Patient outcomes and procedure working time for digital versus conventional impressions: A systematic review.
Limited evidence is available comparing digital versus conventional impressions from the point of view of patient preference. The purpose of this systematic review was to identify and summarize the available literature related to patient-centered outcomes for digital versus conventional impression techniques. The databases Medline, Cochrane, Science Direct, Scopus, and Embase were electronically searched and complemented by hand searches. All published papers available on the databases from 1955 to July 2016 were considered for title and abstract analysis. A total of 2943 articles were initially identified through database searches, of which only 5 met the inclusion criteria for qualitative analysis. Four studies comparing patient-reported outcome measures (PROMs) between conventional and digital impressions revealed that the digital technique was more comfortable and caused less anxiety and sensation of nausea. Only 1 study reported no difference between the techniques regardless of patient comfort. Two studies reported a shorter procedure for the conventional technique, whereas 3 studies reported a shorter procedure for the digital technique. A lack of clinical studies addressing patient outcomes regarding digital prosthodontic treatments was observed among the included articles. However, current evidence suggests that patients are more likely to prefer the digital workflow than the conventional techniques.


ApoE gene and familial risk of Alzheimer's disease as predictors of odour identification in older adults.
The study examined odour identification ability in healthy older adults at increased risk for developing Alzheimer's disease (AD). We recruited a sample (n = 24) of siblings related to probable AD cases and an age-matched control sample (n = 47). All participants were genotyped for the presence of the ApoE epsilon4 allele. Performance on a simple olfactory task of odour identification was compared according to positive family history of AD and ApoE epsilon4 status. The sibling group showed an odour identification deficit compared to the control group. Whilst there was no independent influence of ApoE epsilon4 status on odour identification, there was a significant interaction between positive family history and ApoE epsilon4 status. Sibling epsilon4 carriers showed the greatest odour identification deficit and their performance was significantly poorer than both the sibling non-epsilon4 carrier and control epsilon4 carrier groups. Odour identification deficits like those reported here are considered to be early cognitive markers of incipient AD. In this respect, these findings support the need to both monitor individuals at increased risk of the disease and introduce olfactory-mediated cognitive tasks into the diagnostic setting.


Introducing the individual Teamwork Observation and Feedback Tool (iTOFT): Development and description of a new interprofessional teamwork measure.
The individual Teamwork Observation and Feedback Tool (iTOFT) was devised by a consortium of seven universities in recognition of the need for a means of observing and giving feedback to individual learners undertaking an interprofessional teamwork task. It was developed through a literature review of the existing teamwork assessment tools, a discussion of accreditation standards for the health professions, Delphi consultation and field-testing with an emphasis on its feasibility and acceptability for formative assessment. There are two versions: the Basic tool is for use with students who have little clinical teamwork experience and lists 11 observable behaviours under two headings: 'shared decision making' and 'working in a team'. The Advanced version is for senior students and junior health professionals and has 10 observable behaviours under four headings: 'shared decision making', 'working in a team', 'leadership', and 'patient safety'. Both versions include a comprehensive scale and item descriptors. Further testing is required to focus on its validity and educational impact.


Rationalization of some genetic anticodonic assignments.
The genetic code appears to be a logic matrix in which, generally speaking, there is a correlation between the hydrophobicities of amino acids and their anticodonic nucleotides. There are several exceptions to this generality, however, and using previous data on hydrophobicity and binding constants, coupled with new data on reaction rates, we rationalize several of the anticodonic assignments.


Toad Intoxication in the Dog by Rhinella marina : The Clinical Syndrome and Current Treatment Recommendations.
Oral exposure to the secretions of Rhinella marina (formerly Bufo marinus ) can carry a high fatality rate without early and appropriate treatment. In dogs, the clinical syndrome, which is evident almost immediately, manifests in profuse ptyalism along with gastrointestinal, respiratory, and neurologic signs. Severe cardiac arrhythmias develop less frequently. This review will cover the history, toxicology, and clinical syndrome of Rhinella marina intoxication, and will discuss the recommended therapies for stabilization.


Giant cell arteritis following varicella zoster vaccination.
Giant cell arteritis (GCA) is a form of large-vessel vasculitis affecting patients older than 50years old. Recent reports have suggested that the condition is caused by reactivation of varicella zoster virus (VZV). If that is indeed the case, a vaccine that prevents VZV reactivation should reduce the incidence of GCA. To further test that hypothesis, we assessed the incidence of GCA among patients older than 50years of age who were vaccinated against VZV and compared it to GCA incidence in the general population. Using a centralized electronic medical database of the major medical insurer in Israel, Clalit Health Services (CHS), we have calculated the incidence of newly-diagnosed GCA patients in the general population, as well as the incidence of GCA among patients previously vaccinated against VZV between 1.1 2014-31.10.2016. The mean incidence of newly-diagnosed GCA among non-vaccinated patients older than 50years of age was 41.6/100,000/year, while the mean incidence of GCA among patients previously vaccinated against VZV in the same time period was 75.2/100,000/year (P=0.07). These findings do not support the hypothesis that GCA is due to VZV reactivation.


Prosthetic Design in Total Wrist Arthroplasty.
Total wrist arthroplasty (TWA) provides a motion-preserving alternative to total wrist arthrodesis for low-demand patients with debilitating pancarpal arthritis. The earlier generation total wrist implants had high complication and failure rates. Advances in prosthetic design have contributed to improved clinical outcomes and implant survivorship. The current fourth-generation implants allow for expansion of indications for TWA. Careful patient selection remains critical; patients with high-demand lifestyles and poor bone stock may not be candidates. Long-term studies on implant survival and patient outcomes are critical for the current generation total wrist implants in assessing their long-term value compared with total wrist arthrodesis.


Transport, utilization and biliary secretion of lysophosphatidylcholine in the rat liver.
The hepatic uptake, transport and utilization of plasma lysophosphatidylcholine (lysoPC) and its contribution to biliary lipid secretion have been investigated in bile-fistula rats. The animals were given a single intravenous dose of sn-1-[1-14C]palmitoyl-lysoPC, under constant intravenous sodium taurocholate infusion (1 mumol/min), and the fate of the label was followed in blood, bile and liver for up to 3 h. The livers were excised at given time points, extracted and/or homogenized to determine the lipid distribution and subcellular location of radioactivity. LysoPC was rapidly cleared from plasma, though a consistent fraction of the label persisted in plasma over the experimental time-period in the form of either lysoPC or PC. Recovery of radioactivity in the liver varied from 15.6% after 5 min to 19.5% after 3 h. Hepatic lysoPC underwent rapid microsomal acylation to form specific PC molecular species (mainly 16:0-20:4 and, to a lesser extent, 16:0-18:2 and 16:0-16:1). Ultrafiltration, dialysis and gel-chromatographic analyses of cytosolic fractions (post 105,000 X g supernatants) indicated that lysoPC is transported to the site of acylation mostly as a macromolecular aggregate with an approx. Mr of 14,400. Small amounts of radioactivity were secreted into bile over 3 h (20% in the form of lysoPC and the remainder as 16:0-18:2 and 16:0-20:4 PC species). Plasma lysoPC, taken up by the liver, is mostly transported by a cytosolic carrier with a molecular weight close to fatty-acid-binding proteins; it then enters a distinct acylation pathway, selective for some polyunsaturated-PC species and does not contribute significantly to biliary secretion, either directly, or through its products.


Physico-mechanical and antimicrobial properties of tragacanth/hydroxypropyl methylcellulose/beeswax edible films reinforced with silver nanoparticles.
The novel trinary bio-composite film based on Tragacanth/Hydroxypropyl methylcellulose/Beeswax reinforced silver nanoparticles (AgNPs) was developed. This study investigated the effect of AgNPs (2, 4 and 8%) on some physico-mechanical and antimicrobial properties of bio-composite film. It was discovered that AgNPs reduced the composite tensile strength from 33.64 to 16.12 MPa. However, water vapor permeability was improved by addition of the nanoparticles (4.57-2.16 × 10-13 g m/m2 s Pa). The use of AgNPs influenced the apparent color of bio-composite film. The microscopic surface structure and topography of the films were also examined by scanning electron microscopy and Fourier transform infrared, respectively. Dynamic mechanical thermal analysis results showed that the thermal stability of film was slightly decreased through incorporation with AgNPs. Finally, nano-composite films demonstrated strong antibacterial activity against tested pathogen bacteria in the contact surface zone. The antimicrobial results suggest that new nanocomposite film may be used as food active packaging.


Influencing Factors for Cardiometabolic Risk in Korean Adolescents Based on 2010-2015 Data From the Korea National Health and Nutrition Examination Survey.
High academic stress and physical inactivity in Korean adolescents increase cardiometabolic risk factors, such as obesity, making it crucial to identify the factors influencing their risk. Our aims were to determine differences in the prevalence of metabolic syndrome and its 5 components in Korean adolescents according to gender and to identify the influencing factors for cardiometabolic risk (individual risk factor ≥ 1). Data related to adolescents from the Korean National Health and Nutrition Examination Survey (2010-2015) were assessed. Bivariate analyses to compare distribution and logistic regression analyses to examine the influencing factors were performed. Cardiometabolic risk (≥1 risk factor) was found in 33.2% and 32.6% of male and female adolescents, respectively, and metabolic syndrome (≥3 risk factors) was found in 2.0% and 2.3%, respectively. Among male adolescents, cardiometabolic risk was 1.66 times higher for the group that did not perform strength exercises ( P = .007). For female adolescents, the cardiometabolic risk was 2.44 times higher in 16- to 18-year-olds than in 12- to 15-year-olds ( P < .001) and 1.50 times higher in the non-aerobic-exercise group ( P = .030). Central obesity (waist-to-height ratio ≥ 0.47) increased cardiometabolic risk by 5.71 and 13.91 times in male and female adolescents, respectively ( P < .001). To reduce cardiometabolic risk profiles and future cardiovascular risk in Korean adolescents, school-based physical activity programs should be actively provided not only for students with central obesity but also for students who lack aerobic or strength exercises.


Challenging monogamy in a spider with nontraditional sexual behavior.
Each species and sex can develop different reproductive strategies to optimize their fitness while assigning reproductive effort. Allocosa senex is a sex-role reversed spider whose males construct long burrows in the sand. They wait for wandering females to approach, assess their sexual partners and donate their constructions to females after copulation. Females stay in the burrow and lay their egg-sac. When offspring are ready for dispersion, females leave the burrow and gain access to new mating opportunities. Males are choosy during mate courtship, preferring to mate with virgin females over copulated ones, which can even be cannibalized if males reject them. This situation turns new mating opportunities dangerous for copulated females. We wondered whether a copulated female inside the previous mate's burrow responds to courtship from a new male and if this new male can copulate, avoiding burrow construction costs. We also explored whether courtship and copulation behaviors during the first sexual encounter affected the probability of occurrence of a second copulation. For that purposes we exposed copulated females inside male burrows to new males (non-donor males). Males could locate and court females inside the previous male's burrow, and females accepted a second copulation. Hence, A. senex females are not monogamous as was expected but increase their reproductive success by copulating with non-donor males. Also, males can develop opportunistic tactics, suggesting a more dynamic mating system for this sex-role reversed spider than assumed.


Discordance of conflict of interest self-disclosure and the Centers of Medicare and Medicaid Services.
The Open Payments Database (OPD) discloses financial transactions between manufacturers and physicians. The concordance of OPD versus self-reported conflicts of interest (COI) is unknown. Our objectives were to compare (1) industry and self-disclosed COI in clinical literature, (2) payments within each disclosure level, and (3) industry- and self-disclosed COI and payments by specialty. This was an observational study. PubMed was searched for clinical studies accepted for publication from January 2014 to June 2016. Author and OPD-disclosed COIs were compared. Articles and authors were divided into full disclosure, incomplete industry disclosure, incomplete self-disclosure, and no COI. Primary outcome (differences in reported COI per article) was assessed using McNemar's test. Payment differences were compared using Kruskal-Wallis test. OPD- and self-disclosed COI differed (65.0% discordance rate by article, P < 0.001). Percentages of authors within each disclosure category differed between specialties (P < 0.001). Hematology articles exhibited the highest discordance rate (79.0%) and received the highest median payment for incomplete self-disclosure ($30,812). Significant discordance exists between self- and OPD-reported COI. Additional research is needed to determine reasons for these differences.


Should carbogen and nicotinamide be given throughout the full course of fractionated radiotherapy regimens?
Tumor radiosensitization with carbogen and nicotinamide (CON) was compared when both agents were given throughout fractionated radiotherapy with the sensitization observed when administered with only half of the fractions. The effect of overall treatment time on the local control of tumors irradiated in air or with CON was also investigated. Local tumor control of a rodent adenocarcinoma, CaNT, was studied using eight different 20-fraction x-ray regimens. An overall time of either 10 or 20 days was used and CON was given with all, the first half or last half of the treatment. Relative to air, all six sensitizer combinations gave a large and significant increase in sensitization (p << 0.00001). Enhancement ratios were 1.9 and 2.1 when CON was given with all 20 fractions in either 10 or 20 days, respectively. For both overall times, enhancement ratios were reduced by 15-25% when CON was given with only half of the fractions. In air, reducing the treatment time from 20 to 10 days gave a small but significant decrease in the isoeffective doses. When CON was administered with either all or part of a schedule, varying the treatment time had little or no effect on local tumor control. No toxic side-effects were encountered when the sensitizers were administered 10 or 20 times, either once or twice per day. CON is an effective and non-toxic tumor radiosensitizer. In CaNT tumors, a significantly greater effect is seen when CON is given with every fraction of the schedule. The sensitizers reduced or abolished the sparing effect of overall time.


Spatiotemporal characterization of endothelial cell motility and physical forces during exposure to Borrelia burgdorferi.
Cell motility and biomechanics are critical in various (patho)physiological processes, including the regulation of vascular barrier integrity, which can be subverted by bacterial pathogens. Here, we present a protocol on how to expose endothelial cells (ECs) to vector-borne Borrelia burgdorferi (Bb) and characterize EC kinematics and dynamics during exposure to live or heat-inactivated Bb through traction force and monolayer stress microscopy. Modifications to this protocol may be necessary for studying how different cell types interact with Bb or other microorganisms. For complete details on the use and execution of this protocol, please refer to Yuste et al. (2022).1.


Isolation of Magnetospirillum magneticum AMB-1 mutants defective in bacterial magnetic particle synthesis by transposon mutagenesis.
Nonmagnetic mutants of Magnetospirillum magneticum AMB-1 were recovered following mini-Tn5 transposon mutagenesis. Transconjugants with kanamycin resistance were obtained at a frequency of 2.7 x 10(-7) per recipient. Of 3327 transconjugants, 62 were defective for bacterial magnetic particle (BMP) synthesis. The frequency of independent transposition events for nonmagnetic mutants was about 1.4% in transconjugants. Further analysis of DNA sequences flanking transposon by inverted polymerase chain reaction allowed isolation of at least 10 genes or DNA sequences involved in BMP synthesis in M. magneticum AMB-1.


Impact of anemia on surgical outcomes: innovative interventions in resource-poor settings.
The aim of this work was to study the impact of anemia on surgical outcomes and the impact of instituting appropriate workup and treatment of anemia on surgical outcomes. We conducted a case-control retrospective chart review of all hernia repair, hydrocele repair, and hysterectomy cases at the SEARCH Hospital in Gadchiroli, India, from January 2008 to April 2010, and included 340 male and 112 female surgical patients. We also performed a prospective assessment of the impact of the institution of appropriate workup and treatment of anemia on the surgical outcomes for all hernia repair, hydrocele repair, and hysterectomy cases at SEARCH from May 2010 to May 2011 and included 138 male and 76 female surgical patients. The retrospective arm of the study included 340 males and 112 females with a median age of 39 and 41 years, respectively. The mean hemoglobin values were 12.50 (range = 8.8-15.4) for men and 10.39 (range = 5.2-14.8) for women. Patients with anemia had (1) increased incidence of spinal headache after inguinal hernia repair (p = 0.0266) and (2) increased incidence of fever after total hysterectomy (p = 0.0070). There was no statistically significant correlation between anemia and other outcomes (all p > 0.05). The prospective arm of the study included 138 males and 76 females with a median age of 35 and 40, respectively. The mean hemoglobin values were 11.8 (range = 6.4-14.8) for men and 10.6 (range = 6.9-12.8) for women. There was no statistically significant correlation between anemia and any surgical outcomes (p > 0.05). The incidence of complications in both the retrospective and the prospective arm was compared according to increasing severity of anemia across genders. Overall, there was no statistically significant increase in complication rates with increasing severity of anemia (p > 0.05). In the retrospective arm of this study, anemia was associated with increased incidence of spinal headache and fever. In the prospective arm of this study, there was no statistically significant correlation between anemia and any surgical outcome. The incidence of complications did not increase with the severity of anemia in either arm of the study. Further investigation is needed into the optimal management and treatment of anemia prior to surgery in resource-poor settings.


Levels, distributions, and sources of legacy and novel per- and perfluoroalkyl substances (PFAS) in the topsoil of Tianjin, China.
Soil is a major sink for per- and perfluoroalkyl substances (PFAS), wherein PFAS may be transferred through the food chain to predators at upper trophic levels, which poses a threat to human health. Herein, the concentrations and distributions of legacy and novel PFAS in topsoil samples from different functional areas in Tianjin were comprehensively investigated. Seventeen PFAS congeners were identified, with concentrations ranging from 0.21 ng/g to 5.35 ng/g, with a mean concentration of 1.25 ng/g. The main PFAS in the topsoil was perfluorooctanoic acid (PFOA). 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA; <MDL-1.95 ng/g, mean 0.11 ng/g), as an emerging substitute for perfluorooctane sulfonate (PFOS), was also detected in the topsoil. It showed slightly higher concentrations than PFOS (<MDL-1.62 ng/g, mean 0.10 ng/g), indicating it has gradually replaced legacy PFOS in this area. Based on the positive-definite matrix factor (PMF) receptor model, the major PFAS sources was dominated by textile treatment, metal electroplating plants, and some potential precursors of PFAS with longer chains (>C8) were the major sources (43.4%), followed by food packaging as well as coating materials (25.5%). In addition, Spearman correlation analysis and the structural equation model showed that population density significantly impacted the PFAS distribution in the topsoil of Tianjin.


The acceptance of virtual reality devices for cognitive rehabilitation: a report of positive results with schizophrenia.
This study presents a process of virtual environment development supported by a cognitive model that is specific to cognitive deficits of diverse disorders or traumatic brain injury, and evaluates the acceptance of computer devices by a group of schizophrenic patients. The subjects that participated in this experiment accepted to work with computers and immersive glasses and demonstrated a high level of interest in the proposed tasks. No problems of illness have been observed. This experiment indicated that further research projects must be carried out to verify the value of virtual reality technology for cognitive rehabilitation of psychiatric patients. The results of the current study represent a small but necessary step in the realization of that potential.


Quantitative evaluation of hepatic steatosis using novel ultrasound technology normalized local variance (NLV) and its standard deviation with different ROIs in patients with metabolic-associated fatty liver disease: a pilot study.
The purpose of this study was to evaluate the diagnostic performance of novel ultrasound technology normalized local variance (NLV) and the standard deviation of NLV (NLV-SD) using different ROIs for hepatic steatosis in patients with metabolic-associated fatty liver disease (MAFLD) and to identify the factors that influence the NLV value and NLV-SD value, using pathology results as the gold standard. We prospectively enrolled 34 consecutive patients with suspected MAFLD who underwent percutaneous liver biopsy for evaluation of hepatic steatosis from June 2020 to December 2020. All patients underwent ultrasound and NLV examinations. NLV values and NLV-SD values were measured using different ROIs just before the liver biopsy procedure. The distribution of hepatic steatosis grade on histopathology was 4/19/6/5 for none (< 5%)/ mild (5-33%)/ moderate (> 33-66%)/ and severe steatosis (> 66%), respectively. The NLV value with 50-mm-diameter ROI and NLV-SD value with 50-mm-diameter ROI showed a significant negative correlation with hepatic steatosis (spearman correlation coefficient: - 0.449, p = 0.008; - 0.471, p = 0.005). The AUROC of NLV (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.875, 0.735, and 0.583, respectively. The AUROC of NLV-SD (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.900, 0.745, and 0.603, respectively. NLV (50 mm) values and NLV-SD (50 mm) values between two readers showed excellent repeatability and the intraclass correlation coefficient (ICC) was 0.930 (p < 0.001) and 0.899 (p < 0.001). Hepatic steatosis was the only determinant factor for NLV value and NLV-SD value (p = 0.012, p = 0.038). The NLV (50 mm) and NLV-SD (50 mm) provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with great reproducibility. This study showed that the degree of steatosis was the only significant factor affecting the NLV value and NLV-SD value.


The increasing risk of ammonia volatilization in farmland from the recovery product of magnesium-modified biochar after nitrogen and phosphorus adsorption.
Many studies have shown that magnesium modified biochar (MgBC) can recover nutrients from wastewater and be applied as an excellent slow-release fertilizer in farmland. However, the recovery products (NP-loaden MgBC), represented by struvite or magnesium phosphate, have a high degree of self-alkalinity, which may significantly increase the ammonia (NH3) volatilization in farmland. In this study, the optimal adsorption parameters, self-alkaline regulation process and co-adsorption mechanism of MgBC for ammonium ion (NH4+) and phosphate ion (PO43-) were studied through batch experiments. A field experiment was conducted with three treatments, including local conventional fertilization (N1B0) and the application of 5 t·ha-1 or 10 t·ha-1 NP-loaden MgBC in combination with local conventional fertilization (N1B1 and N1B2, respectively), to determine the impact of NP-loaden MgBC on NH3 volatilization, surface water c(NH4+-N) and pH. The results indicated that the maximum NH4+ and PO43- synergistic recovery of MgBC under the optimal adsorption parameters (dosage of 0.6 g·L-1; initial NH4+ and PO43- concentrations of 120 and 60 mg·L-1 and pH of 8) were 59.96 and 98.60 mg·g-1, respectively. Self-regulating alkaline MgBC maintained pH suitable for struvite, and precipitation mechanism controlled the adsorption. The presence of NP-loaden MgBC raised the pH levels in surface water during the basal fertilization stage and increased c(NH4+-N) in surface water during the topdressing stages. This, in turn, led to a significant increase in NH3 volatilization loss during the entire rice-growing period, with N1B1 and N1B2 experiencing a 23.87 % and 48.91 % increase respectively, compared to N1B0. Therefore, it is imperative to take into account the adverse impact of NP-laden MgBC on NH3 loss in paddy fields when considering its application in future field studies.


A Comparison of Accelerated and Non-accelerated MRI Scans for Brain Volume and Boundary Shift Integral Measures of Volume Change: Evidence from the ADNI Dataset.
The aim of this study was to assess whether the use of accelerated MRI scans in place of non-accelerated scans influenced brain volume and atrophy rate measures in controls and subjects with mild cognitive impairment and Alzheimer's disease. We used data from 861 subjects at baseline, 573 subjects at 6 months and 384 subjects at 12 months from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We calculated whole-brain, ventricular and hippocampal atrophy rates using the k-means boundary shift integral (BSI). Scan quality was visually assessed and the proportion of good quality accelerated and non-accelerated scans compared. We also compared MMSE scores, vascular burden and age between subjects with poor quality scans with those with good quality scans. Finally, we estimated sample size requirements for a hypothetical clinical trial when using atrophy rates from accelerated scans and non-accelerated scans. No significant differences in whole-brain, ventricular and hippocampal volumes and atrophy rates were found between accelerated and non-accelerated scans. Twice as many non-accelerated scan pairs suffered from at least some motion artefacts compared with accelerated scan pairs (p ≤ 0.001), which may influence the BSI. Subjects whose accelerated scans had significant motion had a higher mean vascular burden and age (p ≤ 0.05) whilst subjects whose non-accelerated scans had significant motion had poorer MMSE scores (p ≤ 0.05). No difference in estimated sample size requirements was found when using accelerated vs. non-accelerated scans. Accelerated scans reduce scan time and are better tolerated. Therefore it may be advantageous to use accelerated over non-accelerated scans in clinical trials that use ADNI-type protocols, especially in more cognitively impaired subjects.


LPCAT3 Is Transcriptionally Regulated by YAP/ZEB/EP300 and Collaborates with ACSL4 and YAP to Determine Ferroptosis Sensitivity.
Aims: Lipid peroxidation occurring in lung adenocarcinoma (LUAD) cells leads to ferroptosis. Lysophosphatidylcholine acyl-transferase 3 (LPCAT3) plays a key role in providing raw materials for lipid peroxidation by promoting esterification of polyunsaturated fatty acids to phospholipids. Whether LPCAT3 determines ferroptosis sensitivity and the mechanism by which its expression is regulated in LUAD has not been reported. Results: LPCAT3 and acyl-coenzyme A (CoA) synthetase long-chain family member (ACSL)4 levels were positively associated with ferroptosis sensitivity in LUAD cell lines. Overexpression of LPCAT3 and ACSL4 sensitized LUAD cells to ferroptosis, while LPCAT3 and ACSL4 knockout showed the opposite effect. Zinc-finger E-box-binding (ZEB) was shown to directly bind the LPCAT3 promoter to stimulate its transcription in a Yes-associated protein (YAP)-dependent manner. An interaction between YAP and ZEB was also observed. E1A-binding protein p300 (EP300) simultaneously bound with YAP and ZEB, and induced H3K27Ac for LPCAT3 transcription. This mechanism was verified in primary LUAD cell and xenograft models. The ACSL4, LPCAT3, and YAP combination can jointly determine LUAD ferroptosis sensitivity. Innovation: The binding site of ZEB exists in the -1600 to -1401 nt region of LPCAT3 promoter, which promotes LPCAT3 transcription after ZEB binding. ZEB and YAP bind, and the ZEB zinc-finger cluster domain and YAP WW domain are crucial for their binding. EP300 may bind with YAP via its Bromo domain and with ZEB via its CBP/p300-HAT domain. In addition, the combination of ACSL4, LPCAT3, and YAP to determine ferroptosis sensitivity of LUAD cells is better than prostaglandin-endoperoxide synthase 2 (PTGS2), transferrin receptor (TFRC), or NADPH oxidase 1 (NOX1). Conclusion: LPCAT3 transcription is regulated by YAP, ZEB, and EP300. LUAD ferroptosis sensitivity can be determined by the combination of ACSL4, LPCAT3, and YAP. Antioxid. Redox Signal. 39, 491-511.


A two-cohort phase II clinical trial of gemcitabine plus treosulfan in patients with metastatic uveal melanoma.
In-vitro synergy of treosulfan and gemcitabine has been observed in chemotherapy-resistant tumours. This trial investigated the efficacy of gemcitabine plus treosulfan in metastatic uveal melanoma. Patients received 1000 mg/m of gemcitabine and treosulfan at a dose of 2500 or 3000 mg/m2 in cohort 1 and 3500 or 4000 mg/m2 in cohort 2. Chemotherapy was administered on days 1 and 8 every 4 weeks. Thirty-three patients were treated, 14 in cohort 1 and 19 in cohort 2. In cohort 1 with a treosulfan dose of <or=3000 mg/m2, no objective response was observed, four patients had stable disease and ten progressed. Of the patients treated with >or=3500 mg/m2 in cohort 2, one had partial remission (5%), 10 showed disease stabilization and eight progressed. An increased survival was observed in the second cohort with higher treosulfan doses, with median survival times of 6.0 versus 9.0 months (P=0.03) in cohort 1 and 2, respectively, and a 1-year survival of 7.1% versus 47.3%, respectively. Based on the observation of prolonged disease stabilization, we recommend further investigation of the gemcitabine/treosulfan combination with a dose of 3500 mg/m2 of treosulfan in metastatic uveal melanoma.


Receptor protection studies comparing recombinant and native nicotinic receptors: Evidence for a subpopulation of mecamylamine-sensitive native alpha3beta4* nicotinic receptors.
Studies involving receptor protection have been used to define the functional involvement of specific receptor subtypes in tissues expressing multiple receptor subtypes. Previous functional studies from our laboratory demonstrate the feasibility of this approach when applied to neuronal tissues expressing multiple nicotinic acetylcholine receptors (nAChRs). In the current studies, the ability of a variety of nAChR agonists and antagonists to protect native and recombinant alpha3beta4 nAChRs from alkylation were investigated using nAChR binding techniques. Alkylation of native alpha3beta4* nAChRs from membrane preparations of bovine adrenal chromaffin cells resulted in a complete loss of specific [(3)H]epibatidine binding. This loss of binding to native nAChRs was preventable by pretreatment with the agonists, carbachol or nicotine. The partial agonist, cytisine, produced partial protection. Several nAChR antagonists were also tested for their ability to protect. Hexamethonium and decamethonium were without protective activity while mecamylamine and tubocurarine were partially effective. Addition protection studies were performed on recombinant alpha3beta4 nAChRs. As with native alpha3beta4* nAChRs, alkylation produced a complete loss of specific [(3)H]epibatidine binding to recombinant alpha3beta4 nAChRs which was preventable by pretreatment with nicotine. However, unlike native alpha3beta4* nAChRs, cytisine and mecamylamine, provide no protection for alkylation. These results highlight the differences between native alpha3beta4* nAChRs and recombinant alpha3beta4 nAChRs and support the use of protection assays to characterize native nAChR subpopulations.


Coronary Artery Perforation, Subepicardial Hematoma, and Cardiac Tamponade After Complex Percutaneous Coronary Intervention.
This report presents the case of fissured subepicardial hematoma and cardiac tamponade after coronary artery perforation during a complex percutaneous intervention. Surgical therapy was required to achieve hemostasis because a percutaneous sealing result was insufficient. Prompt recognition and cardiac surgery availability are essential for patient survival in such situations. (Level of Difficulty: Beginner.).


High-methylated pectin from walnut processing wastes as a potential resource: Ultrasound assisted extraction and physicochemical, structural and functional analysis.
The ultrasound-assisted extraction of pectin from walnut processing waste was optimized by Box-Behnken design. The highest extraction yield (12.78 ± 0.83%) was obtained at ultrasound power of 200 W, sonication time of 10 min, pH of 1.5 and LS ratio of 15 v/w. The resulting pectin in these conditions was rich in galacturonic acid (69.44%) and was high in degree of esterification (59.21%) which was confirmed by NMR and FTIR spectra. In addition, the molecular weight distribution analysis showed that the obtained pectin had a heterogeneous natural with low molecular weight (6.30-158.48 kDa). The XRD spectrum of the walnut pectin showed an amorphous structure with few crystalline portions. Furthermore, walnut green husk pectin had good emulsifying properties, water and oil holding capacities, and radical-scavenging activity. Given that the obtained result, the extraction of pectin from this by-product in addition to being able to reduce environmental problems, it can also provide financial benefits for the walnut production sector.


Prepregnancy handling of antineoplastic drugs and risk of miscarriage in female nurses.
To examine the association betweenantineoplastic drug (AD) handling and risk of miscarriage. Nurses' Health Study-3 participants self-reported AD administration and engineering controls (ECs) and personal protective equipment (PPE) use at baseline. We estimated the hazard ratio (HR) of miscarriage in relation to baseline AD handling using multivariable Cox proportional regression. Overall, 2440 nurses reported 3327 pregnancies, with 550 (17%) ended in miscarriages. Twelve percent of nurses self-reported currently handling AD and 28% previously handling AD. Compared with nurses who never handled AD, nurses who handled AD at baseline had an adjusted HR of miscarriage of 1.26 (95% confidence interval [CI], 0.97-1.64). This association was stronger after 12-weeks gestation (HR=2.39 [95% CI, 1.13-5.07]). Nurses who did not always use gloves had HR of 1.51 (95% CI, 0.91-2.51) compared with 1.19 (95% CI, 0.89-1.60) for those always using gloves; nurses who did not always use gowns had HR of 1.32 (95% CI, 0.95-1.83) compared with 1.19 (95% CI, 0.81-1.75) for nurses always using gowns. We observed a suggestive association between AD handling and miscarriage, particularly among nurses who did not consistently use PPE and EC with stronger associations for second trimester losses.


Ventilation Strategies During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure: Current Approaches Among Level IV Neonatal ICUs.
To describe ventilation strategies used during extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure among level IV neonatal ICUs (NICUs). Cross-sectional electronic survey. Email-based Research Electronic Data Capture survey. Neonates undergoing ECMO for respiratory failure at level IV NICUs. A 40-question survey was sent to site sponsors of regional referral neonatal ECMO centers participating in the Children's Hospitals Neonatal Consortium. Reminder emails were sent at 2- and 4-week intervals. Twenty ECMO centers responded to the survey. Most primarily use venoarterial ECMO (65%); this percentage is higher (90%) for congenital diaphragmatic hernia. Sixty-five percent reported following protocol-based guidelines, with neonatologists primarily responsible for ventilator management (80%). The primary mode of ventilation was pressure control (90%), with synchronized intermittent mechanical ventilation (SIMV) comprising 80%. Common settings included peak inspiratory pressure (PIP) of 16-20 cm H2O (55%), positive end-expiratory pressure (PEEP) of 9-10 cm H2O (40%), I-time 0.5 seconds (55%), rate of 10-15 (60%), and Fio2 22-30% (65%). A minority of sites use high-frequency ventilation (HFV) as the primary mode (5%). During ECMO, 55% of sites target some degree of lung aeration to avoid complete atelectasis. Fifty-five percent discontinue inhaled nitric oxide (iNO) during ECMO, while 60% use iNO when trialing off ECMO. Nonventilator practices to facilitate decannulation include bronchoscopy (50%), exogenous surfactant (25%), and noninhaled pulmonary vasodilators (50%). Common ventilator thresholds for decannulation include PEEP of 6-7 (45%), PIP of 21-25 (55%), and tidal volume 5-5.9 mL/kg (50%). The majority of level IV NICUs follow internal protocols for ventilator management during neonatal respiratory ECMO, and neonatologists primarily direct management in the NICU. While most centers use pressure-controlled SIMV, there is considerable variability in the range of settings used, with few centers using HFV primarily. Future studies should focus on identifying respiratory management practices that improve outcomes for neonatal ECMO patients.


Electrochemical and crystal structural analysis of alpha- and dehydro-alpha-lapachones.
Lapachones are pharmaceutically active compounds generating reactive oxygen species. The crystal structure and redox behaviour of the title lapachones, derivates of quinones, were determined by X-ray diffraction and cyclovoltametric measurements. The observed results were compared with beta-lapachone.


Colonoscopic screening of persons with suspected risk factors for colon cancer. I. Family history.
A family history of colorectal cancer is believed to place persons at increased risk for development of the disease. It is unclear, however, how "strong" a family history must be to increase this risk or to make colonoscopic screening appropriate. We performed initial colonoscopy in 154 asymptomatic subjects whose only suspected risk factor was one or two first-degree relatives with colorectal cancer; 48 of these subjects also had affected second- and third-degree relatives. We found 45 adenomas in 28 subjects (18%). One subject had a 3-cm villous adenoma. In 6 subjects, the most advanced findings were tubular adenomas 5-9 mm in diameter; in 21 subjects, we found only tubular adenomas that were 2-4 mm in diameter. The prevalence of adenomas increased significantly with age of subjects (p less than 0.01). Although the overall prevalence of colorectal neoplasms in our group was no greater than might be expected in the general population, subjects with two first-degree relatives tended to have more diminutive adenomas than those with one such relative. Our findings suggest that colonoscopy is not an appropriate first step in screening persons with one affected first-degree relative. For those with more complex family histories, more data are needed--particularly on the prevalence of advanced neoplasms--to determine whether a screening technique that is less costly and less invasive than colonoscopy may be adequate.


Heterogeneous nuclear ribonucleoproteins F and H/H' show differential expression in normal and selected cancer tissues.
The heterogeneous nuclear ribonucleoproteins (hnRNPs) F and H/H', containing the quasi-RNA recognition motif (qRRM) domains, are implicated in several steps of pre-mRNA processing and in cellular differentiation. We have compared a set of tissues and found striking differences in their levels of expression as well as in the nuclear versus the cytoplasmic distribution. Generally, hnRNP F is broadly expressed in many tissues with extremely strong expression in the prostate gland while hnRNP H/H' shows a more restricted degree of expression with low expression in some tissues, for example, liver, exocrine acini of the pancreas, thyroid gland and heart. At the cellular level, hnRNP F is, with few exceptions, predominantly expressed in the cytoplasm while hnRNP H/H' is more abundant in the nuclei. A quite pronounced heterogeneous expression pattern is seen in the proximal tubules of the kidney where hnRNP F is present at moderate cytoplasmic levels while hnRNP H/H' is undetectable, whereas both proteins are more evenly expressed in distal tubules and collecting ducts. Generally, tumor tissues reveal a broad expression of hnRNP F in the nuclei as well as in the cytoplasm while hnRNP H/H' is expressed at higher levels in the nuclei than in the cytoplasm. Up-regulation of hnRNP H/H' is found in a few tissues that normally express low cytoplasmic levels of hnRNP H/H', for example, adenocarcinoma of the pancreas, hepatocellular carcinoma and gastric carcinoma. hnRNP F is down-regulated in hepatocellular carcinoma and up-regulated in gastric carcinoma. The present study indicates the important potential role of this subset of hnRNPs on the gene expression in many tissues.


Synthesis of glia-derived nexin in yeast.
Glia-derived nexin (GDN) is a 43-kDa glycoprotein isolated from rat glioma cell cultures. It promotes neurite extension in cultures of neuroblastoma cells and chick sympathetic neurons. Moreover, GDN is a potent serine protease inhibitor (serpin), belonging to the family of protease nexins. We report here the expression of rat GDN in the Saccharomyces cerevisiae strain GRF18 under the control of the PHO5 promoter. We describe the purification of more than 6 mg total GDN from the cellular extract of 1 liter of yeast culture. The amino acid composition and the sequence of CNBr-fragments of the recombinant protein correlate with the values deduced from the rat GDN cDNA. We provide evidence that the recombinant GDN has exactly the same properties as the glioma-derived protein with respect to its protease-inhibitory activity and its ability to promote the extension of neurites from neuroblastoma cells. The large amounts of recombinant protein obtained from this expression system will allow further biochemical and physiological analysis of GDN and of the serpins in general.


Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism.
To investigate age-related differences in morphine requirements and metabolism in full-term neonates. Randomized double-blind study in the pediatric surgical intensive care unit. Sixty-eight neonates (52 aged under 7 days, 16 aged 7 day or older) following major surgery. After surgery patients were randomly assigned to continuous morphine (10 micro g/kg per hour) or intermittent morphine (30 micro g/kg per 3 hours). Additional morphine was administered on guidance of pain scores. Pain was measured by the Comfort behavioral scale and visual analogue scale. Morphine and morphine-6-glucuronide (M6G) plasma concentrations were determined before and 0, 6, 12, and 24 h after surgery. The younger neonates differed significantly from the older neonates in morphine requirement (median 10 vs. 10.8 micro g/kg per hour), morphine plasma concentration [23.0 vs. 15.3 ng/ml), and M6G/morphine ratio (0.6 vs. 1.5). Pain scores did not differ between age groups or morphine treatment groups. Neonates who were mechanically ventilated longer than 24 h had significantly higher morphine plasma concentrations than the spontaneously breathing neonates 12 and 24 h after surgery (29.1 vs. 13.1 ng/ml and 26.9 vs. 12.0 ng/ml, respectively). Morphine plasma concentrations were not correlated with analgesia or respiratory depression. Five neonates (intermittent morphine) showed respiratory insufficiency; however, the difference between the groups was not significant. Neonates aged 7 days or younger require significantly less morphine postoperatively than older neonates. The two morphine regimens (continuous, intermittent) were equally effective and safe. Mechanical ventilation decreases morphine metabolism and clearance.


Circulating alanine transaminase (ALT) and γ-glutamyl transferase (GGT), but not fetuin-A, are associated with metabolic risk factors, at baseline and at two-year follow-up: the prospective Cyprus Metabolism Study.
To comparatively evaluate traditional liver tests and fetuin A as predictors of cardiometabolic risk, we studied associations between serum alanine transaminase (ALT), γ-glutamyl transferase (GGT), aspartate aminotransferase (AST) and fetuin-A and anthropometric, metabolic, and cardiovascular parameters cross-sectionally at baseline, and prospectively, after 2-years of follow-up. 616 randomly enrolled young healthy participants in the Cyprus Metabolism Study, including all 93 subjects who participated in the follow-up study 2 years after baseline assessment, were included in this study. In the cross-sectional study, serum ALT and GGT were strongly correlated with anthropometric, cardiovascular, and metabolic variables, while serum AST was only correlated with waist circumference and waist-to-hip ratio. Fetuin-A was correlated with anthropometric variables, systolic blood pressure (SBP), insulin, and homeostasis model of assessment-insulin resistance (HOMA-IR) in the unadjusted model. In the fully adjusted model, both serum ALT and GGT levels remained positively correlated with total and low-density lipoprotein (LDL) cholesterol. GGT levels also remained correlated with triglycerides. ALT levels remained strongly positively correlated with insulin (r=0.17, p<.0001) and HOMA-IR (r=0.16, p=0.0001). Serum fetuin-A levels were no longer significantly correlated with any variables. Prospectively, ALT and GGT were predictors of anthropometric variables and LDL cholesterol, while baseline levels of AST and fetuin-A were not predictors of any variables at 2-year follow-up. We confirmed associations of ALT and GGT levels but failed to demonstrate an independent association between fetuin-A and cardiometabolic risk factors in young healthy men. Traditional liver tests (LFTs) are thus better than fetuin-A predictors of metabolic risk factors cross-sectionally and prospectively in young healthy adults.


Expression of the PE_PGRS 33 protein in Mycobacterium smegmatis triggers necrosis in macrophages and enhanced mycobacterial survival.
Research on mycobacteria-specific PE_PGRS genes indicates that they code for cell surface proteins that may influence virulence and the infection of host cells by mycobacteria. In the studies presented here, we have expressed the PE_PGRS 33 gene in a non-pathogenic fast-growing Mycobacterium smegmatis strain and demonstrated that it survives better in macrophage cultures, in vitro as well as in mice after intraperitoneal administration, than the parental strain containing the vector only or a strain expressing only the PE domain of PE_PGRS 33. In macrophages, enhanced colonization by the M. smegmatis expressing PE_PGRS 33 was associated with macrophage aggregation and clearance of macrophage monolayers, visible cell necrosis and significantly greater levels of TNF (TNF-alpha) in the cultures compared with controls. The presence of macrophage cell necrosis was confirmed by measurement of significantly greater levels of lactate dehydrogenase and nucleosomes in the supernatants of the macrophage cultures infected with M. smegmatis expressing PE_PGRS 33. Antibodies directed against TNF partially reduced cytolysis, suggesting that this cytokine is critical but not sufficient for the observed macrophage necrosis and enhanced mycobacterial survival. These results extend earlier observations, which suggested that PE_PGRS proteins may have a role in the pathogenesis of mycobacterial disease and that there may be a specific role for these proteins in influencing host cell responses to infection.


Trauma exposure, PTSD, and HIV sexual risk behaviors among labor migrants from Tajikistan.
Little is known about the role of trauma and PTSD symptoms in the context of migration-associated HIV risk behaviors. A survey of Tajik married male seasonal labor migrants in Moscow was completed by 200 workers from 4 bazaars and 200 workers from 18 construction sites as part of a mixed method (quantitative and qualitative) study. The mean PC-PTSD score was 1.2 with one-quarter of migrants scoring at or above the cutoff of 3 indicating likely PTSD diagnosis. PC-PTSD score was directly correlated with both direct and indirect trauma exposure, but PC-PTSD score did not predict either HIV sexual risk behaviors or HIV protective behaviors. HIV sexual risk behavior was associated with higher indirect trauma exposure. PC-PTSD score was associated with some indicators of increased caution (e.g., more talking with partners about HIV and condoms; more use of condom when drinking). Qualitative findings were used to illustrate the differences between direct and indirect traumas in terms of HIV sexual risk. The study findings call for future efforts to address labor migrant's mental health needs and to integrate trauma dimensions into HIV prevention.


The automatic sampling shield: a device for sampling suckled breast milk.
The automatic sampling shield uses the negative pressure exerted by the breast-feeding baby during sucking to withdraw a series of small samples from the milk stream. Shield performance was studied at four feeds for each of 13 babies. Acceptance of the shield was good (96% of feeds) and samples were obtained in 88% of feeds. Sample weight was large enough for micro-biochemical analysis of composition (median weight 1.3 g), without depriving the baby of important amounts of milk (median percentage of weight of milk intake was 4.3% and sample weight was less than 5 g in all cases). The shield should sample a constant proportion throughout the feed, in order to obtain a sample that is representative of the infant's nutrient intake. Fractional test-weighing of feeds showed a tendency for a larger proportion of the feed to be collected at slower flow rates. Modelling on the basis of the observed flow profiles in conjunction with a theoretical fat concentration profile showed that the observed 'disproportionality' would have over-estimated fat intake by a mean of 2.6% per feed (S.D.9.1 range -18.9% to + 16.9%). Using the shield in random sequence at two out of the first four feeds after 0800 h, showed that an infant's mean milk intake with the shield was on average 32% less than on control feeds. Allowing for possible compensation by the infant when control feeds followed low shield intakes, mean milk intakes with the shield were 17% smaller than without the shield.


Doxycycline: A sclerosant agent to treat a case of recurrent thyroglossal duct cyst.
Thyroglossal duct cyst (TGDC) is one of the most common congenital anterior midline neck masses in children. Sistrunk operation is considered as the cornerstone in TGDC removal. Nevertheless, 5% to 7 % of patients have been reported to show a recurrence even after adequate resection. This necessitates at times multiple resections with potential complications. One interesting emerging technique is sclerotherapy of TGDC remnants post resection. We present here a case of a child who had a successfully treated recurrent TGDC using sclerotherapy with doxycycline.


Sequential pure red cell and megakaryocyte aplasia associated with chronic liver disease and ulcerative colitis.
The clinical course of a patient with chronic hepatitis and previous ulcerative colitis who subsequently developed pure red cell aplasia (PRCA) is described. The PRCA remitted initially with corticosteroid therapy. A subsequent relapse responded to cyclophosphamide therapy following splenectomy. This was followed by a fatal third episode of red cell aplasia associated with megakaryocyte aplasia.


An infant with 49XXXXY syndrome: a case report.
49XXXXY syndrome is the rarest X chromosome aneuploidy, with approximate incidence of 1:85,000-100,000 male births. Worldwide, around 100 cases have been reported. In this report, we describe one such case seen in Sri Lanka. A 10-day-old Sri Lankan neonate born in a tertiary care center was referred to the pediatric endocrinology unit of Lady Ridgeway Hospital due to detection of ambiguous genitalia at birth. He was the first child born to nonconsanguineous healthy parents following an uncomplicated antenatal period. He was born at term via normal vaginal delivery, with a birth weight of 2.385 kg. The baby was active, and there was no documented hypoglycemia or alteration in basic biochemical investigations. On examination, the child had hypertelorism, upslanting palpebral fissures, flat occiput, and mild webbing of the neck. System examination was normal. Genitalia examination revealed bifid scrotum, perineal urethra, 2 cm phallus, and bilateral testis in situ. Hormonal analysis, including dehydroepiandrosterone sulfate, testosterone, and 17-OH progesterone levels, was normal except for an elevated level of follicle-stimulating hormone, indicating gonadal dysgenesis. Ultrasound of the abdomen detected testis located at bilateral inguinal canal, and no Müllerian structures were visible. Echocardiography showed a small patent foramen ovale with otherwise normal heart. Chromosome analysis revealed 49XXXXY syndrome. 49XXXXY syndrome should be entertained as a rare possibility for ambiguous genitalia, and karyotyping is an essential investigation for evaluation of such patients.


Assisted reproductive travel: UK patient trajectories.
Media reporting of 'fertility tourism' tends to portray those who travel as a cohesive group, marked by their desperation and/or selfishness and propensity towards morally questionable behaviour. However, to date little has been known about the profile of those leaving the UK for treatment. This paper discusses the first UK-based study of patient assisted reproduction travel that was designed to explore individual travel trajectories. It is argued that existing ways of conceptualizing cross-border reproductive care as 'fertility or reproductive tourism' are in danger of essentializing what the data suggest are diverse, complex and often ambiguous motivations for reproductive travel. The concept of seriality is used to suggest that, whilst 'reproductive tourists' share some characteristics, they also differ in significant ways. This paper argues that, through an examination of the personal landscapes of fertility travel, the diverse processes involved in reproductive travel can be better understood and policymakers can be assisted to avoid what might be regarded as simplistic responses to cross-border reproductive care.


The natural history of ventriculomegaly in a fetus without obstructive hydrocephalus.
Fetal ventriculomegaly is an abnormal increase in the size of the lateral cerebral ventricles. Presented here is a case of fetal ventriculomegaly in which there was spontaneous intrauterine improvement in its severity.


[Gene technology and biological safety].
A "European Biosafety Workshop on the Uncontained Use of Modified Organisms in the Environment" was held in Berlin on 27-30 November 1988. The author's concluding remarks are given here in a free German translation. The article briefly summarizes the overall conditions for a general evaluation of potential benefits and risks that may be associated with the use of genetically modified organisms.


Analysis of long non-coding RNA and mRNA profiles in epicardial adipose tissue of patients with atrial fibrillation.
Accumulating studies have suggested that epicardial adipose tissue (EAT) play an important role in the pathogenesis of atrial fibrillation (AF), but few have characterized the underlying mechanism between their interactions. Recent evidence suggested that bioactive molecules secreted from EAT, including exosomes carrying long non-coding RNAs (lncRNAs), may modulate atrial remodeling. LncRNAs are associated with cardiovascular disorders, including AF, but their roles in EAT remain elusive. The aim of the present study was to investigate the expression profile of lncRNAs in EAT with AF. Differentially expressed lncRNAs and nearby mRNAs interaction networks were constructed. Epicardial adipose samples were collected from patients with persistent non-valvular AF (n = 6) and sinus rhythm (SR) (n = 6), and the expression of lncRNAs and mRNAs were profiled using RNA-sequencing method. A total of 46,577 transcripts, including 35,552 protein-coding pattern, corresponding to 15,404 genes in EAT, among which, 655 mRNAs (265 upregulated and 390 downregulated) and 57 lncRNAs (17 upregulated and 40 downregulated) were differentially expressed between AF and SR (P < 0.05; fold change>1.5). GO enrichment, KEGG pathway analysis and interaction network construction showed that these differentially expressed lncRNAs were enriched in functional categories, including metabolism and stress response, which might contribute to the pathogenesis of AF. Our study demonstrated a differentially expressed lncRNA profile in EAT with AF, and provide a novel insight into the interactions between EAT and AF.


New perspectives on schizophrenia in later life: implications for treatment, policy, and research.
Worldwide, in the past few decades, the demographics of older people (ie, people 55 years and over) with schizophrenia have changed completely with respect to absolute numbers of people affected, the proportion of all people with the disorder, life expectancy, and residential status. The ageing schizophrenia population has created vast health-care needs and their medical comorbidity contributes to higher mortality than in the general population. Proposals to classify schizophrenia into early-onset, late-onset, and very-late-onset subtypes now should be tempered by the recognition that comorbid medical and neurological disorders can contribute to psychotic symptoms in later life. The concept of outcome has become more nuanced with an appreciation that various outcomes can occur, largely independent of each other, that need different treatment approaches. Data show that schizophrenia in later life is not a stable end-state but one of fluctuation in symptoms and level of functioning, and show that pathways to improvement and recovery exist. Several novel non-pharmacological treatment strategies have been devised that can augment the clinical options used to address the specific needs of older adults with schizophrenia.


BrainPath-Mediated Resection of a Ruptured Subcortical Arteriovenous Malformation.
Although tubular retractor systems have gained popularity for other indications, there have been few reports of their use for arteriovenous malformation (AVM) surgery. A patient was diagnosed with a ruptured 1.2-cm subcortical AVM after presenting with intracerebral hemorrhage in the right frontal lobe and anterior basal ganglia. The characteristics of this AVM made it amenable to resection using a tubular retractor. To demonstrate the feasibility and safety of AVM resection using a tubular retractor system. Resection of the ruptured 1.2-cm subcortical AVM was performed utilizing the BrainPathTM (NICO corp, Indianapolis, Indiana) tubular retractor system. The BrainPathTM approach provided sufficient visualization and surgical freedom to permit successful AVM resection and hematoma evacuation. Postoperative imaging demonstrated near total hematoma removal and angiographic obliteration of the AVM. There were no complications, and the patient made an excellent recovery. Tubular retractors warrant consideration for accessing small, deep, ruptured AVMs. The nuances of such systems and their role in AVM surgery are discussed.


Physical Therapists' Views and Experiences of Pregnancy-Related Low Back Pain and the Role of Acupuncture: Qualitative Exploration.
Low back pain is often accepted as a "normal" part of pregnancy. Despite research suggesting that quality of life for women who are pregnant is adversely affected, most are advised to self-manage. Although the use of acupuncture for the management of persistent nonspecific low back pain has been recommended in recent UK national guidelines, its use in the management of pregnancy-related low back pain remains limited. This study aimed to explore the perceptions and experiences of physical therapists involved in treating women who are pregnant and have low back pain with the objective of informing the pretrial training program for a pilot randomized trial (Evaluating Acupuncture and Standard care for pregnant womEn with Back pain [EASE Back]). A qualitative phenomenological method with purposive sampling was used in the study. Three focus groups and 3 individual semistructured interviews were undertaken, and an iterative exploratory thematic analysis was performed. To ensure transparency of the research process and the decisions made, an audit trail was created. Twenty-one physical therapists participated, and emergent issues included: a lack of experience in treating pregnancy-related complaints, mixed messages from previous acupuncture education, a mistrust of the current evidence for acupuncture safety and effectiveness, and personal and professional fear of causing harm. The findings suggest that UK physical therapists are reluctant to use acupuncture in the management of pregnancy-related low back pain. The explanations for these findings include perceived lack of knowledge and confidence, as well as a pervasive professional culture of caution, particularly fears of inducing early labor and of litigation. These findings have been key to informing the content of the training program for physical therapists delivering acupuncture within the pilot EASE Back trial.


Recall bias in disease status associated with perceived exposure to hazardous substances.
Recall bias was assessed in a study of cancers reported by persons living in a community with a hazardous waste treatment facility (A) and a control community (B). The self-reported cancers were verified against medical records and pathology reports. Of the 56 cancer cases reported, 43 were in community A and 13 were in community B. The difference in incorrect reporting of neoplasms between community A and community B was 12% for neoplasms and 23% for malignancies. Before verification, there was a borderline significant association (P = 0.049) between living in community A and all self-reported cancers [odds ratio (OR) 1.88, 95% confidence interval 0.99-3.57]. The verified data showed that ORs decreased with the increasing precision of diagnosis. The effect of misclassification on the OR was an inflation by 15% for neoplasms and by 31% for malignancies. The results demonstrate the importance of verifying reported cases of disease, even a disease as well defined as cancer.


Expression and clinical significance of the NEK7-NLRP3 inflammasome signaling pathway in patients with systemic lupus erythematosus.
The aim of the study was to investigate the expression of the NEK7-NLRP3 inflammasome signaling pathway in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as its clinical significance. A total of 38 SLE patients and 33 healthy volunteers were recruited. Real time PCR and western blotting were performed to determine mRNA and protein levels of NEK7, NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1), and downstream cytokines (IL-1b and IL-18) in PBMCs from the two groups. ELISA was used to detect serum levels of IL-1b and IL-18. The same methods were used to detect changes in the above indices in the 25 SLE patients after treatment. Correlations between clinical and laboratory parameters were also analyzed. Compared to those in healthy controls, levels of NEK7, NLPR3, and ASC were lower in SLE patients; however, Caspase-1, IL-1b, and IL-18 were expressed at higher levels. mRNA levels of NEK7, NLRP3, and ASC were inversely correlated with disease activity, whereas a positive correlation was observed with IL-1b and IL-18. After treatment, mRNA levels of NEK7 and NLRP3 increased, whereas Caspase-1, IL-1b, and IL-18 decreased significantly. Compared to those in SLE patients without renal damage, patients with lupus nephritis (LN) exhibited lower mRNA levels of NEK7, NLRP3, and ASC but higher levels of Caspase-1, IL-1b, and IL-18. Results indicate that the expression of the NEK7-NLRP3 complex might play a protective role in the pathogenesis of SLE and is inversely correlated with disease activity. A positive effect of NEK7 on NLRP3 was observed, and the low expression of NLRP3 in SLE patients might be related to the low expression of NEK7. Overexpression of Caspase-1 in SLE patients mediates the maturation and release of IL-1b and IL-18, and contributes to the pathogenesis of SLE and LN.


Effects of cysteine on the pharmacokinetics of intravenous clarithromycin in rats with protein-calorie malnutrition.
Effects of cysteine on the pharmacokinetics of clarithromycin were investigated after intravenous administration of the drug at a dose of 20 mg/kg to control rats (4-week fed on 23% casein diet) and rats with PCM (protein-calorie malnutrition, 4-week fed on 5% casein diet) and PCMC (PCM treated with 250 mg/kg for oral cysteine twice daily during the fourth week). Clarithromycin has been reported to be metabolized via hepatic microsomal cytochrome P450 (CYP) 3A4 to 14-hydroxyclarithromycin (primary metabolite of clarithromycin) in human subjects. It has also been reported that in rats with PCM, CYP3A23 level decreased to 40-50% of control level, but decreased CYP3A23 level in rats with PCM completely returned to control level by oral cysteine supplementation (rats with PCMC). Human CYP3A4 and rat CYP3A23 proteins have 73% homology. In rats with PCM, the area under the plasma concentration-time curve from time zero to time infinity, AUC (567, 853 and 558 microg min/ml for control rats and rats with PCM and PCMC, respectively) and percentage of clarithromycin remaining after incubation with liver homogenate (69.6, 83.9 and 71.7%) were significantly greater than those in control rats and rats with PCMC. Moreover, in rats with PCM, the total body clearance, CL (35.3, 23.4 and 35.8 ml/min/kg), nonrenal clearance, CL(NR) (21.3, 15.2 and 24.1 ml/min/kg) and maximum velocity for the disappearance of clarithromycin after incubation with hepatic microsomal fraction, V(max) (351, 211 and 372 pmol/min/mg protein) were significantly slower than those in control rats and rats with PCMC. However, above mentioned each parameter was not significantly different between control rats and rats with PCMC. The above data suggested that metabolism of clarithromycin decreased significantly in rats with PCM as compared to control due to significantly decreased level of CYP3A23 in the rats. By cysteine supplementation (rats with PCMC), some pharmacokinetic parameters of clarithromycin (AUC, CL, CL(NR) and V(max)) were restored fully to control levels because CYP3A23 level was completely returned to control level in rats with PCMC.


Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence.
Copper (Cu) is an essential metal that is toxic at high concentrations. Thus, pathogens often rely on host Cu for growth, but host cells can hyperaccumulate Cu to exert antimicrobial effects. The human fungal pathogen Cryptococcus neoformans encodes many Cu-responsive genes, but their role in infection is unclear. We determined that pulmonary C. neoformans infection results in Cu-specific induction of genes encoding the Cu-detoxifying metallothionein (Cmt) proteins. Mutant strains lacking CMTs or expressing Cmt variants defective in Cu-coordination exhibit severely attenuated virulence and reduced pulmonary colonization. Consistent with the upregulation of Cmt proteins, C. neoformans pulmonary infection results in increased serum Cu concentrations and increases and decreases alveolar macrophage expression of the Cu importer (Ctr1) and ATP7A, a transporter implicated in phagosomal Cu compartmentalization, respectively. These studies indicate that the host mobilizes Cu as an innate antifungal defense but C. neoformans senses and neutralizes toxic Cu to promote infection.


Use of a pedicled omental flap in the treatment of chest wall tuberculosis.
The most effective way to treat the chest wall tuberculosis is to fill the residual space with a muscle flap after complete resection of the lesion. However, in some situations a muscle flap cannot be used. The greater omentum has been widely used for reconstruction and the treatment of infections. We describe our technique of using a pedicled omental transposition flap in the management of chest wall tuberculosis for closing the dead space created by excision of the lesion.


Attractiveness biases are the tip of the iceberg in biological markets.
Physical attractiveness affects how one gets treated, but it is just a single component of one's overall "market value." One's treatment depends on other markers of market value, including social status, competence, warmth, and any other cues of one's ability or willingness to confer benefits on partners. To completely understand biased treatment, we must also incorporate these other factors.


Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells.
Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of 15.6 ± 1.49 and 41.1 ± 2.19 μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200 μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.


HUVECs from newborns with a strong family history of myocardial infarction overexpress adhesion molecules and react abnormally to stimulating agents.
Atherosclerosis is a complex disease involved in major fatal events such as myocardial infarction and stroke. It is the result of interactions between metabolic, dietetic and environmental risk factors acting on a genetic background that could result in endothelial susceptibility. Our aim was to determine the patterns of expression of adhesion molecules and whether phosphatidylserine is translocated to the cell surface of human umbilical vein endothelial cells (HUVECs) isolated from healthy newborns born to parents with a strong family history of myocardial infarction under TNF-alpha or oxLDL stimulated conditions. Compared to control HUVECs, experimental cords showed: (a) a four-fold increase in VCAM-1 expression under basal conditions, which showed no change after stimulation with the pro-atherogenic factors; (b) a two-fold increase in basal P-selectin expression that reached a 10-fold increase with any of the pro-atherogenic factors; (c) a basal ICAM-1 expression similar to P-selectin that was not modified by the pro-atherogenic molecules; (d) a similar PECAM-1 expression. Unexpectedly, phospathidylserine expression in experimental cord HUVECs was significantly increased (211 817 versus 3354 TFU) but was not associated to apoptotic death as the percentage of dead cells induced by TNF-alpha treatment was very low (0.55 versus 9.87% in control HUVECs). The latter result was corroborated by TUNEL staining. T cell adherence to HUVECs was highly up-regulated in the genetically predisposed samples. The analysis of nonpooled HUVECs, from newborns to family predisposed myocardial-infarction individuals, might represent a useful strategy to identify phenotypical and functional alterations, and hopefully, to take early preventive actions.


Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo.
Dendritic cells (DCs) are key regulators of immune responses that activate naive antigen-specific T lymphocytes. In draining lymph nodes, antigen-bearing DCs are reported to be rare and short-lived. How such small numbers of short-lived DCs can activate rare antigen-specific T cells is unclear. Here we show that after immunization of mouse skins by gene gun, the number of antigen-bearing DCs that migrate to draining lymph node is 100-fold higher than previously estimated and that they persist for approximately 2 weeks. The substantial frequency and longevity of DCs in situ ensures ample antigen presentation and stimulation for the rare antigen-specific T cells in draining lymph nodes.


Drug utilization in a general intensive care unit.
Drug utilization in 200 general ICU patients was retrospectively studied. One hundred and two different drugs were prescribed with a mean of 7.0 +/- 4.6 drugs/patient. The potential for polypharmacy and drug interactions is discussed, as is the cost of such therapy.


In utero exposure to tobacco and alcohol modifies neurobehavioral development in mice offspring: consideration a role of oxidative stress.
To determine whether in utero tobacco and alcohol exposure induces long-term neurobehavioral alterations and whether oxidative stress/damage is a possible causal factor. Gravid mice were subjected to tobacco smoking and alcohol consumption. Their offspring were subsequently evaluated in developmental and behavioral tests. Antioxidative enzymes and erythrocyte membrane fluidity of adult offspring were measured. The intrauterine tobacco and alcohol exposure has resulted in significant reduced postnatal body and organ weights accompanied by reduced gestational body weight gain in their mothers. Such exposure also induced remarkable developmental delay in neonatal reflexes and notable behavioral deficit in adulthood, namely reduced motive coordination and locomotor activity as well as impaired learning and memory abilities. Furthermore, the formation of malondialdehyde (MDA) increased significantly whereas the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (Cat) and glutathione S-transferases (GST) decreased in the cerebral cortex and liver of prenatal intoxicated offspring. The embryonic intoxication also markedly reduced erythrocyte membrane fluidity in offspring. Our study shows the long-term neurotoxicity associated with prenatal tobacco and alcohol exposure, and suggests that the deleterious outcome may be in relation to increased free radicals formation and oxidative stress.


The impact of OAB on physical activity in the United States: results from OAB-POLL.
To provide data on physical activity among those with and without overactive bladder (OAB) in a large, ethnically diverse U.S. sample. A cross-sectional survey was conducted via the Internet among 10,000 men and women aged 18-70 (2000 African Americans, 2000 Hispanics, and 6000 whites) using the lower urinary tract symptoms (LUTS) tool and questions from the 2007-2008 National Health and Nutrition Examination Survey (NHANES). OAB cases and those with no/minimal symptoms (NMS) were compared on federal guidelines of indices of physical activity: 2008 guidelines and 2010 Healthy People. Descriptive statistics were used to evaluate differences between OAB and NMS. Logistic regressions examined the impact of OAB on physical activity. Response rate, 57%; 818 men and 1505 women with OAB, and 1857 men and 1615 women with NMS. Respondents with other LUTS were excluded from this analysis (2302 men and 1904 women). Those with OAB were significantly less likely to report moderate and vigorous physical activities in their leisure time and to satisfy recommended physical activity levels compared to those with NMS. Symptoms of OAB (men and women: urgency and urinary frequency; women: urinary urge incontinence) were associated with limitations in physical activity in the logistic regressions. This study benchmarks physical activity levels among people with OAB. Men and women with OAB were significantly less likely to achieve recommended physical activity levels than people with NMS. More research is needed to further evaluate how OAB affects physical activity and health status and to determine causal relationships.


A novel technique to center the donor punch for descemet stripping endothelial keratoplasty.
This report describes a method to improve the accuracy of centration of the donor trephination for Descemet stripping endothelial keratoplasty. Using trypan blue, the donor corneal cap is outlined. The donor punch is centered on the actual cap rim rather than on a centration mark made either by the surgeon or by the eye bank preparing the precut tissue. Using the described technique, eccentric donor trephination was reduced from 7.7% to 2.4%. We have described a method to improve the centration of donor trephination and reduce the incidence of eccentric donor punching.


Recognition of iron ions by carbazole-desferrioxamine fluorescent sensor and its application in total iron detection in airbone particulate matter.
This work reports on an efficient microwave irradiation synthesis of a new fluorescent chemosensor based on desferrioxamine B (DFO-B) and carbazole moiety. Furthermore, this novel chemosensor was employed for a comparative study of real environmental samples of airbone particulate matter collected from Dunkirk (Northern of France). Among selected relevant metal cations present in its airbone particulate matter, such as Na(+), K(+), Mg(2+), Ca(2+), Al(3+), Cr(3+), Mn(2+) and Zn(2+), this molecular device proved to be outstandingly sensitive toward Fe(3+) with a limit of detection of 1.49 ppb (2.1×10(-8) M) in methanol allowing the estimation of total iron in atmospheric particles.


Role of cholecystostomy in the management of critically ill patients suffering from acute cholecystitis.
Between the years 1976 and 1985, 60 patients underwent cholecystostomy for acute cholecystitis in the surgical department of the Rokach hospital in Tel Aviv. The patients' average age was 73 years; 78 per cent were 70 years or older at the time of operation. The decision to perform cholecystostomy was taken before the operation which was performed as an emergency procedure for patients considered to be at high risk for cholecystectomy. Forty-six patients (77 per cent) had severe concomitant diseases, and 42 per cent of them had two or more associated diseases simultaneously. The cardiac risk index was high in most patients (90 per cent). Fifty-two patients recovered promptly after surgery. Five patients (8 per cent) developed significant postoperative complications. Three other patients (5 per cent) died of cardiovascular complications. Forty-two patients (70 per cent) underwent an elective cholecystectomy 6-8 weeks later with no further morbidity or mortality. Eleven patients who were at high risk had no further surgery. No residual stones were found in these patients and no relapse of the disease was recorded in the long term follow-up. Four patients were lost to follow-up. We conclude that cholecystostomy may still be used as an initial life saving procedure for critically ill patients with acute cholecystitis, and serves as a definitive procedure for patients considered to be at very high operative risk and who have no residual stones.


Clinical comparison of ICD detection algorithms that include rapid-VT zones.
The safe use of antitachycardia pacing (ATP) to terminate rapid ventricular tachycardias (VTs) (cycle length 240-320 ms) is predicated on the ability of implantable cardioverter defibrillators (ICDs) to distinguish rapid VT from ventricular fibrillation (VF). We set out to compare the time to device charging following the induction of VF of various ICD multizone detection algorithms for rapid VT/VF discrimination. Data on the time to device charging following the induction of VF at the time to device implantation were collected on 62 consecutive patients in a nonrandomized prospective cohort fashion. Multizone programming for the Boston Scientific, Medtronic, and St. Jude Medical devices was based on prior clinically validated data. Sixty-two subjects were studied (Boston Scientific = 16, Medtronic = 27, St. Jude Medical = 19) and 124 tests for VF detection were performed (Boston Scientific = 32, Medtronic = 54, St. Jude Medical = 38). Mean time to charging was significantly prolonged in the Boston Scientific group as was the percentage of tests where charge initiation occurred >5 seconds from VF-induction: 4.24, 3.99, and 3.00 seconds and 19%, 4%, and 0% for the Boston Scientific, Medtronic, and St. Jude Medical groups, respectively, P < 0.05. ATP was the first therapy administered in 9.4% of tests in the Boston Scientific group. The Boston Scientific multizone VT/VF discrimination algorithm results in a prolonged time to VF detection, and consequently, prolonged time to appropriate initiation of device charging. Further studies are needed to determine whether prolonged detection times lead to clinically significant events.


Review of current and "omics" methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms.
The increasing use of traditional herbal medicines around the world requires more scientific evidence for their putative harmlessness. To this end, a plethora of methods exist, more or less satisfying. In this post-genome era, recent reviews are however scarce, not only on the use of new "omics" methods (transcriptomics, proteomics, metabonomics) for genotoxicity, teratogenicity, and nephrotoxicity assessment, but also on conventional ones. The present work aims (i) to review conventional methods used to assess genotoxicity, teratogenicity and nephrotoxicity of medicinal plants and mushrooms; (ii) to report recent progress in the use of "omics" technologies in this field; (iii) to underline advantages and limitations of promising methods; and lastly (iv) to suggest ways whereby the genotoxicity, teratogenicity, and nephrotoxicity assessment of traditional herbal medicines could be more predictive. Literature and safety reports show that structural alerts, in silico and classical in vitro and in vivo predictive methods are often used. The current trend to develop "omics" technologies to assess genotoxicity, teratogenicity and nephrotoxicity is promising but most often relies on methods that are still not standardized and validated. Hence, it is critical that toxicologists in industry, regulatory agencies and academic institutions develop a consensus, based on rigorous methods, about the reliability and interpretation of endpoints. It will also be important to regulate the integration of conventional methods for toxicity assessments with new "omics" technologies.


Prediction of the in vivo OATP1B1-mediated drug-drug interaction potential of an investigational drug against a range of statins.
To support drug development, the drug-drug interaction potential (DDI) of an investigational drug (AZX) was assessed against the probe estradiol 17β-glucuronide as well as against simvastatin acid, atorvastatin, pravastatin, pitavastatin, fluvastatin, rosuvastatin and estrone 3-sulfate. The inhibitory potentials of the OATP1B1 inhibitors rifamycin SV and gemfibrozil were assessed in parallel. Monolayer cellular uptake assays were used to determine inhibition of human OATP1B1. Apparent K(m) values for the OATP1B1-mediated transport of [(3)H] substrates were determined prior to their use as probes in inhibition studies, and ranged from 0.6 to 29 μM for statins. The K(m) of lipophilic simvastatin acid could not be determined due to its high passive permeability that masked OATP1B1 transport, and therefore this statin could not be used as a probe. Estrone 3-sulfate exhibited biphasic kinetics, whereas estradiol 17β-glucuronide demonstrated simple Michaelis-Menton kinetics. AZX moderately inhibited OATP1B1-mediated transport of all statins (IC(50)=4.6-9.7 μM), except fluvastatin, of estradiol 17β-glucuronide (IC(50)=5.3 μM), and weakly inhibited estrone 3-sulfate (IC(50)=79 μM). Rifamycin SV strongly, and gemfibrozil weakly, inhibited the OATP1B1-mediated transport of substrates. Estradiol 17β-glucuronide was identified as a good surrogate probe for statins when assessing OATP1B1 inhibitory potential using this test system. Inhibition data was used to predict the likelihood of a clinical DDI, using current draft US FDA guidance and recommendations of the International Transporter Consortium. Predictions for AZX indicated the potential for an OATP1B1-mediated DDI in vivo and that a clinical interaction study is warranted to confirm whether AZX is an OATP1B1 inhibitor in the clinic.


Impact of Universal Antiretroviral Treatment Eligibility on Rapid Treatment Initiation Among Young Adolescents with Human Immunodeficiency Virus in Sub-Saharan Africa.
Young adolescents with perinatally acquired human immunodeficiency virus (HIV) are at risk for poor care outcomes. We examined whether universal antiretroviral treatment (ART) eligibility policies (Treat All) improved rapid ART initiation after care enrollment among 10-14-year-olds in 7 sub-Saharan African countries. Regression discontinuity analysis and data for 6912 patients aged 10-14-years were used to estimate changes in rapid ART initiation (within 30 days of care enrollment) after adoption of Treat All policies in 2 groups of countries: Uganda and Zambia (policy adopted in 2013) and Burundi, Democratic Republic of the Congo, Kenya, Malawi, and Rwanda (policy adopted in 2016). There were immediate increases in rapid ART initiation among young adolescents after national adoption of Treat All. Increases were greater in countries adopting the policy in 2016 than in those adopting it in 2013: 23.4 percentage points (pp) (95% confidence interval, 13.9-32.8) versus 11.2pp (2.5-19.9). However, the rate of increase in rapid ART initiation among 10-14-year-olds rose appreciably in countries with earlier treatment expansions, from 1.5pp per year before Treat All to 7.7pp per year afterward. Universal ART eligibility has increased rapid treatment initiation among young adolescents enrolling in HIV care. Further research should assess their retention in care and viral suppression under Treat All.


Interposition of the right colic angle between the liver and thoracic wall: an unusual cause of massive rectal bleeding following percutaneous biopsy in a liver transplant recipient.
A 37-year-old male liver transplant recipient developed hemorrhagic shock from massive rectal bleeding a few hours after a protocol liver biopsy. Conservative treatment was not possible and the patient underwent a radiological investigation of the celiac and mesenteric arterial trunks, which showed active bleeding from a branch of the middle colic artery. Embolization with Tabotamp (Ethicon, Neuchatel, CH Switzerland) particles led to successful hemostasis. We thus discuss the possible mechanisms of injury. To our knowledge, no other cases of major rectal bleeding following percutaneous liver biopsy have been reported in the literature. We emphasize the need for Doppler ultrasound assistance, in terms of either preoperative examination with or without marking or guidance. The latter is the safest and most reliable technique, given the low risk of puncture of other organs and the low probability of obtaining an inadequate sample.


Intrinsic bacterial burden associated with intensive care unit hospital beds: effects of disinfection on population recovery and mitigation of potential infection risk.
Commonly touched items are likely reservoirs from which patients, health care workers, and visitors may encounter and transfer microbes. A quantitative assessment was conducted of the risk represented by the intrinsic bacterial burden associated with bed rails in a medical intensive care unit (MICU), and how disinfection might mitigate this risk. Bacteria present on the rails from 36 patient beds in the MICU were sampled immediately before cleaning and at 0.5, 2.5, 4.5, and 6.5 hours after cleaning. Beds were sanitized with either a bottled disinfectant (BD; CaviCide) or an automated bulk-diluted disinfectant (ABDD; Virex II 256). The majority of bacteria recovered from the bed rails in the MICU were staphylococci, but not methicillin-resistant Staphylococcus aureus. Vancomycin-resistant enterococci were recovered from 3 beds. Bottled disinfectant reduced the average bacterial burden on the rails by 99%. However, the burden rebounded to 30% of that found before disinfection by 6.5 hours after disinfection. ABDD reduced the burden by an average of 45%, but levels rebounded within 2.5 hours. The effectiveness of both disinfectants was reflected in median reductions to burden of 98% for BD and 95% for ABDD. Cleaning with hospital-approved disinfectants reduced the intrinsic bacterial burden on bed rail surfaces by up to 99%, although the population, principally staphylococci, rebounded quickly to predisinfection levels.


Stress reactions to cognitively demanding tasks and open-plan office noise.
To investigate the effects of cognitively demanding work tasks and office noise on heart rate variability (HRV), cardiovascular responses and electromyography (EMG) activity in the trapezius muscles. Ten female volunteers were exposed to simulated open-plan office noise for 35 min (Leq 65 dBA), while engaged in cognitively demanding tasks. Task performance, self-rated stress and energy, affective state, perceived exertion in the shoulders and in the head, EMG in the left and right trapezius muscle, blood pressure, heart period length, HRV, and salivary cortisol were measured. Cognitively demanding work tasks were associated with changes in HRV, systolic blood pressure and EMG that reflects increased sympathetic activity in the autonomic nervous system. No effect of noise was observed, except for a higher rating of perceived exertion in the head and, contrary to expectations, a 4% lower diastolic blood pressure in the noise conditions. Psychophysiological measures reflected the mental load imposed by cognitive work tasks. Short-term exposure to office noise resulted in increased ratings of perceived exertion in the head, but not in physiological stress reactions.


A new species of Lygistorrhina Skuse (Diptera: Sciaroidea: Lygistorrhinidae) from South Africa.
A new species of Lygistorrhina (Diptera, Sciaroidea, Lygistorrhinidae) from South Africa is described and a key for Afrotropical species of the genus is provided.


[Observation on biological characteristics of Hedyotis diffusa].
The present work enunciats the phenophase and plant organ development of Hedyotis diffusa Willd, at Nanjing region. These results can give a reference for the plant growing practice.


Discovery of Potent Inhibitors of Cyclin-Dependent Kinases 7 and 9: Design, Synthesis, Structure-Activity Relationship Analysis and Biological Evaluation.
Cyclin-dependent kinases (CDKs) 7 and 9 are deregulated in various types of human cancer and are thus viewed as therapeutic targets. Accordingly, small-molecule inhibitors of both CDKs are highly sought-after. Capitalising on our previous discovery of CDKI-73, a potent CDK9 inhibitor, medicinal chemistry optimisation was pursued. A number of N-pyridinylpyrimidin-2-amines were rationally designed, chemically synthesised and biologically assessed. Among them, N-(6-(4-cyclopentylpiperazin-1-yl)pyridin-3-yl)-4-(imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-amine was found to be one of the most potent inhibitors of CDKs 7 and 9 as well as the most effective anti-proliferative agent towards multiple human cancer cell lines. The cellular mode of action of this compound was investigated in MV4-11 acute myeloid leukaemia cells, revealing that the compound dampened the kinase activity of cellular CDKs 7 and 9, arrested the cell cycle at sub-G1 phase and induced apoptosis.


The aniracetam metabolite 2-pyrrolidinone induces a long-term enhancement in AMPA receptor responses via a CaMKII pathway.
The present study was conducted to assess the effect of aniracetam and its metabolites, such as 2-pyrrolidinone, p-anisic acid, and anisamide butyrate, on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, heteromerically formed of GluR1,2 (GluR1 and GluR2), GluR1,3 (GluR1 and GluR3), and GluR1,2,3 (GluR1, GluR2, and GluR3), expressed in Xenopus oocytes. 2-Pyrrolidinone potentiated kainate-evoked currents through GluR1,2,3 channels in a bell-shaped dose-dependent manner at concentrations ranged from 1 nM to 300 microM, with a maximal effect at 100 microM. The potentiation was long-lasting, reaching approximately 180% of basal levels 60 min after 5-min treatment with 2-pyrrolidinone at 100 microM. 2-Pyrrolidinone (100 microM) potentiated GluR1,3 channel currents as observed in GluR1,2,3, but instead it depressed GluR1,2 currents. Aniracetam and p-anisic acid potentiated GluR1,2,3 channel currents, but to a lesser extent, each about 130 and 103% of basal levels 60 min after treatment at 100 microM. In contrast, anisamide butyrate had no potentiating effect on the currents. Potentiation of GluR1,2,3 channel currents obtained with 2-pyrrolidinone was inhibited by KN-93, a selective inhibitor of calcium/calmodulin-dependent protein kinase (CaMKII), while it was not affected by GF109203X, a selective inhibitor of protein kinase C or H-89, a selective inhibitor of cAMP-dependent protein kinase. The results of the present study suggest that 2-pyrrolidinone persistently enhances activity of the Ca2+-permeable AMPA receptors, GluR1,3 and GluR1,2,3, by interacting with CaMKII.


Unravelling the genetic causality of immunoglobulin G N-glycans in ischemic stroke.
Evidence suggests that immunoglobulin G (IgG) N-glycosylation is associated with ischemic stroke (IS). However, the causality of IgG N-glycosylation for IS remains unknown. Two-sample Mendelian randomization (MR) analyses were performed to investigate the potential causal effects of genetically determined IgG N-glycans on IS using publicly available summarized genetic data from East Asian and European populations. Genetic instruments were used as proxies for IgG N-glycan traits. IgG N-glycans were analysed using ultra-performance liquid chromatography. Four complementary MR methods were performed, including the inverse variance weighted method (IVW), MR‒Egger, weighted median and penalized weighted median. Furthermore, to further test the robustness of the results, MR based on Bayesian model averaging (MR-BMA) was then applied to select and prioritize IgG N-glycan traits as risk factors for IS. After correcting for multiple testing, in two-sample MR analyses, genetically predicted IgG N-glycans were unrelated to IS in both East Asian and European populations, and the results remained consistent and robust in the sensitivity analysis. Moreover, MR-BMA also showed consistent results in both East Asian and European populations. Contrary to observational studies, the study did not provide enough genetic evidence to support the causal associations of genetically predicted IgG N-glycan traits and IS, suggesting that N-glycosylation of IgG might not directly involve in the pathogenesis of IS.