Vertical cross contamination of trichloroethylene in a borehole in fractured sandstone.
Boreholes drilled through contaminated zones in fractured rock create the potential for vertical movement of contaminated ground water between fractures. The usual assumption is that purging eliminates cross contamination; however, the results of a field study conducted in a trichloroethylene (TCE) plume in fractured sandstone with a mean matrix porosity of 13% demonstrates that matrix-diffusion effects can be strong and persistent. A deep borehole was drilled to 110 m below ground surface (mbgs) near a shallow bedrock well containing high TCE concentrations. The borehole was cored continuously to collect closely spaced samples of rock for analysis of TCE concentrations. Geophysical logging and flowmetering were conducted in the open borehole, and a removable multilevel monitoring system was installed to provide hydraulic-head and ground water samples from discrete fracture zones. The borehole was later reamed to complete a well screened from 89 to 100 mbgs; persistent TCE concentrations at this depth ranged from 2100 to 33,000 microg/L. Rock-core analyses, combined with the other types of borehole information, show that nearly all of this deep contamination was due to the lingering effects of the downward flow of dissolved TCE from shallower depths during the few days of open-hole conditions that existed prior to installation of the multilevel system. This study demonstrates that transfer of contaminant mass to the matrix by diffusion can cause severe cross contamination effects in sedimentary rocks, but these effects generally are not identified from information normally obtained in fractured-rock investigations, resulting in potential misinterpretation of site conditions.


Tentative identification of RNA-dependent RNA polymerases of dsRNA viruses and their relationship to positive strand RNA viral polymerases.
Amino acid sequence stretches similar to the four most conserved segments of positive strand RNA viral RNA-dependent RNA polymerases have been identified in proteins of four dsRNA viruses belonging to three families, i.e. P2 protein of bacteriophage phi 6 (Cystoviridae), RNA 2 product of infectious bursa disease virus (Birnaviridae), lambda 3 protein of reovirus, and VP1 of bluetongue virus (Reoviridae). High statistical significance of the observed similarity was demonstrated, allowing identification of these proteins as likely candidates for RNA-dependent RNA polymerases. Based on these observations, and on the previously reported sequence similarity between the RNA polymerases of a yeast dsRNA virus and those of positive strand RNA viruses, a possible evolutionary relationship between the two virus classes is discussed.


Mandibular metastasis of primary extrahepatic biliary carcinoma: Case report.
Cholangiocarcinoma is a malignant neoplasm with a difficult diagnosis and unfavorable prognosis that can appear anywhere in the biliary tree. Anatomically, it can be classified as intra- or extrahepatic, the latter being the most common primary malignancy of the biliary tract. Although bone tissue is the third most common target for metastases in general, metastatic lesions from cholangiocarcinomas are uncommon in the head and neck. A 33-year-old female patient undergoing cancer treatment for cholangiocarcinoma was referred to the Oral and Maxillofacial Surgery and Traumatology Service (CTBMF) of the São Vicente de Paulo Hospital in Passo Fundo, Rio Grande do Sul, Brazil, for interdisciplinary follow-up. She presented trismus, dysphagia, pain, necrosis and drainage in the mental region, and an increased volume on the right side of the mandibular body in the region of teeth 47 and 48. An incisional biopsy was performed in this bulging region. The histopathological diagnosis was poorly differentiated carcinoma. The patient was followed-up weekly by the CTBMF team, receiving analgesia and palliative treatment for the extra- and intraoral lesions, controlling opportunistic infections, and improving food intake. Metastatic cholangiocarcinomas in the mandible are rare, hence their diagnosis is often late, which may disfavor the prognosis of these conditions. Carefully examining patients with mandibular bone lesions is strongly suggested, especially patients with known or previous concomitant malignancy.


Injury prevalence and causality in developing nations: Results from a countrywide population-based survey in Nepal.
Traumatic injury affects nearly 5.8 million people annually and causes 10% of the world's deaths. In this study we aimed to estimate injury prevalence, to describe risk-factors and mechanisms of injury, and to estimate the number of injury-related deaths in Nepal, a low-income South Asian country. A cluster randomized, cross-sectional nationwide survey using the Surgeons OverSeas Assessment of Surgical Need tool was conducted in Nepal in 2014. Questions were structured anatomically and designed around a representative spectrum of operative conditions. Two-stage cluster sampling was performed: 15 of 75 districts were chosen randomly proportional to population; within each district, after stratification for urban and rural populations, 3 clusters were randomly chosen. Injury-related results were analyzed. A total of 1,350 households and 2,695 individuals were surveyed verbally, with a response rate of 97%. A total of 379 injuries were reported in 354 individuals (13.1%, 95% confidence interval 11.9-14.5%), mean age of 32.6. The most common mechanism of injury was falls (37.5%), road traffic injuries (19.8%), and burns (14.2%). The most commonly affected anatomic site was the upper extremity (42.0%). Of the deaths reported in the previous year, 16.3% were injury-related; 10% of total deaths may have been averted with access to operative care. This study provides baseline data on the epidemiology of traumatic injuries in Nepal and is the first household-based countrywide assessment of injuries in Nepal. These data provide valuable information to help advise policymakers and government officials for allocation of resources toward trauma care.


Controlled-ventilation volumetric CT scan in the evaluation of acquired pulmonary lobar emphysema: a case report.
Acquired lobar emphysema (ALE), a clinical entity often associated with bronchopulmonary dysplasia (BPD) in premature infants, carries significant morbidity and mortality. Because of compression of adjacent lung tissue and poor response to medical therapy, patients may require surgical resection of the hyperinflated region of lung. The decision of proceed to surgery is often problematic, relying upon standard chest radiographs, ventilation-perfusion scans, and high resolution CT (HRCT) scans. We report the use of controlled volume HRCT with breath-holding at TLC and FRC in an infant with severe BPD and ALE. Using reconstruction software, we could estimate total lung volume as well as the volume of the lobe affected by ALE at both lung volumes, permitting the determination of the degree of air trapping. This is turn afforded us confirmatory data of the extent of the affected lung, justifying surgical removal.


Seasonal changes of spatial variation of some groundwater quality variables in a large irrigated coastal Mediterranean region of Turkey.
Soil and groundwater degradations have taken considerable attention, recently. We studied spatial and temporal variations of groundwater table depth and contours, and groundwater pH, electrical conductivity (EC), and nitrate (NO3) content in a large irrigated area in Western Mediterranean region of Turkey. These variables were monitored during 2009 and 2010 in previously constructed 220 monitoring wells. We analyzed the data by geostatistical techniques and GIS. Spatial variation of groundwater table depth (GTD) and groundwater table contours (GTC) remained similar across the four sampling campaigns. The values for groundwater NO3 content, EC, and pH values ranged from 0.01 to 454.1 gL(-1), 0.06 to 46.0 dS m(-1) and 6.53-9.91, respectively. Greatest geostatistical range (16,964 m) occurred for GTC and minimum (960 m) for groundwater EC. Groundwater NO3 concentrations varied both spatially and temporally. Temporal changes in spatial pattern of NO3 indicated that land use and farming practices influenced spatial and temporal variation of groundwater NO3. Several hot spots occurred for groundwater NO3 content and EC. These localities should be monitored more frequently and land management practices should be adjusted to avoid soil and groundwater degradation. The results may have important implications for areas with similar soil, land use, and climate conditions across the Mediterranean region.


Catheter ablation of atrial arrhythmias following lung transplant: Electrophysiological findings and outcomes.
Data on the mechanisms of atrial arrhythmias (AAs) and outcomes of catheter ablation (CA) in lung transplantation (LT) patients are insufficient. We evaluated the electrophysiologic features and outcomes of CA of AAs in LT patients. METHODS AND RESULTS: We conducted a retrospective study of all the LT patients who underwent CA for AAs at our institution between 2004 and 2019. A total of 15 patients (43% males, age: 61 ± 10 years) with a history of LT (60% bilateral and 40% unilateral) were identified. All patients had documented organized AA on surface electrocardiogram and seven patients also had atrial fibrillation (AF; 47% with >1 clinical arrhythmia). At electrophysiological study, 19 organized AAs were documented (48% focal and 52% macro-re-entrant). Focal atrial tachycardias/flutters were targeted along the pulmonary vein (PV) anastomotic site at the left inferior PV (n = 2), ridge and carina of the left superior PV (n = 2), left atrium (LA) posterior wall (n = 3), LA roof (n = 1), and tricuspid annulus (n = 1). Macro-re-entrant AAs included cavotricuspid isthmus-dependent flutter (n = 2), incisional LA flutter (n = 4), LA roof-dependent flutter (n = 1), and mitral annular flutter (n = 3). In patients with LA mapping (n = 13), PV reconnection on the side of the LT was found in six patients (40%, all with clinically documented AF), with a mean of 2.1 ± 0.9 PVs reconnected per patient. Patients with AF underwent successful PV isolation. After a median follow-up of 19 months (range: 6-86 months), 75% of patients remained free from recurrent AAs. No procedural major complications occurred. In patients with prior LT, recurrent AAs are typically associated with substrate surrounding the surgical anastomotic lines and/or chronically reconnected PVs. CA of AAs in this population is safe and effective to achieve long-term arrhythmia control.


Changes in systolic and diastolic functions of the left ventricle and endothelium function against the background of electric stimulation in athletes.
Against the background of 10 procedures of electric stimulation of the quadriceps muscle of the thigh performed in 72 athletes we observed a significant increase in volume parameters of the left-ventricular systolic function and increase in diastolic function in a group of athletes during the recovery period. Significant increase in endothelium-dependent values was noted in both groups during electric myostimulation; it directly correlated with all metric and integral echocardiography parameters in main group.


Use of physicochemical parameters in distance geometry and related three-dimensional quantitative structure-activity relationships: a demonstration using Escherichia coli dihydrofolate reductase inhibitors.
In earlier distance geometry related three-dimensional quantitative structure-activity relationships (Ghose, A. K.; Crippen, G. M. J. Med. Chem. 1984, 27, 901) the interactions of the ligand atom or group with the receptor site were evaluated empirically by using mathematical optimization techniques, without considering their physicochemical properties. In the present work we show how to use various physicochemical parameters in our three-dimensional receptor mapping. We have developed a model for E. coli DHFR using the inhibition data of 25 pyrimidines and 14 triazines. It gave a correlation coefficient of 0.893 and standard deviation of 0.530. It successfully predicted the binding data of five pyrimidines and five triazines.


Genetic contributions to lupus-like disease in NZB/NZW mice.
In contrast to parental New Zealand Black (NZB) or New Zealand White (NZW) mice, (NZB x NZW)F1 mice exhibit a lupus-like disease characterized by high levels of immunoglobulin G (IgG) antinuclear antibodies in their serum and a fatal immune-complex glomerulonephritis. At least three gene loci have been identified in NZW mice that could potentially contribute to a T cell-dependent autoimmune disease, including the T cell receptor alpha- and beta-chain gene complexes and the major histocompatibility complex (MHC). The NZW T cell receptor beta-chain complex appeared to be particularly unusual in that the C-beta-1, D-beta-2, and J-beta-2 gene segments have been deleted. Approximately one half of (NZB x NZW)F1 x NZB backcross mice developed severe renal disease and elevated levels of IgG antibodies to double-stranded deoxyribonucleic acid and histone, suggesting that only one dominant gene or closely linked group of genes accounts for the NZW genetic contribution to F1 disease. Despite the extremely unusual nature of the NZW T cell receptor beta-chain gene complex, we found no association of disease expression with the presence of this allele in the backcross mice. There was also no correlation of disease incidence with the presence of the NZW T cell receptor alpha-chain allele. In contrast, nearly 90 percent of the backcross mice with the NZW MHC expressed severe autoimmune disease compared with 12 percent of the mice that did not carry this haplotype. Thus, the NZW MHC or gene(s) linked to this locus appears to be the only dominant NZW genetic contribution to F1 disease. Recent preliminary studies mapping genes that are located centromeric and telomeric to the NZW MHC suggest that the disease-associated gene(s) lies within the MHC.


Role of 5-HT(1A) and 5-HT(1B) receptors in the antidepressant-like effect of piperine in the forced swim test.
Our previous studies have showed that treating mice with piperine significantly decreased the immobility time of the animals in the forced swim test and tail suspension test, which was related to up-regulation of serotonin (5-HT) level in the brain. The purpose of this study is to explore the contribution of 5-HT receptors in the antidepressant-like effect of piperine. The results showed that pre-treating mice with methiothepin (a non-selective 5-HT receptor antagonist, 0.1mg/kg, intraperitoneally), 4-(2'-methoxy-phenyl)-1-[2'-(n-2″-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (a selective 5-HT(1A) receptor antagonist, 1mg/kg, subcutaneously) or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (a 5-HT(1B) receptor antagonist, 2.5mg/kg, intraperitoneally) was found to abolish the anti-immobility effect of piperine (10mg/kg, intraperitoneally) in the forced swim test. On the other hand, a sub-effective dose of piperine (1mg/kg, intraperitoneally) produced a synergistic antidepressant-like effect with (+)-8-hydroxy-2-(di-n-propylamino)tetralin (a 5-HT(1A) receptor agonist, 1mg/kg, intraperitoneally) or anpirtoline (a 5-HT(1B) receptor agonist, 0.25mg/kg, intraperitoneally). Taken together, these results suggest that the antidepressant-like effect of piperine in the mouse forced swim test may be mediated, at least in part, by the activation of 5-HT(1A) and 5-HT(1B) receptors.


Theoretical analysis of independent VA and Q inequalities upon pulmonary gas exchange.
A 10-compartment model is used to study the effects independent regional inequalities in ventilation (VA) and blood flow (Q) upon overall gas exchange in the lung. For the particular distribution considered, it is demonstrated that unequal ventilation always gives rise to a greater degree of hypoxaemia than unequal blood flow, and that these differences become more marked when minute volume is high. In contrast, hypercarbia is more pronounced in situations where blood flow is unequal; however, the differences diminish with increases in minute volume. Increases in cardiac output are found to have a lesser effect upon the gas exchange process. The reasons for the findings are explained by reference to the gas dissociation curves, the spread of VA/Q ratios, and the weighting influence of regional blood flow. The apparent disparity of the present results with those obtained by assuming a log normal distribution of the respiratory parameters (VA and Q) are reconciled.


Plasma amino acid response to single test meals in humans. II. Healthy young adults given synthetic amino acid mixtures.
The postprandial plasma amino acid response to test meals containing different amino acid mixtures was analysed in six young adults. The amount of amino acids given in each test meal was equivalent with 3.5 g of nitrogen. Each test meal also contained a large amount of carbohydrate (mainly as wheat starch). Five different amino acid mixtures were used, and the effects on the plasma amino acid response of different dietary levels of lysine, isoleucine and methionine were studied in detail. The plasma amino acid responses were evaluated both by a modified Longenecker and Hause procedure (PAA ratios) and by the procedure proposed by Graham and Placko (percentage changes in the postprandial essential amino acid molar ratios). The plasma amino acid response of lysine was found to be less sensitive to reductions in the dietary supply than the isoleucine and methionine responses evaluated by these procedures. The influence of altered levels of dietary supply on the postprandial plasma concentrations of isoleucine and methionine seemed to be specifically great at the intake levels where these essential amino acids become limiting for protein utilization according to the amino acid score of the test mixtures. The nutritional significance of the postprandial pattern and level of essential amino acids is discussed on basis of the present results. Experimental conditions and evaluation models are examined with regard to the use of single-meal plasma amino acid responses to assess the protein quality of human diets.


Urinary tract infection is common in VLBW infants.
Determine the significance of urinary tract infection (UTI) as a cause of late onset sepsis (LOS) in very low birth weight (VLBW) infants in the Neonatal Intensive Care Unit (NICU). Analysis of blood, cerebrospinal fluid and urine culture results in VLBW infants >72-h old, admitted to the Georgetown University Hospital NICU between 2005 and 2015. Of 527 VLBW infants, 297 (56.4%) underwent 911 evaluations for LOS; only one-third included urine cultures. UTI was diagnosed in 8.5% of VLBW infants (range 2-15.9%) and in 13.8% of infants weighing < 1000 g at birth. Gram-negative infections predominated. Concomitant blood cultures were negative in 96% of infants. UTI was more common than bloodstream infection by 2015. UTI is a significant cause of infection in VLBW infants. Urine culture should be included in all LOS evaluations in order to facilitate accurate diagnosis and appropriate antibiotic therapy.


CDR1as promotes arrhythmias in myocardial infarction via targeting the NAMPT-NAD+ pathway.
Cardiac ventricular arrhythmia triggered by acute myocardial infarction (AMI) is a major cause of sudden cardiac death. We have reported previously that an increased serum level of circular RNA CDR1as is a potential biomarker of AMI. However, the possible role of CDR1as in post-infarct arrhythmia remains unclear. This study in MI mice investigated the effects and underlying mechanism of CDR1as in ventricular arrhythmias associated with MI. We showed that knockdown of CDR1as abbreviated the duration of the abnormally prolonged QRS complex and QTc intervals and decreased susceptibility to ventricular arrhythmias. Optical mapping demonstrated knockdown of CDR1as also reduced post-infarct arrhythmia by increasing the conduction velocity and decreasing dispersion of repolarization. Mechanistically, CDR1as led to the depletion of NAD+ and caused mitochondrial dysfunction by directly targeting the NAMPT protein and repressing its expression. Moreover, CDR1as aggravated dysregulation of the NaV1.5 and Kir6.2 channels in cardiomyocytes, a change which was alleviated by the replenishment of NAD+. These findings suggest that anti-CDR1as is a potential therapeutic approach for ischemic arrhythmias.


Granular cell tumors of the esophagus.
Three cases of granular cell tumor of the esophagus are added to the 17 previously reported in the literature. These tumors, thought to be of neural origin, are difficult to diagnose preoperatively. The diagnosis should be considered in adult females presenting with an intramural mass of the proximal or distal third of the esophagus. Symptoms of dysphagia and substernal discomfort are likely to occur with lesions greater than one centimeter in diameter. Preoperative biopsy is not advised as a mistaken diagnosis of squamous cell carcinoma can result.


The unbearable lightness of technocratic efforts at dengue control.
To identify key elements that should provide an added value and assure sustainable effects of the deployment of technical tools for Aedes aegypti control. An observational study was conducted between April 2001 and March 2002 in 30 blocks (1574 houses) in the central zone of Guantanamo city. A trial that combined two complementary technical interventions, the distribution of new ground level water tanks and the intensive use of insecticide, was nested in May 2001. Another 30 blocks (1535 houses) were selected as control area. We assessed community perceptions and household risk behaviour at baseline and after 9 months, and measured the trial's impact through entomological indices. Perceived self efficacy to solve A. aegypti infestation and prevent dengue was not modified. We found no changes in behaviour. In the study area the container indices decreased significantly from 0.7% before to 0.1% 1 month after the intervention. Six months later, they had increased to 2.7% and uncovered new water tanks constituted 75.9% of all breeding sites. Over the 9 months after the trial the average monthly house indices were similar in the study and control areas. A technical approach and lack of community involvement in the trial's implementation were the main causes of these short-lived results. Top-down deployment of technical tools without active involvement of the community has a temporary effect and does not lead to the behavioural changes necessary for sustainable A. aegypti control.


Immune and Circulating Tumor DNA Profiling After Radiation Treatment for Oligometastatic Non-Small Cell Lung Cancer: Translational Correlatives from a Mature Randomized Phase II Trial.
NCT01725165 was a phase II prospective trial in which patients with non-small cell lung cancer were randomized to local consolidative therapy (LCT) versus maintenance therapy or observation (MT/O). Peripheral blood from patients enrolled on NCT01725165 were labeled as (1) baseline, (2) early follow-up (FU) if obtained in the first or second FU evaluation (6-18 weeks), and (3) late FU if obtained in the third to sixth FU evaluations (22-50 weeks). All patients who underwent LCT and were included in this analysis received radiation. Among 49 randomized patients, 21 patients underwent T cell CDR3 variable region sequencing using immunoSEQ, 31 patients underwent circulating tumor DNA (ctDNA) analysis using next-generation sequencing with a 1021 cancer gene panel, and cytokine concentration was assayed in 19 patients using enzyme-linked immunosorbent assay. All analyses were exploratory and not corrected for multiple testing. No associations were identified between baseline T cell repertoire and ctDNA metrics with patient outcomes. Among baseline cytokines, interleukin 1α was the only cytokine associated with both overall survival (hazard ratio, 0.02; 95% confidence interval, 0.1-0.5; P = .0006) and progression-free survival (hazard ratio, 0.5; 95% confidence interval, 0.2-0.9; P = .03). At early FU, LCT was associated with decreased ctDNA burden, including lower number of detected mutations (median, 2 [interquartile range {IQR}, 1-6] vs 6 [IQR, 4-18]) and decreased average variable allele frequency (VAF; median, 0.006 [IQR, 0.003-0.010] vs 0.011 [IQR, 0.007-0.014]) compared with MT/O. Among 6 patients with serial ctDNA analysis, a rise in ctDNA detected mutation burden preceded clinical progression by 6.7 months. At early FU, LCT was associated with changes in T cell clonality that suggested oligoclonal expansion specifically increased T cell clonality (median, 0.15 [IQR, 0.12-0.24] vs 0.10 [IQR, 0.05-0.13]) and frequency of top 10 clones (median, 0.14 [IQR, 0.06-0.18] vs 0.21[IQR, 0.19-0.28]). LCT was associated with decreased ctDNA burden and oligoclonal expansion at early FU timepoints. Baseline interleukin 1α was associated with improved patient outcomes.


Elevated temperature and 6- to 7-year outcome of neonatal encephalopathy.
A study was undertaken to determine whether higher temperature after hypoxia-ischemia is associated with death or intelligence quotient (IQ)<70 at 6 to 7 years among infants treated with intensive care without hypothermia. Control infants (noncooled, n=106) of the National Institute of Child Health and Human Development Neonatal Research Network hypothermia trial had serial esophageal and skin temperatures over 72 hours. Each infant's temperature was ranked to derive an average of the upper and lower quartile, and median of each site. Temperatures were used in logistic regressions to determine adjusted associations with death or IQ<70 at 6 to 7 years. Secondary outcomes were death, IQ<70, and moderate/severe cerebral palsy (CP). IQ and motor function were assessed with Wechsler Scales for Children and Gross Motor Function Classification System. Results are odds ratio (OR; per degree Celsius increment within the quartile or median) and 95% confidence interval (CI). Primary outcome was available for 89 infants. At 6 to 7 years, death or IQ<70 occurred in 54 infants (37 deaths, 17 survivors with IQ<70) and moderate/severe CP in 15 infants. Death or IQ<70 was associated with the upper quartile average of esophageal (OR=7.3, 95% CI=2.0-26.3) and skin temperature (OR=3.5, 95% CI=1.2-10.4). CP was associated with the upper quartile average of esophageal (OR=12.5, 95% CI=1.02-155) and skin temperature (OR=10.3, 95% CI=1.3-80.2). Among noncooled infants of a randomized trial, elevated temperatures during the first postnatal days are associated with increased odds of a worse outcome at 6 to 7 years.


'Stunning' CPOE study spurs immediate action in Massachusetts.
Financial penalties threatened for hospitals that do not meet Blue Cross and Blue Shield's deadline. More than 10% of patients in Massachusetts hospitals suffer preventable adverse drug events. Proponents say hospitals should no longer let cost be a disincentive to implement CPOE.


Does the Pirani score predict relapse in clubfoot?
Presented here is a retrospective clinical audit of clubfoot patients to determine the value of the Pirani clubfoot scoring system at initial presentation in the estimation of subsequent relapse. All clubfoot patients treated by the same surgeon from 2002 to 2006 were included. The treatment adhered to the standard protocol, involving weekly stretching and casting until the foot was corrected, followed by Achilles tenotomy and plasters for 3 weeks. Thereafter, the child was placed in a foot abduction splint. The severity of clubfoot was assessed using the Pirani scoring system, consisting of two sub-scores-the midfoot contracture score (MFCS) and the hindfoot contracture score (HFCS). The MFCS and HFCS can each be 0.0-3.0, giving rise to a total Pirani score (TPS) of 0.0-6.0. Any recurrent deformity was classed as a relapse. Sixty-one clubfoot patients were treated. Five patients were lost to follow-up and six patients were excluded due to the presence of identified syndromes or having had primary treatment elsewhere. A total of 80 clubfeet were included. There were 17 relapses. The average interval between the initiation of foot abduction splint and relapse was 23 months. The median TPS was 3.5 in the no relapse group and 5.0 in the relapse group. The median MFCS was 1.5 in the no relapse group and 2.0 in the relapse group. The median HFCS was 2.0 in the no relapse group and 3.0 in the relapse group. Higher TPS and HFCS were statistically significant when the relapse group was analysed against the no relapse group (P = 0.05 × 10(-4) and 0.02 × 10(-4), respectively). Higher Pirani scores were associated with the late relapse group. The TPS and HFCS were shown to be statistically significant predictors of potential relapse. Closer follow-up is advised for patients at risk of relapse.


Alteration of vitrified intermediate level nuclear waste in alkaline media: effects of cementitious materials, pH and temperature.
Alteration experiments involving intermediate level nuclear waste (ILW) glass in contact with hardened cement paste (HCP) were performed to assess its behavior under simulated repository conditions. Batch experiments were conducted at 20 °C and 50 °C in several artificial cement pore water (ACW) samples (pH from 10 to 13), in the presence of HCP (CEM-I, CEM-V and low pH), with a ratio of glass surface to volume of solution of 8000 m-1 and a ratio of mass of HCP to volume of solution of 10 g L-1. Glass alteration rates increase up to ∼4 × 10-2 g m-2 d-1 with pH in contact with HCP, notably with CEM-I. This value decreases by 2 orders of magnitude in low pH cement solution and also for residual alteration rates. The effect of calcium on glass alteration was observed, mainly in Ca(OH)2 saturated solution, with an incubation effect on the release of Si in solution. Experimental data were successfully modeled with the PhreeqC geochemical code. Glass and HCP samples were characterized via SEM/EDX and micro-Raman studies. This work showed that vitrified glass exhibits good performance in terms of low alteration rates (∼10-4 g m-2 d-1), the absence of secondary phases, and the formation of a gel layer at the surface, when in contact with low pH conditions (in the presence or absence of low pH HCP).


Relationship between the tryptophan-kynurenine pathway and painful physical symptoms in patients with major depressive disorder.
To investigate the relationship between the tryptophan-kynurenine (TRP-KYN) pathway and painful physical symptoms (PPS) in major depressive disorder (MDD). Eighty-four patients with MDD (40 patients with PPS and 44 without PPS) and forty-six healthy controls (HC) were recruited. The serum levels of tryptophan (TRP), kynurenine(KYN), kynurenic acid (KA), quinolinic acid (QA), 3-hydroxy-kynurenine (3-HK), serotonin (5-HT) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Depression, anxiety and pain were assessed using Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and Short-form McGill pain questionnaire (SFMPQ) respectively. Patients in the MDD group exhibited significantly lower KA and 5-HT levels than HC, whereas MDD patients with PPS showed higher KYN and QA levels, and a higher KYN/TRP ratio than those without. There was a positive correlation between the scores of SFMPQ and QA levels and a negative correlation between the scores of SFMPQ and TRP levels or KA/QA ratios in MDD patients with PPS group. Stepwise multiple regression analysis showed that the KYN/TRP ratios, the KA/QA ratios, and the HAMD scores were significant predictor factors for SFMPQ scores. These results demonstrated that the TRP-KYN pathway may play a role in the pathophysiology of pain in patients with major depressive disorder, suggesting that further studies of this pathway as a potential biomarker or therapeutic target are required.


Fatal Measles Inclusion-Body Encephalitis in Adult with Untreated AIDS, France.
We report a fatal case of measles inclusion-body encephalitis occurring in a woman from Romania with AIDS. After an extensive but unsuccessful diagnostic evaluation, a pan-pathogen shotgun metagenomic approach revealed a measles virus infection. We identified no mutations previously associated with neurovirulence.


Spatial alignment between faces and voices improves selective attention to audio-visual speech.
The ability to see a talker's face improves speech intelligibility in noise, provided that the auditory and visual speech signals are approximately aligned in time. However, the importance of spatial alignment between corresponding faces and voices remains unresolved, particularly in multi-talker environments. In a series of online experiments, we investigated this using a task that required participants to selectively attend a target talker in noise while ignoring a distractor talker. In experiment 1, we found improved task performance when the talkers' faces were visible, but only when corresponding faces and voices were presented in the same hemifield (spatially aligned). In experiment 2, we tested for possible influences of eye position on this result. In auditory-only conditions, directing gaze toward the distractor voice reduced performance, but this effect could not fully explain the cost of audio-visual (AV) spatial misalignment. Lowering the signal-to-noise ratio (SNR) of the speech from +4 to -4 dB increased the magnitude of the AV spatial alignment effect (experiment 3), but accurate closed-set lipreading caused a floor effect that influenced results at lower SNRs (experiment 4). Taken together, these results demonstrate that spatial alignment between faces and voices contributes to the ability to selectively attend AV speech.


Photoaging's portrait: The road map towards its photoprotection.
To summarize key research published by the author's group, dealing with skin photoaging and its photoprotection. Two methodologies (standard photographs and selfies imaging) resulting from referential skin ageing atlases were applied on 2487 subjects of different ancestries, ages and gender. These aimed at first to best assess and grade the variable severities of some facial signs (texture/wrinkles, pigmentary spots, sagging and vascular disorders) that occur progressively during the photoaging process. Second, such methodologies were used to record the benefits brought by a photoprotective regimen (671 women and men). In all studied ancestries, each facial sign show an increase severity along decades, at its own pace, some showing a linear like progression, whereas some plateau at early ages. These changes differed according to skin innate colour (phototype) and with individual behaviours vis-à-vis sun exposures, more so among European women than North-East Asian women. An effect of gender (less severe alterations) was observed on Chinese men, as compared to Chinese women. Pigmentary disorders were found hallmarks of photo-aged North-East Asian women. Globally, photoaging impact the apparent age of the different subjects. The counteracting effects of strong topical Photoprotective regimens were evidenced along a 6-month seasonality in Chinese and French women or 1-year period in Brazilian women with phototypes II to VI. Photoprotection led to a more even skin complexion among Indian subjects with pigment irregularities. Two factors clearly hamper a better assessment of the efficiency of photoprotection of the sun-induced cutaneous ageing: short durations (months) of the studies with regard to the global fate of photoaging by decades and the number of studied subjects, limited to hundreds for practical reasons. The methodology based on the automatic analysis of facial signs through selfies images could theoretically bypass both factors, allowing thousands of subjects to be studied along years.


Estrogen, statins, and polyunsaturated fatty acids: similarities in their actions and benefits-is there a common link?
To investigate whether there is any common link between estrogen, statins, and polyunsaturated fatty acids (PUFAs), which have similar actions and benefits. To critically review the literature pertaining to the actions of estrogen, statins, and various PUFAs. Estrogen, statins, and PUFAs enhance nitric oxide synthesis, suppress the production of proinflammatory cytokines such as tumor necrosis factor(alpha), interleukin-1, interleukin-2, and interleukin-6, show antioxidant-like and antiatherosclerotic properties, have neuroprotective actions, and by themselves or their products inhibit tumor cell proliferation and improve osteoporosis. Estrogen, statins, and PUFAs not only have similar actions but also appear to interact with each other. For instance, the binding of estrogen to its receptor on the cell membrane may be determined by its lipid content, statins and PUFAs inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, statins influence the metabolism of PUFAs, and PUFA deficiency enhances 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Statins and PUFAs inhibit tumor cell proliferation, suppress ras activity, and may prevent neurodegeneration and improve cognitive functions such as learning and memory. This suggests that PUFAs might be mediators of the actions of statins. Estrogen boosts cognitive performance in women after menopause and may protect against Alzheimer's disease. The common link between estrogen, statins, and PUFAs may be nitric oxide. Hence, a combination(s) of estrogen or its derivatives, statins, and various PUFAs may form a novel approach in the management of various conditions such as hyperlipidemias, coronary heart disease, atherosclerosis, osteoporosis, cancer, neurodegenerative conditions, and to improve memory.


Relationship of p53 mutations to epidermal cell proliferation and apoptosis in human UV-induced skin carcinogenesis.
Human skin is continually subjected to UV-irradiation with the p53 gene playing a pivotal role in repair of UV-induced DNA damage and apoptosis. Consequently, p53 alterations are early events in human UV-induced skin carcinogenesis. We studied 13 squamous cell carcinomas (SCC), 16 actinic keratoses (AK), 13 samples adjacent to an AK (chronically sun-damaged), and 14 normal-appearing skin samples for p53 mutation, p53 immunostaining (IHC), apoptosis (in situ TUNEL and morphology), and proliferation (PCNA). The frequency of p53 mutation increased from 14% in normal skin, to 38.5% in sun-damaged skin, 63% in AK, and 54% in SCC. p53 IHC increased similarly. Apoptosis (TUNEL) increased from 0.06 +/- 0.02%, to 0.1 +/- 0.2, 0.3 +/- 0.3, and 0.4 +/- 0.3 in normal skin, sun-damaged skin, AK, and SCC, respectively. Apoptosis was strongly correlated with proliferation (i.e., TUNEL and PCNA, r = 0.7, P < 0.0001), and proliferation was significantly increased in the progression from normal skin to SCC. Bax was significantly increased in SCC compared to AK. These data imply that apoptosis in samples with a high frequency of p53 mutation may not necessarily be p53-dependent. We suggest that there is a mechanism for apoptosis in response to increased cellular proliferation that is p53-independent.


An Overview of Analytical Methods for the Quantification of Marbofloxacin in Pharmaceutical, Biological, and Food Matrixes.
Marbofloxacin (MAR), a second-generation fluoroquinolone, is used in veterinary medicine in the form of tablets. It has a broad spectrum of action, low toxicity, and limited development of bacterial resistance. The analytical methods available in the literature become more important since MAR in tablets does not have a monograph in official compendiums. Our purpose is to review the methods according to the analyzed matrix and place them according to the conditions used in the scope of green analytical chemistry, in addition to discussing possible gaps and opportunities for the development of new methods. MAR, being an antimicrobial, presents both physicochemical (93%) and microbiological (7%) methods in the literature. Among the methods found, 53% are for analysis of food matrixes using preferably HPLC and TLC-MS, 27% are for analysis of biological matrixes and 20% are for analysis of pharmaceutical matrixes, and in both HPLC is preferably used. Therefore, there is still a gap in the literature in relation to other analytical methods for the analysis of MAR, which are faster, such as microbiological turbidimetry, sustainable, such as miniaturized methods, and ecologically correct, such as those that do not use toxic organic solvents. A review of the analytical methods available in the literature for assessing the quality of MAR and MAR-based products in which the methods, as well as new opportunities for analysis according to green analytical chemistry, were described and discussed.


Stomach Intestinal Pylorus Sparing (SIPS) Surgery for Morbid Obesity: Retrospective Analyses of Our Preliminary Experience.
Although the duodenal switch (DS) has been the most effective weight loss surgical procedure, it is a small minority of the total bariatric surgical cases performed. Modifications that can make the operation technically simpler and reduce a long-term risk of short bowel syndrome would be of benefit. The aim of this study was to detail our initial experience with a modified DS called stomach intestinal pylorus sparing (SIPS) procedure. Data from patients who underwent a primary SIPS procedure performed by two surgeons at two centers from January 2013 to August 2014 were retrospectively analyzed. All revisions of prior bariatric procedures were excluded. Regression analyses were performed for all follow-up weight loss data. One hundred twenty-three patients were available. One hundred two patients were beyond 1 year postoperative, with data available for 64 (62 % followed up). The mean body mass index (BMI) was 49.4 kg/m(2). Two patients had diarrhea (1.6 %), four had abdominal hematoma (3.2 %), and one had a stricture (0.8 %) in the gastric sleeve. Two patients (1.6 %) were readmitted within 30 days. One patient (0.8 %) was reoperated due to an early postoperative ulcer. At 1 year, patients had an average change in BMI of 19 units (kg/m(2)), which was compared to an average of 38 % of total weight loss or 72 % of excess weight loss. Modification of the classic DS to one with a single anastomosis and a longer common channel had effective weight loss results. Morbidity seems comparable to other stapling reconstructive procedures. Future analyses are needed to determine whether a SIPS procedure reduces the risk of future small bowel obstructions and micronutrient deficiencies.


Keeping track to keep Australia's overseas aid on track.
In the competition for official development assistance, health is losing out to governance and security.


Fall Risk Index predicts functional decline regardless of fall experiences among community-dwelling elderly.
The 21-item Fall Risk Index (FRI-21) has been used to detect elderly persons at risk for falls. The aim of this longitudinal study was to evaluate the FRI-21 as a predictor of decline in basic activities of daily living (BADL) among Japanese community-dwelling elderly persons independent of fall risk. The study population consisted of 518 elderly participants aged 65 years and older who were BADL independent at baseline in Tosa, Japan. We examined risk factors for BADL decline from 2008 to 2009 by multiple logistic regression analysis on the FRI-21 and other functional status measures in all participants. We carried out the same analysis in selected participants who had no experience of falls to remove the effect of falls. A total of 45 of 518 participants showed decline in BADL within 1 year. Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05-1.20), FRI-21 ≥ 10 (OR 3.81, 95% CI 1.49-9.27), intellectual activity dependence (OR 3.25, 95% CI 1.42-7.44) and history of osteoarthropathy (OR 3.17, 95% CI 1.40-7.21) were significant independent risk factors for BADL decline within 1 year. FRI-21 ≥ 10 and intellectual activity dependence (≤ 3) remained significant predictors, even in selected non-fallers. FRI-21 ≥ 10 and intellectual activity dependence were significant predictive factors of BADL decline, regardless of fall experience, after adjustment for confounding variables. The FRI-21 is a brief, useful tool not only for predicting falls, but also future decline in functional ability in community-dwelling elderly persons.


Characterization of a single-stranded DNA-binding protein from Klebsiella pneumoniae: mutation at either Arg73 or Ser76 causes a less cooperative complex on DNA.
Single-stranded DNA-binding protein (SSB) plays an important role in DNA metabolism, such as in processes like DNA replication, repair and recombination, and is essential for cell survival. Here, we characterized the ssDNA-binding properties of Klebsiella pneumoniae SSB (KpSSB) by using fluorescence-quenching measurements, electrophoretic mobility shift analysis (EMSA) and site-directed mutagenesis. Analysis of purified KpSSB by gel-filtration chromatography showed a stable tetramer in solution. In fluorescence titrations, KpSSB bound to 25-40 nucleotides (nt) per tetramer depending on the salt concentration. Using EMSA, we characterized the stoichiometry of KpSSB complexed with a series of ssDNA homopolymers, and the size of the binding site was determined to be 26 ± 1 nt. Mutation at either Arg73 or Ser76 of KpSSB caused a less cooperative complex on DNA. Arg73 forms an intermolecular hydrogen bond with Ser76, and this appears to be a likely driving force that directs the self-assembly of SSB on DNA.


Inducible knockdown of Mycobacterium smegmatis MSMEG_2975 (glyoxalase II) affected bacterial growth, antibiotic susceptibility, biofilm, and transcriptome.
Tuberculosis (TB) causes millions of deaths each year across the globe. Multiple drug-resistant (MDR) and extensively drug-resistant (XDR) mycobacterial strains have made the treatment extremely difficult. To overcome this hurdle, the development of new drug targets and an effective treatment strategy are desperately needed. This can be achieved by deciphering the role of essential genes and enzymes which are involved in cell survival. One such enzyme is glyoxalase II. The glyoxalase system (glyoxalase I and glyoxalase II) has a pivotal role in cellular survival and detoxification by converting methylglyoxal (MG) into lactate. Otherwise, the increased concentration of MG then modifies DNA, proteins, and lipids, resulting in abnormalities and cell death. Interestingly, the function and physiological role of glyoxalase II have remained undetermined in mycobacteria. In this study, the functional activity of MSMEG_2975 (putative glyoxalase II) after heterologous cloning and expression was determined. And the knockdown strain Mycobacterium smegmatis KD for MSMEG_2975 was constructed with tetracycline-inducible vector pMIND. The inducible knockdown of MSMEG_2975 affected bacterial growth, biofilm formation, transcriptome, and enhanced the susceptibility to antibiotics. This work represents mycobacterial glyoxalase II as a potential drug target against mycobacterial pathogens and indicates the crucial regulatory role of glyoxalase II in mycobacteria.


Annual plasma testosterone and thyroxine cycles in relation to hibernation in the edible dormouse Glis glis.
Twelve male edible dormice, captured in the autumn of 1979, were studied for 2 years under natural lighting in an animal enclosure with permanently open windows, at Montpellier, in Southern France (latitude 43 degrees 50' N). Ambient temperature fluctuated annually between +4 and 27 degrees, and the photoperiod between 10L:14D and 16L:8D. Another group of 26 animals, captured in the autumn of 1980, was observed under the same conditions for 1 year. Body weight and plasma testosterone and thyroxine concentrations were measured at monthly intervals under standardized conditions. Hibernation generally extended from October to February but lasted till May in a few cases, and the critical temperature for dormancy varied between 13 and 16 degrees in November and 23 degrees in May. Body weight fluctuated annually according to a biphasic pattern, with two maxima, respectively, in spring and autumn (prehibernation), and two minima, in summer and winter. However, plasma testosterone and thyroxine concentrations displayed clearly monophasic annual cycles, closely correlated, both to each other and to the ambient temperature and photoperiod. Both the testosterone and thyroxine cycles culminated in June-July. Interestingly, the annual ascending phase for both hormonal cycles never preceded the terminal arousal of the animal. Further, whatever the season, 30 degrees was clearly the critical minimal body temperature required for a seasonal increase to occur in plasma testosterone. These annual cycles are discussed in the light of the data acquired recently for hibernators other than the dormouse.


Ozone decomposition of 2-methylisoborneol (MIB) in adsorption phase on high silica zeolites with preventing bromate formation.
This work elucidates the applicability of our newly developed adsorptive ozonation process for the decomposition of 2-methylisoborneol (MIB), a typical taste and odor chemical, without the formation of possibly carcinogenic bromate ions. First, zeolite adsorbents were screened for their ability to adsorb MIB with a batch-type adsorption experimental apparatus and a flow-type decomposition experimental apparatus included an adsorbent-packed column. The USY zeolite with the highest silica to alumina ratio (SiO(2)/Al(2)O(3) molar ratio=70) showed the best performance as an adsorbent. Using this adsorbent, an ozonation experiment on an MIB solution including bromide ions was performed under various retention times using the flow-type apparatus. As a result, sufficient decomposition of MIB was achieved with preventing bromate formation.


First detection of Candidatus Rickettsia barbariae in the flea Vermipsylla alakurt from north-western China.
Vermipsylla is a genus of the family Vermipsyllidae within the order Siphonaptera of fleas. Vermipsylla alakurt is mainly distributed in alpine pastoral areas of Kazakhstan, Mongolia, China and Nepal, and infests sheep, yaks and horses, causing irritation, poor condition, anaemia and even death. However, to date, no rickettsial agents have been reported in V. alakurt. A total of 133 fleas were collected directly from the tails of three sheep flocks (n = 335) in Minfeng County, Xinjiang Uygur Autonomous Region, north-western China. Of these, 55 fleas were identified by morphological examination and molecular analysis of four loci (the ribosomal 18S and 28S rDNA genes and the mitochondrial genes cytochrome c oxidase subunit II and elongation factor 1-alpha). Eight Rickettsia-specific gene fragments originated from seven genes: the 17-kilodalton antigen gene (17-kDa), citrate synthase gene (gltA), 16S rRNA gene (rrs), outer membrane protein A gene (ompA), surface cell antigen 1 gene (sca1), PS120 protein gene (gene D), and outer membrane protein B gene (ompB, two fragments), were used to identify the species of Rickettsia in 53 fleas. The amplified products were sequenced and included in a phylogenetic analysis to verify the taxonomic identification of the rickettsial agents. Based on morphological and molecular evidence, the flea was identified as Vermipsylla alakurt. Nine samples were positive (16.98 %, 9/53) for Rickettsia spp. The phylogenetic tree revealed that the rickettsial agents found in V. alakurt cluster with Candidatus Rickettsia barbariae. Our study suggests that: (i) V. alakurt may serve as a carrier for Candidatus R. barbariae; and (ii) Candidatus R. barbariae, previously reported in Israel, is the eighth newly discovered validated Rickettsia species in China. This finding extends our knowledge of the distribution of Candidatus R. barbariae and the profile of carriers, which not only comprise ticks but also fleas.


A longitudinal study of indoor nitrogen dioxide levels and respiratory symptoms in inner-city children with asthma.
The effect of indoor nitrogen dioxide concentrations on asthma morbidity among inner-city preschool children is uncertain. Our goal was to estimate the effect of indoor NO2 concentrations on asthma morbidity in an inner-city population while adjusting for other indoor pollutants. We recruited 150 children (2-6 years of age) with physician-diagnosed asthma from inner-city Baltimore, Maryland. Indoor air was monitored over a 72-hr period in the children's bedrooms at baseline and 3 and 6 months. At each visit, the child's caregiver completed a questionnaire assessing asthma symptoms over the previous 2 weeks and recent health care utilization. Children were 58% male, 91% African American, and 42% from households with annual income < $25,000; 63% had persistent asthma symptoms. The mean (+/- SD) in-home NO2 concentration was 30.0 +/- 33.7 (range, 2.9-394.0) ppb. The presence of a gas stove and the use of a space heater or oven/stove for heat were independently associated with higher NO2 concentrations. Each 20-ppb increase in NO2 exposure was associated significantly with an increase in the number of days with limited speech [incidence rate ratio (IRR) = 1.15; 95% confidence interval (CI), 1.05-1.25], cough (IRR = 1.10; 95% CI, 1.02-1.18), and nocturnal symptoms (IRR = 1.09; 95% CI, 1.02-1.16), after adjustment for potential confounders. NO2 concentrations were not associated with increased health care utilization. Higher indoor NO2 concentrations were associated with increased asthma symptoms in preschool inner-city children. Interventions aimed at lowering NO2 concentrations in inner-city homes may reduce asthma morbidity in this vulnerable population.


Complete Nucleotide Sequence of pGA45, a 140,698-bp IncFIIY Plasmid Encoding bla IMI-3-Mediated Carbapenem Resistance, from River Sediment.
Plasmid pGA45 was isolated from the sediments of Haihe River using Escherichia coli CV601 (gfp-tagged) as recipients and indigenous bacteria from sediment as donors. This plasmid confers reduced susceptibility to imipenem which belongs to carbapenem group. Plasmid pGA45 was fully sequenced on an Illumina HiSeq 2000 sequencing system. The complete sequence of plasmid pGA45 was 140,698 bp in length with an average G + C content of 52.03%. Sequence analysis shows that pGA45 belongs to IncFIIY group and harbors a backbone region which shares high homology and gene synteny to several other IncF plasmids including pNDM1_EC14653, pYDC644, pNDM-Ec1GN574, pRJF866, pKOX_NDM1, and pP10164-NDM. In addition to the backbone region, plasmid pGA45 harbors two notable features including one bla IMI-3-containing region and one type VI secretion system region. The bla IMI-3-containing region is responsible for bacteria carbapenem resistance and the type VI secretion system region is probably involved in bacteria virulence, respectively. Plasmid pGA45 represents the first complete nucleotide sequence of the bla IMI-harboring plasmid from environment sample and the sequencing of this plasmid provided insight into the architecture used for the dissemination of bla IMI carbapenemase genes.


Patient Reported Outcome Measures: Challenges in the Reporting!
Patient-reported outcome measures are increasingly important in the era of value-based healthcare. We use the example of total joint arthroplasty to demonstrate how current reporting measures may hide poorer outcomes. There is thus a need for a standardized approach in reporting patient-reported outcome measure tied to clinically relevant thresholds.


Structure-activity analysis of microsomal antigen/thyroid peroxidase.
The interaction between thyroid microsomal autoantibodies and thyroid microsomal antigen/thyroid peroxidase (TPO) has been studied using both intact antigen preparations and their water-soluble trypsin fragments. In an analysis of sera from 30 patients with Graves' or Hashimoto's diseases, microsomal antibodies showed similar reactivity towards trypsin fragments (with TPO activity) and intact detergent (sodium deoxycholate, DOC)-solubilized human microsomal antigen preparations (r = 0.96). This raised the possibility that both the peroxidase-active site and the major autoantigenic site(s) of microsomal antigen were present on the same trypsin fragments. Studies with porcine TPO showed that only a few sera contained microsomal antibodies which cross-reacted strongly with the porcine preparations. Further analysis was carried out by immunoprecipitation of 125I-labelled microsomal antigen followed by SDS-PAGE and autoradiography. These studies suggest that intact human microsomal antigen (a single-chain protein with Mr = 110,000) contains an intrachain loop of amino acids formed by a disulphide bridge. Trypsin treatment cleaves the antigen close to its transmembrane section and releases a water-soluble fragment (Mr = 100,000), containing the intact disulphide-linked loop of amino acids. Further trypsin action causes cleavage of the peptide bonds within the loop in some preparations. Consequently, three major water-soluble trypsin fragments (Mr = 100,000, 73,000 and 68,000) are formed all of which contain an intact disulphide bridge and have microsomal antibody binding activities. The integrity of the disulphide bridge in intact antigen/TPO preparations and their trypsin fragments is essential for autoantibody binding activity.


Perfluorinated alkyl acids in water, sediment and wildlife from Sydney Harbour and surroundings.
Perfluorinated alkyl compounds (PFCs) including perfluorooctane sulphonate (PFOS) and perfluorooctanoate (PFOA) were measured in environmental samples collected from around Homebush Bay, an urban/industrial area in the upper reaches of Sydney Harbour and Parramatta River estuary. Water, surface sediment, Sea Mullet (Mugil cephalus), Sydney Rock Oyster (Saccostrea commercialis) and eggs of two bird species; White Ibis (Threskiornis molucca), and Silver Gull (Larus novaehollandiae) were analysed. In most samples PFOS was the dominant PFC. Geometric mean PFOS concentrations were 33 ng/gww (wet weight) in gull eggs, 34 ng/gww in ibis eggs, and 1.8 ng/gww and 66 ng/gww in Sea Mullet muscle and liver, respectively. In sediment the PFOS geometric mean was 1.5 ng/g, in water average PFOS and PFOA concentrations ranged from 7.5 to 21 ng/L and 4.2 to 6.4 ng/L, respectively. In oysters perfluorododecanoic acid was most abundant, with a geometric mean of 2.5 ng/gww.


Safety and Effectiveness of Same-Day Chlamydia trachomatis and Neisseria gonorrhoeae Screening and Treatment Among Gay, Bisexual, Transgender, and Homeless Youth in Los Angeles, California, and New Orleans, Louisiana.
Gay, bisexual, transgender, and homeless youth are at risk of sexually transmitted infections. As part of an adolescent human immunodeficiency virus prevention study, we provided same-day Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing and treatment. We aimed to evaluate the feasibility and effectiveness of same-day CT and NG treatment on the proportion of participants receiving timely treatment. We recruited adolescents with high sexual risk behaviors aged 12 to 24 years from homeless shelters, lesbian, gay, bisexual, and transgender organizations, and community health centers in Los Angeles, California, and New Orleans, Louisiana from May 2017 to June 2019. Initially, participants were offered point-of-care pharyngeal, rectal, and urethral/vaginal CT and NG testing and referral to another clinic for treatment. After March 2018 in Los Angeles and November 2018 in New Orleans, we provided same-day treatment (and partner treatment packs) for study participants. We measured the proportion of participants who received same-day treatment and the median time to treatment. We collected frequency of partner treatment and any reported adverse treatment-related events. The proportion of participants receiving same-day CT and NG treatment increased from 3.6% (5/140) to 21.1% (20/95; Δ17.5%; 95% confidence interval, 9.2%-26.9%) after implementation of same-day testing and treatment. The median time to treatment decreased from 18.5 to 3 days. Overall, 36 participants took a total of 48 partner treatment packs. There were no reported treatment-related adverse events. Providing sexually transmitted infection treatment to adolescents at the same visit as testing is feasible and safe, and can increase the proportion of individuals receiving timely treatment.


Electrophoretic determination of the myosin/actin ratio in the diagnosis of critical illness myopathy.
To develop a rapid method to quantify myosin in muscle biopsy specimens from patients with critical illness myopathy (CIM). Percutaneous muscle biopsy specimens at different stages of CIM were examined by light microscopy and transmission electron microscopy (TEM) and by horizontal pore gradient SDS electrophoresis (SDS-PAGE). The myosin/actin ratio was calculated densitometrically. Neurophysiological examinations were performed at various times during the course of CIM. All patients were treated in intensive care units at Karolinska Hospital. We studied 11 patients with CIM, 5 patients with axonal neuropathies, and 42 control individuals. The histopathological changes included in all cases muscle fiber atrophy, degeneration, regeneration, nuclear changes, and reduction in myofibrillar ATPase activity in both type I and II fibers. In severely affected muscles fiber type differentiation was lost. On TEM preferential loss of thick filaments was the dominant finding. In some patients changes were present only in parts of the specimen. The neurophysiological examinations indicated myopathy in five patients and combined myopathy and neuropathy in five and suggested neuropathy in one. The SDS-pore PAGE used showed a technical variation of 4-5%. Quantitative results were obtained within 1 day and night. The mean value of the myosin/actin ratio in controls was 1.37+/-0.21 and in CIM patients 0.37+/-0.17, without overlapping with the control values. Considering the diagnostic difficulty using morphological and neurophysiological methods, especially in early stages of CIM, we suggest including SDS-pore PAGE to determine the myosin/actin ratio for rapid diagnosis of CIM.


Main pulmonary artery aneurysm.
Pulmonary artery aneurysm is a rare lesion of the thoracic cavity. Different etiologies have been reviewed, but idiopathic lesions without other symptoms are seldom reported. Usually, surgical interventions are suggested, but the long-term outcomes are not well established. Here, we report a 24-year-old man with main pulmonary artery aneurysm who successfully underwent aneurysmectomy and polytetrafluoroethylene vascular graft replacement. The postoperative course was uneventful, and the following image study revealed normal size of the great vessels.


Delineating disorder-general and disorder-specific dimensions of psychopathology from functional brain networks in a developmental clinical sample.
The interplay between functional brain network maturation and psychopathology during development remains elusive. To establish the structure of psychopathology and its neurobiological mechanisms, mapping of both shared and unique functional connectivity patterns across developmental clinical populations is needed. We investigated shared associations between resting-state functional connectivity and psychopathology in children and adolescents aged 5-21 (n = 1689). Specifically, we used partial least squares (PLS) to identify latent variables (LV) between connectivity and both symptom scores and diagnostic information. We also investigated associations between connectivity and each diagnosis specifically, controlling for other diagnosis categories. PLS identified five significant LVs between connectivity and symptoms, mapping onto the psychopathology hierarchy. The first LV resembled a general psychopathology factor, followed by dimensions of internalising- externalising, neurodevelopment, somatic complaints, and thought problems. Another PLS with diagnostic data revealed one significant LV, resembling a cross-diagnostic case-control pattern. The diagnosis-specific PLS identified a unique connectivity pattern for autism spectrum disorder (ASD). All LVs were associated with distinct patterns of functional connectivity. These dimensions largely replicated in an independent sample (n = 420) from the same dataset, as well as to an independent cohort (n = 3504). This suggests that covariance in developmental functional brain networks supports transdiagnostic dimensions of psychopathology.


Comparison of cartilage with temporalis fascia tympanoplasty: A meta-analysis of comparative studies.
To systematically review the results of type 1 tympanoplasty with temporalis fascia (TF) versus cartilage in patients with chronic otitis media (COM) for graft integration and hearing improvement. The English language literature (until June 1, 2016) was searched, using Medline (via PubMed), Scopus, ProQuest, Ovid, Cochrane database, and Google Scholar. A comprehensive review of the literature was performed. Prospective and retrospective studies enrolling patients with COM were included. Relevance and validity of selected articles were evaluated. Heterogeneity was assessed using I2 statistics. For dichotomous variables, absolute rate differences, and number needed to treat (NNT) were calculated. For continuous variables, standard mean differences were calculated. A total of 11 prospective and 26 retrospective studies involving 3,606 patients were included. In general, the overall graft integration rates of cartilage and fascia tympanoplasty were 92% and 82%, respectively (NNT = 11.1, P < 0.001). Although there was no significant difference in the air-bone gap (ABG) closure of < 10 dB between the two groups, the subanalysis of prospective studies showed that patients in the TF group had less mean postoperative ABG (P = 0.02). Subgroup analysis of palisade grafts compared with that of TF graft revealed a significant difference in the graft integration rate favoring cartilage tympanoplasty (P = 0.01). Cartilage grafting seemed to show a higher graft integration rate compared with TF grafting. Both cartilage and fascia tympanoplasty provided similar improvements in the hearing outcome postoperatively. Large prospective trials are necessary to collect high-quality data. NA. Laryngoscope, 127:2139-2148, 2017.


Chinese expert consensus on adult ventral abdominal wall defect repair and reconstruction.
Surgical management of patients with ventral abdominal wall defects, especially complex abdominal wall defects, remains a challenging problem for abdominal wall reconstructive surgeons. Effective surgical treatment requires appropriate preoperative assessment, surgical planning, and correct operative procedure in order to improve postoperative clinical outcomes and minimize complications. Although substantial advances have been made in surgical techniques and prosthetic technologies, there is still insufficient high-level evidence favoring a specific technique. Broad variability in existing practice patterns, including clinical pre-operative evaluation, surgical techniques and surgical procedure selection, are still common. With the purpose of providing a best practice algorithm, a comprehensive search was conducted in Medline and PubMed. Sixty-four surgeons considered as experts on abdominal wall defect repair and reconstruction in China were solicited to develop a Chinese consensus and give recommendations to help surgeons standardize their techniques and improve clinical results. This consensus serves as a starting point to provide recommendations for adult ventral abdominal wall repair and reconstruction in China and may help build opportunities for international cooperation to refine AWR practice.


Respiratory syncytial virus (RSV) suppression of glucocorticoid receptor phosphorylation does not account for repression of transactivation.
Respiratory syncytial virus (RSV)-induced bronchiolitis in infants, although inflammatory in nature, is not responsive to glucocorticoids. We have recently shown that RSV-infected lung epithelial cells have impaired glucocorticoid receptor (GR)-mediated transactivation. In this study, we show that the N-terminal region of GR is required for RSV repression of GR transactivation and that RSV infection of lung epithelial cells reduces ligand-dependent GR phosphorylation at serine 211 and serine 226. However, we also show that these changes in GR phosphorylation do not account for the RSV repression of GR transactivation suggesting other regions of the GR N-terminus must also be involved.


Structural analysis of the KRIT1 ankyrin repeat and FERM domains reveals a conformationally stable ARD-FERM interface.
Cerebral cavernous malformations (CCM) are vascular dysplasias that usually occur in the brain and are associated with mutations in the KRIT1/CCM1, CCM2/MGC4607/OSM/Malcavernin, and PDCD10/CCM3/TFAR15 genes. Here we report the 2.9 Å crystal structure of the ankyrin repeat domain (ARD) and FERM domain of the protein product of KRIT1 (KRIT1; Krev interaction trapped 1). The crystal structure reveals that the KRIT1 ARD contains 4 ankyrin repeats. There is an unusual conformation in the ANK4 repeat that is stabilized by Trp-404, and the structure reveals a solvent exposed ankyrin groove. Domain orientations of the three copies within the asymmetric unit suggest a stable interaction between KRIT1 ARD and FERM domains, indicating a globular ARD-FERM module. This resembles the additional F0 domain found N-terminal to the FERM domain of talin. Structural analysis of KRIT1 ARD-FERM highlights surface regions of high evolutionary conservation, and suggests potential sites that could mediate interaction with binding partners. The structure therefore provides a better understanding of KRIT1 at the molecular level.


Robust optimization and strategic analysis for agri-food supply chain under pandemic crisis: Case study from an emerging economy.
Pandemic crises like the coronavirus disease 2019 (COVID-19) have severely influenced companies working in the Agri-food industry in different countries. Some companies could overcome this crisis by their elite managers, while many experienced massive financial losses due to a lack of the appropriate strategic planning. On the other hand, governments sought to provide food security to the people during the pandemic crisis, putting extreme pressure on companies operating in this field. Therefore, the aim of this study is to develop a model of the canned food supply chain under uncertain conditions in order to analyze it strategically during the COVID-19 pandemic. The problem uncertainty is addressed using robust optimization, and also the necessity of using a robust optimization approach compared to the nominal approach to the problem is indicated. Finally, to face the COVID-19 pandemic, after determining the strategies for the canned food supply chain, by solving a multi-criteria decision-making (MCDM) problem, the best strategy is specified considering the criteria of the company under study and its equivalent values are presented as optimal values of a mathematical model of canned food supply chain network. The results demonstrated that "expanding the export of canned food to neighboring countries with economic justification" was the best strategy for the company under study during the COVID-19 pandemic. According to the quantitative results, implementing this strategy reduced by 8.03% supply chain costs and increased by 3.65% the human resources employed. Finally, the utilization of available vehicle capacity was 96%, and the utilization of available production throughput was 75.8% when using this strategy.


Telithromycin in the treatment of pneumococcal community-acquired respiratory tract infections: a review.
A pooled analysis of 14 Phase III studies was performed to establish the clinical and bacteriologic efficacy of telithromycin 800 mg once daily in the treatment of pneumococcal community-acquired respiratory tract infections (RTIs). Data were examined from 5534 adult/adolescent patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), or acute bacterial sinusitis, who had received telithromycin for 5-10 days or a comparator antibacterial. Streptococcus pneumoniae was identified in 704/2060 (34.2%) bacteriologically evaluable patients. The respective per-protocol clinical cure rates for telithromycin and comparators were 94.3% and 90.0% (CAP); 81.5% and 78.9% (AECB); 90.1% and 87.5% (acute sinusitis); 92.7% and 87.6% (all indications). Clinical cure rates were 28/34 (82.4%) and 5/7, respectively, for penicillin-resistant infections, and 44/52 (84.6%) and 11/14, respectively, for erythromycin-resistant infections. Of 82 patients with pneumococcal bacteremia, 74 (90.2%) were clinically cured after telithromycin treatment, including 5/7 and 8/10 with penicillin- or erythromycin-resistant strains, respectively. Adverse events considered possibly related to study medication were reported by 1071/4045 (26.5%) telithromycin and 505/1715 (29.4%) comparator recipients. These events were generally of mild/moderate severity, and mainly gastrointestinal in nature. As S. pneumoniae is the leading bacterial cause of community-acquired RTIs, and antibacterial resistance is increasing among this species, these findings support the use of telithromycin as first-line therapy in this setting.


Vitamin D deficiency is associated with digital ulcer but not with atherosclerosis or arterial stiffness in patients with systemic sclerosis: a pilot study.
The objective of this study was to investigate the association of vitamin D deficiency with digital ulcers (DUs) that result from microvasculopathy, carotid intima-media thickness (CIMT) as surrogate markers of atherosclerosis, and brachial-ankle pulse wave velocity (baPWV) representing arterial stiffness in patients with systemic sclerosis (SSc). In this cross-sectional study, 40 female SSc patients and 80 healthy controls matched for sex, age, and blood sampling season were recruited. Vitamin D deficiency was defined as serum 25-OHD levels <30 ng/mL. "DUs ever" included active and healed DUs. CIMT and carotid plaque were examined using high-resolution ultrasonography, and baPWV was measured using an automatic waveform analyzer. Vitamin D deficiency was more prevalent in SSc patients than in controls (30 vs. 11.3%). Regarding SSc patients, 9 (22.5%) had DUs ever, and the mean CIMT and baPWV were 0.68 mm and 1561.1 cm/s, respectively; carotid plaque was detected in 13 (34.2%) patients. The frequency of DUs ever was significantly higher for SSc patients with vitamin D deficiency than those without this feature (50 vs. 10.7%, p = 0.012), but the median CIMT and baPWV and the frequency of carotid plaque did not differ according to the presence of vitamin D deficiency. Multivariable logistic regression analysis showed that vitamin D deficiency was an independent risk factor for DUs ever (OR = 7.72, p = 0.024). Vitamin D deficiency was associated with DUs, but not with atherosclerosis or arterial stiffness, potentially indicating that vitamin D may have different effects on the microvascular and macrovascular involvement in SSc pathophysiology.


Expression of the enhanced green fluorescent protein by herpes simplex virus type 1 (HSV-1) as an in vitro or in vivo marker for virus entry and replication.
Glycoprotein K (gK) is involved in membrane fusion phenomena during infectious virus production and egress and is an important determinant for neurovirulence. To assess better the in vitro and in vivo roles of gK in virus replication, a recombinant virus was constructed expressing an engineered enhanced green fluorescent protein (EGFP) under the control of the human cytomegalovirus immediate early gene promoter (HCMV-IEP) inserted in place of the gK gene. The EGFP gene insertion was confirmed by diagnostic polymerase chain reaction (PCR), and the presence of the EGFP protein was detected by western immunoblot analysis using anti-GFP monoclonal antibody. Fluorescence microscopy revealed that virus infected cells emitted bright fluorescence when examined using filters for fluorescein. Fluorescence emission was detected as early as 4 h post-infection. Fluorescence intensity increased over time and was stable at late times after infection at which point viral plaques continued to emit bright green fluorescence. The amount of fluorescence emitted by virus infected Vero cells was monitored by fluorescence cytometry using a FACS cytometer. At an MOI of 3, all infected cells emitted strong green fluorescence as quantified by cytometry at 48 h post-infection. The deltagK-EGFP expressing recombinant virus will enable the determination of the role of gK in virus entry and egress as well as the role of gK in the molecular pathogenesis of herpes simplex virus type 1 (HSV-1).


The synthesis of symmetrical spermine conjugates using solid-phase chemistry.
The utility of spermine, selectively functionalised and immobilised on a solid support by means of the Wang "oxycarbonyl" linker is demonstrated by the solid-phase synthesis of a number of spermine conjugates including the natural product and potent antihypertensive agent kukoamine. The synthesis opens up the area of solid-phase spermine chemistry and library generation based on the symmetrical spermine scaffold.


[Prosthetic loading considered in the biomechanical design of removable partial dentures].
The prosthetic loads in removable partial dentures are analyzed. Different clinics and laboratory methods to make retain and support are discussed. From its study is infered a therapeutic prognostic.


Investigating Associations Between Physical Activity and Presenteeism - A Scoping Review.
The aim of this study is to scope the literature on what is currently known between physical activity and presenteeism. A search strategy was conducting in six scientific databases. Studies written in English about the relation between physical activity and presenteeism were considered for inclusion. Data on definitions and measurement of presenteeism and physical activity were extracted. The data is categorized according to the understanding of presenteeism of the studies to give a better idea of how this phenomenon is studied in relation to physical activity. After screening 9773 titles and abstracts and 269 full-text articles, 57 unique articles fulfilled our eligibility criteria. The majority of the articles were published since 2010 and originated predominantly in the United States. Most studies (70%) define presenteeism as lost productivity due to health problems, according to the American line of research, whereas 19% of the studies define it as "working while ill" which refers to the European line of research. The studies that reflected the American school of thought tends to report more results that supported their hypothesis (i.e., that more physical activity is associated with less presenteeism). This review has highlighted the homogeneity in how presenteeism is conceptualized and measured in studies included in our sample. Research on physical activity and presenteeism should be expanded across various disciplines in social sciences to respond to the needs that many researchers have expressed to promote healthier organizations.


KPNβ1 promotes palmitate-induced insulin resistance via NF-κB signaling in hepatocytes.
It has been intensively studied that inflammation contributes to the insulin resistance development in obesity-induced type 2 diabetes mellitus (T2DM). In this study, we assessed the effect of karyopherin β1 (KPNβ1) in hepatic insulin resistance and the underlying mechanisms using high-fat diet (HFD) fed mice and palmitate (PA)-stimulated hepatocytes (HepG2). KPNβ1 expression is increased in the HFD fed mice liver. PA upregulated KPNβ1 expression in HepG2 cells in a time-dependent manner. PA also increased pro-inflammatory cytokines expression, including tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β). KPNβ1 knockdown reversed PA-induced pro-inflammatory cytokines expression and insulin-stimulated glucose uptake in HepG2 cells. In addition, KPNβ1 knockdown reduced intracellular lipid accumulation. Mechanistically, KPNβ1 transports nuclear factor kB (NF-κB) p65 from the cytoplasm to the nucleus to increase pro-inflammatory genes expression. In summary, KPNβ1 acts as a positive regulator in the NF-κB pathway to enhance palmitate-induced inflammation response and insulin resistance in HepG2 cells.


Coupling the cell cycle to cell growth.
In order to multiply, both prokaryotic and eukaryotic cells go through a series of events that are collectively called the cell cycle. However, DNA replication, mitosis and cell division may also be viewed as having their own, in principle independent, cycles, which are tied together by mechanisms extrinsic to the cell cycle--the checkpoints--that maintain the order of events. We propose that our understanding of cell-cycle regulation is enhanced by viewing each event individually, as an independently regulated process. The nature of the parameters that regulate cell-cycle events is discussed and, in particular, we argue that cell mass is not such a parameter.


Use of clinical decision support to identify i.v.-to-oral conversion opportunities and cost savings.
The use of a clinical decision support (CDS) tool to determine patients' eligibility for oral medication therapy and the opportunity cost of i.v.-to-oral conversion practices in a large health system was evaluated. This multicenter, retrospective, process improvement study comprised CDS data generated by 149 hospitals from May 1 through October 31, 2015. Data related to i.v.-to-oral conversions were identified and compiled for evaluation. For each patient with an opportunity for i.v.-to-oral therapy conversion, corresponding barcode-assisted medication administration data were evaluated to determine the number of doses that were administered within prespecified time periods. A total of 121,685 i.v.-to-oral conversion opportunities, corresponding to 71,342 unique patients and encompassing 31 different medications, were evaluated. The top 13 medications representing 94% of the total number of alerts and over 1.4 million doses were included for analysis. Current i.v.-to-oral conversion practices saved the hospitals 9% on medication costs. Upon further evaluation, additional cost savings of 29-78% for those 13 medications could be achieved with more timely conversion from i.v. to oral therapy. Hospital pharmacists' i.v.-to-oral conversion practices with the CDS tool resulted in medication cost savings of 9%, or $1.48 million, for 13 medications evaluated over a 6-month period.


The κ-statistics approach to epidemiology.
A great variety of complex physical, natural and artificial systems are governed by statistical distributions, which often follow a standard exponential function in the bulk, while their tail obeys the Pareto power law. The recently introduced [Formula: see text]-statistics framework predicts distribution functions with this feature. A growing number of applications in different fields of investigation are beginning to prove the relevance and effectiveness of [Formula: see text]-statistics in fitting empirical data. In this paper, we use [Formula: see text]-statistics to formulate a statistical approach for epidemiological analysis. We validate the theoretical results by fitting the derived [Formula: see text]-Weibull distributions with data from the plague pandemic of 1417 in Florence as well as data from the COVID-19 pandemic in China over the entire cycle that concludes in April 16, 2020. As further validation of the proposed approach we present a more systematic analysis of COVID-19 data from countries such as Germany, Italy, Spain and United Kingdom, obtaining very good agreement between theoretical predictions and empirical observations. For these countries we also study the entire first cycle of the pandemic which extends until the end of July 2020. The fact that both the data of the Florence plague and those of the Covid-19 pandemic are successfully described by the same theoretical model, even though the two events are caused by different diseases and they are separated by more than 600 years, is evidence that the [Formula: see text]-Weibull model has universal features.


Clinical skill development for community pharmacists.
The importance of establishing clinical pharmacy services in the community cannot be understated in light of current challenges to the traditional dispensing role as the primary service of the community pharmacist. Advancements in automated dispensing technology and declining prescription fee reimbursement are rapidly forcing pharmacists to seek alternative sources of revenue. Providing pharmaceutical care is a viable option to increase customer loyalty job satisfaction, and reimbursement. To support the development of clinical services, academic institutions are forming partnerships with individual community practitioners to overcome perceived educational and training barriers. The authors describe the design and development of two unique clinical skill development programs at the University of Illinois at Chicago. This paper also outlines the patient focused services that the participants have established upon completing the training. These programs successfully enhanced participants' therapeutic knowledge base and facilitated development of the clinical skills necessary for direct patient care.


Ni-Catalyzed Reductive Dibenzylation of Trifluoromethylalkenes for CF3-Containing All-Carbon Quaternary Center Construction.
A Ni-catalyzed reductive dicarbofunctionalization of α-CF3 styrenes with benzyl bromides has been accomplished. This transformation obviates the commonly facile β-F elimination effectively and enables the creation of CF3-substituted all-carbon quaternary centers of pharmaceutical interests. Preliminary mechanistic studies suggest a pathway consisting of benzyl radical addition and subsequent nickel-mediated benzylation of the resulting α-CF3-embedded tertiary C radical.


Effects of propofol ('Diprivan') on histamine release, immunoglobulin levels and activation of complement in healthy volunteers.
This randomized study compared the effects of the emulsion formulation of propofol with those of the Cremophor-containing agent Althesin. Plasma histamine concentration, immunoglobulin levels, total complement C3 and complement C3 conversion were measured prior to and following induction of anaesthesia in 32 male volunteers with either 2 mg/kg propofol or 0.05 ml/kg Althesin. In only one volunteer, in the Althesin group, was an increase in plasma histamine to a value greater than 1 ng/ml associated with a relatively large increase over the base line value. Cutaneous signs, such as flushing, did not correlate with the plasma concentrations of histamine. No changes consistent with a propensity to produce anaphylactoid reactions could be seen from measurements of immunoglobulin levels, complement C3 or plasma histamine concentration in the propofol treated subjects.


The effects of sexual orientation in the courtroom: a double standard.
Homonegativity is a term that many psychologists use to describe irrational fear of homosexuality. Due to a growing number of male rapes in the United States and the unchecked levels of homonegativity, it is hypothesized that homosexuals will be treated differently from heterosexuals in sexual assault trials. Four conditions were examined controlling for the gender and sexuality of both the defendant and the victim and a sexual assault trial text was created controlling for factors known to affect juror's decisions. Seventy-two participants were divided among the four conditions. This research supports the hypothesis with highly significant results. Future research is suggested.


Plastic wastes in the time of COVID-19: Their environmental hazards and implications for sustainable energy resilience and circular bio-economies.
The global scope of pollution from plastic waste is a well-known phenomenon associated with trade, mass consumption, and disposal of plastic products (e.g., personal protective equipment (PPE), viral test kits, and vacuum-packaged food). Recently, the scale of the problem has been exacerbated by increases in indoor livelihood activities during lockdowns imposed in response to the coronavirus disease 2019 (COVID-19) pandemic. The present study describes the effects of increased plastic waste on environmental footprint and human health. Further, the technological/regulatory options and life cycle assessment (LCA) approach for sustainable plastic waste management are critically dealt in terms of their implications on energy resilience and circular economy. The abrupt increase in health-care waste during pandemic has been worsening environmental quality to undermine the sustainability in general. In addition, weathered plastic particles from PPE along with microplastics (MPs) and nanoplastics (NPs) can all adsorb chemical and microbial contaminants to pose a risk to ecosystems, biota, occupational safety, and human health. PPE-derived plastic pollution during the pandemic also jeopardizes sustainable development goals, energy resilience, and climate control measures. However, it is revealed that the pandemic can be regarded as an opportunity for explicit LCA to better address the problems associated with environmental footprints of plastic waste and to focus on sustainable management technologies such as circular bio-economies, biorefineries, and thermal gasification. Future researches in the energy-efficient clean technologies and circular bio-economies (or biorefineries) in concert with a "nexus" framework are expected to help reduce plastic waste into desirable directions.


Donepezil in a narrow concentration range augments control and impaired by beta-amyloid peptide hippocampal LTP in NMDAR-independent manner.
Acetylcholinesterase (AChE) inhibitor donepezil is widely used for the treatment of Alzheimer's disease (AD). The mechanisms of therapeutic effects of the drug are not well understood. The ability of donepezil to reverse a known pathogenic effect of β-amyloid peptide (Abeta), namely, the impairment of hippocampal long-term potentiation (LTP), was not studied yet. The goal of the present study was to study the influence of donepezil in 0.1-10 μM concentrations on control and Abeta-impaired hippocampal LTP. Possible involvement of N-methyl-D: -aspartate receptors (NMDARs) into mechanisms of donepezil action was also studied. LTP of population spike (PS) was studied in the CA1 region of rat hippocampal slices. Change of LTP by donepezil treatment had a bell-shaped dose-response curve. The drug in concentrations of 0.1 and 1 μM did not change LTP while in concentration of 0.5 μM significantly increased it, and in concentration of 5 and 10 μM suppressed LTP partially or completely. Abeta (200 nM) markedly suppressed LTP. Addition of 0.1, 0.5 or 1 μM donepezil to Abeta solution caused a restoration of LTP. N-methyl-D: -aspartate (NMDA) currents were studied in acutely isolated pyramidal neurons from CA1 region of rat hippocampus. Neither Abeta, nor 0.5 μM donepezil were found to change NMDA currents, while 10 μM donepezil rapidly and reversibly depressed it. Results suggest that donepezil augments control and impaired by Abeta hippocampal LTP in NMDAR-independent manner. In general, our findings extend the understanding of mechanisms of therapeutic action of donepezil, especially at an early stage of AD, and maybe taken into account while considering the possibility of donepezil overdose.


7-H-Pyrrolo[2,3-d]pyrimidine derivative acts as promising agent for gastric cancer treatment by inducing cell death.
In the present study effect of 7-H-pyrrolo[2,3-d]pyrimidine derivative (7-HPPD) on viability of MKN28 and MKN74 gastric cancer cells was investigated. There was no significant change in GES-1 cell viability on treatment with 7-HPPD for 48 h. MKN28 and MKN74 cell viability was reduced to 21 and 23%, respectively, on treatment with 7-HPPD at concentration of 50 µM. Hoechst 33342 staining showed that the cells treated with 7-HPPD showed condensation of chromatin material, presence of apoptotic bodies and intense blue fluorescence. Treatment of MKN28 and MKN74 cells with 7-HPPD markedly increased the release of LDH. Z-VAD-FMK prevented 7-HPPD-induced suppression of MKN28 and MKN74 cell viability. Exposure to 15, 20, 25, 30 and 50 µM concentrations of 7-HPPD caused concentration-based increase in caspase-8, -9, -3 and cleaved PARP. A significant increase in ROS production was caused by 7-HPPD in MKN28 and MKN74 cells. Increasing the concentration of 7-HPPD from 10 to 50 µM did not increase the expression of RIP3 protein. In summary, 7-HPPD suppresses gastric cancer cell growth by inducing apoptosis through increase in caspase expression and ROS production. Consequently, 7-HPPD may be used for the development of treatment strategy for gastric cancer.


Novel inhibitors of AP-1 and NF-kappaB mediated gene expression: structure-activity relationship studies of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)++ +pyrimidi ne-5-carboxylate.
In an effort to identify novel inhibitors of AP-1 and NF-kappaB mediated transcriptional activation, several analogues of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyr imidine-5-carboxylate (1) were synthesized and tested in two in vitro assays. The 2-(2'-thienyl) substituted compound (11) was identified as the most potent in this series.


Long-term prognosis for children with nephrotic syndrome.
Follow-up survival and health information were obtained, after a median of 27.5 years, from 132 patients who had been seen originally as children with nephrotic syndrome between 1951 and 1967. Ninety seven patients were alive. Recurring edema or proteinuria, or both, persisted in 15 percent of those still alive. Eight of 11 parous women reported relapses during pregnancy. There was no apparent increase in malignancies, atopic diseases, clinical defects in cell-mediated immunity, or cardiovascular diseases. Twenty two patients (17%) died of renal causes between 3 months and 8 years after the onset of nephrotic syndrome. Steroid resistance was the presenting feature universally predictive of a poor outcome; nine of the 11 such patients died and the other two are now receiving hemodialysis. Hematuria was present initially in 41 percent of the patients who died of renal causes, compared with 14 percent of those still alive. Hypertension was noted on the first examination in 22 percent of those who died of renal causes, compared with 10 percent of those alive.


Training in laparoscopic renal surgery, in a few weeks of intense exposure.
Laparoscopic renal surgery has only recently become popular in the UK and, still, only a handful of pediatric urologists are offering the laparoscopic approach to their patients; therefore, there are only limited places available for training in this discipline. In this institution, which is a major tertiary referral center for pediatric urology having four consultants, one urologist specializes in laparoscopic renal surgery and about 50 laparoscopic ablative renal surgical procedures are performed annually. The aim of this study was to determine the effectiveness of the training provided, for three trainees, in light of the complexity of the ablative procedures performed. Patients who required laparoscopic ablative renal surgery from June 2003 to May 2004 were identified from the prospectively maintained database and data were analyzed. During this period of 12 months, 49 operations have been performed laparoscopically. There were three trainees, A, B and C, who joined the mentor, at different times, for a continuous period of 6, 12 and 6 weeks, respectively. The training was one to one and, at an appropriate level of expertise, the trainees were allowed to perform operations independently; they continued to do so after returning to their units. There were 22 males and 27 females, age ranging from 8 months to 16 years (mean 3.6 years). There were 25 nephrectomies, 23 via the prone retroperitoneal (PRP) approach and two via the transperitoneal (TP) approach; the mean time taken was 70 min. There were 12 nephroureterectomies, six via the PRP, three via the TP, and the other three via the lateral retroperitoneal (LRP) approach; the mean time taken was 100 min. There were 10 heminephroureterectomies (six upper pole and four lower pole), six via the PRP, three via the TP and one via the LRP approach; the mean time taken was 160 min. Of two bilateral nephrectomies one was via the PRP and one the TP approach, and the mean time taken was 170 min. The mean time to discharge for nephrectomy was 7 h, and for nephroureterectomy, heminephroureterectomy and bilateral nephrectomy 21, 23 and 43 h, respectively. Trainee A had been in pediatric surgery for 4 years and during a period of 6 weeks he assisted in five operations, but did not get the opportunity to perform independently. Trainee B had been in pediatric surgery for 13 years and during a period of 12 weeks he assisted in nine operations and performed three. Trainee C had been in pediatric surgery for 20 years and during a period of 6 weeks he assisted in five operations and performed one. Since returning to their overseas units, trainee B and trainee C have successfully performed two nephrectomies each. Retroperitoneoscopic renal surgery is within the grasp of any experienced urologist or urology trainee. With intensive exposure and one-to-one mentoring, 6-12 weeks would be sufficient to achieve adequate competence and confidence to perform a prone retroperitoneoscopic nephrectomy.


An outlier theory of cancer curability. Tumor cell differentiation as a therapeutic goal.
Combinations of cytotoxic agents that cure a substantial percentage of patients with several childhood and adult malignancies are much less efficacious for the majority of solid tumors. Standard approaches for curability that rely solely on the concept of cytotoxicity may not be applicable for most epithelial and mesenchymal solid malignancies. Differentiation may play a more important role in cancer cure than heretofore suspected. Clinical and experimental evidence supports further investigation into models of inducing tumor cell differentiation. The question of why such models could predict for curative modalities of treatment is discussed.