Degradation of micropolluants in flow-through VUV/UV/H2O2 reactors: Effects of H2O2 dosage and reactor internal diameter.
The degradation of atrazine (ATZ), sulfamethoxazole (SMX) and metoprolol (MET) in flow-through VUV/UV/H2O2 reactors was investigated with a focus on the effects of H2O2 dosage and reactor internal diameter (ID). Results showed that the micropollutants were degraded efficiently in the flow-through VUV/UV/H2O2 reactors following the pseudo first-order kinetics (R2 > 0.92). However, the steady-state assumption (SSA) kinetic model being vital in batch reactors was found invalid in flow-through reactors where fluid mixing was less sufficient. With the increase of H2O2 dosage, the ATZ removal efficiency remained almost constant while the SMX and MET removal was enhanced to different extents, which could be explained by the different reactivities of the pollutants towards HO•. A larger reactor ID resulted in lower degradation rate constants for all the three pollutants on account of the lower average fluence rate, but the change in energy efficiency was much more complicated. In reality, the electrical energy per order (EEO) of the investigated VUV/UV/H2O2 treatments ranged between 0.14-0.20, 0.07-0.14 and 0.09-0.26 kWh/m3/order for ATZ, SMX and MET, respectively, with the lowest EEO for each pollutant obtained under varied H2O2 dosages and reactor IDs. This study has demonstrated the efficiency of VUV/UV/H2O2 process for micropollutant removal and the inadequacy of the SSA model in flow-through reactors, and elaborated the influential mechanisms of H2O2 dosage and reactor ID on the reactor performances.


Antimicrobial activity and chemical composition of the essential oil of Hofmeisteria schaffneri.
The aims of this study were to establish the antimicrobial potential of Hofmeisteria schaffneri essential oil and its chemical composition. The essential oils of Hofmeisteria schaffneri harvested at flowering (batches I and IV) and non-flowering (batches II and III) seasons were prepared by hydrodistillation and analysed by GC and GC-MS. The aqueous and organic (CH(2) Cl(2) -MeOH 1 : 1) extracts were prepared by using infusion and maceration techniques, respectively. The in-vitro antimicrobial activity of the preparations and compounds against Candida albicans and some bacteria (Gram-negative and Gram-positive) was assessed using the broth dilution method in 96-microplate wells. Forty-four compounds, representing ∼90% of the total constituents, were identified in the essential oil of Hofmeisteria schaffneri collected in flowering (batches I and IV) and non-flowering (batches II and III) seasons. In all cases, several thymol analogues were the major components of the oils (∼65%); some small differences in the relative proportions of these constituents were observed. The infusion exhibited an antibacterial activity against Staphylococcus aureus and Bacillus subtilis, with a MIC value of 64 µg/ml in each case. The essential oil batches were active against Staphylococcus aureus, with MIC ranging from 48 to 192 µg/ml. They were, however, inactive against Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi (MIC > 1024 µg/ml). On the other hand, the infusion of the plant as well as the oil from batch I displayed anti-Candida albicans activity, with MIC of 128 and 192 µg/ml, respectively. Finally, the organic extract did not displayed significant activity against the tested microorganisms (MIC ≥ 1024 µg/ml). Some of the compounds isolated from the plant were also tested. Compounds 8 and 38, which were present in the essential oils, displayed the best antibacterial effect against Gram-positive bacteria (MIC ranging between 32 and 64 µg/ml). Compounds 6 (present in the infusion) and 10 (present in all preparations) showed higher activity against the yeast (MIC = 128 µg/ml) than the remaining compounds, with MIC values ranging from 256 to 512 µg/ml. The composition and antimicrobial activity of the oils changed slightly from flowering to non-flowering seasons. The results of the present investigation provide in-vitro scientific support for the use of the plant against skin infections in Mexican folk medicine.


Reduction in complication and revision rates for robotic-guided short-segment lumbar fusion surgery: results of a prospective, multi-center study.
Studies evaluating robotic guidance in lumbar fusion are limited primarily to evaluation of screw accuracy and perioperative complications. This is the first study to evaluate granular differences in short and long-term complication and revision rate profiles between robotic (RG) fluoroscopic (FG) guidance for minimally invasive short-segment lumbar fusions. A retrospective analysis of a prospective, multi-center database was performed. Complications were subdivided into surgical (further subcategorized into adjacent segment disease, new-onset back pain, radiculopathy, motor-deficit, hardware failure, pseudoarthrosis), wound, and medical complications. Complication and revision rates were compared between RG and FG groups cumulatively at 30, 90 days, and 1 year. 374 RG and 111 FG procedures were performed. RG was associated with an 86.25, 83.20, and 69.42% cumulative reduction in complication rate at 30, 90 days, and 1 year, respectively, compared to FG (p < 0.001). At all follow-up points, new-onset radiculopathy and medical complications were most prevalent in both groups. The greatest reductions in complication rates were seen for new-onset back pain (88.13%; p = 0.001) and wound complications (95.05%; p < 0.001) at 30 days, new-onset motor deficits (90.11%; p = 0.004) and wound complications (85.16%; p < 0.001) at 90 days, and new-onset motor deficits (85.16%; p = 0.002), wound (85.16%; p < 0.001), and medical complications (75.72%; p < 0.001) at 1 year. RG was associated with a 92.58% (p = 0.002) reduction in revision rate at 90 days and a 66.08% (p = 0.026) reduction at 1 year. RG was associated with significant reductions in postoperative complication rates at all follow-up time points and significant reductions in revision rates at 90 days and 1 year.


Coverage, utilization, and impact of Ayushman Bharat scheme among the rural field practice area of Saveetha Medical College and Hospital, Chennai.
Ayushman Bharat scheme, otherwise called as Pradhan Mantri Jan Arogya Yojana (PMJAY), is a National Health Protection Scheme introduced on 23 September 2018 by the government of India to aid the economically disadvantaged families. The study was initiated to estimate the coverage, utilization, and impact of Ayushman Bharat scheme in the rural field practice area of Saveetha Medical College and Hospital, Chennai. This is the cross-sectional study conducted in the rural field practice area of Saveetha Medical College and Hospital, Chennai. This cross-sectional study done among 300 households in Mappedu region of Thiruvallur district, Tamil Nadu. Simple random sampling was done to choose the study participants to reach the sample size of 300. Data was collected using semi-structured questionnaire. After the entry of data, the descriptive statistics was presented in frequency tables and graph. The study found that out of 300 households only about 42.33% of the households were covered under Ayushman Bharat scheme. Among the households covered under Ayushman Bharat scheme, 47.24% households have availed Ayushman Bharat scheme in the past 1 year and only 10% of those availed the scheme has spent additional amount for health care. Around 39.88% of the households not having Ayushman Bharat scheme has faced financial burden because of health care expenditure. Creating awareness, appropriate governance, and working toward quality assurance, prompt referral pathways in both public and private healthcare providers can make Ayushman Bharat scheme effective.


Occurrence of Candida orthopsilosis in Brazilian tomato fruits (Lycopersicum esculentum Mill.).
We aimed to isolate and identify yeasts found in the tomato fruit in order to obtain isolates with biotechnological potential, such as in control of fungal diseases that damage postharvest fruits. We identified Candida orthopsilosis strains LT18 and LT24. This is the first report of this yeast on Lycopersicum esculentum fruits in Brazil.


Fattening responses to daily intervals of heat exposure in the Syrian hamster.
Warm ambient temperature (38 degrees C) provided daily for one hr induced time-dependent changes in body weight and fat stores in the Syrian hamster. In animals held on 10-hr daily photoperiods and room temperature (23 degrees C), daily one-hour thermopulses at 8 and 20 hr after light onset stimulated increases in body weights and indices of body fat storage. Abdominal fat pad weights of these groups were twice those of untreated controls after 17 and 28 days of thermoperiodic treatments. On the other hand, daily thermopulses were completely ineffective at 0 and 16 hr after light onset. These results demonstrate that body fat stores may be influenced by a temporal interaction of environmental stimuli and implicate underlying circadian mechanisms in the regulation of body fat.


A prospective sero-epidemiological study of visceral leishmaniasis in Baringo District, Rift Valley Province, Kenya.
The incidence of visceral leishmaniasis (VL) was studied in 30 clusters with an average of 98 individuals in each cluster in a defined, endemic rural area of Baringo District, Kenya. The clusters were centred around recent cases of VL. Anti-leishmanial antibodies were measured by the direct agglutination test (DAT) and a clinical examination was performed on 2 occasions between April 1991 and May 1993. Of 2934 individuals tested by the DAT during the first visit, 78 (2.7%) were seropositive, 54 with and 24 without a history of VL. The seroconversion rate was 9/1000 person-years of observation (95% confidence interval 5.1-12.92) among 2332 seronegative individuals retested the following year. During the entire study period, VL was diagnosed in 10 patients, with an incidence rate of 2.2/1000 person-years of observation (95% confidence interval 0.8-3.6). Household contacts of individuals with previously confirmed VL had a higher frequency of DAT positivity than the rest of the population. This difference was significant for both sexes. These results suggest transmission in and around houses.


Distinct neurobehavioral dysfunction based on the timing of developmental binge-like alcohol exposure.
Gestational exposure to alcohol can result in long-lasting behavioral deficiencies generally described as fetal alcohol spectrum disorder (FASD). FASD-modeled rodent studies of acute ethanol exposure typically select one developmental window to simulate a specific context equivalent of human embryogenesis, and study consequences of ethanol exposure within that particular developmental epoch. Exposure timing is likely a large determinant in the neurobehavioral consequence of early ethanol exposure, as each brain region is variably susceptible to ethanol cytotoxicity and has unique sensitive periods in their development. We made a parallel comparison of the long-term effects of single-day binge ethanol at either embryonic day 8 (E8) or postnatal day 7 (P7) in male and female mice, and here demonstrate the differential long-term impacts on neuroanatomy, behavior and in vivo electrophysiology of two systems with very different developmental trajectories. The significant long-term differences in odor-evoked activity, local circuit inhibition, and spontaneous coherence between brain regions in the olfacto-hippocampal pathway that were found as a result of developmental ethanol exposure, varied based on insult timing. Long-term effects on cell proliferation and interneuron cell density were also found to vary by insult timing as well as by region. Finally, spatial memory performance and object exploration were affected in P7-exposed mice, but not E8-exposed mice. Our physiology and behavioral results are conceptually coherent with the neuroanatomical data attained from these same mice. Our results recognize both variable and shared effects of ethanol exposure timing on long-term circuit function and their supported behavior.


In vitro reconstitution of SCF substrate ubiquitination with purified proteins.
The development of in vitro systems to monitor ubiquitin ligase activity with highly purified proteins has allowed for new insights into the mechanisms of protein ubiquitination to be uncovered. This chapter describes the methodologies employed to reconstitute ubiquitination of the budding yeast cyclin-dependent kinase inhibitor Sic1 by the evolutionarily conserved ubiquitin ligase SCF(Cdc4) and its ubiquitin-conjugating enzyme Cdc34. Based on our experience in reconstituting Sic1 ubiquitination, we suggest some parameters to consider that should be generally applicable to the study of different SCF complexes and other ubiquitin ligases.


Two novel alleles, HLA-A*32:01:01:09 and 32:01:01:10, identified by Pacific Bioscience's SMRT sequencing.
Pacific Bioscience's SMRT DNA sequencing was used to identify two novel intronic variants of HLA-A*32:01:01:01.


Late death after arterial switch operation for transposition of the great arteries.
Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average.


Predictors of non-use of illicit heroin in opioid injection maintenance treatment of long-term heroin dependence.
To investigate baseline and concurrent predictors of non-use of illicit heroin among participants randomized to injectable opioids in the North American Opiate Medication Initiative (NAOMI) clinical trial. NAOMI was an open-label randomized controlled trial comparing the effectiveness of injectable diacetylmorphine and hydromorphone for long-term opioid-dependency. Outcomes were assessed at baseline and during treatment (3, 6, 9, 12months). Days of non-use of illicit heroin in the prior month at each follow-up visit were divided into three categories: Non-use; Low use (1 to 7days) and High use (8days or more). Tested covariates were: Sociodemographics, Health, Treatment, Drug use and illegal activities. Mixed-effect proportional odds models with random intercept for longitudinal ordinal outcomes were used to assess the predictors of the non-use of illicit heroin. 139 participants were included in the present analysis. At each follow-up visit, those with non-use of illicit heroin represented 47.5% to 54.0% of the sample. Fewer days of cocaine use (p=0.074), fewer days engaged in illegal activities at baseline (p<0.01) and at each visit (p<0.01), less money spent on drugs (p<0.001), days with injection opioid or oral methadone treatment (p<0.001) and total mg of injectable opioids taken (p<0.001), independently predicted lower use of illicit heroin. The independent effect of several concurrent factors besides the injection of opioid dose suggests benefits from the clinic that go beyond the provision of the medication alone. Thus, this supervised model of care presents an opportunity to maximize the beneficial impact of medical and psychosocial components of the treatment on improving outcomes associated with non-use of illicit heroin.


Lens thickness and associated ocular biometric factors among cataract patients in Shanghai.
To evaluate the distribution of lens thickness (LT) and its associations with other ocular biometric factors among cataract patients in Shanghai. Twenty-four thousand thirteen eyes from 24,013 cataract patients were retrospectively included. Ocular biometric factors including LT, central corneal thickness (CCT), anterior chamber depth (ACD), white-to-white (WTW) distance, anterior corneal curvature, and axial length (AL) were obtained using the IOLMaster700. The associations between LT and general or ocular factors were assessed. The mean age was 62.5 ± 13.6 years and 56.1% were female. The mean LT was 4.51 ± 0.46 mm. The LT was greater in older patients (P < 0.001). LT was positively correlated with CCT, while negatively correlated with ACD, WTW, and anterior corneal curvature (P < 0.001). Multivariate analysis revealed that increased LT was associated with older age, male gender, thicker CCT, shallower ACD, larger WTW, and flatter anterior corneal curvature (P < 0.001). LT changed with a variable behavior according to AL. In short eyes LT increased as AL increased, then decreased with longer AL in normal eyes and moderate myopic eyes, but increased again as AL increased in highly myopic eyes. Thickest LT was found in the 20.01-22 mm AL group. The correlation between LT and other biometric factors remained significant when stratified by ALs. In a large Chinese cataractous population, we found that the thicker lens may be associated with older age, male gender, thicker CCT, shallower ACD, larger WTW, and flatter anterior corneal curvature. As AL increased, the change of LT was nonlinear, with the thickest lens seen in the 20-22 mm AL group.


Reduction of erythrocyte (Na+-K+)ATPase activity in type 1 (insulin-dependent) diabetic subjects and its activation by homologous plasma.
The (Na+-K+)ATPase and (Mg2+)ATPase activities of erythrocyte membranes of Type 1 (insulin-dependent) diabetic patients were found to be significantly reduced compared to matched controls (p less than 0.005). On the contrary, erythrocyte Na+ and K+ contents were similar in diabetic patients and in normal subjects. When erythrocyte membranes from diabetic patients were incubated with their own plasma, a significant increase was observed in sodium-potassium ATPase activity (p less than 0.005), whereas (Mg2+)ATPase activity was not affected. The plasma stimulatory effect showed saturation kinetics. Maximum average stimulation was 96% (+/- 21.3). A similar stimulation pattern, although more limited in extent (maximum 48.3% +/- 12.2), was found when erythrocyte membranes from normal subjects were incubated with diabetic plasma. Normal plasma exhibited a modest stimulatory effect on erythrocyte (Na+-K+)ATPase activity. Similar stimulatory effects by diabetic plasma were observed on a (Na+-K+) ATPase preparation from beef heart. It is proposed that diabetic plasma contains a specific (Na+-K+)ATPase activator in a higher concentration than normal plasma. This may explain why a normal cellular electrolyte content was found in diabetic erythrocytes in spite of a reduced Na+-K+ pump activity. Purification experiments indicate that the plasma activator is a protein with a molecular weight greater than 50,000. Both the (Na+-K+)ATPase activity and the stimulatory effect of diabetic plasma were not influenced by the metabolic control, since they did not correlate significantly with fasting blood glucose and daily insulin dosage. Moreover, no correlation was found with duration of diabetes or age at diagnosis of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)


Kinetics of phenol and chlorophenol utilization by Acinetobacter species.
Although microbial transformations via cometabolism have been widely observed, the few available kinetic models of cometabolism have not adequately addressed the case of inhibition from both the growth and nongrowth substrates. The present study investigated the degradation kinetics of self-inhibitory growth (phenol) and nongrowth (4-chlorophenol, 4-CP) substrates, present individually and in combination. Specifically, batch experiments were performed using an Acinetobacter isolate growing on phenol alone and with 4-CP present. In addition, batch experiments were also performed to evaluate the transformation of 4-CP by resting, phenol-induced Acinetobacter cultures. The Haldane kinetic model adequately predicted the biodegradation of phenol alone, although a slight discrepancy was noted in cases of higher initial phenol concentrations. Similarly, a Haldane model for substrate utilization was also able to describe the trends in 4-CP transformation by the resting cell cultures. The 4-CP transformation by the Acinetobacter species growing on phenol was modeled using a competitive kinetic model of cometabolism, which included growth and nongrowth substrate inhibition and cross-inhibition terms. Excellent agreement was obtained between the model predictions using experimentally estimated parameter values and the experimental data for the synchronous disappearance of phenol and 4-CP.


CYP1A1, GSTT1, IL-6 and IL-8 transcription and IL-6 secretion on umbilical endothelial cells from hypertensive pregnant women: Preliminary results.
The impact of pregnancy hypertension in the offspring endothelia remains unknown. We evaluated the transcriptional expression of four genes that participate in the process of endothelial dysfunction using umbilical vein endothelial cell cultures (HUVEC) from healthy pregnant women (PW) and those with hypertensive disorders (HD). The cytochrome P450 1A1 (CYP1A1), gluthathione S-transferase subtype T1 (GSTT1), interleukin 6 (IL-6) and 8 (IL-8) mRNA and IL-6 protein levels were assessed. IL-6 and IL-8 transcripts were significantly reduced in HUVEC obtained from HD women. Our results suggest that a hypertensive environment in utero modifies the transcriptional expression of key inflammatory molecules in the newborn.


mTOR Signaling in Growth, Metabolism, and Disease.
The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.


Trauma-Related Shame, Sexual Assault Severity, Thwarted Belongingness, and Perceived Burdensomeness Among Female Undergraduate Survivors of Sexual Assault.
This study evaluated trauma-related shame as a mediator of the association between sexual assault severity and perceived burdensomeness and thwarted belongingness. A total of 164 female undergraduates who reported attempted or completed sexual assault completed self-report measures of sexual assault, trauma-related shame, perceived burdensomeness, and thwarted belongingness. Using path analysis, trauma-related shame mediated the association between sexual assault severity and perceived burdensomeness, and between sexual assault severity and thwarted belongingness. The findings of this study are limited by the retrospective, self-report, and cross-sectional nature of these data, and do not allow for causal inference. Trauma-related shame warrants additional investigation as a mechanism that explains the association between sexual assault and psychosocial risk factors for suicidal ideation and behavior.


Computer analysis of defined populations of lymphocytes irradiated in vitro. III. Evaluation of human T and B cells of peripheral blood origin.
The radiosensitivities of lymphocytes of peripheral blood origin obtained from two healthy 45 year old male donors were studied simultaneously at yearly intervals over a three year period. Hypaque-Ficoll purified cells were exposed in vitro to 0, 5, 50, and 500 rads and then evaluated serially for viability of T and B cells, responsiveness to PHA and Con A, and morphologic evidence of injury as documented by standard light microscopy and computer assisted morphometric analysis. The results showed that T cells in both subjects were less radiosensitive than B cells. Differences between the two subjects also existed in the radiosensitivity of these two subpopulations of lymphocytes, differences that remained constant over the three years period of observation. The differences correlated with similar discrepancies in mitogenic responsiveness and are thought to relate to variations in the relative proportions of subpopulations of T and B cells. In the mouse, T and B cell subpopulations differ in radiosensitivity. The data reported herein are consistent with a similar situation in man.


Species dependent accumulation and transformation of 8:2 polyfluoroalkyl phosphate esters in sediment by three benthic organisms.
Sediment is a major sink for 8:2 polyfluoroalkyl phosphate diester (8:2 diPAP) in the environment. In the present study, three representative benthic organisms, including carp (Cyrinus carpio), loach (Misgurnus anguillicaudatus) and worm (Limnodrilus hoffmeisteri), were exposed to 8:2 diPAP spiked sediment at 300 ng g-1. 8:2 diPAP in the sediment was bioavailable to carp, loach and worm even though the biota-sediment accumulation factors (BSAFs) (0.137, 0.0273, 0.413 g g-1, respectively) were relatively low due to its large molecular weight and high log KOW value. The worm displayed the greatest enrichment ability among the three species, implying the utility of using worm as a bio-indicator of 8:2 diPAP pollution in sediment. The biotransformation products (e.g. 8:2 FTUCA and 7:3 FTCA) were detected in all the three species, suggesting that they had the ability to transform 8:2 diPAP. Loach displayed the strongest metabolism capacity while worm displayed the weakest. Transformation of 8:2 diPAP also took place in the sediment by microorganisms. Notably, the concentration ratio of 7:3 FTCA and 8:2 FTUCA in the sediment was much lower than that in benthic organisms, suggesting that the aquatic benthic organisms and microorganisms had different transformation activities and mechanisms.


Salvianolic acid A alleviates renal injury in systemic lupus erythematosus induced by pristane in BALB/c mice.
The purpose of this study was to investigate the effects of salvianolic acid A (SAA) in systemic lupus erythematosus (SLE) induced by pristane in BALB/c mice. Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane. Mice were then treated with daily oral doses of SAA for 5 months in parallel with mice treated with prednisone and aspirin as positive controls. The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. Western blot analysis of renal tissue was also employed. SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects. SAA treatment also significantly inhibited the phosphorylation of IKK, IκB and NFκB in renal tissues of lupus mice. In conclusion, the results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK, IκB and NFκB.


Developmental profiles and temperament patterns in children with spastic cerebral palsy: relationships with subtypes and severity.
Elucidating developmental profiles and temperament patterns in children with cerebral palsy (CP) could help clinicians elaborate more flexible strategies for treating these children. This study investigated the developmental profiles and temperament patterns in children with spastic CP (sCP) of different subtypes and severities. One hundred and five children, aged 3-6 years, with sCP and 66 children with typical development (TD) were analyzed. Children with sCP were classified into spastic diplegia (SD; n = 60), and spastic quadriplegia (SQ; n = 45) groups. Motor severity was classified via the Gross Motor Function Classification System (GMFCS). Development quotients (DQs) of eight domains and temperament scores of nine dimensions were evaluated. The SQ group had lower DQs in all developmental functions than the SD group (p < 0.01). The DQ distributions of developmental profiles showed the same trend in SD and SQ groups, and both groups displayed lowest DQs in the gross motor domain. The SQ group was less adaptable and approachable than the TD group (p < 0.05), and both sCP groups had lower attention span and persistence and a higher threshold of responsiveness than the TD group (p < 0.05). Correlation analysis showed that GMFCS levels were highly related to all developmental functions (r < -0.54, p<0.01) and weakly related to some temperament dimensions in children with sCP. The subtype and severity of sCP were associated with developmental profiles in children with sCP Temperament patterns were different between SD and SQ groups, but only weakly related to motor deficit. These data could allow clinicians to anticipate the developmental profiles and temperament patterns and plan appropriate therapeutic strategies for children with sCP.


Reverse facial artery-submental artery mandibular osteomuscular flap for the reconstruction of maxillary defects following the removal of benign tumors.
Functional and aesthetic restoration in maxillary reconstruction remains a challenge. Although many free flap procedures have become popular in maxillary reconstruction, these microsurgical methods have certain limitations and risks. This study assessed the reliability of the reverse facial artery-submental artery mandibular osteomuscular flap for reconstructing maxillary defects. Eight maxillary defects following benign tumor ablation were repaired with reverse facial artery-submental artery mandibular osteomuscular flaps. The patients ranged in age from 16 to 33 years; 5 were male and 3 were female. Maxillary odontogenic myxoma was present in 3 cases, maxillary fibrous dysplasia and ameloblastoma in 2 cases each, and chondromyxoid fibroma in 1 case. The defects were classified as class 2a. Primary reconstruction of the maxilla was carried out using a pedicled mandibular osteomuscular flap. No flap failures occurred. Dental reconstruction was successful in all patients. Proper aesthetics and complete functionality were obtained, and there were no donor-site problems. The patients were followed for 12 to 24 months, with an average of 18.6 months, and no recurrence was encountered. The reverse facial artery-submental artery mandibular osteomuscular flap is safe, quick, and simple to elevate. The flap can be used reliably for reconstructing maxillary defects.


Canine erythrocyte pyruvate kinase. I. Properties of the normal enzyme.
We have compared the kinetic, immunological, and electrophoretic properties of human and canine erythrocyte pyruvate kinase. Both enzymes are allosteric and subject to positive and negative regulation. The allosteric properties of the canine enzyme are more pronounced than those of the human enzyme; however, the properties of both enzymes are consistent with a regulatory function in the glycolytic pathway of their respective erythrocytes. Antiserum against the human enzyme gives precipitin lines of partial identity between the human and canine enzymes on immunodiffusion. The anti-human serum inactivates the enzymatic activity of both enzymes, although it is more effective against the human enzyme than the canine. The two enzymes have slightly different mobilities on starch gel electrophoresis. While we have demonstrated differences between erythrocyte pyruvate kinase from dogs and that from humans, we conclude that the enzymes are sufficiently similar in properties and function to allow use of the dog as a model for human erythrocyte pyruvate kinase deficiency.


The effects of ibotenic acid lesions of the nucleus basalis and cholinergic-rich neural transplants on win-stay/lose-shift and win-shift/lose-stay performance in the rat.
Rats were trained to criterion performance in 2-lever operant conditional memory tasks that required them to follow either a Win-stay/Lose-shift, or else a Win-shift/Lose-stay response rule. Substantial impairments in performance of both pretrained conditional tasks were seen following ibotenic acid lesions of the nucleus basalis, but not of the globus pallidus. The deficit in both tasks was apparent at all inter-response retention intervals, indicating that nucleus basalis lesions produced a general impairment in the performance of the complex conditional operant tasks, and not a specific deficit in short-term memory. The nucleus basalis lesion rats were then divided into groups matched for equivalent performance. One group was given cell suspension grafts into neocortex of E15 cholinergic-rich forebrain tissue; a second group was given similar grafts of E17 hippocampal tissue; and a third group was given sham transplants. Testing beginning 3 months post-transplant showed that there was no evidence of recovery of performance on these tasks in the cholinergic-rich transplanted groups compared to the controls. However, the rats with cholinergic-rich transplants subsequently showed a significant improvement in retention of a step-through passive avoidance task. The results indicate that either cholinergic deafferentation of the neocortex is not critical for the observed deficits in the operant conditional tasks, or recovery of function following cholinergic-rich transplants is task-specific, in that more complex cognitive tasks may require different levels of graft-host neural integration.


SARS-CoV-2 infection in dogs and cats is associated with contact to COVID-19-positive household members.
Several domestic and wild animal species are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Reported (sero)prevalence in dogs and cats vary largely depending on the target population, test characteristics, geographical location and time period. This research assessed the prevalence of SARS-CoV-2-positive cats and dogs (PCR- and/or antibody positive) in two different populations. Dogs and cats living in a household with at least one confirmed COVID-19-positive person (household (HH) study; 156 dogs and 152 cats) and dogs and cats visiting a veterinary clinic (VC) (VC study; 183 dogs and 140 cats) were sampled and tested for presence of virus (PCR) and antibodies. Potential risk factors were evaluated and follow-up of PCR-positive animals was performed to determine the duration of virus shedding and to detect potential transmission between pets in the same HH. In the HH study, 18.8% (27 dogs, 31 cats) tested SARS-CoV-2 positive (PCR- and/or antibody positive), whereas in the VC study, SARS-CoV-2 prevalence was much lower (4.6%; six dogs, nine cats). SARS-CoV-2 prevalence amongst dogs and cats was significantly higher in the multi-person HHs with two or more COVID-19-positive persons compared with multi-person HHs with only one COVID-19-positive person. In both study populations, no associations could be identified between SARS-CoV-2 status of the animal and health status, age or sex. During follow-up of PCR-positive animals, no transmission to other pets in the HH was observed despite long-lasting virus shedding in cats (up to 35 days). SARS-CoV-2 infection in dogs and cats appeared to be clearly associated with reported COVID-19-positive status of the HH. Our study supports previous findings and suggests a very low risk of pet-to-human transmission within HHs, no severe clinical signs in pets and a negligible pet-to-pet transmission between HHs.


Deubiquitination and stabilization of estrogen receptor α by ubiquitin-specific protease 7 promotes breast tumorigenesis.
Breast cancer is the most common malignancy in women around the world. Estrogen receptor α (ERα) is expressed in approximately 70% of breast tumors, and considered as one of most effective targets in breast cancer therapy. It has been reported that the degradation of ERα protein is mediated by ubiquitin-proteasome system. However, little is known about the regulation of ERα deubiquitination, a critical constituent of its degradation control. The current study first reports that there is a positive correlation between ERα and ubiquitin specific protease 7 (USP7) protein levels in human breast tumor tissues. Subsequent studies showed that USP7 physically interacted with the ERα, thereby mediating the deubiquitination and stabilization of ERα. In addition, USP7 inhibition or silencing led to growth inhibition and apoptosis of ERα-positive breast cancer cells both in vitro and in vivo. Furthermore, overexpression of ERα rescued the USP7 silencing-induced cell cycle arrest and apoptosis, supporting that ERα status is essential to the function of USP7 in breast carcinogenesis. Overall, this study suggests that targeting USP7-ERα complex could be a potential strategy to treat ERα-positive breast cancer.


Systematic review with meta-analysis: impact of one-handed vs. two-handed technique on quality outcomes of colonoscopy.
Colonoscopy is usually performed with the one-handed technique (1HT), although several countries and operators still adopt the two-handed technique (2HT). It is still uncertain whether the 1HT can improve the quality outcomes of colonoscopy. We performed a systematic review with meta-analysis to explore the quality outcomes in patients undergoing 1HT or 2HT colonoscopy. We performed a systematic review with meta-analysis to compare the pooled rates of adenoma detection rate (ADR), cecal intubation rate (CIR), cecal intubation time (CIT), and withdrawal time (WT), in patients undergoing 1HT or 2HT colonoscopy via PubMed/EMBASE, SCOPUS, and Cochrane databases. The primary outcome was the pooled rate of ADR and CIR. CIT and WT were also assessed. Pooled odds ratio (OR), standard mean differences (SMD), and 95% confidence intervals (CI) were calculated using fixed or random-effect models. Five studies (15,763 patients) met the inclusion criteria. The pooled ADR was not significantly different between the two techniques (OR 1.10; 95% CI 0.88-1.39; p=0.16), and CIR was not significantly different in 1HT from 2HT (OR 0.757; 95% CI 0.55-1.02; p=0.07), with no significant heterogeneity. Furthermore, no significant differences were seen for CIT (SMD 0.95; p=0.62) and WT (SMD 0.58; p=0.74). The 1HT colonoscopy does not add relevant improvement in the quality and efficacy of colonoscopy.


Influence of skinfold sum and peak VO(2) on immune function in children.
To measure the relationship of skinfold sum and peak VO(2) power with immune function in children. Cross-sectional, with all children tested twice during a 2 month period for peak VO(2), sum of two skinfolds, and immune function, with data from the two measures averaged and then correlated (alpha level, < or = 0.01). Immune measures included leukocyte and lymphocyte subset counts, delayed-typed hypersensitivity (DTH), global IgG antibody response over 4 weeks to pneumococcal vaccination (pIgG), salivary IgA concentration (sIgA), PHA-stimulated lymphocyte proliferation (PHA-SLP), natural killer cell activity (NKCA), and granulocyte and monocyte phagocytosis and oxidative burst activity. Seventy-three children (n=42 males, n=31 females) ranging in age from 7 to 13 y (mean+/-s.d. age, 9.9+/-1.7 y). The mean skinfold sum was 28.9+/-17.1 mm, and peak VO(2) 45.8+/-8.1 ml/kg/min. Peak VO(2), skinfold sum, and immune measures did not differ significantly by age or gender. Therefore, correlations were made on combined indices for all subjects. Peak VO(2) and the skinfold sum were not significantly correlated with NKCA, oxidative burst activity, plgG or DTH. Peak VO(2) was negatively correlated with monocyte phagocytosis (r=-0.30, P=0.012) and positively correlated with PHA-SLP (6.25 microg/ml; r=0.35, P=0.004). The skinfold sum was positively correlated with the total leukocyte count (r=0.39, P<0.001), granulocyte count (r=0.36, P=0.002), monocyte count (r=0.38, P=0.001), monocyte phagocytosis (r=0.41, P<0.001), granulocyte phagocytosis (r=0.35, P=0.003), and sIgA (r=0.32, P=0.006), and negatively correlated with PHA-SLP (6.25 microg/ml; r=-0.39, P=0.001). Data from this study indicate that a high skinfold sum is related to elevated leukocyte subset counts and monocyte/granulocyte phagocytosis, and low PHA-SLP in children.


Insulin secretion and glucose tolerance in adults with protein-calorie malnutrition.
Glucose tolerance, insulin secretion, and responses to arginine infusion were studied in 17 adults with severe protein-calorie malnutrition (PCM) in Calcutta, India. Patients were selected for the severity of their malnutrition and for absence of other diseases. After 2-4 mo of refeeding there was complete clinical recovery, and control studies were performed. Glucose tolerance, as assessed by intravenous glucose-tolerance test (IVGTT), was reduced in PCM. Insulin response, both to glucose and to arginine infusion, was clearly reduced. The K value of the IVGTT correlated well with the ratio of mean to basal serum insulin during the first 40 min of the test. Basal serum insulin was nearly unchanged in PCM as compared with after recovery, although one patient studied serially showed a temporary drop in basal insulin during the first week of refeeding. In PCM, plasma amino acid levels failed to fall in response to arginine-induced insulin secretion as they did in the control studies. It appears that insulin secretory response is severely reduced in PCM and that a degree of insulin resistance in relation to body weight is present. These changes result in diminished glucose tolerance and probably in a reduced rate of tissue utilization of amino acids. Such alterations may be of adaptive significance in chronic PCM.


Flood damage inspection and risk indexing data for an inventory of bridges in Central Greece.
This dataset is related to the research paper entitled "Bridge-specific flood risk assessment of transport networks using GIS and remotely sensed data" published in the Science of the Total Environment. It provides the information necessary for the reproduction of the case study that was used for the demonstration and validation of the proposed risk assessment framework. The latter integrates indicators for the assessment of hydraulic hazards and bridge vulnerability with a simple and operationally flexible protocol for the interpretation of bridge damage consequences on the serviceability of the transport network and on the affected socio-economic environment. The dataset encompasses (i) inventory data for the 117 bridges of the Karditsa Prefecture, in Central Greece, which were affected by a historic flood that followed the Mediterranean Hurricane (Medicane) Ianos, in September 2020; (ii) results of the risk assessment analysis, including the geospatial distribution of hazard, vulnerability, bridge damage, and associated consequences for the area's transport network; (iii) an extensive damage inspection record, compiled shortly after the Medicane, involving a sample of 16 (out of the 117) bridges of varying characteristics and damage levels, ranging from minimal damage to complete failure, which was used as a reference for validation of the proposed framework. The dataset is complemented by photos of the inspected bridges which facilitate the understanding of the observed bridge damage patterns. This information is intended to provide insights into the response of riverine bridges to severe floods and a thorough base for comparison and validation of flood hazard and risk mapping tools, potentially useful for engineers, asset managers, network operators and stakeholders involved in decision-making for climate adaptation of the road sector.


GFR Estimation Using a Panel of Filtration Markers in Shanghai and Beijing.
Estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys) may be less accurate compared to measured GFR (mGFR) in China than in North America, Europe, and Australia due to variation across regions in their non-GFR determinants. The non-GFR determinants of β2-microglobulin (B2M) and β-trace protein (BTP) differ from those of creatinine and cystatin C. Thus, the average eGFR using all 4 markers (eGFRavg) could be more accurate than eGFRcr-cys in China. Diagnostic test study. 1,066 participants in Shanghai and Beijing with creatinine and cystatin C and 666 participants with all 4 filtration markers. Index tests were previously developed equations for eGFR using creatinine, cystatin C, B2M, and BTP and combinations. The reference test was mGFR using plasma clearance of iohexol. We compared the performance of eGFRavg to eGFRcr-cys using the proportion of participants with errors in eGFR >30% of mGFR (1 - P30) and root mean square error (RMSE) of the regression of eGFR on mGFR on the logarithmic scale. We also compared classification and reclassification of mGFR categories using eGFRavg compared to eGFRcr-cys. Accuracy was significantly better for eGFRavg (1 - P30 of 10.4% and RMSE of 0.214) compared to eGFRcr-cys (1 - P30 of 13.8% and RMSE of 0.232; P = 0.004 and P = 0.006, respectively). However, improvements in accuracy did not generally translate into significant improvement in classification or reclassification of mGFR categories. Study population may not be generalizable to clinical settings other than large urban medical centers in China. A panel of endogenous filtration markers including B2M and BTP in addition to creatinine and cystatin C may improve GFR estimation in China. Further study is necessary to determine whether GFR estimation using B2M and BTP can be improved and whether these improvements lead to useful clinical applications.


Language Experience Changes Language and Cognitive Ability.
The sustained use of two languages by bilinguals has been shown to induce broad changes in language and cognitive abilities across the lifespan. The largest changes are seen as advantages in executive control, a set of processes responsible for controlled attention, inhibition, and shifting. Moreover, there is evidence that these executive control advantages mitigate cognitive decline in older age and contribute to cognitive reserve. In this paper, we examine some of the evidence for these findings and explain their relation to bilingual language use. These effects are considered in terms of their implications for our understanding of cognitive and brain plasticity. Some implications for social policy are discussed.


Potential role of human challenge studies for investigation of influenza transmission.
The importance of different routes of influenza transmission (including the role of bioaerosols) and the ability of masks and hand hygiene to prevent transmission remain poorly understood. Interest in transmission of influenza has grown as the effectiveness of prevention measures implemented during the 2009 H1N1 pandemic are questioned and as plans to better prepare for the next pandemic are debated. Recent studies of naturally infected patients have encountered difficulties and have fallen short of providing definitive answers. Human challenge studies with influenza virus date back to the 1918 pandemic. In more recent decades they have been undertaken to investigate the efficacy of antiviral agents and vaccines. Could experimental challenge studies, in which volunteers are deliberately infected with influenza virus, provide an alternative approach to the study of transmission? Here, we review the latest intervention studies and discuss the potential of challenge studies to address the remaining gaps in our knowledge.


Real-Life Efficacy, Safety, and Use of Dexamethasone Intravitreal Implant in Posterior Segment Inflammation Due to Non-infectious Uveitis (LOUVRE 2 Study).
To evaluate real-life efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in posterior segment inflammation due to non-infectious uveitis (treatment-naïve or not) in French clinics. In this prospective, multicenter, observational, non-comparative, post-reimbursement study, consecutive patients with posterior segment inflammation due to non-infectious uveitis were enrolled and evaluated at baseline (day 0). Those who received DEX on day 0 were re-evaluated at months 2, 6, and 18. Retreatment with DEX and/or alternative therapies was allowed during follow-up. patients (%) with at least a 15-letter gain in best corrected visual acuity (BCVA) at 2 months. Secondary outcomes included patients (%) with at least 15-letter BCVA gains at 6 and 18 months; mean BCVA change from baseline at 2, 6, and 18 months; and patients (%) retreated, mean central retinal thickness (CRT), and adverse events (AEs) at all post-baseline visits. Ninety-seven of 245 enrolled patients with posterior segment inflammation due to non-infectious uveitis (80% previously treated) and disease duration of 5 years (average) received DEX on day 0 and were included in efficacy analyses. At month 2 (n = 91), 20.5% of patients (95% CI 12.0-28.9) gained at least 15 letters from a baseline mean of 60.9 letters; the mean gain was 6.2 letters (95% CI 3.5-8.9). At month 6, 50.0% (n = 38/76) of patients did not receive alternative treatment or DEX retreatment, mostly because inflammation had sufficiently subsided (n = 27/38, 71.1%). Although early study termination prevented efficacy analysis at 18 months (n = 12), CRT reductions persisted throughout follow-up. From baseline to month 18, 21/245 (8.6%) patients had DEX-related AEs; 17/245 (6.9%) had ocular hypertension (most common AE). LOUVRE 2 confirms DEX efficacy on visual acuity and CRT in predominantly DEX-pretreated patients with relatively old/stabilized uveitis. DEX tolerability was consistent with known/published data, confirming treatment benefits in posterior segment inflammation due to non-infectious uveitis. NCT02951975.


Improved methane fermentation of chicken manure via ammonia removal by biogas recycle.
This study demonstrates methane fermentation that was carried out along with ammonia striping to avoid ammonia accumulation that significantly inhibited methane production. Ammonia was successfully removed by means of recycling of biogas followed by gas washing in sulfuric acid to capture ammonia, when chicken manure was anaerobically digested for 4 days at 55 degrees C and at an initial pH of 8-9. By using this method, 80% of total nitrogen in chicken manure was converted to ammonia and 82% of the produced ammonia was removed. A bench scale reactor equipped with an ammonia-stripping unit for methane production from chicken manure was developed and operated in repeated batch mode. At an initial pH of 8 and at 55 degrees C, 195 and 157 ml g-VS(-1) of methane was successfully produced from the treated chicken manure and the mixture of treated chicken manure and raw chicken manure in the ratio of 1:1, respectively. In this method, ammonia concentration was maintained at a level lower than 2g-N kg-wet sludge(-1) in the reactor.


[Treatment of metastatic renal cell carcinoma].
The median survival of patients with metastatic renal cell carcinoma (mRCC) increased from 10 to more than 40 months since the advent of targeted therapy. The transformation of mRCC from an initially lethal disease to a more favorable entity, albeit incurable, occurred with the transition from best supportive care, to cytokines, to finally sequential targeted therapies. Sunitinib and bevacizumab (level 1b) represent the first-line standard of care for patients with clear-cell mRCC vs temsirolimus (level 2) for those with high-risk features. Additionally, exploratory analyses of the temsirolimus data indicate important benefits for those with nonclear-cell mRCC histological subtypes. In second-line, everolimus proved its efficacy (level 1b). Nonetheless, sunitinib and sorafenib are also effective for nonclear-cell histological subtypes and after failure of other first-line treatment. The PFS benefits of first- and subsequent treatment-lines were confirmed in virtually all subgroup analyses. Potential survival benefits can be derived from cytoreductive nephrectomy (CNT), as was shown for cytokines in the general population, in sunitinib and bevacizumab-exposed patients. Phase III studies are ongoing to address the importance of CNT. This information is crucial to ensure timely delivery of a combination of medical and surgical therapies in this patient population.


[Quality of life of persons with HIV infection in an academic hospital].
Comparison of the quality of life of asymptomatic (n = 24) and symptomatic (n = 20) HIV-infected patients and description of the changes in quality of life during the symptomatic stage. Prospective study. University Hospital Utrecht. Every four months questionnaires on quality of life were completed by 44 of 55 consecutive HIV-infected patients. Physically, asymptomatic HIV-infected patients were better off than symptomatic HIV-infected patients; psychologically, however, both groups of patients showed similar responses. During the symptomatic stage the patients' physical functioning diminished further, but feelings of anxiety or depression showed no marked change; self-evaluations of health conditions became slightly more negative with time.


Aortic remodelling and late outcomes following thoracic endovascular repair with a bare-metal stent distal extension among patients with complicated type-B aortic dissection.
The goal of this study was to describe the factors affecting mid and late aortic remodelling following thoracic endovascular aortic repair with the PETTICOAT (Provisional Extension To Induce Complete Attachment) technique among patients with complicated acute or subacute type B aortic dissection. A retrospective single-centre study that evaluates clinical and morphological outcomes among 65 consecutive patients. The area and diameter of the true and false lumen, overall aortic diameter and false lumen perfusion were evaluated. Concomitant direct visceral artery stenting was successfully conducted in 32 (49%) patients. There was one (1.5%) postoperative stroke; three (4.6%) patients developed spinal cord ischaemia; two (3%) patients suffered retrograde type A dissection; and two (3%) patients had mesenteric ischaemia, despite successful reperfusion, that required a bowel resection. Median postoperative follow-up was 63.1 (interquartile range, 32.1- 91.8) months. The probability of survival was 96.9% [95% confidence interval (CI) 88.3%-99.2%] at 30 days, 93.9% (95% CI 84.4%-97.6%) at 1 year, 78.0 (95% CI 64.2%-87.0%) at 5 years and 72.8% (95% CI at 57.9%-83.2%) at 10 years postoperatively. There was a statistically significant postoperative increase in true-lumen area, diameter and true-lumen index in all five aortic levels measured. Complete false lumen (FL) thrombosis at the coeliac trunk, renal arteries and aortic bifurcation levels was observed in 47%, 15% and 24% of patients at midterm (6-15 months) and in 29%, 21% and 29% on late (later than 21 months) computed tomography angiograms (CTA). Persistent false lumen (FL) perfusion at the coeliac level on midterm CTA was associated with a larger extent of late aortic growth (P = 0.042) and was, in the majority of cases, caused by iliac re-entries either alone (28.57) or in combination with visceral and lumbar (28.57%) or distal aortic (10.71%) re-entries. A larger abdominal aortic diameter at midterm was associated with an increased probability of distal aortic reinterventions (hazard ratio 7.26, 95% CI 2.41-21.9, P < 0.001). Persistent FL perfusion of the distal aorta at midterm following TEVAR with the PETTICOAT technique among patients with acute and subacute type B dissection is caused mainly by iliac, visceral, lumber and distal aorta re-entries. Patients with persistent FL perfusion have an increased risk of aortic aneurysmal growth at late follow-up.


Specificity and reproducibility of nasal biomarkers in patients with allergic rhinitis after allergen challenge chamber exposure.
Allergic rhinitis is an inflammatory disease that causes cellular influx and mediator release in the nose. These inflammatory changes might be used as nasal biomarkers to assess the efficacy of novel anti-allergic treatments. To assess the specificity and reproducibility of nasal biomarkers in patients with allergic rhinitis after grass pollen exposure in an allergen challenge chamber. In a monocenter pilot study, 15 patients with allergic rhinitis and 19 healthy individuals underwent two 4-hour Dactylis glomerate pollen challenges in the challenge chamber with an interval of 21 days. Before challenge, on exit, and after 2 and 22 hours, a nasal lavage was performed and nasal secretions were collected on filter paper to determine a wide panel of cells and mediators. Furthermore, total nasal symptom score, nasal flow, and nasal nitric oxide were measured. Pollen exposure significantly increased eosinophil, interleukin (IL) 5, IL-6, IL-13, and macrophage inflammatory protein 1β levels in allergic patients but not in healthy individuals. The effect could be reproduced for eosinophils, IL-5, IL-6, and macrophage inflammatory protein 1β after the second allergen challenge. By contrast, the IL-13 levels were higher and eotaxin levels first increased after repetitive allergen challenge. There was no correlation between total nasal symptom score and elevated cell or cytokine levels. Nasal nitric oxide levels were nonspecifically elevated in both patients with allergy and healthy controls. A subset of cellular and soluble biomarkers in nasal lavage and secretion reveals specificity and reproducibility in patients with allergic rhinitis. These can be used to measure the immunologic efficacy of antiallergic treatments in an allergen challenge chamber. Carryover effects attributable to priming must be considered when designing cross-over studies. clinicaltrials.gov Identifier: NCT00297843.


Prospective, randomized comparison between raloxifene and clomiphene citrate for ovulation induction in polycystic ovary syndrome.
To compare the ovulation rate between raloxifene and clomiphene citrate (CC) in patients with polycystic ovary syndrome (PCOS). Double-blind, randomized, superiority clinical trial. Tertiary university hospital. Women with ovulatory dysfunction and PCOS based on the Rotterdam criteria. One of two oral treatments: 5 days of 100 mg/day of CC or R. Ovulation, based on follicle collapse on serial ultrasound and midsecretory serum progesterone concentration (≥3 ng/dL). The women with PCOS (n = 82) were randomized to receive CC (n = 40) or raloxifene (n = 42). From these, 68 patients finished the trial according to the protocol (CC: n = 37; raloxifene: n = 31). There were no statistically significant differences between the groups in ovulation rates per an intention-to-treat analysis based on ultrasound alone (CC: 21 of 40 vs. raloxifene: 17 of 42) or on progesterone levels (CC: 16 of 40 vs. raloxifene: 11 of 42). No serious adverse events were observed in either group. No statistically significant difference in ovulation was observed between raloxifene and clomiphene citrate in patients with PCOS with ovulatory dysfunction.


Long-term follow-up after percutaneous transluminal coronary angioplasty in patients with single-vessel disease.
Seven hundred ninety-eight patients with symptomatic single-vessel disease who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1977 and 1985 were reevaluated by questionnaire 78 +/- 23 months after dilatation. Indication for PTCA was stenosis of > or = 70%, anginal symptoms, and objective signs of myocardial ischemia. The immediate success rate was 81.2%, and severe complications occurred in 7.1%, which included two fatal complications (0.3%). Repeat angiograms were performed in 582 of 648 patients who underwent successful dilatation and showed restenosis in 143 cases (24.6%). Within 1 year after the first dilatation, 586 patients had been successfully revascularized by PTCA (i.e., there was no evidence of restenosis or redilatation was successful), and 113 patients had undergone bypass surgery. The remaining 99 patients were treated medically if PTCA was unsuccessful or if restenosis (> or = 70%) that was not amenable to redilatation was present. The 8-year overall survival probability was 91.7%, and cardiac survival was 95.5%. The 8-year event-free survival probability was 52.7% for all patients: 62.5% in patients who had successful PTCA and 14.5% in patients who had unsuccessful PTCA (p = 0.0000). The cardiac survival probabilities of patients with lasting PTCA success at 1 year and of surgically treated patients were significantly better than those of patients who did not have successful revascularization (at 8 years 97.2% and 98.1% vs 88.9%; p < 0.04). Late events (> or = 1 year) occurred more often in patients who did not have successful revascularization compared with patients who had successful PTCA (at 8 years 57.9% were event-free vs 74.4%; p < 0.0001); even fewer late events were observed in surgically treated patients (at 8 years 88.2% were event-free; p < 0.004). Cox's proportional hazards regression analysis revealed left ventricular ejection fraction and revascularization status at 1 year as determinants of overall, cardiac, infarct-free, and event-free survival probabilities. At the time of reevaluation significantly more patients in the successful PTCA subgroup were still free of symptoms or had experienced improvement than patients in the bypass or medical subgroups (86.8% vs 68.9% and 59.5%, respectively; p < 0.0001), and more patients in the successful PTCA subgroup were still working (75.4% vs 53.3% and 56.9%, respectively; p < 0.001). We concluded that patients with single-vessel disease who have undergone successful dilatation have an excellent long-term prognosis with regard to survival, cardiac symptoms, and vocational status.(ABSTRACT TRUNCATED AT 400 WORDS)


Liver transplantation after DRESS syndrome: A case report and review of the literature.
This study reports a patient with DRESS syndrome, associated with liver failure, treated with orthotopic liver transplantation.


Effect of porosity on the release kinetics of propafenone-loaded PEG-g-PLA nanoparticles.
Nanoparticle preparation by the emulsification-solvent evaporation method is a complex phenomenon. Various formulation factors can affect the internal structure and release of drug from nanoparticles (NPs). The aim of the present study is to optimize NPs of PEG-g-PLA polymer and study the effect of various factors on the porosity as well as release profile of drug-loaded NPs. Propafenone hydrochloride (Prop.HCl), a model drug, was encapsulated in NPs using different amounts of triethylamine (TEA) and initial drug loading levels. NPs were also prepared without TEA by using propafenone base (Prop). All the formulations were characterized for surface morphology, size and size distribution, encapsulation efficiency, thermal analysis, porosimetry and in vitro release studies. Encapsulation efficiency of Prop ranged between 10% and 43% and was dependent on initial drug loading as well as amount of TEA added. Porosity studies revealed different pore size distribution (PSD) for formulations with and without TEA. Formulations with higher drug loading showed greater volume contribution of small pores, higher fractal dimension suggesting more complex pore structure and slower drug release, probably due to decrease in the effective diffusion coefficient of Prop. Results suggest that formulation factors play an important role affecting the porosity and release rate of NPs. Also, fractal dimension could be one of the most important factors in determining the release behavior of NPs.


Origin and voltage dependence of asparagine-induced depolarization in intestinal cells of Xenopus embryo.
The kinetics and voltage dependence of asparagine (Asn)-induced depolarization in endoderm cells from Xenopus laevis embryos were analysed using current-clamp techniques. The depolarization is assumed to reflect the activation of an amino acid membrane carrier; it is accompanied by a slight increase in membrane resistance and cannot be explained by only the electrogenic character of the Asn carrier. It is proposed that the Asn depolarization arises, at least in part, from the decrease of the permeability ratio PK/PNa indirectly associated with the Na-coupled amino acid uptake. At room temperature (20-23 degrees C) the Asn response develops according to a single exponential function whose time constant is correlated with the final level of depolarization. Both amplitude and rise time of the depolarization are sensitive to variations of membrane potential and changes in Asn or Na external concentrations. Lowering the temperature decreases the amplitude of the Asn depolarization and increases its rise time with a Q10 factor of two; the kinetics remain of the Michaelis-Menten type, with a marked decrease in delta Emax and no change in Km. When the holding potential is altered by depolarizing and hyperpolarizing currents, the Asn response varies according to a bell-shaped characteristic presenting an optimum near the normal resting level. Membrane depolarizations induced by Na/K-pump inhibitors or high external K concentrations reduce the size of the Asn response; repolarizing the cell by current injection does not reverse the inhibitory effect of external K ions. Hyperpolarizing the membrane with a K-free Ringer solution increases the amplitude of the Asn response. In all these cases a decrease in delta Emax accounts for the apparent voltage sensitivity of the carrier mechanism. When induced by alterations of [K]o, an additional change in Km is observed, suggesting a K/Na-competitive inhibition of the Asn carrier. The results are discussed in terms of the amino acid carrier and passive membrane properties. It is suggested that the outward K-electrochemical gradient contributes an additional source of energy to the Na-dependent Asn uptake.


Quantitative evaluation in tumor SPECT and the effect of tumor size: fundamental study with phantom.
An experimental study with phantoms was performed in order to evaluate the effect of the tumor volume on the quantitative estimation in tumor SPECT. The ratio of mean count/pixel in the phantom to that of the background (T/N ratio) was well correlated with the size of the phantom: even when the concentration of the Tc-99m O-4 solution of globular phantoms with diameters of 29, 37 and 46 mm was constant, the greater the size of the phantom, the higher was the T/N ratio. This study showed that we should understand that the T/N ratio was certainly affected by the reduction of the tumor size itself whenever we evaluate treatment-response or assess tumor viability after treatment by reference to the T/N ratio.


Transpetrosal Routes to the Skull Base-Anterior and Posterior Transpetrosal Approaches.
The extended middle fossa approach with anterior petrosectomy, or anterior transpetrosal approach, is a highly effective and direct approach to difficult-to-access petroclival tumors and basilar artery aneurysms. This surgical approach exposes a significant window of the posterior fossa dura between the mandibular nerve, internal auditory canal, and petrous internal carotid artery, below the level of the petrous ridge, and provides an unobstructed view of the middle fossa floor to the upper half of the clivus and petrous apex, without requiring removal of the zygoma. The posterior transpetrosal approaches, including the perilabyrinthine, translabyrinthine, and transcochlear approaches, provide direct and wide exposure of the cerebellopontine angle and posterior petroclival region. The translabyrinthine approach is commonly used for the removal of acoustic neuromas and other lesions of the cerebellopontine angle. We provide a stepwise description of how we perform these approaches and how to combine and extend them in order to achieve transtentorial exposure.


Pyridoxine for prevention and treatment of PARP inhibitor induced nausea and vomiting.
Poly-ADP ribose polymerase inhibitors (PARPi) are a promising new treatment option for patients with ovarian cancer and are moderately emetogenic. Tolerance of therapy is paramount, and uncontrolled nausea and vomiting may limit use. Although most patients will experience improvement in nausea and vomiting after one to two months, approximately one in twenty patients will discontinue therapy due to unrelieved symptom burden. Three cases of olaparib-related nausea and vomiting mitigated by primary pyridoxine use are reported. Case 1 demonstrates successful use of pyridoxine in breakthrough nausea. Case 2 details the use of pyridoxine following refractory nausea and vomiting requiring hospitalization. Case 3 describes a prophylactic approach for a patient with significant anticipatory nausea. All three patients tolerated olaparib after starting and continuing pyridoxine. Vitamin B6, or pyridoxine, was successful as both a therapeutic and prophylactic option for significant treatment-related nausea and vomiting with PARPi use.


Discrimination of isomeric monosaccharide derivatives using collision-induced fingerprinting coupled to ion mobility mass spectrometry.
Because of the isomeric heterogeneity that is ubiquitous in analytical science, a formidable analytical challenge is to fully discriminate multiple isomers, especially those candidate isomers with various biological functions. Ion mobility mass spectrometry (IM-MS) has gained impressive advances for gaining molecular conformations, whereas coexisting structurally similar isomers often make unambiguous discrimination impossible due to the limited IM resolution of commercially available instruments. Herein, we demonstrate an energy-resolved collision-induced fingerprint (CIF) method to fully discriminate isomeric monosaccharide derivatives that differ in terms of composition, connectivity and configuration without complex instrument modifications. By simply increasing the collisional energy in the trap cell, the full width at half maximum (FWHM) of IM peaks can be markedly narrowed by at least 2-fold. Given the excellent reproducibility of CIF measurements, the full discrimination of isomers can benefit from their unique feature values and root-mean square deviation (RMSD) in CIF spectra. Moreover, rapid discrimination of each monosaccharide derivate isomer from binary mixtures is demonstrated. This strategy will expand the horizons of IM-MS platform in the rapid differentiation of a wider range of isomers more than monosaccharide derivatives in complex systems, which facilitates the identification and evaluation of innovative isomer candidates with unexplored functions.


Early-life Stress Modifies the Reactivity of Neurons in the Ventral Tegmental Area and Lateral Hypothalamus to Acute Stress in Female Rats.
Early-life stress (ELS) has long-term consequences, including an increased risk for drug abuse and psychiatric disorders later in life, which is higher in women than in men. The consequences of ELS include heightened sensitivity to stressful events. Here, we hypothesized that ELS changes the stress sensitivity of dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) and orexin (OXA) neurons in the lateral hypothalamus (LH), that are crucial for the control of motivated behaviors. We combined morphological and immunohistochemical approaches to investigate the effect of maternal separation (MS), a rodent model of the ELS, on the expression of c-Fos protein in putative DAergic and non-DAergic VTA and LH OXA neurons, as well as on dendritic spine density and morphology in the VTA of adult female rats. We showed that MS increased basal and acute restraint stress-induced c-Fos expression in putative DAergic neurons, specifically in the dorsomedial VTA, an area implicated in responsiveness to aversive stimuli. Conversely, restraint-induced increase in c-Fos expression in non-DAergic dorsolateral VTA neurons was dampened by MS. Furthermore, an increase in spine head diameter of VTA neurons and a concurrent decrease in dendritic spine density in dorsal VTA were observed. We also showed that MS changed the stress sensitivity of OXA neurons selectively in the dorsomedial hypothalamus (DMH), which is implicated in arousal and the stress response. These findings show the long-lasting consequences of ELS and indicate the selective, regional sensitivity of structures involved in the control of arousal, motivational behaviors and the stress response to ELS.


Genes, lifestyles and obesity.
To review the role of genes and lifestyle factors, particularly dietary habits and physical activity patterns, in obesity risk as well as their potential interactions. A descriptive report of a number of genes definitely ascribed or potentially implicated in excessive fat accumulation leading to obesity as assessed by different research approaches (Mendelian transmission, genetic animal models, epidemiological association/linkage studies and genome-wide scans). Also, the involvement of macronutrient intake and composition (fat/carbohydrate) as well as the role of activity-linked energy expenditure in obesity onset is reviewed. Examples of the role of the genotype as well as of the dietary macronutrient composition/intake and sedentary/low energy cost of physical activities in obesity prevalence are reported. Both genes and everyday life environmental factors such as cultural and social mediated food intake and reduced domestic and living work activities are involved in the obesity pandemia. The occurrence of gene x gene and gene x environmental factors interactions makes it more difficult to interpret the specific roles of genetics and lifestyle in obesity risk.


Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with high-altitude pulmonary oedema: a meta-analysis.
High-altitude pulmonary oedema (HAPE) is a non-cardiogenic hydrostatic oedema involving a genetic component. Considering the low incidence of HAPE, sample sizes in current reports are relatively limited. We aimed to assess the association between the angiotensin-converting enzyme (ACE) I/D polymorphism and HAPE via a meta-analysis of published and unpublished data. We searched PubMed, CBM, CNKI, and Cochrane Library Database before 20 November 2010. A random-effects model was applied (STATA) and study quality was assessed in duplicate. A total of five studies including 305 cases and 662 controls were meta-analysed. The summary odds ratio (OR) indicated that no significant differences in risk of developing HAPE were found between carriers of ACE D and I alleles (OR = 1.20; 95% confidence interval (CI), 0.98-1.48; p = 0.084). Lack of association persisted for genotypes under the recessive mode. However, genotype association under the dominant mode showed D allele carriers significantly conferred a 1.55-fold increased HAPE risk compared with II genotype carriers (95% CI, 1.15-2.08; p = 0.004). Funnel plot and Egger's test suggested no evidence of publication bias. Our results supported the notion that ACE D allele carriers were at significant increased risk of developing HAPE.


Human dendritic cells transfected with allergen-DNA stimulate specific immunoglobulin G4 but not specific immunoglobulin E production of autologous B cells from atopic individuals in vitro.
Atopic/allergic diseases are characterized by T helper 2 (Th2)-dominated immune responses resulting in immunoglobulin E (IgE) production. DNA-based immunotherapies have been shown to shift the immune response towards Th1 in animal models. In further studies we showed that human dendritic cells (DC) transfected with allergen-DNA are able to stimulate autologous CD4(+) T cells from atopic individuals to produce Th1 instead of Th2 cytokines and to activate interferon-gamma (IFN-gamma)-producing CD8(+) T cells. The aim of this study was to analyse whether DC transfected with allergen-DNA are also able to influence immunoglobulin production of B cells from atopic donors. For this purpose, human monocyte-derived DC from grass-pollen allergic donors were transfected with an adenovirus encoding the allergen Phleum pratense 1 and cocultured with B cells, autologous CD4(+) T cells, and CD40 ligand-transfected L-cells. B cells receiving help from CD4(+) T cells stimulated with allergen-transfected dendritic cells produced more allergen-specific IgG4 compared to stimulation with allergen protein pulsed DC or medium, while total IgG4 production was not affected. In contrast, specific IgE production was not enhanced by stimulation with allergen-DNA transfected DC compared to medium and inhibited compared to allergen protein-pulsed DC with similar effects on total IgE production in vitro. Allergen-DNA transfected dendritic cells are able to direct the human allergic immune response from Th2-dominance towards Th1 and Tc1 also resulting in decreased IgE and increased IgG4 production.


The Deinococcus radiodurans uvr A gene: identification of mutation sites in two mitomycin-sensitive strains and the first discovery of insertion sequence element from deinobacteria.
Deinococcus radiodurans (Dr) possesses a prominent ability to repair the DNA injury induced by various DNA-damaging agents including mitomycin C (MC), ultraviolet light (UV) and ionizing radiation. DNA damage resistance was restored in MC sensitive (MC(S)) mutants 2621 and 3021 by transforming with DNAs of four cosmid clones derived from the gene library of strain KD8301, which showed wild type (wt) phenotype to DNA-damaging agents. Gene affected by mutation (mtcA or mtcB) in both mutants was cloned and its nucleotide (nt) sequence was determined. The deduced amino acid (aa) sequence of the gene product consists of 1016 aa and shares homology with many bacterial UvrA proteins. The mutation sites of both mutants were identified by analyzing the polymerase chain reaction (PCR) fragments derived from the genomic DNA of the mutants. A 144-base pair (bp) deletion including the start codon for the uvrA gene was observed in DNA of the mutant 3021, causing a defect in the gene. On the other hand, an insertion sequence (IS) element intervened in the uvrA gene of the mutant 2621, suggesting the insertional inactivation of the gene. The IS element comprises 1322-bp long, flanked by 19-bp inverted terminal repeats (ITR), and generated a 6-bp target duplication (TD). Two open reading frames (ORFs) were found in the IS element. The deduced aa sequences of large and small ORFs show homology to a putative transposase found in IS4 of Escherichia coli (Ec) and to a resolvase found in ISXc5 of Xanthomonas campestris (Xc), respectively. This is the first discovery of IS element in deinobacteria, and the IS element was designated IS2621.


The value of vaccines.
Optimizing vaccine spending depends on recognizing the full value of vaccination (VoV). Existing taxonomies of such value are not comprehensive because they are not guided by general theories. I rely on two such theories: subjective-value theory claims that what has value is determined by what people actually or ideally want in life. A welfarist theory of government states that a fundamental objective of government is to promote social value (or social welfare). These jointly imply that any aspect of life that individuals actually or ideally value and that could be negatively affected by vaccine-preventable diseases (and therefore positively affected by preventive vaccines) is an element of VoV. I build a more comprehensive-value taxonomy than currently exists based on this implication.


Multi-practice survey on MR imaging practice patterns in rectal cancer in the United States.
To investigate practice patterns related to MR technique and structured reporting for MRI of rectal cancer at academic centers and private practice groups in the United States. A survey developed by active members of the Society of Abdominal Radiology Rectal and Anal Cancer Disease Focus Panel was sent to 100 private practice and 189 academic radiology groups. The survey asked targeted questions about practice demographics and utilization, technical MR parameters and reporting practices related to MRI of rectal cancer. The results were analyzed using software in an online survey program. The survey received 47 unique responses from academic (37/47, 78.7%) and private practice (10/47, 21.3%) groups. Most practices report using rectal MR for staging newly diagnosed rectal cancer always (29/47, 61.7%), and less than half always do so for re-staging after neoadjuvant chemoradiation (20/47, 42.6%). Most groups perform between 1 to 5 rectal MR studies for baseline staging per week (32/47, 68.1%) and most groups perform 0 to 2 MR studies for re-staging per week (27/47, 57.4%). Regarding patient preparation and MR technical parameters, there is variability, but a few key points include most practices (27/47, 57.4%) acquire axial T2-weighted images at a slice thickness of 3 mm or less, axial T2-weighted images with 2D acquisition (30/47, 63.8%), a T2-weighted axial oblique sequence through the tumor (43/47, 91.5%), and T2-weighted images without fat suppression (37/47, 78.7%). Equal numbers of groups report using a maximal b-value less than 1000 s/mm2 (19/43, 44.2%) and 1000 s/mm2 or greater (19/43, 44.2%); the rest were unsure. A substantial portion of respondents do not use intravenous contrast (13/47, 27.7%). Most believe that structured report templates contribute to uniformity of reporting practices (39/47, 83.0%), though there is considerable heterogeneity in usage and included elements. There is considerable technical heterogeneity among respondents' answers and reporting practices in MR for rectal cancer, and most of the groups report reading only a modest number of studies per week. Our findings suggest there may be room for improvement in terms of radiologist education for performance and standardization of clinical practice for MR imaging of rectal cancer.


Synthesis and anti-inflammatory/antioxidant activities of some new ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues.
We report the synthesis, anti-inflammatory and antioxidant activities of novel ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues. The tested compounds inhibit the carrageenin-induced rat paw edema (4.5-56.1%) and present important scavenging activities. Compound 2a is the most potent (56.1%) in the in vivo experiment and exhibits promising in vitro inhibition of soybean lipoxygenase (IC(50)<1microM).


Atypical Radiological Findings of Capillary Hemangioma in Right Atrium: A Case Report.
Cardiac hemangiomas account for only 2.8% of primary cardiac tumors and are caused by the abnormal proliferation of endothelial cells and excess blood vessels. Typical radiological findings of cardiac hemangioma demonstrate intense contrast enhancement. Here we report the case of a 69-year-old man who presented with a right atrial mass found incidentally with multimodal imaging findings, including echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI). This case presented with poor enhancement within right atrial mass on dynamic contrast-enhanced CT scan and gadolinium-enhanced first-pass perfusion image of cardiac MRI. After surgical resection, the pathologic diagnosis of cardiac capillary hemangioma was made. Cardiac hemangioma could be included in the differential diagnosis for cardiac neoplasms demonstrating poor enhancements on CT and MRI scans.


Interhelical interaction and receptor phosphorylation regulate the activation kinetics of different human β1-adrenoceptor variants.
G protein-coupled receptors represent the largest class of drug targets, but genetic variation within G protein-coupled receptors leads to variable drug responses and, thereby, compromises their therapeutic application. One of the most intensely studied examples is a hyperfunctional variant of the human β1-adrenoceptor that carries an arginine at position 389 in helix 8 (Arg-389-ADRB1). However, the mechanism underlying the higher efficacy of the Arg-389 variant remained unclear to date. Despite its hyperfunctionality, we found the Arg-389 variant of ADRB1 to be hyperphosphorylated upon continuous stimulation with norepinephrine compared with the Gly-389 variant. Using ADRB1 sensors to monitor activation kinetics by fluorescence resonance energy transfer, Arg-389-ADRB1 exerted faster activation speed and arrestin recruitment than the Gly-389 variant. Both activation speed and arrestin recruitment depended on phosphorylation of the receptor, as shown by knockdown of G protein-coupled receptor kinases and phosphorylation-deficient ADRB1 mutants. Structural modeling of the human β1-adrenoceptor suggested interaction of the side chain of Arg-389 with opposing amino acid residues in helix 1. Site-directed mutagenesis of Lys-85 and Thr-86 in helix 1 revealed that this interaction indeed determined ADRB1 activation kinetics. Taken together, these findings indicate that differences in interhelical interaction regulate the different activation speed and efficacy of ADRB1 variants.


NLRP3 as a sensor of metabolism gone awry.
The NLRP3 inflammasome is an important player in innate immunity and pathogenic inflammation. Numerous studies have implicated it in sensing endogenous danger signals, yet the precise mechanisms remain unknown. Here, we review the current knowledge on the organismal and cellular metabolic triggers engaging NLRP3, and the mechanisms involved in integrating the diverse signals.


Influence of the hydromechanical stress and temperature on growth and antibody fragment production with Bacillus megaterium.
Bacillus megaterium was used for production of the lysozyme-specific recombinant scFv D1.3 antibody fragment. Key process parameters like the temperature and the hydromechanical stress play a very important role for significant product formation during process development or scale-up. In this study, the influence of these two variables on growth and recombinant antibody fragment production in a 2-L lab-scale bioreactor system was investigated using a central composite design. Especially a significant influence of the hydromechanical stress on antibody fragment production was detected in batch cultivations. While volumetric power inputs of about 0.5 kW/m(3) (agitation rates around 500 min(-1)) are usually employed in batch cultivations, in this work maximal product concentration was found at a volumetric power input of about 0.06 kW/m(3) (agitation rate around 250 min(-1)) and at a high cultivation temperature of 41 °C. The influence of the two process variables at single-cell level was estimated using flow cytometry too. The characterization was done by estimating the membrane potential giving a hint on bioprocess productivity and secretion capability: the best production was obtained through big cells with low specific membrane potential, which grew at low volumetric power inputs and high cultivation temperatures.


Model assessment of additional contamination of water bodies as a result of wildfires in the Chernobyl exclusion zone.
Forest fires and wild fires are recognized as a possible cause of resuspension and redistribution of radioactive substances when occurring on lands contaminated with such materials, and as such are a matter of concern within the regions of Belarus and the Ukraine which were contaminated by the Chernobyl accident in 1986. Modelling the effects of such fires on radioactive contaminants is a complex matter given the number of variables involved. In this paper, a probabilistic model was developed using empirical data drawn from the Polessie State Radiation-Ecological Reserve (PSRER), Belarus, and the Maximum Entropy Method. Using the model, it was possible to derive estimates of the contribution of fire events to overall variability in the levels of (137)Cs and (239,240)Pu in ground air as well as estimates of the deposition of these radionuclides to specific water bodies within the contaminated areas of Belarus. Results indicate that fire events are potentially significant redistributors of radioactive contaminants within the study area and may result in additional contamination being introduced to water bodies.


Molecular subtyping of cancer and nomination of kinase candidates for inhibition with phosphoproteomics: Reanalysis of CPTAC ovarian cancer.
Molecular subtyping of cancer aimed to predict patient overall survival (OS) and nominate drug targets for patient treatments is central to precision oncology. Owing to the rapid development of phosphoproteomics, we can now measure thousands of phosphoproteins in human cancer tissues. However, limited studies report how to analyse the complex phosphoproteomic data for cancer subtyping and to nominate druggable kinase candidates. In this work, we reanalysed the phosphoproteomic data of high-grade serous ovarian cancer (HGSOC) from the Clinical Proteomic Tumour Analysis Consortium (CPTAC). Our analysis classified HGSOC into 5 major subtypes that were associated with different OS and appeared to be more accurate than that achieved with protein profiling. We provided a workflow to identify 29 kinases whose increased activities in tumours are associated with poor survival. The altered kinase signalling landscape of HGSOC included the PI3K/AKT/mTOR, cell cycle and MAP kinase signalling pathways. We also developed a "patient-specific" hierarchy of clinically actionable kinases and selected kinase inhibitors by considering kinase activation and kinase inhibitor selectivity. Our study offered a global phosphoproteomics data analysis workflow to aid in cancer molecular subtyping, determining phosphorylation-based cancer hallmarks and facilitating nomination of kinase inhibition in cancer.


Debittering effect of Actinomucor elegans peptidases on soybean protein hydrolysates.
Effects of the enzymes in Actinomucor elegans extract and the enzyme Alcalase 2.4L on debittering the soybean protein hydrolysates were investigated. When the protein was treated only with the latter, a strong bitterness formed; but it decreased if the protein was treated with both the enzymes. The more the enzymes were used, weaker was the bitterness tasted. SDS-PAGE profile and ESI-MS spectrum of the hydrolysates evidenced that the Alcalase could convert the protein into peptides rapidly, while the enzymes in the A. elegans extract were able to further degrade some peptides which were difficult or unable to be hydrolyzed by the Alcalase. Further systematic analysis of the peptidases showed that the Alcalase exhibited a significant endopeptidase activity towards NBZ-Phe-pNA substrate (p < 0.01), whereas many exopeptidases in the A. elegans extract had the carboxypeptidase activity towards N-CBZ-Ile-Leu (p < 0.01). It is concluded that those exopeptidases presented in the A. elegans extract can benefit by decreasing the bitterness of the soybean protein hydroysate. They are also capable of being used with the Alcalase in a single-step enzymatic reaction to prepare the bitterless protein hydrolysate, which may be an efficient application for food industry.


A big data analysis of COVID-19 impacts on Airbnbs' bookings behavior applying construal level and signaling theories.
This study investigates the impact of the COVID-19 pandemic on consumer booking behavior in the peer-to-peer accommodation sector. This study used a dataset composed of 2041,966 raws containing 69,727 properties located in all 21 Italian regions in the pre- and post-COVID-19. Results show that in the pre-COVID-19 period, consumers preferred P2P accommodations with price premiums and located in rural (versus urban) areas. Although the findings reveal a preference for entire apartments over shared accommodation (i.e., room, apartment), this preference did not change significantly after COVID-19 lockdowns. The contribution of this study lies in combining psychological distance theory and signaling theory to assess P2P performance in the pre- and post-COVID-19 periods.


Asparagine residue in the rho gene product is the modification site for botulinum ADP-ribosyltransferase.
We reported previously that the ADP-ribosyltransferase in C1 and D botulinum toxins specifically catalyzes ADP-ribosylation of an Mr 22,000 guanine nucleotide-binding protein and that this substrate named Gb (b = botulinum) has an amino acid sequence homologous to that deduced from the rho gene (Narumiya, S., Sekine, A., and Fujiwara, M. (1988) J. Biol. Chem. 263, 17255-17257). In this study we have determined the amino acid sequence at its ADP-ribosylation site. Purified substrate was [32P]ADP-ribosylated by C1 botulinum toxin and digested with trypsin. The radioactive peptides were isolated by reversed-phase high performance liquid chromatography and digested further either with protease V8, with proteases V8 and thermolysin, or with proline endopeptidase and thermolysin. By this procedure three radioactive peptides were obtained, and their amino acid sequences were X-Tyr-Val-Ala-Asp-Ile-Glu, X-Tyr, and Val-Phe-Glu-X-Tyr in which no amino acid peak was found in X. During the sequencing the radioactivity quantitatively adhered to the sequencing filter and was not eluted with either of the identified amino acid residues. Analysis of the protein without the ADP-ribosylation yielded the corresponding sequence as Thr-Val-Phe-Glu-Asn-Tyr which corresponds to Thr37-Tyr42 in the amino acid sequence deduced from the Aplysia rho gene. These results strongly suggest that the asparagine residue is the ADP-ribosylation site in the rho gene product. This ADP-ribose protein bond was stable in 0.5 M hydroxylamine at pH 7.5 at 37 degrees C for at least 5 h. The ADP-ribosylation of this protein affected neither its GTPase- nor its [35S]guanosine 5'-O-thiotriphosphate-binding activity.


Uracil-tegafur/leucovorin and mitomycin C salvage therapy in patients with advanced colorectal cancer: a phase II study.
We investigated the efficacy and safety of oral Uracil/tegafur (UFT) with leucovorin and mitomycin C (MMC) as third-line treatment for patients with extensively pretreated metastatic colorectal cancer (mCRC). This was a multicenter, prospective phase II study. Patients received MMC 7 mg/m² on day 1 and UFT 300 mg/m² with leucovorin 90 mg, both divided into three daily doses, on days 1-28 every 5 weeks. All patients had failed prior treatment with irinotecan, oxaliplatin, fluoropyrimidine, bevacizumab, and cetuximab. The primary endpoint was tumor control rate evaluated after 2 cycles. Twenty-one patients were included: median age was 66 years (41.1-87.8 years). Tumor control rate was observed in 26.7% of the 15 patients evaluable for response. Median overall survival was 6.4 months. Grade 3 adverse events were asthenia, anorexia, and vomiting. In patients with mCRC who have progressed after as many as two prior therapies, the combination of UFT/leucovorin and MMC is safe and may produce a short stabilization of disease in approximately 25% of patients.


The effects of marijuana smoking on lung function in older people.
Previous studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear. We determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1 in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively. ∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55-3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV1 by 29.5 mL·year-1 (p=0.0007) and 21.1 mL·year-1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year-1 (p<0.0001). Heavy marijuana smoking increases the risk of COPD and accelerates FEV1 decline in concomitant tobacco smokers beyond that observed with tobacco alone.


Molecular classification of soft tissue sarcomas for adequate diagnosis: A study on the northeast population of Morocco.
Soft tissue sarcomas (STS) are a heterogeneous group of tumors. For adequate therapeutic management, an accurate diagnosis is necessary. In Morocco, the diagnosis is essentially based on the morphological and immunohistochemical study. Compared to other techniques, fluorescence in situ hybridization (FISH) is easier to develop and less expensive. This study aims to assess the feasibility and utility of implementing FISH technique to improve diagnostic accuracy and establish a good classification. This is a retrospective cohort study. 211 cases of mesenchymal tumors were included. Hematoxylin Eosin Safran (HES) staining was performed in all cases followed by immunohistochemistry (IHC). FISH was performed in all cases with suspected STS. The probes used were EWSR1, MDM2 and SS18. The performance of FISH and histopathological test were evaluated by the ROC curve method (receiver operating characteristic). We evaluated the concordance between FISH and real time PCR by Cohen test. The real-time PCR technique showed good agreement with the FISH test by a Kappa coefficient of 60% (p = 0.035). FISH was able to confirm that it is more accurate (Youden's Index = 91%) than histological/immunohistochemical analysis (Youden's Index = 51%), as well as the positive predictive value was higher (100%) with an ROC curve finding a larger area under the curve of 0.953 (95% CI: 0.918-0.988), p = 0.000 which supports that FISH shows high performance to present an accurate final diagnosis. This is the first and the largest Moroccan series for the molecular diagnosis of STS by FISH. Our study shows that paraffin FISH is a sensitive and specific ancillary tool in the diagnosis of STS when used in the appropriate clinicopathological context.