Bland-Altman plot showed that all observations were clustered around the zero bias line if the LIC average was ≤8 mg/g, and r was very strong (reader 1 r=0.93, reader 2 r=0.92, both P-values <0.001). With increasing LIC, there was a pattern of poor agreement on the Bland-Altman plot, with observations crossing the lower limits of agreement, and r was very weak (reader 1 r=0.05, P-value 0.84; reader 2 r=0.17, P-value 0.44). Vendor-based 3-D multi-echo Dixon allows for excellent interobserver correlation in liver T2* estimation. LIC estimated by this method has a very strong correlation with conventional T2* relaxometry if liver iron overload is mild-moderate (LIC ≤8 mg/g).


Endogenous nitrosyl factors may inhibit the desensitization of 5-HT3 receptors on vagal cardiopulmonary afferents.
The pronounced tachyphylaxis to the Bezold-Jarisch reflex (BJR) responses elicited by systemic injections of the 5-HT(3) receptor (5-HT(3)R) agonists such as phenylbiguanide (PBG) may involve desensitization and/or reduced rate of resensitization of 5-HT(3)Rs on vagal cardiopulmonary afferents. The presence of nitric oxide synthase (NOS) in vagal afferents raises the possibility that endogenous nitrosyl factors regulate the status of 5-HT(3)Rs in these afferents. Accordingly, the aim of this study was to determine whether the inhibition of NOS alters the development of tachyphylaxis to the BJR responses elicited by PBG in conscious rats. The first injection of PBG (100 microg/kg, i.v.) elicited robust reductions in heart rate (HR), diastolic arterial blood pressure (BP(D)), and cardiac output (CO) but minor changes in total peripheral resistance in saline-treated rats. Subsequent injections elicited progressively smaller responses such that the sixth injections elicited minor responses only. The first injection of PBG (100 microg/kg, i.v.) in rats treated with the NOS inhibitor, L-NAME (25 micromol/kg, i.v.) elicited similar reductions in HR, BP(D), and CO as in saline-treated rats. However, the rate of development of tachyphylaxis to PBG was markedly faster in the L-NAME-treated rats. The BJR responses elicited by 5-HT (40 microg/kg, i.v.) were markedly attenuated after the development of tachyphylaxis to PBG in saline- and in L-NAME-treated rats whereas the BJR responses elicited by the S-nitrosothiol, L-S-nitrosocysteine (5 micromol/kg, i.v.), were not attenuated in either group. These findings suggest that tachyphylaxis to PBG was not due to the loss of central or efferent processing of the BJR. Taken together, these findings suggest NOS exists in vagal cardiopulmonary afferents mediating the BJR and that nitrosyl factors influence 5-HT(3)R function.


Blood-based biomarkers in Alzheimer's disease: a mini-review.
Alzheimer's disease (AD) is the most common cause of dementia and has far reaching consequences for patients and their caregivers. Early detection and treatment are key factors in limiting the impact of the disease. However, a definitive diagnosis of AD requires an examination of brain tissue during an autopsy. Although a plethora of biomarkers such as neuroimaging, electrophysiological, and cerebrospinal fluid (CSF) biomarkers are available, their utility is limited to research due to their poor reach and prohibitive cost. In order for biomarkers to be widely used, they need to be accessible, affordable, and conducive for the patient population or disease stage. Blood-based biomarkers may not only be less expensive and more accessible compared to neuroimaging or CSF tests, but they are also preferred by patients with AD as they are much less invasive. In this mini-review article, we expand on the rationale for the use of blood-based biomarkers, review currently available biomarkers and discuss the need for the standardization of these biomarkers. We contrast the blood-based biomarkers with other available biomarkers and discuss the advantages of using a panel of blood-based biomarkers to strengthen their accuracy.


TAO-kinase 3 governs the terminal differentiation of NOTCH2-dependent splenic conventional dendritic cells.
Antigen-presenting conventional dendritic cells (cDCs) are broadly divided into type 1 and type 2 subsets that further adapt their phenotype and function to perform specialized tasks in the immune system. The precise signals controlling tissue-specific adaptation and differentiation of cDCs are currently poorly understood. We found that mice deficient in the Ste20 kinase Thousand and One Kinase 3 (TAOK3) lacked terminally differentiated ESAM+ CD4+ cDC2s in the spleen and failed to prime CD4+ T cells in response to allogeneic red-blood-cell transfusion. These NOTCH2- and ADAM10-dependent cDC2s were absent selectively in the spleen, but not in the intestine of Taok3-/- and CD11c-cre Taok3fl/fl mice. The loss of splenic ESAM+ cDC2s was cell-intrinsic and could be rescued by conditional overexpression of the constitutively active NOTCH intracellular domain in CD11c-expressing cells. Therefore, TAOK3 controls the terminal differentiation of NOTCH2-dependent splenic cDC2s.


Robots are not immune to bias and injustice.
Human-human social constructs drive human-robot interactions; robotics is thus intertwined with issues surrounding inequity and racial injustices.


NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma.
Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients. Data from 360 HCC patients in The Cancer Genome Atlas database and 231 patients in the Gene Expression Omnibus database were analyzed. Kaplan-Meier analysis and a Cox regression model were used to determine median survival time (MST) and overall and recurrence-free survival by calculating the hazard ratio (HR) and 95% confidence interval (CI). High NOD2 and low NLRX1 expression in tumor tissue was associated with short MST (P = 0.012 and 0.014, respectively). A joint-effects analysis of NOD2 and NLRX1 combined revealed that groups III and IV had reduced risk of death from HCC as compared to group I (adjusted P = 0.001, adjusted HR = 0.31, 95% CI = 0.16-0.61 and adjusted P = 0.043, adjusted HR = 0.63, 95%CI = 0.41-0.99, respectively). NOD2 and NLRX1 expression levels are potential prognostic markers in HCC following hepatectomy.


The banana E2 gene family: Genomic identification, characterization, expression profiling analysis.
The E2 is at the center of a cascade of Ub1 transfers, and it links activation of the Ub1 by E1 to its eventual E3-catalyzed attachment to substrate. Although the genome-wide analysis of this family has been performed in some species, little is known about analysis of E2 genes in banana. In this study, 74 E2 genes of banana were identified and phylogenetically clustered into thirteen subgroups. The predicted banana E2 genes were distributed across all 11 chromosomes at different densities. Additionally, the E2 domain, gene structure and motif compositions were analyzed. The expression of all of the banana E2 genes was analyzed in the root, stem, leaf, flower organs, five stages of fruit development and under abiotic stresses. All of the banana E2 genes, with the exception of few genes in each group, were expressed in at least one of the organs and fruit developments, which indicated that the E2 genes might involve in various aspects of the physiological and developmental processes of the banana. Quantitative RT-PCR (qRT-PCR) analysis identified that 45 E2s under drought and 33 E2s under salt were induced. To the best of our knowledge, this report describes the first genome-wide analysis of the banana E2 gene family, and the results should provide valuable information for understanding the classification, cloning and putative functions of this family.


Postoperative Obstructive Sleep Apnea Management Following Endoscopic Pituitary Surgery: A Systematic Review.
There is currently no consensus on the appropriate timing of noninvasive positive pressure ventilation (PPV) resumption in patients with obstructive sleep apnea (OSA) after endoscopic pituitary surgery. We performed a systematic review of the literature to better assess the safety of early PPV use in OSA patients following surgery. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases in English were searched using the keywords: "sleep apnea," "CPAP," "endoscopic," "skull base," "transsphenoidal" and "pituitary surgery." Case reports, editorials, reviews, meta-analyses, unpublished and abstract-only articles were all excluded. Five retrospective studies were identified, comprising 267 patients with OSA who underwent endoscopic endonasal pituitary surgery. The mean age of patients in four studies (n = 198) was 56.3 years (SD = 8.6) and the most common indication for surgery was pituitary adenoma resection. The timing of PPV resumption following surgery was reported in four studies (n = 130), with 29 patients receiving PPV therapy within two weeks. The pooled rate of postoperative cerebrospinal fluid leak associated with PPV resumption was 4.0% (95% CI: 1.3-6.7%) in three studies (n = 27) and there were no reports of pneumocephalus associated with PPV use in the early postoperative period (<2 weeks). Early resumption of PPV in OSA patients after endoscopic endonasal pituitary surgery appears relatively safe. However, the current literature is limited. Additional studies with more rigorous outcome reporting are warranted to assess the true safety of re-initiating PPV postoperatively in this population.


PI3K/PTEN/mTOR pathway dynamic tracking and prognostic value in HR+/HER2- BC patients with residual disease after neoadjuvant chemotherapy: a cohort study.
Hormone receptor-positive (HR)+/HER2- breast cancer (BC) is highly heterogeneous, with PI3K/PTEN/mTOR pathway alterations emerging as possible players within this complexity. We longitudinally tracked PI3K/PTEN/mTOR pathway dynamics from baseline biopsy to residual disease (RD)-and to metastases in case of relapse-in HR+/HER2- BC patients receiving neoadjuvant chemotherapy (NACT). HR+/HER2- BC patients with RD after NACT were identified. We assessed PIK3CA mutational, Pten-loss and phosphorylation levels of mTOR and its substrates (p70S6K and 4EBP1) on baseline biopsies and matched RD samples; in case of disease relapse, we also assessed PIK3CA mutational status on metastatic samples. Recurrence-free survival (RFS) was adopted as endpoint. 92 patient were included. The conversion rate of PIK3CA mutational status was 12.8%; 1 patient acquired PIK3CA mutation at relapse; the rate of Pten conversion was 33.3%; mTOR phosphorylation levels significantly increased from baseline biopsy to RD, while its substrates significantly decreased. Baseline phosphorylated-mTOR significantly predicted poorer RFS in patients with PIK3CA wild-type status; baseline phosphorylated-70S6K was positively associated with RFS. We observed that PI3K/PTEN/mTOR pathway is highly dynamic under NACT exposure and the assessment of PIK3CA mutations may capture only a small fraction of such complexity. In this context, mTOR activation trough alternative pathways with respect to PIK3CA signalling may have a crucial role in shaping the molecular landscape of HR+/HER2- BC with RD after NACT. It is imperative to further elucidate the role of PIK3CA and mTOR-dependent pathways in shaping chemoresistance and endocrine resistance in high-risk HR+/HER2- early/locally advanced BC patients.


[Quality of life and caregiver burden in caregivers with patients with complications from type 2 diabetes mellitus].
Chronic diseases with partial dependence, including type 2 diabetes mellitus, modify the way of life of the patient and his family, who adopt the role of caregiver having to reorganize, rethink their expectations and adapt their goals and objectives to the situation, this may generate a deterioration of the quality of life and an overload syndrome. To identify the relationship between quality of life and caregiver overload in caregivers with patients with complications from type 2 diabetes mellitus assigned to the Family Medicine Unit No. 7. Cross-sectional study, carried out with 138 caregivers with a patient with complications from type 2 diabetes mellitus. The sociodemographic profile instruments, the SF-36 health questionnaire, and the Zarit scale were used for data collection. The analysis was carried out through descriptive statistics and Spearman's correlation test, with a significance level of p≤0.05. It was identified that the health-related quality of life in caregivers with patients with complications from type 2 diabetes mellitus evaluated with the SF-36 questionnaire had a mean value of 74.8; with a score in the physical and mental components of 63.9 and 38.1 respectively. The best qualified dimensions were social function (84.9) and physical function, on the other hand, vitality obtained a lower qualification. It was observed that 5.05% of the caregivers present light overload and 5.05% intense overload. When performing the correlation between the global rating of the Zarit scale with the 8 dimensions of the SF-36 health questionnaire in caregivers of patients with complications of type 2 diabetes mellitus, a moderate negative correlation was observed between the dimensions of mental health, physical function, emotional role and vitality, as well as a weak negative correlation between the dimensions of social role and physical role. The results show an inverse correlation between the caregiver's burden and the quality-of-life dimensions, that is, if one decreases, the other increases; It is important to carry out health promotion activities in this population to prevent caregiver overload.


Antimicrobial resistance of Campylobacter coli isolates from swine.
Eighty-three swine isolates of Campylobacter coli were tested for mechanisms underlying resistance to nalidixic acid, ciprofloxacin, erythromycin and tetracycline. Four isolates harbored class 1 integrons but none carried class 2 and 3 integrons. Most of the tetracycline-resistant isolates (97%) possessed tet(O). A Thr-86-Ile substitution in GyrA and an A-2230-G mutation in 23S rRNA were the main resistance mechanisms for quinolones and erythromycin, respectively.


A Schiff base modified graphene oxide film for anodic stripping voltammetric determination of arsenite.
A protocol is described for chemical modification of graphene oxide with a Schiff base derived from diethylenetriamine and 2-hydroxy-4-methoxybenzophenone. The base was grafted onto an indium tin oxide (ITO) film and applied to electroanalytical determination of arsenite. Successful grafting was confirmed by Fourier transform-infrared spectroscopy, spectrophotometry, field emission scanning electron microscopy and cyclic voltammetry. Secondly, the coated ITO film served as a working electrode for the stripping voltammetric determination of arsenite. The analytical signal is generated by selective oxidation of metal species via multi-donor sites present in the derivatized Schiff base. The electroanalytical protocol was optimized by investigating the effects of deposition time, working potential, frequency and amplitude of square wave anodic stripping voltammetry. The method has attractive features including (a) the usage of a non-metallic, non-toxic and cost-effective material; (b) improved sensitivity (with limit of detection as low as 156 pM) due to better adsorption of arsenite in the Schiff base pockets on the ITO, and (c) the application to the determination of arsenite in real samples. Graphical abstract Schematic representation of the fabrication of a Schiff base-functionalized graphene oxide on an indium tin oxide (SB@SiO2@GO@ITO) electrode for selective electrochemical sensing of arsenite due to adsorption on multi-donor sites.


The role of glutamate and its receptors in central nervous system in stress-induced hyperalgesia.
To explore the potential mechanisms of glutamate and its receptors in stress-induced hyperalgesia. The stress-induced hyperalgesia, glutamate and its receptors are listed as key items in the pubmed database and the related articles are searched. Glutamate level is increased under stress and associated with stress-induced hyperalgesia. Moreover, the role of glutamate in stress-induced hyperalgesia depends on its subtypes of its receptors. Increased glutamate during stress connect with ionotropic glutamate receptors can prompt hyperalgesia, but connect with metabotropic glutamate receptors can inhibit hyperalgesia.


Multimodal imaging guided photothermal therapy using functionalized graphene nanosheets anchored with magnetic nanoparticles.
In this work, a nanoscale reduced graphene oxide-iron oxide nanoparticle (RGO-IONP) complex is noncovalently functionalized with polyethylene glycol (PEG), obtaining a RGO-IONP-PEG nanocomposite with excellent physiological stability, strong NIR optical absorbance, and superparamagnetic properties. Using this theranostic nanoprobe, in-vivo triple modal fluorescence, photoacoustic, and magnetic resonance imaging are carried out, uncovering high passive tumor targeting, which is further used for effective photothermal ablation of tumors in mice.


Recovery of the hopping response after complete spinal cord transection in the cat.
The hopping response reappears in the hind limb of the cat after complete spinal cord transection at postoperative day means = 11.6. This response is hypermetric and slow compared with that in the normal cat and only forward, medial, and lateral hopping can be elicited. Anatomical and physiological changes in the spinal cord which may account for the reappearance of the hopping response are discussed.


A topic models analysis of the news coverage of the Omicron variant in the United Kingdom press.
The COVID-19 pandemic has caused numerous casualties, overloaded hospitals, reduced the wellbeing of many and had a substantial negative economic impact globally. As the population of the United Kingdom was preparing for recovery, the uncertainty relating to the discovery of the new Omicron variant on November 24 2021 threatened those plans. There was thus an important need for sensemaking, which could be provided, partly, through diffusion of information in the press, which we here examine. We used topic modeling, to extract 50 topics from close to 1,500 UK press articles published during a period of approximately one month from the appearance of Omicron. We performed ANOVAs in order to compare topics between full weeks, starting on week 48 of 2021. The three topics documenting the new variant (Omicron origins, Virus mutations, News of a new variant) as well as mentions of vaccination excluding booster, Scotlands First minister statement (Communications) travel bans and mask wearing (Restrictions) and the impact of market and investing (Domains and events) decreased through time (all ps < .01). Some topics featured lower representation at week two or three with higher values before and after: Government's Scientific Advisory Group for Emergencies recommendations (Communications), Situation in the US, Situation in Europe (Other countries and regions), all ps < .01. Several topics referring to symptoms and cases-e.g., rises of infections, hospitalisations, the pandemic the holidays, mild symptoms and care; restrictions and measures-e.g., financial help, Christmas and Plan B, restrictions and New Year; and domains of consequences and events-e.g., such as politics, NHS and patients, retail sales and airlines, featured increasing representation, (all ps < .01). Other topics featured less regular or non-significant patterns. Changes in sensemaking in the press closely matched the changes in the official discourse relating to Omicron and reflects the trajectory of the infection and its local consequences.


Efficacy of Lorlatinib in Treatment-Naive Patients With ALK-Positive Advanced NSCLC in Relation to EML4::ALK Variant Type and ALK With or Without TP53 Mutations.
Lorlatinib, a third-generation ALK tyrosine kinase inhibitor, improved outcomes compared with crizotinib in patients with previously untreated ALK-positive advanced NSCLC in the phase 3 CROWN study. Here, we investigated response correlates using plasma circulating tumor DNA (ctDNA) and tumor tissue profiling. ALK fusions and ALK with or without TP53 mutations were assessed by next-generation sequencing. End points included objective response rate (ORR), duration of response, and progression-free survival (PFS) by blinded independent central review on the basis of EML4::ALK variants and ALK with or without TP53 or other mutation status. ALK fusions were detected in the ctDNA of 62 patients in the lorlatinib arm and 64 patients in the crizotinib arm. ORRs were numerically higher with lorlatinib versus crizotinib for EML4::ALK variant 1 (v1; 80.0% versus 50.0%) and variant 2 (v2; 85.7% versus 50.0%) but were similar between the arms for variant 3 (v3; 72.2% versus 73.9%). Median PFS in the lorlatinib arm was not reached for EML4::ALK v1 and v2 and was 33.3 months for v3; in the crizotinib arm, median PFS was 7.4 months, not reached, and 5.5 months, respectively. ORRs and PFS were improved with lorlatinib versus crizotinib regardless of TP53 mutation status and in patients harboring preexisting bypass pathway resistance alterations. In the lorlatinib arm, PFS was lower in patients who had a co-occurring TP53 mutation. Results from ctDNA analysis were similar to those observed with tumor tissue samples. Patients with untreated ALK-positive advanced NSCLC derived greater clinical benefits, with higher ORRs and potentially longer PFS, when treated with lorlatinib compared with crizotinib, independent of EML4::ALK variant or ALK mutations, TP53 mutations, or bypass resistance alterations.


Intraparenchymal cerebral cysticercosis in children: a benign prognosis.
This paper reports 26 consecutive cases of cerebral cysticercosis in children, 21 presenting with intraparenchymal mass lesions, two with encephalitic disease, and three with intraventricular (racemous) cysticercosis. The intraparenchymal and encephalitic forms of the disease were benign. Regression of the lesions occurred within four months of diagnosis in all children treated conservatively with antiepileptic drugs, but no antiparasitic drugs. Major morbidity was limited to those patients who were subjected to operative intervention. Intraventricular disease was most malignant; all three patients manifested acute, severely increased intracranial pressure, all required immediate surgical decompression, and one patient died. The apparent overall benign course of intraparenchymal cerebral cysticercosis in children appears not to warrant antiparasitic drug therapy.


Dialysis "no-shows" on saturdays: implications of the weekly hemodialysis schedules on nonadherence and outcomes.
The prevalence of skipped hemodialysis or no-show is higher among African Americans, younger Sages, smokers and illicit drug users. The effect of the weekly hemodialysis treatment schedules (Mondays, Wednesdays, Fridays (MWF); or Tuesdays, Thursdays, Saturdays (TTS)] on adherence is unknown. Our hemodialysis patients were prospectively monitored for compliance over a 12-month duration. Regression analyses were employed for associations between variables and outcomes. A total of 114 African-American patients-mean age 55 +/- 14 and 53% male--were surveyed. Compared to the MWF, the TTS patients had higher rates of no show (2.4% vs. 1.7%, p = NS); shortened hemodialysis time (30% vs. 26%, p = NS); cocaine use (18% vs. 8%, p = 0.09); higher interdialytic weight gain 14.3 +/- 1.8 kg vs. 3.4 +/-1.3 kg, p = 0.005); prolonged length of hospital stay (9 +/- 12 days vs. 4 +/- 5 days, p = 0.02); and higher mortality (16% vs. 8%, p = NS). Compared to other days of the week, the Saturday no-show rate was significantly higher: 31% vs. 13%, 15%, 16%, 17%, 8%, Monday through Friday, respectively. Length of hospital stay correlated with no show (R2 = 0.4, p < 0.0001), while early termination was associated with smoking, cocaine use, female gender, TTS schedule, low serum albumin, hematocrit and adequacy of dialysis (Kt/V) (R2 = 0.6, p = 0.009). The TTS-scheduled hemodialysis patients are less adherent, and have higher morbidity than the MWF Spatients and a predilection for skipping on Saturdays.


Oxidative stress and the pathogenesis of heart failure.
There is strong evidence for an adverse role of oxidative stress in CHF in both animals and humans. Antioxidant supplement have been very effective in the treatment of animal paradigms; however, the data for the possible benefits of treatment for patients with CHF is either retrospective or inferential. Such information is important and should be the subject of prospective randomized trials.


White paper from the ACR Task Force on Print Media in Radiology.
The rapidly changing technological and business environment in which scientific journals are published will necessitate ongoing reassessment of operations, goals, and priorities. In this white paper, the ACR Task Force on Print Media in Radiology reviews the history and role of print media in radiology; discusses current and anticipated societal, technological, and financial challenges; and explores a variety of strategies to help ensure the relevance of professional society publishing in the future.


Effects and safety of Tanreqing injection on viral pneumonia: A protocol for systematic review and meta-analysis.
Influenza-related viral pneumonia is a severe threat to human health, which has caused high morbidity and mortality each year. The objective of this study was to assess the efficacy and safety of Tanreqing Injection therapy in patients with viral pneumonia. This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Web of Science, PubMed, EMBASE and the Cochrane Library were searched for clinical randomized trials in cases with viral pneumonia until 1st of July 2020. We will use a combination of Medical Subject Heading and free-text terms with various synonyms to search based on the Eligibility criteria. Two investigators independently reviewed the included studies and extracted relevant data. The relative risk (RR) and 95% confidence intervals (CIs) of were used as effect estimate. I-square (I) test, substantial heterogeneity, sensitivity analysis and publication bias assessment will be performed accordingly. Stata 14.0 and Review Manger 5.3 are used for meta-analysis and systematic review. The results will be published in a peer-reviewed journal. The results of this review will be widely disseminated through peer-reviewed publications and conference presentations. This evidence may also provide helpful evidence of whether Tanreqing Injection therapy was efficient and safe in patients with viral pneumonia. CRD42020164164.


New approaches concerning the testis of Astyanax lacustris (Characidae): immunohistochemical studies.
Astyanax lacustris, locally known as lambari-do-rabo-amarelo, is a study model for Neotropical fish. Testis of A. lacustris shows deep morphophysiological changes throughout the annual reproductive cycle. This work analyzed the distribution of claudin-1, actin, and cytokeratin as elements of the cytoskeleton in germinal epithelium and interstitium; the distribution of type I collagen, fibronectin, and laminin as extracellular matrix compounds; and the localization of androgen receptor in the testis of this species. Claudin-1, cytokeratin, and actin were present in the Sertoli cells and modified Sertoli cells, and actin was also detected in peritubular myoid cells. Type I collagen were in the interstitial tissue, laminin in the basement membrane of germinal epithelium and endothelium, but fibronectin was additionally detected in the germinal epithelium compartment. The labeling of androgen receptor was higher in peritubular myoid cells and undifferentiated spermatogonia, and weaker labeling was detected in type B spermatogonia. Therefore, the present work highlights new aspects of the biology of the testis of A. lacustris, and contribute to amplify the understanding of this organ.


Gold nanoparticle-enhanced target (AuNPET) as universal solution for laser desorption/ionization mass spectrometry analysis and imaging of low molecular weight compounds.
Preparation is described of a durable surface of cationic gold nanoparticles (AuNPs), covering commercial and custom-made MALDI targets, along with characterization of the nanoparticle surface properties and examples of the use in MS analyses and MS imaging (IMS) of low molecular weight (LMW) organic compounds. Tested compounds include nucleosides, saccharides, amino acids, glycosides, and nucleic bases for MS measurements, as well as over one hundred endogenous compounds in imaging experiment. The nanoparticles covering target plate were enriched in sodium in order to promote sodium-adduct formation. The new surface allows fast analysis, high sensitivity of detection and high mass determination accuracy. Example of application of new Au nanoparticle-enhanced target for fast and simple MS imaging of a fingerprint is also presented.


Bone, sweet bone--osteoporotic fractures in diabetes mellitus.
Diabetes mellitus adversely affects the skeleton and is associated with an increased risk of osteoporosis and fragility fractures. The mechanisms underlying low bone strength are not fully understood but could include impaired accrual of peak bone mass and diabetic complications, such as nephropathy. Type 1 diabetes mellitus (T1DM) affects the skeleton more severely than type 2 diabetes mellitus (T2DM), probably because of the lack of the bone anabolic actions of insulin and other pancreatic hormones. Bone mass can remain high in patients with T2DM, but it does not protect against fractures, as bone quality is impaired. The class of oral antidiabetic drugs known as glitazones can promote bone loss and osteoporotic fractures in postmenopausal women and, therefore, should be avoided if osteoporosis is diagnosed. A physically active, healthy lifestyle and prevention of diabetic complications, along with calcium and vitamin D repletion, represent the mainstay of therapy for osteoporosis in patients with T1DM or T2DM. Assessment of BMD and other risk factors as part of the diagnostic procedure can help design tailored treatment plans. All osteoporosis drugs seem to be effective in patients with diabetes mellitus. Increased awareness of osteoporosis is needed in view of the growing and aging population of patients with diabetes mellitus.


Development of an artificial placenta V: 70 h veno-venous extracorporeal life support after ventilatory failure in premature lambs.
An artificial placenta would change the paradigm of treating extremely premature infants. We hypothesized that using a veno-venous extracorporeal life support (VV-ECLS) artificial placenta after ventilatory failure would stabilize premature lambs and maintain normal fetal physiologic parameters for 70 h. A near-term neonatal lamb model (130 days; term=145) was used. The right jugular vein (drainage) and umbilical vein (reinfusion) were cannulated with 10-12 Fr cannulas. Lambs were then transitioned to an infant ventilator. After respiratory failure, the endotracheal tube was filled with amniotic fluid, and VV-ECLS total artificial placenta support (TAPS) was initiated. Lambs were maintained on TAPS for 70 h. Six of seven lambs survived for 70 h. Mean ventilation time was 57 ± 22 min. During ventilation, mean MAP was 51 ± 14 mmHg, compared to 44 ± 14 mmHg during TAPS (p=0.001). Mean pH and lactate during ventilation were 7.06 ± 0.15 and 5.7 ± 2.3 mmol/L, compared to 7.33 ± 0.07 and 2.0 ± 1.8 mmol/L during TAPS (p<0.001 for both). pO(2) and pCO(2) remained within normal fetal parameters during TAPS, and mean carotid blood flow was 25 ± 7.5 mL/kg/min. Necropsy showed a patent ductus arteriosus and no intracranial hemorrhage in all animals. The artificial placenta stabilized premature lambs after ventilatory failure and maintained fetal circulation, hemodynamic stability, gas exchange, and cerebral perfusion for 70 h.


4-Aminopyridine and low Ca2+ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2-chloroadenosine in rat hippocampal CA1 in vitro.
1. Presynaptic inhibition is mediated by several receptors at the stratum radiatum-CA1 synapse of rat hippocampus. We tested whether the same mechanism is activated by neuropeptide Y (NPY), baclofen and 2-chloroadenosine (2-CA), reasoning that if the receptors all activated the same process, then they should all respond to indirect manipulations of transmitter release in the same manner. 2. The effects on presynaptic inhibition by the potassium channel blocker, 4-aminopyridine (4-AP) and low extracellular concentrations of Ca2+ in the presence of 4-AP were compared using evoked population excitatory postsynaptic potentials (p.e.p.s.p.) responses in the rat hippocampal slice in vitro. 3. Log concentration-effect relationships for the inhibition of excitatory transmission were constructed for all 3 drugs in normal saline, and in the presence of 30 and 100 microM 4-AP. 4-AP reduced the inhibition mediated by all three substances, 100 microM 4-AP was only slightly more effective than 30 microM. 4. Lowering extracellular Ca2+ from 1.5 to 0.75 mM in the presence of 30 microM 4-AP restored the presynaptic inhibition caused by all effective concentrations of NPY and baclofen. By contrast, inhibition caused by 2-CA was not restored by lowering Ca2+, except at concentrations of 2-CA greater than 10 microM. 5. The results are consistent with the hypothesis that presynaptic NPY Y2 and GABAB receptors both inhibit transmitter release by the inhibition of voltage-dependent Ca2+ influx, but that the A1 adenosine receptor may activate a different presynaptic mechanism.


Effects of Tai chi in knee osteoarthritis patients: An overview of systematic reviews and meta-analyses.
Tai Chi (TC) is a complementary therapy for knee osteoarthritis (KOA). Although systematic reviews (SRs) and meta-analyses (Mas) of efficacy studies have been published, the results remain uncertain, and their quality has not yet been fully evaluated. Here, we summarize the existing SRs/Mas, evaluate their quality and level of evidence, and provide a reference for the effectiveness of TC. SRs/Mas of TC therapy for KOA published before February 2023 were retrieved from eight databases in Chinese and English. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, and the Risk of Bias in Systematic (ROBIS) scale were used to assess methodological quality, reporting quality, and risk of bias. Seven SRs/Mas were finally included. One was deemed high quality by AMASTAR-2, while the rest were of critically low quality. In the PRISMA2020 assessment, the response rate of "Yes" for Q7, Q15, Q22, Q24, and Q27 was less than 50%. In the ROBIS assessment, three reports in Phase 3 were high risk and four were low risk. In the efficacy assessment, TC has shown varying degrees of improvement in physical function, pain, stiffness, 6-minute walk test, mental quality of life, TUG, and balance in patients with KOA. TC effectively treats KOA-associated pain, stiffness, body function, and mental quality of life. However, the low methodological quality of the studies and the high risk of migration reduced their reliability. Therefore, these conclusions should be taken with caution. High-quality, large-sample research is needed to provide stronger and more scientific evidence.


Conduction Threshold in Accumulation-Mode InGaZnO Thin Film Transistors.
The onset of inversion in the metal-oxide-semiconductor field-effect transistor (MOSFET) takes place when the surface potential is approximately twice the bulk potential. In contrast, the conduction threshold in accumulation mode transistors, such as the oxide thin film transistor (TFT), has remained ambiguous in view of the complex density of states distribution in the mobility gap. This paper quantitatively describes the conduction threshold of accumulation-mode InGaZnO TFTs as the transition of the Fermi level from deep to tail states, which can be defined as the juxtaposition of linear and exponential dependencies of the accumulated carrier density on energy. Indeed, this permits direct extraction and visualization of the threshold voltage in terms of the second derivative of the drain current with respect to gate voltage.


Microscopic level investigation of Ni(II) sorption on Na-rectorite by EXAFS technique combined with statistical F-tests.
Extended X-ray absorption fine structure (EXAFS) spectroscopy combined with statistical F-tests is used to investigate the local atomic structures of Ni(II) adsorbed on Na-rectorite. The EXAFS analysis results of Ni(II) sorption samples indicate that the first coordination shell consists of ~6 O at the Ni-O interatomic distance (R) of ~2.04 Å. The presence of Ni backscattering at R(Ni-Ni) = 3.06 Å in the second coordination shell suggests the formation of Ni(II) precipitate. The results of F-tests show that the Ni(II) precipitate is Ni-Al layered double hydroxide (LDH). Our results demonstrate that Ni(II) ions are retained via different mechanisms depending on solution conditions. At low pH, Ni retention is controlled mainly by the outer-sphere surface complexation. With increasing pH, outer-sphere and inner-sphere surface complexation dominate Ni uptake. Furthermore, Ni surface loading increases with temperature increasing at pH 6.5 due to the formation of inner-sphere surface complexes and Ni-Al LDH. The formation of Ni-Al LDH becomes the dominate mechanism at the elevated pH and temperature. In the presence of humic substances, the sorption of Ni(II) on Na-rectorite is dominated by the formation of ternary surface complexes. These results are important to understand the physicochemical behavior of Ni(II) in the natural environment.


A novel technique for the optimization and reduction of gamma spectroscopy geometry uncertainties.
Material activation can sometimes cause large heterogeneities in the distribution of radioactivity (hotspots). Moreover, the sample geometry parameters are not always well known. When performing gamma-spectroscopy to quantify the radionuclide inventory in activated materials, often predefined models are used to represent the sample geometry (dimensions, source-to-detector distance, material type) and their activity distribution, for efficiency calibration. This simplification causes uncertainties of the efficiency curves associated with the model and consequently, to the activity results. In this paper, we develop a new approach, based on ISOCS/LabSOCS to quantify and reduce uncertainties originating from the geometry model. The theory is described in this document and an experimental case is discussed.


Targeting EZH2 in SMARCB1-deficient sarcomas: Advances and opportunities to potentiate the efficacy of EZH2 inhibitors.
Soft tissue sarcomas (STSs) are rare mesechymal malignancies characterized by distintive molecular, histological and clinical features. Many STSs are considered as predominatly epigenetic diseases due to underlying chromatin deregulation. Discovery of deregulated functional antagonism between the chromatin remodeling BRG1/BRM-associated (BAFs) and the histone modifying Polycomb repressor complexes (PRCs) has provided novel actionable targets. In epithelioid sarcoma (ES), extracranial, extrarenal malignant rhabdoid tumors (eMRTs) and synovial sarcoma (SS), the total or partial loss of the BAF core subunit SMARCB1, driven by different alterations, is associated with PRC2 deregulation and dependency on its enzymatic subunit, EZH2. In these SMARCB1-deficient STSs, aberrant EZH2 expression and/or activity emerged as a druggable vulnerability. Although preclinical investigation supported EZH2 targeting as a promising therapeutic option, clinical studies demonstrated a variable response to EZH2 inhibitors. Actually, whereas the clinical benefit recorded in ES patients prompted the FDA approval of the EZH2 inhibitor tazemetostat, the modest and sporadic responses observed in eMRT and SS patients highlighted the need to deepen mechanistic as well as pharmacological investigations to improve drug effectiveness. We summarize the current knowledge of different mechanisms driving SMARCB1 deficiency and EZH2 deregulation in ES, eMRT and SS along with preclinical and clinical studies of EZH2-targeting agents. Possible implication of the PRC2- and enzymatic-independent functions of EZH2 and of its homolog, EZH1, in the response to anti-EZH2 agents will be discussed together with combinatorial strategies under investigation to improve the efficacy of EZH2 targeting in these tumors.


The relationship between homotropic and heterotropic cooperativity for angiotensin receptors in smooth muscle.
1. Angiotensin-induced contraction of smooth muscle is accompanied by both homotropic (receptor-receptor) and heterotropic (receptor-G protein) cooperativity. 2. Binding constants for angiotensins II and III at uterine smooth muscle receptors have been compared in bioassays and binding assays, using the competitive antagonist Sarmesin to verify the binding assay/bioassay interrelationship. 3. Agonist affinities determined from binding studies in the presence of GTP/S were found to be similar to the affinities observed in responding rat uterine tissues under conditions which eliminate positive homotropic cooperativity, suggesting that heterotropic cooperativity and homotropic cooperativity are interdependent events for smooth muscle contraction. 4. The data are consistent with an allosteric or autosteric mechanism of receptor function involving cooperativity between two agonist binding sites on the receptor. 5. The model has been used to calculate homotropic efficacies for angiotensins II and III from bioassay data and binding data, respectively.


Syncytin 1 in the human placenta.
This study characterises HERV-W (syncytin 1) expression in normal and pathologic placenta and in BeWo cells. HERV-W mRNA levels were higher in the first trimester than at term, and similar patterns were observed with another retrovirally-derived mRNA species, ERV-3. N-glycosylated syncytin 1 precursor (73 kDa) is cleaved to surface-associated (SU) and transmembrane (TM) subunits. Both were evident in villous trophoblast, where perinuclear and punctate cytoplasmic deposits were observed, and linear TM subunit immunoreactivity was seen at the syncytial microvillous membrane. Punctate immunoreactivity was seen in BeWo cells with antibodies to SU and TM, and the two were co-localised. SU immunoreactivity was observed in association with fetal endothelium, and this effect was increased in tissue from pre-eclamptic placentas, which also showed a higher level of total SU protein. Absence of the TM subunit from endothelium suggests it is not a biosynthetic source. We suggest that SU is released from trophoblast into fetal circulation where it may bind vascular endothelium.


Alterations in prealbumin concentration after adrenal autotransplantation for Parkinson's disease.
The cerebrospinal fluid of eight patients with Parkinson's disease who underwent adrenal medullary autotransplantation was analyzed using SDS-polyacrylamide gel electrophoresis. A protein, subsequently identified as prealbumin, was noted to change in concentration over the intraoperative to 18-month postoperative time course. The qualitative changes observed on visual inspection were confirmed and quantified using laser densitometry. The concentration of prealbumin increased by an average of 90% when the intraoperative and 12-month samples were compared. This increase persisted at 18 months. The ratio of prealbumin to albumin also increased from intraoperative to 12 months by an average of 56%. This suggests that the increases in PA are the result of choroid plexus activation rather than a nonspecific breakdown of the blood-brain barrier. Given the association of prealbumin with other nervous system diseases, as well as its known ability to bind multiple substances, these findings may have important implications. Alterations in prealbumin may be responsible for the improvement seen in some patients who receive adrenal medullary autotransplants. Alternatively, prealbumin may be implicated in the pathophysiology of Parkinson's disease.


Chronic exposure to sublethal concentrations of saxitoxin reduces antioxidant activity and immunity in zebrafish but does not affect reproductive parameters.
Saxitoxin produced by dinoflagellates and cyanobacteria can be transferred to humans through intoxicated organisms such as fish, but limited research has addressed the adverse effects of this toxin on aquatic organisms. In this study, we measured the potential effects of a 90-day exposure to saxitoxin (0.1 or 1 µg·L - 1) on body weight and length, antioxidant defense system, immunity, sex hormones, and genes involved in associated key metabolic pathways in zebrafish (Danio rerio). Significant impairments in body weight and length were observed in response to 1 µg·L - 1 saxitoxin in both male and female zebrafish. A significant increase in the levels of malondialdehyde, together with decreased enzymatic activities of catalase and superoxide dismutase, was observed in fish of both sexes exposed to 1 µg·L - 1 saxitoxin, indicating the occurrence of lipid peroxidation and oxidative stress. Immune parameters such as alternative complement activity, lysozyme activity, and immunoglobulin content were also significantly reduced. However, exposure of male and female zebrafish to saxitoxin for 90 days did not significantly affect reproductive parameters such as the gonadosomatic index and plasma concentrations of vitellogenin, estradiol, and 11-keto testosterone. Transcriptional responses showed similar trends to those of the biochemical parameters, as genes involved in the antioxidant defense system and immunity were downregulated, whereas the transcription of genes related to reproductive metabolism showed no significant change upon treatment with 1 µg·L - 1 saxitoxin. Our findings indicate that long-term exposure to a sublethal concentration of saxitoxin can inhibit growth through induction of oxidative stress and immunosuppression, while the reproductive parameters of zebrafish are not a main target of this toxin at sublethal concentrations.


Redistribution of iron oxides in aggregates induced by pe + pH variation alters Cd availability in paddy soils.
In this study, the effect of unstable pe + pH levels on the transformation of Fe oxides in different-sized soil fractions and its impact on Cd speciation were explored. Paddy soil samples collected from two locations in China were cultivated for two months under one of four pe + pH conditions: flooding + N2 (T1), flooding (T2), 70% water holding capacity (T3), and 70% water holding capacity + O2 (T4). Chemical analysis and X-ray diffraction (XRD) were used to identify the mineralogical phases and species of Fe and Cd in paddy soils. The results show that the decrease of soil pe + pH level favored the transformation of well-crystallized Fe oxides (Fec), such as hematite and goethite, into poorly-crystallized (Feo) and organically-complexed (Fep) forms. The transformation promoted the binding of Cd to Fe oxides and was primarily responsible for up to a 41.8% decrease of soil DTPA (diethylenetriaminepentaacetic acid)-extractable-Cd content. In addition, the decline in pe + pH value reduced Fe concentrations in soil particle fractions of 0.2-2-mm (17.8%-30.6%) and <0.002-mm (20.7%-31.7%) of the two flooding treatments. The decreased Fe concentrations were closely associated with less Fec contents in these same fractions and more Feo and Fep in coarser aggregates (P < 0.01). Importantly, the increase in contents of Feo and Fep in the 0.002-2 mm fraction were significantly correlated with content of Fe-/Mn-oxide-bound Cd (OX-Cd) in larger particle-size fractions (P < 0.01). Furthermore, the increasing content of OX-Cd played a crucial role in reducing DTPA-Cd content. This study demonstrates that low pe + pH values favor the transformation of crystalline Fe oxides into a poorly-crystallized and organically-complexed phase, which facilitates Cd accumulation in coarser aggregates and enhances Cd stability in paddy soils.


Longitudinal observation of mandibular motion pattern in patients with skeletal Class III malocclusion subsequent to orthognathic surgery.
The aims of the present study were to delineate the characteristic patterns of 3-dimensional (3D) mandibular movement in patients with skeletal Class III malocclusion compared with normal individuals and to investigate the longitudinal changes in mandible and condylar motion after orthognathic surgery (OGS). The subjects in the present prospective study consisted of 2 groups. The OGS group included 24 patients with skeletal Class III who underwent OGS. The control group consisted of 25 patients who underwent orthodontic treatment only. The patient records included demographic data, lateral and posteroanterior cephalometric radiographs before treatment, and serial mandibular motion data. In the OGS group, the mandibular motion data were obtained before OGS (T1), 1 month after OGS (T2), and at least 6 months after OGS (T3). The differences in cephalometric measurements and mandibular movements between the 2 groups were compared. The Pearson correlation test was performed to assess the relationship between the cephalometric measurements and the mandibular movements. Serial changes in mandibular movement in the OGS group were also compared. The skeletal pattern in the OGS group demonstrated retrusive maxilla and a protrusive mandible, with a larger mandibular plane angle. For the incisal range of motion, the OGS group's maximal mouth opening was larger than the control group's by 6.9 mm. In the OGS group, the condylar range of motion in retrusion and the Bennett angle were asymmetric. Skeletal Class III patients tended to have a smaller range of condylar retrusion. At 1 month after OGS, the maximal incisal range of motion decreased from 57.23 to 25.61 mm. Other variables, including laterotrusion, movement velocity, and angle and distance of condylar movement in protrusion, reduced significantly. The Bennett angle demonstrated increased symmetry on both sides. Six months after OGS, the condylar motion in opening demonstrated improvements, but to a lesser extent than at T1. The condylar motion in retrusion recovered totally. The maximum incisal range of motion reduced slightly, but remained similar in value to that of the control group. The variables, including laterotrusion, movement velocity, and angle and distance of condylar movement in protrusion, demonstrated total recovery. The mandibular movement variables at T3 were not significantly different from those of the control group. Skeletal Class III patients demonstrated a larger maximal mouth opening than did the controls, along with similar laterotrusion, but with a smaller retrusive condylar range of movement. The range of incisor motion and condylar movement did not correlate. The deterioration in mandibular motion after OGS can recover totally within 6 months. At T3, the mandibular movement remained consistent with the amount in normal subjects.


Synthesis and antimicrobial activity evaluation of pyrazole derivatives containing the imidazo[2,1-b][1,3,4]thiadiazole moiety.
Four series of novel pyrazole derivatives (compounds 17a-m, 18a-m, 19a-g, and 20a-g) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds (17a-m, 18k-m, and 19b-g) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gram-negative bacteria. Among them, compounds 17l (minimum inhibitory concentration [MIC] = 0.25 µg/mL) and 17m (MIC = 0.25 µg/mL) showed the strongest antifungal activity, being 2- and 4-fold more active than the positive controls gatifloxacin and fluconazole, respectively. In particular, compound 17l showed little cytotoxicity against human LO2 cells and did not exhibit hemolysis at ultrahigh concentrations, as did the positive control compounds gatifloxacin and fluconazole. These results indicate that these compounds are valuable for further development as antifungal agents.


Increase in inflammatory cytokines in median nerves in a rat model of repetitive motion injury.
We examined cytokines in rat median nerves following performance of a high repetition reaching and grasping task at a rate of 8 reaches/min for up to 8 weeks. IL-1alpha, IL-1beta, TNF-alpha, IL-6 and IL-10 were analyzed by immunohistochemistry. Double-labeling immunohistochemistry for ED1, a marker of phagocytic macrophages, was also performed. We found increased immunoexpression of IL-6 by week 3, increases in all 5 cytokines by week 5. This response was transient as all cytokines returned to control levels by 8 weeks of performance of a high repetition negligible force task. Cytokine sources included Schwann cells, fibroblasts and phagocytic macrophages (ED1-immunopositive). These findings suggest that cytokines are involved in the pathophysiology of repetitive motion injuries in peripheral nerves.


Alterations in cartilage type-II procollagen and aggrecan contents in synovial fluid in equine osteochondrosis.
The etiology and pathophysiology of osteochondrosis remain poorly understood because it is difficult to obtain material from lesions in the early stage of this disease and because there is no satisfactory experimental animal model. We wished to determine whether there are changes in articular cartilage turnover in equine osteochondrosis, which closely resembles the human disease, by assaying cartilage matrix molecules in synovial fluids. We used immunoassays that measure a keratan sulfate epitope and the epitope 846 on the cartilage proteoglycan aggrecan and the C-propeptide of cartilage type-II procollagen, which is released following the synthesis of this molecule, to analyse synovial fluids from equine tarsocrural joints with and without osteochondrosis. In young horses with osteochondrosis, there was a significant increase of C-propeptide of type-II procollagen accompanied by a decrease in the 846 and keratan sulfate epitopes. The results identify differential alterations in aggrecan and type-II collagen turnover in the cartilage matrix in young animals with osteochondrosis that may contribute to the pathological degeneration of articular cartilage in this disease.


Cocaine Effects on Reproductive Behavior and Fertility: An Overview.
Cocaine is one of the most widely used drugs that, due to its molecular properties, causes various behavioral alterations, including sexual behavior. In vivo and in vitro studies conducted mainly in mammals have shown various disorders of sexual activity and morpho-functional dysfunctions of the gonads in both sexes. Although the modalities are still unclear, cocaine has been shown to alter the cell cycle, induce apoptosis, and alter sperm motility. In females, this drug alters the formation of the meiotic spindle as well as may obstruct the ovulation mechanism of mature oocytes. The data provided in this review, in addition to reviewing the current literature on the main effects of cocaine on spermatogenesis and oogenesis mainly in mammals, will hopefully provide a basic overview that may help and support further future studies on the molecular interaction of cocaine and its metabolites with germ cells.


Synthesis and comparative evaluation of 4-oxa- and 4-aza-podophyllotoxins as antiproliferative microtubule destabilizing agents.
A series of novel 4-oxa-podophyllotoxin derivatives 7 featuring the intact lactone ring D and various substituents in rings B and E has been synthesized and evaluated in a phenotypic sea urchin embryo assay along with the representative 4-aza-analogs 5 for their antimitotic and microtubule destabilizing activity. The most active compounds exhibited myristicin-derived or a 3',5'-dimethoxy substitution pattern in the ring E and a 6-methoxy moiety replacing the methylenedioxy ring A. Compounds 5xb, 5xe, 5yb, 7xa, 7xb, and 7xc showed potent antiproliferative effects in the NCI60 cytotoxicity screen. Notably, growth of the multi-drug resistant NCI/ADR-RES cells was more affected by these agents than the parent OVCAR-8 cell line. Although generally 4-oxa-podophyllotoxins were less potent than the respective 4-aza-derivatives in these assays, stability of the former series towards oxidation may prove to be of interest for the development of anticancer agents with in vivo activity.


The features of acquired thrombotic thrombocytopenic purpura occurring at advanced age.
Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare life-threatening thrombotic microangiopathy (TMA) affecting more frequently women of 30-50 years of age. There is scarce information on the clinical features of aTTP occurring in the elderly. Our goal was to evaluate the impact of an elderly-onset disease on the expression, severity and management of aTTP. We performed a cross-sectional study of patients enrolled in the Milan TTP Registry (www.ttpdatabase.org) after a first acute episode of aTTP from January 2002 to March 2018. The aTTP diagnosis was suspected on the basis of the presence of thrombocytopenia and microangiopathic hemolytic anemia with no alternative causes, and was confirmed centrally by a severe plasma deficiency of ADAMTS13 activity (<10%). Triggers, clinical manifestations, laboratory parameters, management and outcome of the first acute events of elderly-onset aTTP patients (≥65 years) were compared with those of younger patients. Among 143 eligible patients, 16 (11%) were elderly at onset. In comparison with younger cases they showed a lower rate of bleeding symptoms and severe anemia (30% and 18%), with a trend towards a higher rate of neurological and renal signs and symptoms. These patients were less frequently treated with plasma exchange and corticosteroids and more often with plasma infusion. No difference for gender, triggers and episode outcomes was observed. Older patients with aTTP differed from younger patients mainly for being treated less frequently with plasma exchange and corticosteroids, perhaps for the perceived risks associated with these treatments in the elderly.


Clinical applications of BMP-7/OP-1 in fractures, nonunions and spinal fusion.
Since the identification of the osteogenic protein-1 (OP-1) gene, also called bone morphogenetic protein-7 (BMP-7), almost 20 years ago, OP-1 has become one of the most characteristic members of the BMP family. The biological activity of recombinant human OP-1 has been defined using a variety of animal models. These studies have demonstrated that local implantation of OP-1 in combination with a collagen matrix results in the repair of critical size defects in long bones and in craniofacial bones and the formation of bony fusion masses in spinal fusions. Clinical trials investigating long bone applications have provided supportive evidence for the use of OP-1 in the treatment of open tibial fractures, distal tibial fractures, tibial nonunions, scaphoid nonunions and atrophic long bone nonunions. Clinical studies investigating spinal fusion applications have provided supportive evidence for the use of OP-1 in posterolateral lumbar models and compromised patients as an adjunct or as a replacement for autograft. Both long bone repair and spinal fusion studies have demonstrated the efficacy and safety of OP-1 by clinical outcomes and radiographic measures. Future clinical investigations will be needed to better define variables, such as dose, scaffold and route of administration. Clearly the use of BMPs in orthopaedics is still in its formative stage, but the data suggest an exciting and promising future for the development of new therapeutic applications.


Evaluation of oil-producing algae as potential biodiesel feedstock.
This study attempted to connect the dots between laboratory research and the outdoors. Chlorella sp. NJ-18 was selected among seven oil-producing algae cultivated in this study because it had the highest lipid productivity. The nitrogen and phosphorus concentrations for cultivating this Chlorella strain were optimized indoors. This strain was incubated outdoors in a 70 L photobioreactor, containing the favorable nitrogen (8.32 mM urea) and phosphorus (0.18 mM monopotassium phosphate) concentrations. Semi-continuous cultivation was performed by harvesting 30 L biomass and replacing it with fresh medium. The maximum biomass and lipid productivity acquired outdoors were 91.84 and 24.05 mg L(-1) d(-1), respectively. Furthermore, biomass productivity could be maintained at a high level throughout the cultivation process when using the semi-continuous mode, whereas it decreased dramatically in batch cultures. More than 95% of the total fatty acids obtained were C16 and C18, which are the main components for biofuel.


Epidemiology of hepatitis delta virus (HDV) infection.
Markers of hepatitis delta virus (HDV) infection have been detected all over the five continents. Geographical prevalence varied heavily: HDV infection is very rare in Far East Asia, but extremely frequent in Arabian countries, in Romania and in certain Indian populations of South America. In Europe and in the USA the infection is widely spread among high risk groups such as intravenous drug abusers and haemophiliacs.


A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity.
We report the characterization of BopE, a type III secreted protein that is encoded adjacent to the Burkholderia pseudomallei bsa locus and is homologous to Salmonella enterica SopE/SopE2. Inactivation of bopE impaired bacterial entry into HeLa cells, indicating that BopE facilitates invasion. Consistent with this notion, BopE expressed in eukaryotic cells induced rearrangements in the subcortical actin cytoskeleton, and purified BopE exhibited guanine nucleotide exchange factor activity for Cdc42 and Rac1 in vitro.


Spatial and temporal variation in Chaetanaphothrips orchidii Moulton (Thysanoptera: Thripidae) population and its damage on lemon.
Chaetanaphothrips orchidii Moulton has recently been detected in lemon (Citrus limon) orchards in northwest Argentina, causing high levels of damage on fruits. Severe damage results in the rejection of fruit for export, which must then be sold in the industry. However, the restrictions imposed by the citrus industry on insecticide residues sometimes also result in fruit rejection. Here, we studied the ecology and behavior of C. orchidii in order to propose a pest management strategy that could meet both export and industry demands. Seasonal occurrence and canopy distribution of C. orchidii in lemon orchards were evaluated, and field experimental manipulations of thrips populations were performed to analyze how the length (45, 100, 130, and 200 days) and timing (January, February, or March) of C. orchidii activity related with fruit damage. Lemons harvested during summer showed lower infestation levels (∼0.64 individual per fruit) than those harvested in winter (∼1.88 individuals per fruit). Higher proportions of damaged fruits were recorded in the lower part of the tree. Changes in the population levels of C. orchidii were closely associated with fruit phenology. The longer the lemon fruits were exposed to the thrips, the higher was the damage. However, the time of infestations did not affect fruit damage. Our data provide a first step towards understanding the factors that determine the severity of fruit damage caused by C. orchidii in northwest Argentina.


Biological effects of lysophospholipids.
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are potent biologically active lipid mediators that exert a wide range of cellular effects through specific G protein-coupled receptors. To date, four LPA receptors and five S1P receptors have been identified. These receptors are expressed in a large number of tissues and cell types, allowing for a wide variety of cellular responses to lysophospholipid signaling, including cell adhesion, cell motility, cytoskeletal changes, proliferation, angiogenesis, process retraction, and cell survival. In addition, recent studies in mice show that specific lysophospholipid receptors are required for proper cardiovascular, immune, respiratory, and reproductive system development and function. Lysophospholipid receptors may also have specific roles in cancer and other diseases. This review will cover identification and expression of the lysophospholipid receptors, as well as receptor signaling properties and function. Additionally, phenotypes of mice deficient for specific lysophospholipid receptors will be discussed to demonstrate how these animals have furthered our understanding of the role lysophospholipids play in normal biology and disease.


Resident impression management within feedback conversations: A qualitative study.
Medical education is moving to conceptualise feedback as a bidirectional learning conversation. Within this conversation, learners experience a tension between assessment and feedback. That perceived tension affects learners' outward performances. In this study, we aimed to characterise residents' experiences with this tension and its effect on learner authenticity within feedback conversations. In this constructivist grounded theory study, the authors were informed by Goffman's theory of impression management. During data analysis, Dweck's theory of mindset was adopted. The authors conducted semi-structured interviews with 15 internal medicine residents. Data collection and analysis were conducted iteratively, using constant comparison to identify themes coinciding with impression management and mindset, ultimately developing a theoretical model to help explain residents' responses to tensions within feedback conversations. Residents constantly felt 'scrutinized', and this affected their engagement in feedback conversations. They staged a performance within those conversations, linked to their underlying mindset: growth or fixed. Growth mindset was characterised by a focus on development as a physician and was associated with asking questions and seeking opportunities for growth. Fixed mindset was characterised by a focus on achieving a favourable evaluation and was associated with a hesitation to ask questions when faced with uncertainty and admit opportunities for growth, because they were concerned about impression management. Context influenced mindset and impression management. Residents adopted a fixed mindset and managed impressions when they perceived the permanence or consequences of evaluations within feedback. Residents adopted a growth mindset when they trusted the supervisor. Residents assess the context of feedback conversations, altering the authenticity of their behaviours. Context, including the perceptions of formal assessment and relationships with supervisors, affected residents' mindset and impression management. Providing space for relationship-building and clarifying the purpose and structure of assessment may be helpful in supporting effective learning conversations in graduate medical education.


Products, reactive species and mechanisms of PFOA degradation in a self-pulsing discharge (SPD) plasma reactor.
Non-thermal plasma is a promising tool for novel technologies to treat water contaminated by recalcitrant pollutants. We report here on products, reactive species and mechanisms of the efficient degradation of perfluorooctanoic acid (PFOA) achieved with a self-pulsing discharge developed previously in our lab. Air or argon were used as plasma feed gas, ultrapure or tap water as aqueous medium. Identified organic intermediate products arise from chain-shortening and defluorination reactions, the latter achieving not only C-F to C-H exchange (hydro-de-fluorination), as reported in the literature, but also C-F to C-OH exchange (hydroxy-de-fluorination). In contrast with chain-shortening, yielding lower homologues of PFOA via selective cleavage of the C-C bond at the carboxylate group, defluorination occurs at various sites of the alkyl chain giving mixtures of different isomeric products. Plasma generated reactive species were investigated under all experimental conditions tested, using specific chemical probes and optical emission spectroscopy. Cross-analysis of the results revealed a striking direct correlation of energy efficiency for PFOA degradation and for production of plasma electrons. In contrast, no correlation was observed for emission bands of either Ar+ or OH radical. These results indicate a prevalent role of plasma electrons in initiating PFOA degradation using self-pulsing discharge plasma above the liquid.


ADP-induced platelet aggregation and metoprolol treatment of myocardial infarction patients. A controlled study.
The effect of metoprolol on platelet aggregation was investigated in a group of postmyocardial infarction (MI) patients. The study was double-blind and included 63 subjects; 30 patients were maintained on metoprolol and 33 received placebo treatment. Adenosine diphosphate (ADP)-induced platelet aggregation was carried out in each subject close to 4 weeks after the acute MI. It was demonstrated that metoprolol as compared to placebo did not influence ADP-induced platelet aggregation in the present clinical setting.


Glycated albumin.
Glycated hemoglobin (HbA1c) is the reference test for long-term glucose monitoring. However, HbA1c is not recommended in several situations such as hemoglobinopathies, pregnancy or chronic kidney disease. The quantification of serum glycated albumin (GA) can serve as an alternative in these situations. In fact, serum albumin may undergo structural changes by glycation which impacts on its function and plays a major role in the genesis of diabetes mellitus complications. GA can be measured accurately either on serum or plasma collected on tubes containing lithium heparin or EDTA as anticoagulant. The introduction of a new enzymatic assay has increased the diffusion of this test, in both research and clinical settings. This enzymatic assay is rapid, sensitive and adaptable on routine clinical chemistry analyzers. GA allows an evaluation of the glycemic balance over a period of approximately three weeks, and it is particularly interesting for diabetic patients with chronic kidney disease.


Visual disorders associated with Alzheimer's disease and optometric management.
Patients with early or undiagnosed Alzheimer's disease commonly experience visual disorders that may cause them to seek optometric evaluation. As this condition is difficult to diagnose, clinicians may be faced with a confusing presentation of symptoms. Typically, visual perceptual disorders exist in the absence of abnormal ocular findings. Familiarity with the visual disorders associated with Alzheimer's disease and recognition of the value of neuropsychological evaluation are critical to accurate diagnosis and management. Case presentations are used to illustrate these issues.


Promoting agricultural innovation as a means of improving China's rural environment.
Farmer-led agricultural innovation is increasingly viewed as a potential approach to sustainable agriculture especially promoting rural revitalization as well as mitigating agricultural non-point source pollution. However, little research has yet been paid to evaluating the environmental contribution caused by these emerging agricultural innovations. Using data generated in the Qingpu District of Shanghai, this paper focuses on the new agri-business entities and evaluates the impact of agricultural innovation on changes in their use of chemical fertilizers. The findings indicate that different forms of agricultural innovation have radically different outcomes. Innovation of new production technologies and sales tend to have negative impacts on the environment, while both vertical integration with manufacturing-processing-sales activities, and horizontal integration with service activities, are found to make a positive environmental contribution. The paper argues that the different sources of value added generated by innovation provide different incentives for farmers. Those with a narrow concentration on efficiency and market scale tend to intensify their output-maximized production, while those shifting to processing and service activities rely more on the quality and service centered production, which tends to create less damage to the environment.