Differences in Survival of Clear Cell Metastatic Renal Cell Carcinoma According to Partial vs. Radical Cytoreductive Nephrectomy.
It is unknown whether previously reported other-cause mortality (OCM) advantage of partial cytoreductive nephrectomy (PCN) vs. radical cytoreductive nephrectomy (RCN) still applies to contemporary clear cell metastatic renal cell carcinoma (ccmRCC) patients. We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify ccmRCC patients treated with PCN and RCN. Temporal trends of PCN rates within the SEER database were tabulated. After propensity score matching (PSM), cumulative incidence plots depicted 5-year OCM and cancer-specific mortality (CSM) of PCN and RCN patients. Multivariable Cox regression models tested for differences between PCN vs. RCN. Of 5149 study patients, 237 (5%) underwent PCN vs. 4912 (95%) RCN. In the SEER database 2004 to 2019, rates of PCN in ccmRCC patients increased from 3.0% to 8.0% (estimated annual percent change [EAPC]: 3.0%; P = .04). After PSM, 5-year OCM rates were 2.4 vs. 7.5% for respectively PCN vs. RCN patients (P = .036). 5-year CSM rates were 50.8 vs. 53.6% for respectively PCN and RCN patients (P = .57). In multivariable Cox regression models, PCN was associated with lower OCM (Hazard Ratio (HR): 0.39; 95% confidence interval (CI): 0.18-0.84; P = .02) but did not affect CSM rates (HR: 0.99; 95% CI: 0.76-1.29; P = .96). We confirm the existence of OCM advantage after PCN vs. RCN in contemporary ccmRCC patients.


The 2022 India Report Card on physical activity for children and adolescents.
With strong evidence of physical inactivity's link to chronic disease and economic burden - particularly with childhood active living behaviors tracking into adulthood - it is imperative to promote physical activity among children and adolescents in India. To evaluate active living patterns among Indian children and adolescents. The India Report Card (IRC) team, which consists of experts in India and Canada, systematically collected and appraised evidence on 11 indicators of active living, including 5 behavioral (Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behavior), 2 individual-level (Physical Fitness, Yoga) and 4 sources of influence (Family and Peers, School, Community and Built Environment, Government). Peer-reviewed articles were appraised based on national representativeness, sample size, and data quality. Grey literature was appraised based on comprehensiveness, validity of the sources, and representativeness. All indicators were assessed against parameters provided by the Active Healthy Kids Global Alliance. Active Transportation and Government Strategies were ranked highest with a B- and C+ grade, respectively. Overall Physical Activity and Schools were assigned a C grade, while Sedentary Behavior and Community and Built Environment were given D grades. Yoga was the lowest ranking indicator with a D- grade. Organized Sport Participation, Active Play, Family and Peers, and Physical Fitness were all graded incomplete. Active Transportation, Government Strategies, and Overall Physical Activity have improved since the 2018 IRC, a positive trend that needs to be translated to other indicators. However, Sedentary Behavior has consistently worsened, with grades C, C-, and D-, in 2016, 2018, and 2022, respectively. Evidence generated by the 2022 IRC suggests opportunities for improvement not only in India, but also the 56 other countries taking part in Global Matrix 4.0.


Effects of ethanol feeding and withdrawal on plasma glutathione elimination in the rat.
Chronic ethanol feeding increases hepatic turnover and sinusoidal efflux of glutathione in rats. The present study was performed to determine whether the observed increase in glutathione efflux was due to increased extrahepatic requirements for glutathione. The concentration and disposition of plasma glutathione were determined in rats fed liquid diets containing 36% of calories as ethanol or pair-fed an isocaloric mixture with carbohydrate replacing ethanol calories for 5 to 8 weeks. The half-life and plasma clearance of [35S]glutathione were found to be similar in ethanol-fed and control rats and in rats withdrawn 24 hr from ethanol. Uptakes of the sulfur moiety of [35S]glutathione by kidney, jejunal mucosa, liver, lung, spleen, muscle and heart were also unchanged by ethanol feeding. The plasma glutathione concentration was significantly higher in ethanol-withdrawn rats 22.30 +/- 3.06 nmoles per ml (p less than 0.05) compared to pair-fed controls (13.51 +/- 2.04), while rats continuing to drink ethanol had intermediate levels (16.96 +/- 2.22). Plasma cysteine levels were slightly, but not significantly, higher in ethanol-fed rats. These findings suggest that increased sinusoidal efflux of glutathione in ethanol-fed rats is due to a direct effect of ethanol on hepatic glutathione transport and not due to an alteration in extrahepatic disposition of glutathione. In order to characterize further the effects of ethanol feeding on glutathione-dependent detoxification, activities of glutathione S-transferase, glutathione reductase and gamma-glutamyltransferase were determined.(ABSTRACT TRUNCATED AT 250 WORDS)


PANDA: A comprehensive and flexible tool for quantitative proteomics data analysis.
As the experiment techniques and strategies in quantitative proteomics are improving rapidly, the corresponding algorithms and tools for protein quantification with high accuracy and precision are continuously required to be proposed. Here, we present a comprehensive and flexible tool named PANDA for proteomics data quantification. PANDA, which supports both label-free and labeled quantifications, is compatible with existing peptide identification tools and pipelines with considerable flexibility. Compared with MaxQuant on several complex datasets, PANDA was proved to be more accurate and precise with less computation time. Additionally, PANDA is an easy-to-use desktop application tool with user-friendly interfaces. PANDA is freely available for download at https://sourceforge.net/projects/panda-tools/. Supplementary data are available at Bioinformatics online.


Duration and specificity of antibodies to hepatitis C virus in chronic active hepatitis.
To determine the duration and specificity of antibodies to hepatitis C virus in hepatitis B surface antigen-negative chronic active hepatitis, sera from 19 patients seropositive by enzyme immunoassay were assessed by recombinant immunoblot assay. Only 12 of the 19 patients were reactive by immunoblot assay (63%). Patients nonreactive by immunoblot assay had lower signal-cutoff ratios by enzyme immunoassay (1.3 +/- 0.2 vs. 6.5 +/- 0.1; P less than 0.05), higher serum immunoglobulin G levels (4082 +/- 301 vs. 1760 +/- 143 mg/dL; P less than 0.05), and higher serum gamma globulin levels (3.3 +/- 0.5 vs. 2.04 +/- 0.1 g/dL; P less than 0.05) than reactive patients. Twelve of 14 patients with serial studies remained seropositive after 39 +/- 11 months of follow-up (range, 7-113 months). Only patients nonreactive by immunoblot assay became seronegative by enzyme immunoassay during corticosteroid therapy (2/3 vs. 0/6 patients). It is concluded that seropositivity by enzyme immunoassay may not be documented by immunoblot assay. Patients nonreactive by immunoblot assay have lower signal-cutoff ratios and higher gamma globulin levels than reactive patients, and their seropositivity may be nonspecific. Patients nonreactive by immunoblot assay may lose seropositivity by enzyme immunoassay during corticosteroid therapy.


Quantitative Proteomic analysis on Activated Hepatic Stellate Cells reversion Reveal STAT1 as a key regulator between Liver Fibrosis and recovery.
Understanding the changes of activated HSCs reversion is an essential step toward clarifying the potential roles of HSCs in the treatment of liver fibrosis. In this study, we chose adipocyte differentiation mixture to induce LX-2 cells for 2 days in vitro as reversion phase, comparing with normal cultured LX-2 cells as activation phase. Mass spectrometric-based SILAC technology was adopted to study differentially expressed proteome of LX-2 cells between reversion and activation. Compared with activated HSCs, 273 proteins showed significant differences in reverted HSCs. The main pathway of up-regulated proteins associated with reversion of HSCs mainly related to oxidation-reduction and lipid metabolism, while the top pathway of down-regulated proteins was found in regulated cytoskeleton formation. Changes in the expression levels of selected proteins were verified by Western blotting analysis, especially STAT1, FLNA, LASP1, and NAMPT proteins. The distinct roles of STAT1 were further analyzed between activated and reverted of HSCs, it was found that STAT1 could affect cell proliferation of HSCs and could be viewed as a key regulator in the reversion of HSCs. Thus, the proteomic analysis could accelerate our understanding of the mechanisms of HSC reversion on cessation of fibrogenic stimuli and provide new targets for antifibrotic liver therapy.


Author Correction: Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.


Clinical Value of PET/CT in Staging Melanoma and Potential New Radiotracers.
18F-FDG PET/CT has been suggested as an effective tool to stage patients affected by melanoma. In the latest years, new radiopharmaceuticals have been proposed and the use of hybrid PET/ceCT has emerged. To review recent evidence on the role of PET/CT in melanoma staging as well as its potential for future developments. A comprehensive computer literature search of PubMed/MEDLINE was carried out to find relevant published articles concerning the feasibility of PET/CT in patients with malignant melanoma. Some recent studies about potentials and limitations of 18F-FDG PET/CT in staging melanoma, new PET radiotracers beyond 18F-FDG and application of hybrid PET/ceCT have been reviewed and discussed. PET/CT plays an important role in the staging workup of patients affected by melanoma. New radiopharmaceuticals and hybrid PET/ceCT could improve the potential of this diagnostic tool in this field.


Quantum Knowledge in Phase Space.
Quantum physics through the lens of Bayesian statistics considers probability to be a degree of belief and subjective. A Bayesian derivation of the probability density function in phase space is presented. Then, a Kullback-Liebler divergence in phase space is introduced to define interference and entanglement. Comparisons between each of these two quantities and the entropy are made. A brief presentation of entanglement in phase space to the spin degree of freedom and an extension to mixed states completes the work.


Valve replacement in children: guidelines for selection of prosthesis and timing of surgical intervention.
One hundred fifty-nine patients ranging from 3 months to 18 years old (mean, 8.1 +/- 3.7 years) underwent 162 primary valve implantations. A porcine valve was used in 104 patients, a St. Jude Medical valve in 40, and a Björk-Shiley valve in 18. The valve replaced was the aortic in 25 patients, the mitral (systemic atrioventricular [AV] valve) in 43, the pulmonary in 71, and the tricuspid (pulmonary AV valve) in 23. Hospital mortality was 6%. Patients with a Björk-Shiley valve received warfarin sodium anticoagulation, and those with a St. Jude Medical valve were given salicylates and dipyridamole. Follow-up is available on all patients 0.6 to 12 years postoperatively (mean, 6.3 +/- 2.6 years). New York Heart Association Functional Class improved in 62% and remained unchanged in 38% of the patients. Thromboembolic complications occurred in only 8 (57%) of 14 patients with a St. Jude Medical valve in the right (pulmonary) side and in 3 (12%) of 26 with the valve in the left (systemic) side of the circulation. Bacterial endocarditis developed in 3 patients, all with porcine valves. Early valve replacement, less than 2 years after detection of hemodynamic deterioration, resulted in improvement in the ventricular ejection fraction in 25 of 29 patients (from 81 +/- 14% to 90 +/- 12% of normal; p less than 0.05). In contrast, the ejection fraction remained abnormal in all 22 patients with delayed valve insertion (more than 2 years) (81 +/- 16% of normal preoperatively and 80 +/- 10% of normal following operation; p = not significant).


Violence against teachers in South Korea: negative consequences and factors leading to emotional distress.
Empirical studies indicate that violence against teachers is a globally prevalent phenomenon and has damaging negative effects on victimized teachers' physical and emotional well-being and teaching effectiveness. Nevertheless, limited empirical research has been conducted to identify factors affecting emotional distress among victimized teachers. This research contributes to the literature by exploring negative consequence of victimization and factors associated with victimized teachers' emotional distress in a South Korean context. The results indicate that students' verbal and noncontact physical aggression are highly correlated with teachers' emotional distress. Teachers' gender, student-oriented approach, and several incident characteristics (number of offending students, direct settlement with offending students) are significant predictors of emotional distress caused by either students' verbal threat or noncontact aggressive behaviors. Directions for future research and policy implications are discussed.


Quantitative Evaluation of Primordial Follicles in Rat Ovaries during the Early and Delayed Terms after Different Cytostatic Exposures.
Experiments on female Wistar rats showed that cytostatic agents (farmorubicin, platidiam, carboplatin, and etoposide) induce an initial significant decrease in the number of primordial follicles. Over the next 2-3 estrous cycles after administration of farmorubicin, platidiam, and carboplatin, this index practically did not differ from the control. The number of primordial follicles in the third and fourth estrous cycles after farmorubicin administration, as well as in the second and sixth estrous cycles after etoposide administration was much higher than the follicular reserve after cytostatic treatment (first estrous cycle). The ovarian reserve was exhausted in the delayed period after the start of the experiment. This dynamics of the pool of primordial follicles suggests that the ovary of rats in the postnatal period of life contains a limited number of female germline stem cells.


Posterior migration of cervical spinal cord between split laminae as a complication of laminoplasty.
This is a case report. To focus attention on a possible neurologic complication of laminoplasty. An iatrogenic spinal cord lesion developed after laminoplasty as an operative complication of unknown cause. Two patients had iatrogenic damage to the spinal cord from an unknown cause after laminoplasty of the cervical spine, but recovered soon after an additional laminectomy. They were evaluated with regard to the mechanism of damage and prevention. The spinal cord damage occurred when the spinal cord migrated posteriorly and deformed between the split laminae at the apex of the lordosis, where the maximum posterior displacement of the spinal cord was achieved. This damage was caused by a relatively narrower canal resulting from the split laminae of the apex of the adjacent laminae.


Cementation technique for elbow arthroplasty; an international survey.
Modern cementation techniques have markedly improved survivorship in lower limb arthroplasty, which have been heavily researched in the hip and knee but less so for upper limb procedures. Aseptic loosening is a leading cause of failure in total elbow arthroplasty (TEA) which could be related to the quality of cementation. The aim of this study was to investigate the cementation techniques used for TEA among practicing elbow surgeons. An electronic questionnaire was emailed to members of the British elbow and shoulder society (BESS) and PubMed identified experts. Questions focused on the type of prosthesis, operative rates for elective and trauma cases, nature of cement used, canal preparation and cement insertion. Opinions regarding satisfaction with current techniques and mantle quality were also collected. A total of 26 surgeons completed the questionnaire. The Coonrad-Moorey was the most popular device amongst respondents. Most cemented both components, used antibiotic loaded cement, washed the canal with saline and inserted the cement retrograde. There was wide variation in cementation techniques used for the humerus and ulna, particularly regarding cement preparation, insertion, and use of a restrictor and pressurisation. Modern cementation techniques are not being utilised in TEA which could be contributing to implant loosening rates and longevity.


Chromogenic substrates for horseshoe crab clotting enzyme. Its application for the assay of bacterial endotoxins.
An endotoxin-activated hemocyte lysate from the horseshoe crab (Tachypleus and Limulus) was found to hydrolyze Bz-Ile-Glu-(gamma-OR)-Gly-Arg-p-nitroanilide (PNA), Bz-Val-Gly-Arg-PNA, Boc-Val-Leu-Gly-Arg-PNA, and Boc-Leu-Gly-Arg-PNA, all of which have the COOH-terminal Gly-Arg sequence. This amidase activity was due to a clottting enzyme contained in the lysate. Furthermore, the amidase activity increased by increasing the concentration of bacterial endotoxin (E. coli, 0111-B4) added to the lysate. Therefore, the measurement of the endotoxin-induced amidase activity made it possible to determine the concentration of the endotoxin.


Possible sites of temperature-dependent changes in sensitivity of the positive inotropic and chronotropic responses to sympathomimetic amines by comparisons of the temperature optima for a range of agonists.
The temperature optimum for the positive inotropic response of guinea-pig isolated atria to single submaximal doses of isoprenaline was 25 degrees C. This was well separated from that for rate responses (37.5 degrees C). This separation was not due to changes in catechol-0-methyl-transferase or phosphodiesterase activity since it occurred with orciprenaline alone and in the presence of theophylline. The rate optima for aminophylline, histamine, glucagon, ouabain, calcium chloride and dibutyryl cAMP were essentially the same as for isoprenaline. The temperature-dependences therefore lie at a common ultimate pathway leading to the rate response. The site of temperature-dependence of the inotropic response to isoprenaline is not at the common contractile mechanisms since its optimum differed from those of ouabain and CaCl2. Activity of cAMP and its production were also eliminated as possible sites from differing optima of aminophylline, histamine and dibutyryl cAMP. The temperature-dependence may lie at the beta-adrenoceptor itself, possibly adenyl cyclase. This may be shared by glucagon although tachyphaylaxis made its optimum difficult to determine.


Mast cell death induced by 24(S),25-epoxycholesterol.
Mast cell is one of the central effectors in inflammatory responses. Recent studies suggest that a promising therapeutic approach for various inflammatory immune diseases, including rheumatoid arthritis, multiple sclerosis, and type I allergies, is to inhibit mast cell growth and/or survival. Studies also indicate that a balanced lipid metabolism is crucial for regulating the life span of cells. Oxysterol is a well-known regulator of lipid metabolism and has diverse functions, such as inhibition of the mevalonate isoprenoid pathway, efflux of free cholesterols, and synthesis of cholesterol esters. Here, we show that 24(S),25-epoxycholesterol, a representative endogenous oxysterol, induces apoptosis in bone marrow-derived murine mast cells. Furthermore, we have revealed, for the first time, that the accumulation of neutral lipids catalyzed by acyl-CoA:cholesterol acyltransferase in the cells was involved in induction of mast cell apoptosis. Our present findings confer new insights into the roles of lipid metabolism during oxysterol-mediated mast cell apoptosis.


User and carer involvement in the training and education of health professionals: a review of the literature.
Health policy requires consumer involvement in services, research and education but little is known about how consumers are being involved in healthcare education, the effect on learning and practice, nor how involvement initiatives are being evaluated. To describe methods of involving consumers in healthcare education, discuss ways in which initiatives have been evaluated, and identify areas for development in education, practice and research. All papers reporting specific initiatives involving consumers in health care worker training and education were included. Viewpoint articles and studies of consumers training consumers were excluded. Cinahl, Medline, Assia, PsycINFO, British Nursing Index, Social Science Citation Index, citations from reference lists, relevant websites and personal communication with key people known to be working in this area. A narrative approach was taken with categorisation of data to reflect objectives of selected studies; method of involvement; process issues and evaluation. Thirty-eight papers were included; most provide small-scale qualitative studies of mental health service users and focus on process rather than outcome. Various methods of involvement are described and consumers consistently prioritise the need for training in interpersonal skills over 'technical' skills. There is little research into organisational strategies and no studies investigate the effect of consumer involvement on practice. Two studies indicated that students exposed to consumer involvement demonstrate more empathic understanding and better communication skills. There is tentative evidence that consumer involvement in training enhances workers' skills in the manner prioritised by consumers. However, if consumer involvement in training and education is to facilitate services that reflect the priorities of the people using them, it must be developed in partnership with service providers; further research is needed to explore the impact of consumer involvement and to track the development of organisational consumer involvement strategies, also systems for supporting consumers need to be established, including training for both consumers and staff.


Rudolf Virchow: the father of today's pathology.
This year marks the 200th anniversary of the birth of Rudolf Ludwig Virchow, a pathologist and polymath who, among other things, coined the terms leukaemia, embolism and thrombosis.


Gliotoxin in Aspergillus fumigatus: an example that mycotoxins are potential virulence factors.
Moulds produce several different mycotoxins that may improve their chance of survival in particular environments. For example, Aspergillus fumigatus, an important human pathogen, produces several mycotoxins including gliotoxin. This secondary metabolite, a small lipid soluble dipeptide, exerts toxic effects on phagocytic cells and T-lymphocytes at low concentrations in vitro. A. fumigatus also produces high levels of gliotoxin in vivo, and this suggests that host defense mechanisms might be impaired by this metabolite during host infection. In the past few years, the genes responsible for the production of gliotoxin in A. fumigatus have been identified and more recently gliotoxin-minus mutants have been used in animal experiments to ascertain the biological role of this product. Mycotoxins have also been shown to act as virulence factors in some fungal infections of insects and plants.


Nischarin inhibits Rac induced migration and invasion of epithelial cells by affecting signaling cascades involving PAK.
Nischarin, a cytosolic protein that binds the alpha5beta1 integrin, plays an important role in fibroblast migration, and in regulation of the actin cytoskeleton. The effect of Nischarin on Rac induced migration and invasion by breast and colon epithelial cell lines has been determined. In these cells, Rac potently induced migration, as well as invasion of matrix; both of these events were strongly inhibited by overexpression of Nischarin. To understand the mechanism of Nischarin's inhibitory role in Rac induced cell migration, several effector domain mutants of Rac1 were employed. Nischarin was able to inhibit migration induced by Rac effector mutants that can activate PAK and JNK, but not migration stimulated by other Rac mutants. Further, Nischarin inhibited PAK induced cell migration, while not affecting migration induced by MEKK1, a Rac effector in the JNK pathway. In addition, Nischarin failed to inhibit migration induced by MEK1, a downstream effector in the Ras-Raf-MEK-Erk signaling cascade. Furthermore, Nischarin does not affect Rac mediated JNK and PI3K activities. However, Rac induced migration and invasion were effectively blocked by pharmacological inhibitors of PI-3 kinase and MEK. These results suggest that several pathways contribute to cell migration, but that Nischarin selectively inhibits Rac driven signaling cascades that affect migration through PAK.


Organ ischaemia after thoracic endovascular aortic repair.
The aim of this study was to evaluate the incidence and outcomes of ischaemic organ complications after thoracic endovascular aortic repair (TEVAR). This is a multicentre, retrospective, observational cohort study. We analysed data from patients treated with TEVAR between 22 June 2001 and 10 December 2022. Primary outcomes were postoperative overall organ ischaemic complications and early (≤30 days) survival. Secondary outcomes were long-term survival and freedom from aorta-related mortality. A total of 255 patients were included in this study. We performed 233 (91.4%) isolated TEVARs, 14 (5.5%) fenestrated or branched TEVARs and 8 (3.1%) TEVARs in combination with normal infrarenal stent graft. Overall, 31 organ ischaemic complications were detected in 29 (11.4%) cases, out of which 8 (3.1%) complications were cerebrovascular, 8 (3.1%) spinal cord, 6 (2.3%) visceral, 4 (1.6%) renal, 2 (0.8%) peripheral and 3 (1.2%) myocardial. Binary logistic regression analysis identified grade III-IV aortic arch atheroma [odds ratio (OR): 6.6, P = 0.001; 95% confidence interval: 2.9-14.9] and shaggy aorta (OR: 12.1, P = 0.003; 95% confidence interval: 2.3-64.1) to be associated with the development of organ ischaemic complications. In patients with organ ischaemia, we observed higher early (≤30 days) mortality (20.7% vs 6.2%; OR: 3.6, P = 0.016), prolonged hospitalization (P = 0.001) and inferior estimated survival (log-rank, P = 0.001). Aortic arch atherosclerotic overload as well as the presence of shaggy aorta are predictors of organ ischaemic complications following TEVAR. They are neither uncommon nor negligible and are associated with perioperative mortality, prolonged hospitalization and a negative impact on long-term survival.


Peritoneovenous shunt for intractable ascites of hepatic, nephrogenic, and malignant causes.
A retrospective analysis of 54 patients with a peritoneovenous shunt inserted to control massive ascites refractory to conventional medical treatment is presented. The cause of ascites was hepatic in 29 patients (Group 1, 54 percent), malignant in 13 (Group 2, 24 percent), and nephrogenic in 12 (Group 3, 22 percent). The peritoneovenous shunt failed in 11 patients (20 percent): 6 in Group 1, 3 in Group 2, and 2 in Group 3. Shunt outflow obstruction (thrombosis) was the principal cause. Systemic sepsis in five patients and variceal hemorrhage in three were the factors responsible for most of the deaths (22 percent). Of the 42 patients who survived operation, the peritoneovenous shunt was effective in controlling the massive ascites in 37 (86 percent). Eight patients (15 percent), four with hepatic and four with nephrogenic ascites, survived 3 years or more without ascites. Removal of at least 50 to 70 percent of ascitic fluid at the time of shunt insertion was considered an important factor in decreasing morbidity and mortality. A peritoneovenous shunt can be effective for a long-term period in controlling massive ascites with an hepatic or nephrogenic cause in a selected group of patients; however, in patients with malignant ascites, although the benefit was substantial in half, the survival period did not exceed 6 months.


A study of race matching between donor and recipient in corneal transplantation.
We investigated the influence of a racial match or mismatch between the corneal donor and recipient on the risk of endothelial rejection and subsequent graft failure in 998 corneal transplant recipients. Actuarial survival analysis showed no significant difference in the cumulative risk of endothelial rejection between the 676 race-matched and 322 race-mismatched recipients. Recipients who had preoperative factors that placed them at a higher risk of endothelial rejection (n = 208) also were not subject to a higher incidence of endothelial rejection if they received race-mismatched tissue. Graft failure after endothelial rejection was not found to differ among race-matched or -mismatched groups.


Quantifying Microvascular Changes Using OCT Angiography in Diabetic Eyes without Clinical Evidence of Retinopathy.
To compare quantitative OCT angiography (OCTA) parameters of macular ischemia in diabetic eyes without retinopathy with those in healthy nondiabetic controls. Cross-sectional study from August 2014 through June 2017. Thirty-nine eyes of 39 diabetic patients without clinical evidence of diabetic retinopathy and 40 eyes of 40 healthy nondiabetic subjects. Subjects underwent OCTA imaging using prototype AngioVue software (RTVue XR Avanti). Analyses of the foveal avascular zone (FAZ) and vasculature surrounding the FAZ were performed on the automatically generated en face OCTA images of the superficial and deep retinal vasculatures using vessel-based and FAZ-based metrics. Comparison of measurements made in the superficial and deep retinal capillary plexuses of diabetic eyes and normal eyes. FAZ-based analysis revealed statistically significant differences between diabetic and normal eyes in FAZ area (superficial and deep layers), perimeter (superficial layer), major axis length (superficial layer), and minor axis layer (superficial and deep layers). Vessel-based analysis revealed statistically significant differences in the binarized flow index (superficial and deep layers), both including and excluding the FAZ area. Quantitative OCTA parameters reveal subclinical macular ischemia at both the superficial and deep retinal capillary plexuses in diabetic eyes that do not manifest clinical retinopathy. Vessel-based and FAZ-based metrics applied to OCTA images may serve as effective tools for screening and disease monitoring in patients with diabetes without clinical evidence of retinopathy.


Prediction of target range of intact parathyroid hormone in hemodialysis patients with artificial neural network.
The application of artificial neural network (ANN) to predict outcome and explore potential relationships among clinical data is increasing being used in many clinical scenarios. The aim of this study was to validate whether an ANN is a useful tool for predicting the target range of plasma intact parathyroid hormone (iPTH) concentration in hemodialysis patients. An ANN was constructed with input variables collected retrospectively from an internal validation group (n = 129) of hemodialysis patients. Plasma iPTH was the dichotomous outcome variable, either target group (150 ng/L<or= iPTH <or=300 ng/L) or non-target group (iPTH< 150 ng/L or iPTH hormone >300 ng/L). After internal validation, the ANN was prospectively tested in an external validation group (n = 32) of hemodialysis patients. The final ANN was a multilayer perceptron network with six predictors including age, diabetes, hypertension, and blood biochemistries (hemoglobin, albumin, calcium). The externally validated ANN provided excellent discrimination as appraised by area under the receiver operating characteristic curve (0.83 +/- 0.11, p = 0.003). The Hosmer-Lemeshow statistic was 5.02 (p= 0.08 > 0.05) which represented a good-fit calibration. These results suggest that an ANN, which is based on limited clinical data, is able to accurately forecast the target range of plasma iPTH concentration in hemodialysis patients.


Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength.
CD28 and CTLA-4 engagement with B7 expressed by APCs generates critical regulatory signals for T cell activation. CD28 is expressed on the T cell surface and enhances T cell expansion, while CTLA-4 localizes primarily to an intracellular compartment and inhibits T cell proliferation. We demonstrate that CTLA-4 has several unique trafficking properties that may regulate its ability to attenuate a T cell response. Importantly, accumulation of CTLA-4 at the immunological synapse is proportional to the strength of the TCR signal, suggesting that cells receiving stronger stimuli are more susceptible to CTLA-4-mediated inhibition. This may represent a novel feedback control mechanism in which a stimulatory signal regulates the recruitment of an inhibitory receptor to a functionally relevant site on the cell surface.


On the time resolution of event-related desynchronization: a simulation study.
To investigate the time resolution of different methods for the computation of event-related desynchronization/synchronization (ERD/ERS), including one based on Hilbert transform. In order to better understand the time resolution of ERD/ERS, which is a function of factors such as the exact computation method, the frequency under study, the number of trials, and the sampling frequency, we simulated sudden changes in oscillation amplitude as well as very short and closely spaced events. Hilbert-based ERD yields very similar results to ERD integrated over predefined time intervals (block ERD), if the block length is half the period length of the studied frequency. ERD predicts the onset of a change in oscillation amplitude with an error margin of only 10-30 ms. On the other hand, the time the ERD response needs to climb to its full height after a sudden change in oscillation amplitude is quite long, i.e. between 200 and 500 ms. With respect to sensitivity to short oscillatory events, the ratio between sampling frequency and electroencephalographic frequency band plays a major role. (1) The optimal time interval for the computation of block ERD is half a period of the frequency under investigation. (2) Due to the slow impulse response, amplitude effects in the ERD may in reality be caused by duration differences. (3) Although ERD based on the Hilbert transform does not yield any significant advantages over classical ERD in terms of time resolution, it has some important practical advantages.


Photochemical transformation of atrazine and formation of photointermediates under conditions relevant to sunlit surface waters: laboratory measures and modelling.
By combination of laboratory experiments and modelling, we show here that the main photochemical pathways leading to the transformation of atrazine (ATZ, 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) in surface waters would be direct photolysis, reaction with ·OH and with the triplet states of chromophoric dissolved organic matter ((3)CDOM*). Reaction with (3)CDOM* would be favoured by elevated water depth and dissolved organic carbon content, while opposite conditions would favour direct photolysis and OH reaction. Desethylatrazine (DEA, 4-amino-2-chloro-6-isopropylamino-1,3,5-triazine) was the main detected intermediate of ATZ phototransformation. Its formation yield from ATZ (ratio of DEA formation to ATZ transformation rate) would be 0.93 ± 0.14 for ·OH, 0.55 ± 0.05 for (3)CDOM*, and 0.20 ± 0.02 for direct photolysis. Direct photolysis and ·OH reaction also yielded 4-amino-2-hydroxy-6-isopropylamino-1,3,5-triazine (DEAOH) and 6-amino-2-chloro-4-ethylamino-1,3,5-triazine (DIA). Reaction with excited triplet states also produced 2-hydroxy-4,6-diamino-1,3,5-triazine (AN) and 2-chloro-4,6-diamino-1,3,5-triazine (CAAT). Therefore, if biological processes can be neglected and if the low formation yields do not prevent detection, DEAOH and DIA could be used as markers of ATZ direct photolysis and ·OH reaction, while AN and CAAT could be markers of ATZ reaction with (3)CDOM*. Model predictions concerning ATZ phototransformation were compared with available field data from the literature. When sufficiently detailed field information was provided, good agreement was found with the model.


Effect of acetylsalicylic acid on experimentally induced arterial thrombosis in rats.
Acetylsalicylic acid (ASA) was tested for its antithrombotic activity in the arterial system after prophylactic administration to rats, using a new standardized method. Damage of the vessel wall was produced by chilling a small segment of the left carotid artery. Dose related, significant results were obtained after 3 mg/kg orally. If higher doses (10 and 30 mg/kg) are administered, the formation of non-occlusive thrombi is inhibited by 70--90% on the basis of thrombus weight. As the frequency distributions show, there are significantly more zero-values in the ASA treated groups (total 50%) than in the control groups. However, the incidence of occlusive thrombi was not changed by ASA. The long-lasting effect of ASA in inhibition of platelet aggregation was confirmed. The formation of arterial thrombi is significantly inhibited after prophylactic administration of 30 and 10 mg/kg up to 48 h before initiation of thrombosis. After administration of 3 mg/kg orally, only insignificant effects were observed. Thus the duration of action depends on the dose used.


Left upper lung cancer with persistent left superior vena cava and left azygos vein: a case report.
With the popularization of thoracoscopic surgery, more and more macrovascular malformations have been reported. Understanding some vascular malformations with relatively fixed anatomical site and their range of drainage could avoid severe complications during the surgery. Persistent left superior vena cava (PLSVC) is a common thoracic vascular malformation, and is always combined with other cardiovascular dysplasia. As for the patient with upper left lung cancer in this case, he had PLSVC and left azygos vein, and non-metastatic enlargement of the lymph nodes at the same time, which had influenced the decisions on surgery and treatment. We made a summary of experience regarding this. A 46-years-old male patient, his CT found a space-occupying lesion in the superior lobe of the left lung. The chest CT showed that the patient had PLSVC and left azygos vein, and multiple enlarged lymph nodes in the mediastinum. The patient received thoracoscopic upper left lung lobectomy and lymph node dissection. It was discovered that the left azygos vein had a concealed form, which influenced the lymph node dissection. The post-surgery pathology showed that there was squamous cell carcinoma in the upper left lung (pT2bN0M0 p Phase IIA) and no cancer metastasis with the lymph nodes. The patient had a good post-surgery recovery. PLSVC is not rare, and is always combined with other vascular malformations. If discovering PLSVC before surgery, we suggest completing chest enhanced CT and vascular reconstruction, to find out other cardiovascular malformations that may exist. Left azygos vein is a rare vascular malformation, but it has a relatively fixed anatomical site, and always co-exists with PLSVC, therefore, understanding anatomy of left azygos vein is good for preventing accidental damage. Especially when performing surgery above the left pulmonary artery trunk, attention shall be paid to preventing damage to the left azygos vein. In addition, as for the patient with the diagnosis of lung cancer before surgery, it is not reliable to judge whether there is metastasis or not merely according to the size of the lymph nodes, instead, PET-CT or needle biopsy is recommended.


Analytical methods and environmental processes of nanoplastics.
The degradation of plastic debris may result in the generation of nanoplastics (NPs). Their high specific surface area for the sorption of organic pollutions and toxic heavy metals and possible transfer between organisms at different nutrient levels make the study of NPs an urgent priority. However, there is very limited understanding on the occurrence, distribution, abundant, and fate of NPs in the environment, partially due to the lack of suitable techniques for the separation and identification of NPs from complex environmental matrices. In this review, we first overviewed the state-of-the-art methods for the extraction, separation, identification and quantification of NPs in the environment. Some of them have been successfully applied for the field determination of NPs, while some are borrowed from the detection of microplastics or engineered nanomaterials. Then the possible fate and transport of NPs in the environment are thoroughly described. Although great efforts have been made during the recent years, large knowledge gaps still exist, such as the relatively high detection limit of existing method failing to detect ultralow masses of NPs in the environment, and spherical polystyrene NP models failing to represent the various compositions of NPs with different irregular shapes, which needs further investigation.


Nanomedicine tactics in cancer treatment: Challenge and hope.
Defeating cancer is the ultimate challenge and goal of oncologists, facing various obstacles along with finding effective anti-cancer therapies and understanding drug delivery mechanisms. Additionally, the translation of the experimental findings to the clinical outcomes such as specificity, delivery, toxicity, clearance, and bioavailability is another health concern. Nanomedicine is a branch of nanotechnology that has been drastically developed in the last decades. Due to the fact of various nanomaterial formulas, different nanomedicine drug delivery tactics have been developed as anti-cancer therapies. The most effective and less toxic approaches involved the active targeting drug delivery tactic, which relies on the recognition of the drug nanoparticle carriers and the cell surface marker. Accordingly, FDA approved such a group of nanomedicine drug delivery systems while other formulas are still under the clinical trial phases. Nanomedicine is showing a bright future in the treatment of cancer. Oncologists learned from cancer research the possible drug resistance that could be developed. Consequently, researchers need to be prepared for the possible adverse effect of the nanomedicine approach.


Sedentariness and overweight in relation to mortality in sub-Saharan Africa. A mediation analysis based on the World Health Organization-Global Health Observatory data repository.
Globally, noncommunicable diseases (NCDs) have been continuously reported to be the number one leading cause of reduced life expectancy and poor life quality and have thus become a major public health concern. This study aimed to investigate the complex mediation analysis between physical inactivity and overweight in relation to mortality. The study is based on public data collected by the Global Health Observatory of the World Health Organization. We showed that the median early mortality attributable to NCDs during the period 2016-2019 in both men and women was 23.2% (5th to 95th range=17.2, 35.6) while that in men alone was 25.1% (16.5, 45.7) and that of women alone was 22.0% (17.0, 27.9). When considering regional early NCDs mortality for both men and women, a systematically high median was observed in Southern Africa [28.7% (22.2, 43.8)] and a low median in Eastern Africa [21.1% (17.15, 27.3)]. The analysis of the overall relation between physical inactivity, overweight and early mortality due to NCDs revealed a statistical significance of the direct association between physical inactivity and early mortality due to NCDs. Our findings revealed three main epidemiological and public health concerns. First, early mortality attributable to NCDs in a range of about 20 to 30% across the sub-Saharan African regions for both sexes was observed. Second, there was a direct effect between physical inactivity and early NCDs mortality as well as the indirect effect mediated by overweight. Finally, a percentage point decrease in physical inactivity prevalence and overweight could effectively generate a reduction in mortality due to NCDs. Future studies are needed to confirm the scientific evidence observed in this study. Such studies should be based on observation of individual subjects, adopt a longitudinal design, and collect information that evaluates the complex relationship between physical inactivity and early NCDs mortality, along with the role of overweight as a possible mediator.


Immunocytochemical detection of S-100beta in the periodontal Ruffini endings in the rat incisor.
Subcellular localization of S-100 protein, a kind of calcium binding proteins, was examined immunohistochemically in the Ruffini ending, a primary mechanoreceptor, in the periodontal ligament of the rat incisor. The periodontal ligament of the rat incisor was found to contain many S-100beta-immunoreactive (-IR) structures but no S-100alpha-IR elements. The S-100beta-IR structures ramified extensively to form Ruffini endings and were frequently associated with round cells, the terminal Schwann cells, which also showed S-100beta-like immunoreactivity. In many periodontal Ruffini endings, S-100beta-IR products were recognized in the cytoplasm of Schwann cells, but not in the axoplasm. However, some axon terminals which had fewer or shorter axonal fingers, were filled with S-100beta-IR products. The present findings indicated the existence of S-100beta, not S-100alpha, in axon terminals of the periodontal mechanoreceptive endings which were identified as type II Ruffini endings.


Isotopic studies during surgical convalescence.
We have performed paired isotopic studies in four patients undergoing resection of early colorectal cancer and four having removal of parathyroid adenomas. Kinetic measurements of protein and glucose metabolism were made before resection and at home 10 weeks after surgery. During convalescence there were major changes in both groups in glucose metabolism and the hormonal milieu despite no alterations in protein kinetics or metabolic rate. In particular, the rate of glucose production doubled from (mean +/- s.e.m.) 14.8 +/- 1.3 to 28.1 +/- 2.5 mumol kg-1 min-1 (P less than 0.01), the percentage of available glucose undergoing oxidation decreased from 35.5 +/- 3.9 to 21.5 +/- 2.9 per cent (P less than 0.05) and the percentage of glucose undergoing recycling to lactate increased from 20.1 +/- 10.0 to 52.9 +/- 2.3 per cent (P less than 0.05). During convalescence the basal plasma insulin concentration was significantly higher (P less than 0.05) and there was a proportionately smaller response to glucose infusion. The convalescent state was also associated with an elevation in serum cortisol from 291 +/- 54 to 496 +/- 75 nmol litre-1 (P less than 0.05). The values for resting energy expenditure were not significantly different from the predicted energy expenditure in either the preoperative or the convalescent groups. We conclude that (a) there is a marked increase in both glucose production and glucose recycling to lactate in convalescence from clean uncomplicated surgery, and this is associated with a decrease in the percentage of glucose uptake oxidised; (b) a relative hyperinsulinaemia is seen in convalescent patients and is associated with decreased responsiveness to a glucose load; (c) the plasma cortisol level is significantly elevated after 10 weeks of convalescence; and (d) convalescent patients do not have elevated rates of protein catabolism or energy expenditure.


An elective course to engage pharmacy students in research activities.
To implement problem-based learning exercises in a pharmacy research elective course and assess the impact on students' knowledge and confidence in their ability to analyze, design, and present basic research projects relevant to clinical areas. Hands-on learning activities, including discussions on experimental design, development of collective diagrams, research planning, results analysis, data evaluation, and presentation design, were incorporated into the course and developed as team-based learning experiences. Students gave a seminar presentation to peers and faculty members at the end of the semester and created posters for presentations at professional meetings. Students who decided to work on a continuation project during the following semester were expected to produce data that might be sufficient for the development of manuscripts for submission to scientific journals. Feedback from students revealed an appreciation and renewed interest in analyzing clinical issues with a much wider focus as well as increased understanding of and confidence in using data derived from basic science research.


Deletions of the Plasmodium falciparum histidine-rich protein 2/3 genes are common in field isolates from north-eastern Tanzania.
Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3 (pfhrp2/3) genes have been reported in several parts of the world. These deletions are known to compromise the effectiveness of HRP2-based malaria rapid diagnostic tests (HRP2-RDT). The National Malaria Control Programme (NMCP) in Tanzania adopted HRP2-RDTs as a routine tool for malaria diagnosis in 2009 replacing microscopy in many Health facilities. We investigated pfhrp2/3 deletions in 122 samples from two areas with diverse malaria transmission intensities in Northeastern Tanzania. Pfhrp2 deletion was confirmed in 1.6% of samples while pfhrp3 deletion was confirmed in 50% of samples. We did not find parasites with both pfhrp2 and pfhrp3 deletions among our samples. Results from this study highlight the need for systematic surveillance of pfhrp2/3 deletions in Tanzania to understand their prevalence and determine their impact on the performance of mRDT.


Advances in Complex Congenital Tracheoesophageal Anomalies.
Esophageal atresia with or without tracheoesophageal fistula and tracheobronchomalacia encompass 2 of the most common complex congenital intrathoracic anomalies. Tailoring interventions to address the constellation of problems present in each patient is essential. Due to advances in neonatology, anesthesia, pulmonary, gastroenterology, nutrition and surgery care for patients with complex congenital tracheoesophageal disorders has improved dramatically. Treatment strategies tailored to the individual patient needs are best implimented under the aegis of a comprehensive longitudinal multidisciplinary care team.


The motion path of the digits.
This study investigates whether the path taken by the fingertips of the human hand during unrestricted flexion and extension follows a precise mathematical pattern: an equiangular spiral. Eight normal subjects participated in the study. Subjects performed numerous flexion and extension trials at a random speed. Motion was recorded by a 6-camera, 3-dimensional motion analysis system with 24 retroreflective markers affixed to the dominant hand at predetermined locations. Four hundred eighty flexion-extension arcs were analyzed. We used the coefficient of multiple determination to compare the flexion and extension motion arc of each finger to an equiangular spiral curve derived mathematically. Our results indicate that the path of the hand during flexion and extension closely follows the path of an equiangular spiral with the coefficient of multiple determination values consistently above 0.95.


Insular functional alterations in emotional processing of schizophrenia patients revealed by Multivariate Pattern Analysis fMRI.
Emotion perception is impaired in schizophrenia patients (SP) and related to reduced social skills performance. There is a remarkable variability across subjects for functional neuroimaging alterations related to this phenomenon. In contrast to the univariate approaches of fMRI, Multivariate Pattern Analysis (MVPA) maintains the within-subject voxel-level variability. The purpose of this study was to assess emotion processing in SP, in previously identified ROIs -i.e. amygdala, hippocampus, insula, and thalamus-, while retaining the functional heterogeneity that may exist between subjects. We evaluated 23 SP and 23 healthy controls (HC). Happy, sad, and neutral faces were presented. A single trial fMRI model was applied. Patterns of activation within each ROI were classified at the subject level. Within each group, stimuli classification scores were tested against random label classification scores. In ROIs with significant results, a whole ROI classification was performed, to test whether en bloc stimuli discrimination was present. A between-group analysis was conducted also. For the classification of stimuli above chance, in the HC results were significant in the left insula in all of the stimuli dichotomies, but were non-significant in SP for happy vs. sad. In whole ROI classification, SP had significant results in bilateral insular cortex for happy vs. neutral. The left amygdala showed diminished stimuli classification scores in SP for sad vs. neutral. In conclusion, MVPA seems useful to study emotional processing in schizophrenia. In SP, either en bloc or no stimuli discrimination was seen in the insula, and reduced stimuli discrimination was seen in the left amygdala.


Pelvic insufficiency fractures in postmenopausal woman with advanced cervical cancer treated by radiotherapy.
To assess the predisposing factors and clinical characteristics of pelvic insufficiency fractures (PIF) in postmenopausal women with pelvic irradiation. A total 335 postmenopausal patients with cervical cancer of the intact uterus treated with radiation therapy between 1983 and 1998 were reviewed. Total external dose was delivered between 45 and 50.4 Gy with parallel opposed anteroposterior portals. Total brachytherapy dose at point A was delivered between 10 and 36 Gy. PIF were diagnosed by bone scintigraphy and confirmed by computed tomography. The cumulative incidence of symptomatic PIF was estimated by actuarial methods. Potential risk factors (age, weight, type II diabetes, delivery, menopause, total external dose, total brachytherapy dose) were assessed. Fifty-seven (17.0%) of 335 patients were diagnosed as having PIF. Forty-seven patients were symptomatic and ten were asymptomatic. Parameters carrying a significant association with PIF were body weight 49 kg or below (P=0.044) in stepwise logistic regression analysis. The cumulative incidence of symptomatic PIF at 5 years was 17.9% calculated by the Kaplan-Meier method. A body weight of 49 kg or below and more than three deliveries were identified as having a significant effect on symptomatic PIF in univariate analysis (P=0.021, P=0.003, log-rank test) and Cox life table regression analysis (P=0.038, P=0.013). Five patients required narcotic agents and eight patients required hospital admission. We should consider reducing the dose contribution to the sacrum and sacroilac joints, without underdosing the tumor, especially in postmenopausal women with many deliveries or low body weight.


Healthcare utilization of patients with hereditary angioedema treated with lanadelumab and subcutaneous C1-inhibitor concentrate.
Background: New hereditary angioedema (HAE) treatments have become available in recent years for the treatment of HAE due to C1-inhibitor (C1-INH) deficiency, including two subcutaneous (SC) options: a monoclonal antibody (lanadelumab) and a plasma-derived C1-INH concentrate (SC-C1-INH). Limited real-world data on these therapies have been reported. Objective: The objective was to describe new users of lanadelumab and SC-C1-INH, including demographics, healthcare resource utilization (HCRU), costs, and treatment patterns before and after beginning treatment. Methods: This was a retrospective cohort study that used an administrative claims data base. Two mutually exclusive cohorts of adult (ages ≥18 years) new users of lanadelumab or SC-C1-INH with ≥180 days of continuous use were identified. HCRU, costs, and treatment patterns were assessed in the 180-day period before the index date (new treatment use) and up to 365 days after the index date. HCRU and costs were calculated as annualized rates. Results: Forty-seven patients who used lanadelumab and 38 patients who used SC-C1-INH were identified. The most frequently used on-demand HAE treatments at baseline were the same for both cohorts: bradykinin B₂ antagonists (48.9% of the patients on lanadelumab, 52.6% of the patients on SC-C1-INH) and C1-INHs (40.4% of the patients on lanadelumab, 57.9% of the patients on SC-C1-INH). More than 33% of the patients continued to fill on-demand medications after treatment initiation. Annualized angioedema-associated emergency department visits and hospitalizations decreased after initiation of treatment, from 1.8 to 0.6 for the patients on lanadelumab and from 1.3 to 0.5 for the patients on SC-C1-INH. Annualized total healthcare costs after treatment initiation in the database were $866,639 and $734,460 for the lanadelumab and SC-C1-INH cohorts, respectively. Pharmacy costs accounted for >95% of these total costs. Conclusion: Although HCRU decreased after the initiation of treatment, angioedema-associated emergency department visits and hospitalizations and on-demand treatment fills were not completely eliminated. This indicates ongoing disease and treatment burden despite use of modern HAE medicines.


Money attitudes and personality.
In a sample of 67 students, neuroticism scores were associated with money attitude scores. The higher the neuroticism score the higher the impulsivity and the lower the motivational drive, organization, and planning scores.


Perceived Unfair Treatment and Problem Drinking among U.S. Navy Careerists.
This mixed method paper assessed interrelationships of unfair treatment at work, stress, and problem drinking amongst a sample of U.S. Navy careerists. Survey data from current drinkers (n=2380) were analyzed, along with qualitative interviews from a quota sample of 81. More women than men (51.4% vs. 16.2%) reported gender unfair treatment; approximately 20% of respondents reported ethnic/racial unfair treatment. Unfair treatment was associated with likelihood of problem drinking, but associations were attenuated after adjusting for frequency of work problems and expecting alcohol to alleviate stress. Qualitative results revealed contexts of unfair treatment within bureaucratic structures, tradition, norms, and role modeling.


Phosphorylation processes mediate rapid changes of brain aromatase activity.
The enzyme aromatase (also called estrogen synthase) that catalyzes the transformation of testosterone (T) into estradiol plays a key limiting role in the action of T on many aspects of reproduction. The distribution and regulation of aromatase in the quail brain has been studied by radioenzyme assays on microdissected brain areas, immunocytochemistry, RT-PCR and in situ hybridization. High levels of aromatase activity (AA) characterize the sexually dimorphic, steroid-sensitive medial preoptic nucleus (POM), a critical site of T action and aromatization for the activation of male sexual behavior. The boundaries of the POM are clearly outlined by a dense population of aromatase-containing cells as visualized by both immunocytochemistry and in situ hybridization histochemistry. Aromatase synthesis in the POM is controlled by T and its metabolite estradiol, but estradiol receptors alpha (ERalpha) are not normally co-localized with aromatase in this brain area. Estradiol receptor beta (ERbeta) has been recently cloned in quail and localized in POM but we do not yet know whether ERbeta occurs in aromatase cells. It is therefore not known whether estrogens regulate aromatase synthesis directly or by affecting different inputs to aromatase cells as is the case with the gonadotropin releasing hormone neurons. The presence of aromatase in presynaptic boutons suggests that locally formed estrogens may exert part of their effects by non-genomic mechanisms at the membrane level. Rapid effects of estrogens in the brain that presumably take place at the neuronal membrane level have been described in other species. If fast transduction mechanisms for estrogen are available at the membrane level, this will not necessarily result in rapid changes in brain function if the availability of the ligand does not also change rapidly. We demonstrate here that AA in hypothalamic homogenates is rapidly down-regulated by exposure to conditions that enhance protein phosphorylation (addition of Ca2+, Mg2+, ATP). This inhibition is blocked by kinase inhibitors which supports the notion that phosphorylation processes are involved. A rapid (within minutes) and reversible regulation of AA is also observed in hypothalamic explants incubated in vitro and exposed to high Ca2+ levels (K+-induced depolarization, treatment by thapsigargin, by kainate, AMPA or NMDA). The local production and availability of estrogens in the brain can therefore be rapidly changed by Ca2+ based on variation in neurotransmitter activity. Locally-produced estrogens are as a consequence available for non-genomic regulation of neuronal physiology in a manner more akin to the action of a neuropeptide/neurotransmitter than previously thought.


Adjuvant chemotherapy after resection of adenocarcinoma of the periampullary region and the head of the pancreas. A non-randomized pilot study.
From 1980 till 1984 16 patients were entered into a non-randomized pilot study, to investigate the feasibility of five courses of adjuvant 5-fluorouracil, Adriamycin and mitomycin C (FAM) after a curative resection of pancreatic or periampullary cancer. The survival of this group of patients was compared with that of 36 patients who underwent a curative resection alone between 1977 and 1984. Four patients received less than 20%, 4 patients 50%-60% and 7 patients greater than or equal to 80% of the calculated dose of adjuvant chemotherapy. The chemotherapy was badly tolerated. Only 1 patient resumed some of his normal activity during chemotherapy. The 3-year actuarial survival after curative resection with and without FAM was similar, i.e. 24% and 28% respectively. These data suggest that adjuvant FAM after a Whipple's operation or total pancreatectomy is not feasible because of additive postoperative and chemotherapy-induced morbidity.


Magainin 1-induced leakage of entrapped calcein out of negatively-charged lipid vesicles.
Effects of magainin 1, a novel antimicrobial peptide, on the permeability of lipid vesicles were investigated by using calcein as a trapped fluorescent marker. Magainin 1 induces the leakage of calcein specifically out of negatively-charged vesicles. The peptide binds to bovine brain phosphatidylserine sonicated vesicles according to the Langmuir isotherm with a binding constant of 3.8.10(5) M-1 and a binding-site number of 0.10 per lipid molecule. The leakage seems to occur at a critical binding number of approx. 0.03 per lipid molecule. A circular dichroism study revealed that magainin 1 conforms mainly to an unordered structure both in an aqueous solution and in the presence of egg yolk phosphatidylcholine vesicles, whereas to an amphiphilic helix with the phosphatidylserine vesicles. In conclusion, magainin 1 interacts with acidic lipids through electrostatic interactions followed by hydrophobic interactions to form an amphiphilic helix, inducing the leakage.


Effect of experimental desynchronosis on immunotoxicity of benz(a)pyrene in (CBAxC57Bl)F1 mice.
Experiments on (CBA x C57Bl)F1 mice showed that constant (day and night) illumination for 2 weeks led to the development of internal desynchronosis, which significantly modulated the reaction of the immune system to benz(a)pyrene compared to those in intact animals. Presumably, the differences were associated with changed circadian rhythms of the immune parameters in experimental animals determining different ratios and, presumably, functions of immunocompetent cells during benz(a)pyrene exposure in intact controls and animals with desynchronosis.


A simultaneous liquid chromatographic analysis of niclosamide and bicalutamide in rat plasma by protein precipitation extraction.
The aim of the study was to develop a simple, sensitive and cost-efficient bioanalytical method for the simultaneous determination of niclosamide and bicalutamide in rat plasma with appropriate validation. Real-time estimation was carried out using Ultra Flow Liquid Chromatography. The solvent system consisting of 20mM sodium acetate buffer at pH 4.0 and acetonitrile (65: 35% v/v) is used as the mobile phase. The analytes were extracted by protein precipitation with acetonitrile and separated on an Eclipse plus C18 Column (25cm×5cm×4.6μm) with L1 packing in isocratic mode with a flow rate of 1ml/min at 254nm. The developed method was validated on the basis of the bioanalytical guidelines of the US American FDA. The retention times of niclosamide and bicalutamide were 4.19min and 8.61min, respectively, with a running time of 15minutes. The calibration ranges are 50-600ng/ml for niclosamide and 100-1200ng/ml for bicalutamide. Regression equations for niclosamide and bicalutamide were y=55746x - 1E+06 and y=22051x-576888 with regression coefficient (R2) 0.9952 & 0.9982 using the unweighted and weighted linear regression with a weighting factor of 1/xo, 1/x, 1/√x, and 1/x2. The accuracy of niclosamide and bicalutamide were 46.01ng/ml to 584.10ng/ml and 82.30ng/ml to 1149.13ng/ml, respectively. The percentage recoveries for niclosamide and bicalutamide were 86.51-90.29% & 88.64-93.99%, respectively. The result of the present study show that the method developed is a simple, fast and precise method and is used in bioavailability and bioequivalence studies as well as during routine therapeutic drug monitoring of niclosamide and bicalutamide.


Structure-activity relationships of N-terminal variants of peptidomimetic tissue transglutaminase inhibitors.
Tissue transglutaminase (TG2) is a multifunctional protein that catalyses protein crosslinking in the extracellular matrix, and functions as an intracellular G-protein. While both activities have been associated with human diseases, its role as a G-protein has been linked to cancer stem cell survival and maintenance of a metastatic phenotype. Recently we have shown that targeted covalent inhibitors (TCIs) can react selectively with the enzyme active site of TG2, to allosterically abolish its ability to bind GTP. In the present work, we focused on the variation of the N-terminal group of these peptidomimetic inhibitors, in order to enhance efficiency, while reducing log P and the number of rotatable bonds. This approach led to the synthesis and evaluation of 41 novel inhibitors, some of which had greatly improved efficiency and affinity for TG2 (e.g. TCI 72: KI = 1.0 μM, kinact/KI = 4.4 × 105 M-1 min-1). Molecular modelling provided a hypothetical binding mode for these TCIs. The most efficient inhibitors were evaluated further and shown to have excellent isozyme selectivity, to block GTP binding, and to have improved pharmacokinetic properties, as expected. Their biological activity was also confirmed, in a cellular invasion assay, although with less potency than expected.


Giles Oldroyd.
Interview with Giles Oldroyd, who studies the signalling and developmental processes that are involved in the interaction of mycorrhizal fungi and nitrogen-fixing bacteria in plants at the University of Cambridge.


Multispecialty Nursing During COVID-19:: Lessons Learned in Southern California.
A multispecialty nursing team plays a crucial role in key decision making, education, prevention, screening, assessment, diagnosis, management, data collection and dissemination of best practices during the novel coronavirus disease (COVID-19) pandemic. Using examples from a large, tertiary medical center in Los Angeles, this paper highlights contributions made by multispecialty nursing specialties to optimize health and safety for patients and frontline health care workers. Recognizing nurses' ongoing critical role encourages and informs further collaboration and serves as a catalyst to innovation for a healthier tomorrow. The result of the COVID-19 pandemic will be felt for years to come.


Ovarian steroids counteract serotonergic drugs actions in an animal model of obsessive-compulsive disorder.
Recently, we reported the existence of differences according to the reproductive stage of female rats in a pharmacologically induced animal model of obsessive-compulsive disorder. Therefore, the aim of the present study was to examine the role of endogenous and exogenous ovarian steroids in the induction of perseverative responses in a T-maze by the 5-HT1A agonist 8-OH-DPAT (1.0 and 2.0 mg/kg, SC) and in the preventive action of the selective serotonin reuptake inhibitor, fluoxetine (10.0 mg/kg, three times, SC). The results showed that the perseverant action of 8-OH-DPAT as well as the prevention of such perseverance by fluoxetine were reduced during the estrous-metestrous phases of the female reproductive cycle, and by the exogenous ovarian steroids administration to ovariectomized animals. Data are discussed from the standpoint of the action of ovarian steroids on the serotonergic system and on the putative influence of these hormones on the physiopathology and treatment of this disorder in women.


Studies on immunomodulatory properties of isoniazid. IV. Effect of isoniazid on T lymphocyte activation by phorbol ester tumor promoter.
Human peripheral blood T cells or continuous T cell lines were treated with phorbol myristate (PMA), a direct protein kinase C activator. The effect of isoniazid on PMA-treated cells was investigated. It was found that low doses of isoniazid augmented proliferation of T cells treated with PMA or stimulated with PMA and phytohemagglutinin. Similar results were shown in the Jurkat cell line. There was no influence of isoniazid upon proliferation of PMA-treated HT-2 cells, interleukin 2-dependent cell line. The obtained results suggest that, at least one target mechanism of isoniazid is located in T cell activation pathway after protein kinase C activation.


SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases.
Chilblains ('COVID toes') are being seen with increasing frequency in children and young adults during the COVID-19 pandemic. Detailed histopathological descriptions of COVID-19 chilblains have not been reported, and causality of SARS-CoV-2 has not yet been established. To describe the histopathological features of COVID-19 chilblains and to explore the presence of SARS-CoV-2 in the tissue. We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID-19 pandemic. Immunohistochemistry for SARS-CoV-2 was performed in all cases and electron microscopy in one. Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS-CoV-2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy. Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS-CoV-2. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID-19 chilblains and perhaps also in a group of patients severely affected by COVID-19 presenting with features of microangiopathic damage. What is already known about this topic? Despite the high number of cases of chilblains seen during the COVID-19 pandemic, a definite causative role for SARS-CoV-2 has not yet been proven. Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors. What does this study add? The demonstration of SARS-CoV-2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID-19. Virus-induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID-19 chilblains. Our findings support the hypothesis that widespread endothelial infection by SARS-CoV-2 could have a pathogenetic role in the severe forms of COVID-19. Linked Comment: Wetter. Br J Dermatol 2020; 183:611.


Structure and function of the hemocyanin from a semi-terrestrial crab, Ocypode quadrata.
Structural and functional studies of the hemocyanin of the semi-terrestrial ghost crab, Ocypode quadrata, demonstrate a variety of differences in comparison to the hemocyanin of aquatic crabs. These differences may be related to the terrestrial habit of this crab. Unlike aquatic crabs, the major (56%) blood component is the hexamer; the remaining 44% is dodecamer. The hexamers and dodecamers are not in rapid equilibrium. Electrophoretic analysis of the subunit composition indicates three major components referred to as 1, 3, and 4, and one minor component referred to as component 2. These components, although electrophoretically distinct, are alike immunologically. Components 1 and 2 are essentially absent from purified hexamers, whereas they compose 1/3 of the subunits in dodecamers. These results suggest that they are involved in linking hexamers to form dodecamers, and that two, rather than one, subunits are involved in the bridge. Oxygen-binding measurements show a higher degree of cooperativity, and a much reduced allosteric effect of L-lactate on the dialyzed hemocyanin as compared to the hemocyanin of aquatic crabs. Exercise rapidly induces a large drop in hemolymph pH (0.5 units) and a corresponding increase in lactate concentrations (to 10 mM).


Presynaptic regulation of acetylcholine release in the CNS.
The release of ACh appears to be under the control of autoreceptors localized on cholinergic nerve terminals. Moreover, the process can be regulated by transmitters other than ACh or by modulators either through receptor-mediated or carrier-mediated mechanisms. In this chapter we report on our recent results concerning the regulation of the release of ACh by ACh itself, 5-HT and GABA in the rat hippocampus. In particular it will be shown: 1) that the release of the cholinergic transmitter can be inhibited through muscarinic receptors of the M3 subtype; 2) that 5-HT can interact with ACh by depressing ACh release through the activation of receptors of the 5-HT1B subtype; 3) that the release of ACh can be enhanced by GABA by a novel mechanism involving a selective penetration of the amino acid into the cholinergic terminals.


Dexamethasone increases plasma HVA but not MHPG in normal humans.
Several recent studies in animals and man indicate that corticosteroids may alter catecholaminergic activity in both the peripheral and central nervous systems. We administered 1 mg of the synthetic glucocorticoid, dexamethasone, to 12 drug-free healthy volunteers and measured plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Dexamethasone was administered at 11 p.m. and blood was collected at 4 p.m. on the preceding and subsequent days. Dexamethasone administration resulted in a significant increase in plasma HVA but did not consistently affect MHPG. All subjects showed a suppression of serum cortisol to values less than 5 micrograms/dl while prolactin levels were unaltered. In an additional group of nine volunteers, we administered 2 mg of dexamethasone and observed a similar increase in plasma HVA without change in plasma MHPG, indicating a selective effect on dopamine metabolism. Implications of these findings for an understanding of the neurochemical and behavioral changes seen with steroid administration and in explaining previous results on plasma MHPG/HVA ratios in delusional depression are discussed.


Caliceal-cutaneous fistula after kidney transplantation.
Urinary fistula is a one of the most common complications after kidney transplantation. Conservative treatment with stent and Foley catheter drainage may be tried, however in some cases more invasive approach is needed. Caliceal fistula is a rare condition and the diagnosis may be missed. Here we present an interesting case of caliceal-cutaneous fistula diagnosed by computed tomography after living kidney transplantation. After failure of conservative management, the patient was successfully treated with partial nephrectomy.


Impairment of G(salpha) function in human brain cortex of Alzheimer's disease: comparison with normal aging.
We examined the quantity and quality of G proteins in membrane preparations of post-mortem human brain, i.e. in parietal, temporal and occipital cortical regions, from normal subjects over age (17-89 years old) and with Alzheimer's disease (AD) in comparison with aged-matched controls. In normal aging, the immunoreactivities determined of G(ialpha), G(qalpha) and G(beta) were inversely correlated with age. The function of G proteins was examined by photoaffinity GTP analogue [azidoanilido GTP (AAGTP)] labelling. AAGTP labelling to G(salpha) and G(i/oalpha), and the ratio of G(salpha) to G(i/oalpha) AAGTP labelling showed no age-dependent changes. In AD compared to age-matched controls, there were no significant differences in the levels of G(sHalpha), G(sLalpha), G(ialpha), G(oalpha), G(qalpha) and G(beta) subunits. Functional effects of G proteins, however, as measured by AAGTP labelling to G(salpha), but not to G(i/oalpha), was significantly decreased in AD compared to controls in the parietal and temporal cortex, but not in the occipital cortex. These results suggest that the disturbances of post-receptor trans-membrane signalling in AD can be attributed to functional changes of G(salpha), and these are independent of alterations in the level for those proteins in normal aging.


Parental and provider preferences and concerns regarding text message reminder/recall for early childhood vaccinations.
To assess parental, provider, and medical staff opinions about text message reminder/recall for early childhood vaccination. A cross-sectional survey was conducted between January and March 2011 among 200 parents of 6-59 month-old children, 26 providers, and 20 medical staff at four academically-affiliated pediatric practices in New York City with text messaging experience. Survey questions addressed interest in, preferences for, and concerns/barriers related to vaccine-related text message reminder/recall. Parents were primarily Latino, Spanish-speaking, and had a high school education or less. Most parents owned a text message-enabled cell phone (89%) and used text messaging services (97%). While 84% had never received health-related text messages, 88% were comfortable receiving them. Nearly all parents reported interest in receiving reminder/recall text messages, many endorsing them over phone calls and/or letters. Preferences included personalization, interactivity, and multiple messages. While 25% of parents had no concerns, 38% were concerned about incorrect numbers; only 6% worried about cost. Providers and staff were also supportive of vaccine-related text messages. Their biggest concerns were correct cell phone numbers, appointment availability, and increased call volume. Text message reminder/recall for early childhood vaccination was widely supported. Important barriers were identified that should be addressed to maximize their effectiveness.


Effects of excimer laser on healing of articular cartilage in rabbits.
This study examined healing of 1.0 mm diameter defects in rabbit knee articular cartilage for as long as 14 weeks after creation of the defects by either laser or drilling. The purpose of the research was to determine the effects of laser debridement of cartilage on the intrinsic biomechanical properties of the repair tissue. We therefore imitated chondral shaving and subchondral abrasion of cartilage by creating partial-thickness and full-thickness cartilage defects of standardized size with both excimer laser and drilling. Light and scanning electron microscopic examinations of the repair tissue showed that healing of osteochondral defects created by laser may be delayed compared with defects created by drilling, for at least 6 weeks postoperatively. Even though there initially was a considerable delay in healing in the laser group, neither laser nor drilling had any appreciable effects on the mechanical properties of the repair tissue, as demonstrated by biomechanical testing at 14 weeks. Specifically, the repair cartilage in the defects in the laser group had the following material properties (mean +/- SD): aggregate modulus, 0.40 +/- 0.24 MPa; Poisson's ratio, 0.37 +/- 0.08; permeability, 3.72 +/- 4.28 x 10(-15) m4/N.s; and thickness, 0.20 +/- 0.06 mm. The corresponding values for the defects in the drilling group were 0.39 +/- 0.23 MPa, 0.34 +/- 0.09, 3.82 +/- 3.44 x 10(-15) m4/N.s, and 0.22 +/- 0.09 mm. The repair tissue from both types of defects was pooled, and the values were compared with those for contralateral (control) tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolation and characterization of human breast cancer cells overexpressing S-adenosylmethionine decarboxylase.
We report the first successful isolation and initial characterization of S-adenosylmethionine decarboxylase (SAMDC)-overexpressing cells using a transfection approach. Stably transfected MCF-7 breast cancer overproducing SAMDC (approximately 5-fold) manifested reduced ornithine decarboxylase while levels of N'-spermidine/spermine acetyltransferase were variably increased. Analysis of cellular polyamine profile showed that spermine was selectively increased (approximately 80%), while spermidine and putrescine levels were reduced (approximately 48% and approximately 15% of control, respectively). Since SAMDC-overexpressing clones exhibited increased clonogenicity in soft agar, our data suggest that spermine may be selectively involved in conferring a more invasive phenotype to breast cancer cells.


Central nervous system regulation of adipocyte metabolism.
The white adipose tissue was initially largely known only as an energy storage tissue. It is now well recognized that white adipose tissue is a major endocrine and secretory organ, which releases a wide range of protein signals and factors termed adipokines. The regulation of adipocyte metabolism is an important factor for the understanding of obesity, and some mechanisms are still unknown. Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the central nervous system. There is substantial evidence demonstrating that the central nervous system also directly regulates adipocyte metabolism. In this review, we discuss the central actions of some peptides with an important role in energy balance regulation on adipocyte metabolism and the physiological relevance of these actions.


Psychopathology and thought suppression: a quantitative review.
Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression.


The response of endurance-adapted adults to intense anaerobic training.
The effects of a 6 week program of intense, intermittent hill running was investigated in 5 endurance-trained men (34-37) years. Venous lactate responses averaged 10.7 mM X 1(-1) during training. Biopsies were obtained from the vastus lateralis before and after training for determinations of histochemical classification, phosphagen concentrations (ATP and CP) and activities of total LDH and selected LDH isozymes. Indices of aerobic and anaerobic capacity were also measured. Significant improvements (P less than 0.01) were noted in training distance and loads employed in leg presses, also part of the training: the treadmill test for anaerobic capacity improved by 16.7% and the terminal blood lactate level increased 14%(P less than 0.05). No changes occurred in VO2 max, body fat per cent or anaerobic power. Muscle ATP concentration increased by 14.8% (P less than 0.01) whereas the tissue level of CP remained unchanged. Total LDH activity and the LDH isozymes (LDH-1, LDH-5 and LDH-2, 3, 4) were not altered by training. No changes in fibre distribution were observed. That adaptations to the anaerobic training did occur is evident, but the cellular locus remains to be elucidated further.


Influence of local anaesthesia on pain and distress induced by two bloodless castration methods in young lambs.
To assess short- and long-term effects of bloodless castration methods with and without local anaesthesia, behavioural and cortisol responses of lambs were used as indicators of pain and distress. Seventy lambs, aged 2-7 days, were control-handled or castrated by Burdizzo or rubber ring methods with and without local anaesthesia. Either 5 mL of diluted lidocaine (4 mg/kg) or physiological sodium chloride solution was distributed in both spermatic cords and the scrotal neck. The serum cortisol response was monitored for 48 h, and behavioural and clinical traits were followed for three months. Local anaesthesia tended to reduce behavioural and cortisol responses after Burdizzo castration and provided a significant reduction after rubber ring castration. Prolonged pain after rubber ring castration with anaesthesia was not evident. If combined with local anaesthesia, both the rubber ring and the Burdizzo methods are acceptable methods for castration of lambs up to one week of age.


Pharmacokinetics of ornidazole in patients with acute viral hepatitis, alcoholic cirrhosis, and extrahepatic cholestasis.
Pharmacokinetics of ornidazole, a nitroimidazole derivative, was investigated after intravenous injection in 3 groups of 10 patients with different hepatic diseases: hepatitis, noncholestatic cirrhosis and extrahepatic cholestasis. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 [alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol] and M4 [3-(2-methyl-5-nitroimidazole 1-yl)-1,2-propane diol] were measured by HPLC assay. As a consequence of a decreased clearance (26% to 48%), the half-life and MRT are increased in all patients by 19% to 38% when compared with healthy volunteers. No clear difference could be established between the different groups. The volume of distribution remains the same in all patients and controls except those suffering from cancer. As previously shown in patients with severe liver cirrhosis, both metabolites accumulate in plasma as a result of decreased elimination; formation is no longer the rate-limiting step of their kinetics. This metabolite accumulation is in part due to decreased biliary excretion and to hepatocellular failure.


Right Ventricular Function After Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention (from the Glycometabolic Intervention as Adjunct to Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction III Trial).
Right ventricular (RV) dysfunction is a powerful risk marker after acute myocardial infarction (MI). Primary percutaneous coronary intervention (PCI) has markedly reduced myocardial damage of the left ventricle, but reliable data on RV damage using cardiac magnetic resonance imaging (MRI) are scarce. In a recent trial of patients with acute MI treated with primary PCI, in which the primary end point was left ventricular (LV) ejection fraction after 4 months measured with MRI, we conducted a prospectively defined substudy in which we examined RV function. RV ejection fraction (RVEF) and RV scar size were measured with MRI at 4 months. Tricuspid annular plane systolic excursion (TAPSE) and RV free wall longitudinal strain (FWLS) were assessed using echocardiography before discharge and at 4 months. We studied 258 patients without diabetes mellitus; their mean age was 58 ± 11 years, 79% men and mean LV ejection fraction was 54 ± 8%. Before discharge, 5.2% of patients had TAPSE <17 mm, 32% had FWLS > -20% and 11% had FWLS > -15%. During 4 months, TAPSE increased from 22.8 ± 3.6 to 25.1 ± 3.9 mm (p <0.001) and FWLS increased from -22.6 ± 5.8 to -25.9 ± 4.7% (p <0.001). After 4 months, mean RVEF on MRI was 64.1 ± 5.2% and RV scar was detected in 5 patients (2%). There was no correlation between LV scar size and RVEF (p = 0.9), TAPSE (p = 0.1), or RV FWLS (p = 0.9). In conclusion, RV dysfunction is reversible in most patients and permanent RV ischemic injury is very uncommon 4 months after acute MI treated with primary PCI.


National resilience assessment and improvement based on multi-source data: Evidence from countries along the belt and road.
National resilience is a consensus benchmark to characterize the ability of disaster resistance of a country. The occurrence of various disasters and the ravages of COVID-19 have created urgent needs in assessing and improving the national resilience of countries, especially for countries along the Belt and Road (i.e., B&R countries) with multiple disasters with high frequency and great losses. To accurately depict the national resilience profile, a three-dimensional assessment model based on multi-source data is proposed, where the diversity of losses, fusion utilization of disaster and macro-indicator data, and several refined elements are involved. Using the proposed assessment model, the national resilience of 64 B&R countries is clarified based on more than 13,000 records involving 17 types of disasters and 5 macro-indicators. However, their assessment results are not optimistic, the dimensional resilience are generally trend-synchronized and individual difference in a single dimension, and approximately one-half of countries do not obtain resilience growth over time. To further explore the applicable solutions for national resilience improvement, a coefficient-adjusted stepwise regression model with 20 macro-indicator regressors is developed based on more than 19,000 records. This study provides the quantified model support and a solution reference for national resilience assessment and improvement, which contributes to addressing the global national resilience deficit and promoting the high-quality development of B&R construction.


Molecular tests can allow confirmation of invasive meningococcal disease when isolates yield atypical maltose, glucose or gamma-glutamyl peptidase test results.
Analysis of atypical meningococci from invasive disease that either (i) did not produce acid from maltose and glucose or (ii) were gamma-glutamyl peptidase test negative for porA and porB DNA variable region (VR) type, multilocus sequence type, and for presence of capsule transport gene ctrA, conclusively demonstrated that these are Neisseria meningitidis.


Development of a differential multiplex real-time PCR assay for porcine circovirus type 2 (PCV2) genotypes PCV2a, PCV2b and PCV2d.
A multiplex quantitative real-time polymerase chain reaction (mqPCR) assay was developed and validated for detection and differentiation of porcine circovirus type 2 (PCV2) genotypes, PCV2a, PCV2b and PCV2d. Single nucleotide polymorphism in primers or probes was deployed for different genotype detections, while conserved sequence in the 3' end of a primer and in the middle of a probe was used for the targeted genotype. In silico analysis of 2601 PCV2 ORF2 sequences showed that the predicted strain coverage of the assay was 93.4 % (409/438) for PCV2a, 95.1 % (1161/1221) for PCV2b and 93.6 % (882/942) for PCV2d strains. The PCR amplification efficiencies were 94.5 %, 100.2 %, and 99.2 % for PCV2a, PCV2b and PCV2d, respectively, with correlation coefficients >0.995 for all genotypes. The limits of detection (LOD) were 1.58 × 10-4 TCID50/mL for PCV2a, 5.62 × 10-4 TCID50/mL for PCV2b, and 3.16 × 10-3 TCID50/mL for PCV2d. Sanger sequencing of 74 randomly selected PCV2 positive clinical samples confirmed the genotypes of strains identified by the mqPCR. Validation with clinical samples co-positive for target and non-target pathogens demonstrated that the mqPCR assay specifically detected targeted viruses without cross reacting to each other or to other common porcine viruses.


Cataract associated with high-dose hematopoietic colony stimulating factor, case report and literature review.
Granulocyte-colony stimulating factor (G-CSF) is a lineage-restricted hematopoietic growth factor. It induces proliferation and maturation of neutrophilic precursors and progenitors and activates neutrophil functions. It is used to ameliorate or prevent profound neutropenia and its consequences. G-CSF therapy in neutropenic disorders increases neutrophil count and improves infectious complications. However, it is not without side effects. Here, we discuss the case of a 2 years old patient with Kostmann's disease who developed cataracts following high-dose G-CSF therapy. We also review the relevant literature on G-CSF-related complications.


The incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori.
Although several studies have indicated that Helicobacter pylori eradication develops reflux oesophagitis, others reported that its eradication had a beneficial effect on reflux symptoms. The results are still controversial. To study whether H. pylori eradication increases the occurrence rate of reflux oesophagitis in patients with peptic ulcers. One hundred and two consecutive patients who had peptic ulcers and were H. pylori-positive by C-urea breath testing were followed prospectively. They all received 1-week triple therapy and underwent endoscopy at 1-year intervals or when relapse of the peptic ulcer or occurrence of reflux oesophagitis was suspected. Reflux oesophagitis developed in 32 (31.4%) out of 102 patients and they were of grade A (27 patients) and grade B (five patients) by the Los Angeles classification System. H. pylori infection was cured in 77 (75.5%) out of 102 patients. There was no significant difference in age (53.4+/-1.2 vs. 53.9+/-1.4 years, P = 0.43), gender (male/female, 29/3 vs. 53/17, P = 0.14), ulcer location (gastric/duodenal/both, 15/12/5 vs. 35/26/9, P = 0.97), H. pylori status (persistent/cured, 9/23 vs. 16/54, P = 0.57) or length of follow-up time (355+/-32 vs. 348+/-23 days, P = 0.30) between the 32 patients with reflux oesophagitis and the other 70 patients. Only the presence of hiatal hernia before therapy was significant for the prevalence of reflux oesophagitis by the log-rank test (P = 0.002), and the Cox proportional hazard models confirmed these findings (odds ratio, 3.46; 95% confidence interval, 1.64-7.30; P = 0.0012). The eradication of H. pylori did not increase the prevalence of reflux oesophagitis, and only the presence of hiatal hernia before therapy was significantly related to the development of reflux oesophagitis.


Effectiveness of a Brief Mindfulness-Based Intervention of "STOP touching your face" During the COVID-19 Pandemic: a Randomized Controlled Trial.
Avoiding touching the eyes, nose, and mouth (T-zone) is a strategy to reduce the spread of COVID-19. This study evaluated the effectiveness of a brief mindfulness-based intervention (MBI) named "STOP (Stop, Take a Breath, Observe, Proceed) touching your face" for reducing face-touching behavior. In this online-based, two-arm, wait-list, randomized controlled trial, eligible participants were randomly assigned to the intervention (n = 545) or control group (n = 545). The results of 60-min self-monitoring of face-touching behavior were reported before and after the intervention. Reduction of the percentage of T-zone touching was the primary outcome, and reduction of face-touching frequency was a key secondary outcome. Outcomes were analyzed on an intention-to-treat (ITT) basis with a complete case analysis (CCA). ITT analysis revealed that the percentage of T-zone touching was significantly reduced by 8.1% in the intervention group (from 81.1 to 73.0%, RR = 0.901, OR = 0.631, RD = - 0.081, p = 0.002), and insignificantly reduced by 0.6% in the control group (from 80.0 to 79.4%, p = 0.821). Fewer participants performed T-zone touching in the intervention group than in the control group (73.0% vs. 79.4%, RR = 0.919, OR = 0.700, RD = - 0.064, p = 0.015) after the intervention, and there was a greater reduction of T-zone touching frequency in the intervention group than in the control group [mean ± SD: 1.7 ± 5.13 vs. 0.7 ± 3.98, mean difference (95% CI): 1.03 (0.48 to 1.58), p < 0.001, Cohen's d = - 0.218]. The above results were further confirmed by CCA. This brief mindfulness-based intervention was potentially effective at reducing the spread of COVID-19 and could be further investigated as an intervention for preventing other infectious diseases spread by hand-to-face touching. ClinicalTrials.gov NCT04330352. The online version contains supplementary material available at 10.1007/s12671-022-02019-x.