Central glucocorticoid receptors modulate the expression of spinal cannabinoid receptors induced by chronic morphine exposure.
Central cannabinoid receptors (CBRs) have been implicated in the opioid analgesic effects. However, it remains unclear as to whether the expression of central CBRs would be altered after repeated morphine exposure. Here, we show that chronic intrathecal treatment with morphine (10 microg, twice daily for 6 days) induced a time-dependent upregulation of both CB-1 and CB-2 receptors within the spinal cord dorsal horn. This morphine-induced CB-1 and CB-2 upregulation was dose-dependently attenuated by the intrathecal co-administration of morphine with the glucocorticoid receptor (GR) antagonist RU38486 (0.25, 0.5, or 2 microg). The intrathecal RU38486 treatment regimen also attenuated the development of morphine tolerance. These results indicate that the expression of spinal CBRs was altered following repeated morphine exposure and regulated by the activation of central GRs.


Complications of thoracic spine surgery - Their avoidance and management.
As the surgical techniques have been significantly developed, thoracic spine surgery is currently increasingly indicated for a variety of pathologies such as degenerative spondylosis, ligament ossification, spinal deformity, infectious diseases, trauma and tumors. Thoracic spine has the distinctive anatomy with the rib attachment and the proximity to great vessels and lungs, and spinal cord has particular vulnerability due to its unique circulation system. Thus, both anterior and posterior approach surgeries have their own risks unique to this spinal segment. To be capable of challenging the spinal disorders in thoracic spine, surgeons must be aware of possible complications and their avoidance methods as well as management strategy. In the present narrative review paper, the complications in thoracic spine surgery are categorized into approach-related complications, neurological complications, wound-related complications, mechanical and instrument-related complications, as well as medical complications along with pre-, intra- and post-operative considerations. Their pathologies, possible sequelae, incidence, risk factors, prevention and management are discussed. As for some of the complications that are also commonly seen in cervical or lumbar spine, focus is placed on their importance in thoracic spine surgery. To prevent these adverse events associated with thoracic spine surgery, surgeons should be familiar with detailed knowledge of thoracic anatomy related to its approach as well as physiological characteristics.


Clinical experience with the Lillehei-Kaster valve prosthesis.
The Lillehei-Kaster valve was used in 215 patients over a 7-year period. The aortic valve was replaced in 81 of them. Hospital mortality was 21% (17 patients). Ten patients were lost to follow-up and long-term mortality was 5% (3 patients). The incidence of thromboembolism was 2.6 per 100 patient-years, and actuarial survival was 96% at 5 and 87% at 7 years. Mitral valve replacement was performed in 108 patients. Hospital mortality was 20% (22 patients), 24 patients were lost to follow-up, and long-term mortality was 13% (11 patients). The combined incidence of thromboembolism was 5.0 per 100 patient-years, and actuarial survival was 81% at 5 years and 75% at 7 years. In both groups, the majority of patients improved clinically. Fifteen patients had double-valve replacement, and 11 had coronary revascularization in addition to valve replacement.


Enantioselective SN 2 Alkylation of Homoenolates by N-Heterocyclic Carbene Catalysis.
The functionalization of the β-carbon of enals with electrophiles is a signature umpolung reactivity of N-heterocyclic carbene (NHC) derived homoenolates. However, only a limited number of electrophiles are shown to be compatible, with most of them being π-electrophiles. In this study, the successful enantioselective β-alkylation of homoenolates is reported using Csp3 electrophiles through an SN 2 strategy. The protocol shows a broad scope regarding alkyl electrophiles, delivering good yields, and excellent enantioselectivities (up to 99% ee). It enables the installation of drug-like structural motifs in either enals or alkylating agents, demonstrating its potential as a valuable tool for late-stage modification. Furthermore, a concise synthetic route is presented to chiral pyrroloindoline-type skeletons. Preliminary mechanistic studies support a direct SN 2 mechanism.


Molar absorptivity (ε) and spectral characteristics of cyanidin-based anthocyanins from red cabbage.
Red cabbage extract contains mono and di-acylated cyanidin (Cy) anthocyanins and is often used as food colorants. Our objectives were to determine the molar absorptivity (ε) of different red cabbage Cy-derivatives and to evaluate their spectral behaviors in acidified methanol (MeOH) and buffers pH 1-9. Major red cabbage anthocyanins were isolated using a semi-preparatory HPLC, dried and weighed. Pigments were dissolved in MeOH and diluted with either MeOH (0.1% HCl) or buffers to obtain final concentrations between 5×10(-5) and 1×10(-3) mol/L. Spectra were recorded and ε calculated using Lambert-Beer's law. The ε in acidified MeOH and buffer pH 1 ranged between ~16,000-30,000 and ~13,000-26,000 L/mol cm, respectively. Most pigments showed higher ε in pH 8 than pH 2, and lowest ε between pH 4 and 6. There were bathochromic shifts (81-105 nm) from pH 1 to 8 and hypsochromic shifts from pH 8 to 9 (2-19 nm). Anthocyanins molecular structures and the media were important variables which greatly influenced their ε and spectral behaviors.


Evaluation of the effect of dipping pattern in hypertensive patients on the left ventricular systolic functions by two-dimensional strain analysis.
Nondipping blood pressure pattern carry a high risk of cardiovascular and cerebrovascular complications due to a higher cumulative pressure overload. We aimed to define the role of strain analysis for detecting subclinical left ventricular systolic dysfunction in recently diagnosed nondipper and dipper hypertensive patients with normal left ventricular systolic function. Study population consisted of two groups of patients, Group 1: 45 dipper patients and Group 2: 43 nondipper patients. Global and segmental two-dimensional longitudinal strain analysis were measured by speckle tracking method. The analysis of two-dimensional left ventricular global longitudinal strain and strain rates showed that there was a significant difference between groups (-18.1%±3.1% for nondippers vs -20.5%±2.4% for dippers, P<.001 for global longitudinal strain and -1.2±0.2 1/s for nondippers vs -1.31±0.16 1/s for dippers, P<.001 for global longitudinal strain rate). The nighttime systolic, diastolic, and mean blood pressure measurements were significantly higher in the nondipper group. Nocturnal dipping rates were statistically different between the groups (P<.001). Interventricular septum, posterior wall thickness, relative wall thickness, left atrial dimension, left ventricular mass, and mass index were higher in the nondipper group. Multivariate analysis demonstrated left atrium size, nocturnal dipping rate, daytime mean blood pressure, and nighttime systolic, diastolic, and mean blood pressure as independent predictors of global longitudinal strain. In our study, two-dimensional speckle tracking examination showed that the left ventricular systolic function is impaired even in the subclinical period in recently diagnosed nondipper hypertensive patients with deformational analysis.


Clinical trials of synthetic surfactant in the respiratory distress syndrome of premature infants.
This article outlines the controlled clinical trials that have been performed with synthetic surfactant preparations in the management of premature newborn infants. The results have shown impressive reductions of mortality and in the incidence of air-leak complications. Complications appear to be few and mild, although the occurrence of pulmonary hemorrhage is increased in very small infants. The 1- and 2-year follow-up data suggest that there is not an increase in the number of impaired surviving children.


The loss of humanness in close relationships: An interpersonal model of dehumanization.
To lose one's sense of what it means to be human reflects a profound form of loss. Recent research in the study of dehumanization highlights that the loss of humanness can be experienced at the hands of close others. Moreover, acts of dehumanization can take many forms in close relationships. In this paper, we review the emerging literature on the study of dehumanization within interpersonal relationships, placing a specific emphasis on adult romantic relationships. We situate our review of the literature within a newly developed model of interpersonal dehumanization. This model outlines how many destructive relationship behaviors reflect forms of dehumanization, which can result in a vast array of personal and relational losses.


Monitoring phosphoproteomic response to targeted kinase inhibitors using reverse-phase protein microarrays.
Phosphoproteomic networks mediated by protein kinases are the key drivers of proliferative and survival signals underlying human cancers, and as such a number of kinases have been the subject of intensive drug discovery efforts. A key question that must be answered during clinical development is whether a kinase inhibitor is effectively inhibiting its appropriate target kinase and pathway in the tumor. Reverse-phase protein arrays (RPMAs) offer the ability to analyze behavior of entire signaling networks in response to drug treatment and thus have promise as a technology for monitoring cellular response to kinase inhibitors. We have shown that it is possible to use RPMAs to detect phosphorylation changes in key multiple signaling pathway proteins in response to targeted inhibitors of EGFR, MEK, and PI3 kinase.


Discrimination in employment alleged.
In April 2000, former stockbroker DeWolf Shaw filed a $340-million civil suit in the Québec Superior Court against First Marathon Inc.


Distribution of tenascin in healing incision, excision and laser wounds.
The distribution of the extracellular matrix glycoprotein, tenascin, was studied in normal mucosa and during healing of scalpel incised or excised and CO2 laser-wounded rat tongue dorsal mucosa in 51 male Sprague-Dawley rats over a period of 21 days. A polyclonal antibody specific for tenascin was applied in indirect immunofluorescence microscopy. In normal mucosa tenascin was sparsely distributed in a discontinuous manner at the tips of the connective tissue papillae in association with the basement membrane (BM) and in the walls of the capillaries. In all the healing wounds there was a marked increase in the distribution of tenascin, particularly close to the BMs at the wound edges beneath the proliferating and migrating epithelium, and later on during healing in the regenerating connective tissue (CT) area. This expression subsided later on during healing. Laser surgery did not alter the ability of fibroblasts to synthesize tenascin. The transient expression of tenascin in the BMs and CT of the healing wounds suggests that this protein could play an important role in providing ideal conditions for cell movement, and in the deposition and organization of other extracellular matrix (ECM) glycoproteins during tissue repair.


Comparison of effects on systolic and diastolic left ventricular function of nebivolol versus atenolol in patients with uncomplicated essential hypertension.
This was a double-blind, randomized, prospective study comparing the effects of nebivolol and atenolol on systolic diastolic left ventricular function in patients with essential hypertension. A significant difference was seen in stroke volume between these 2 drugs. The blood pressure lowering effect of atenolol was strongly related to cardiac output and heart rate reduction. The blood pressure lowering effect of nebivolol was related to a reduction in peripheral resistance and an increase in stroke volume with preservation of cardiac output. This preservation of cardiac output, together with a reduced peripheral resistance, may be potentially important in treating heart failure.


Optimal planting pattern of cotton is regulated by irrigation amount under mulch drip irrigation.
It is of great importance to explore agronomic management measures for water conservation and cotton yield in arid areas. A four-year field experiment was conducted to evaluate cotton yield and soil water consumption under four row spacing configurations (high/low density with 66+10 cm wide, narrow row spacing, RS66+10H and RS66+10L; high/low density with 76 cm equal row spacing, RS76H and RS76L) and two irrigation amounts (CI:conventional drip irrigation; LI:limited drip irrigation) during the growing seasons in Shihezi, Xinjiang. A quadratic relationship was observed between the maximum LAI (LAImax) and seed yield. Canopy apparent transpiration rate(CAT), daily water consumption intensity (DWCI) and crop evapotranspiration (ETC) were positively and linearly correlated with LAI. The seed yields, lint yields, and ETC under CI were 6.6-18.3%,7.1-20.8% and 22.9-32.6%higher than those observed under LI, respectively. The RS66+10H under CI had the highest seed and lint yields. RS76L had an optimum LAImax range, which ensured a higher canopy apparent photosynthesis and daily dry matter accumulation and reached the same yield level as RS66+10H; however, soil water consumption in RS76L was reduced ETC by 51-60 mm at a depth of 20-60 cm at a radius of 19-38 cm from the cotton row,and water use efficiency increased by 5.6-8.3%compared to RS66+10H under CI. A 5.0<LAImax<5.5 is optimum for cotton production in northern Xinjiang, and RS76L under CI is recommended for high yield and can further reduce water consumption. Under LI, the seed and lint yield of RS66+10H were 3.7-6.0% and 4.6-6.9% higher than those of RS76L, respectively. In addition, high-density planting can exploit the potential of soil water to increase cotton yields under water shortage conditions.


Secondary correction of nasal deformities in cleft lip patients using acellular dermal matrix grafting on the nasal tip with open rhinoplasty.
Secondary nasal deformities in patients with unilateral cleft lip represent surgical challenges. Open rhinoplasty involving repositioning of the lower lateral cartilage has been shown to be a suitable technique for patients with cleft lip and nose deformities. This study aimed to explore a particular method of rhinoplasty and to assess the aesthetic outcomes for secondary unilateral cleft lip and nose deformities following its use. Fifty-seven patients treated for secondary unilateral cleft lip nasal deformities from January 2012 to December 2018 were enrolled in the study. Open rhinoplasty combined with a reverse-U incision and acellular dermal matrix grafting on the nasal tip was performed in all patients by the same surgeon. In our follow-up study we evaluated the results by measuring angles on photographs and scoring the appearance before and after operation. Data were statistically analysed using the t test. Appearances were improved in all patients. Both the alar base-nasal tip-columellar base angle and the nostril axis angles were smaller postoperatively (p < 0.001). According to the outcome scores, most patients (53/57) agreed that there was an obvious improvement in the appearance of their noses following surgery, and overall they were satisfied with the results of the revision procedure. A distinct improvement in nasal appearance can be achieved with this rhinoplasty. Our surgical method is effective and reliable in patients with secondary unilateral cleft lip and nose deformities, and is worth promoting in the clinic.


A diabetes report card for the United States: quality of care in the 1990s.
Improving diabetes care in the United States is a topic of concern. To document the quality of diabetes care during 1988-1995. National population-based cross-sectional surveys. Third U.S. National Health and Nutrition Examination Survey (NHANES III) (1988-1994) and the Behavioral Risk Factors Surveillance System (BRFSS) (1995). Participants in NHANES III (n = 1026) or BRFSS (n = 3059) who were 18 to 75 years of age and reported a physician diagnosis of diabetes. Women with gestational diabetes were excluded. Glycemic control, blood pressure, low-density lipoprotein (LDL) cholesterol level, biannual cholesterol monitoring, and annual foot and dilated eye examination, as defined by the Diabetes Quality Improvement Project. 18.0% of participants (95% CI, 15.7% to 22.3%) had poor glycemic control (hemoglobin A(1c) level > 9.5%), and 65.7% (CI, 62.0% to 69.4%) had blood pressure less than 140/90 mm Hg. Cholesterol was monitored biannually in 85.3% (CI, 83.1% to 88.6%) of participants, but only 42.0% (CI, 34.9% to 49.1%) had LDL cholesterol levels less than 3.4 mmol/L (<130 mg/dL). During the previous year, 63.3% (CI, 59.6% to 67.0%) had a dilated eye examination and 54.8% (CI, 51.3% to 58.3%) had a foot examination. When researchers controlled for age, sex, ethnicity, education, health insurance, insulin use, and duration of diabetes, insured persons were more likely than uninsured persons to have a dilated eye examination (66.5% [CI, 62.6% to 70.4%]) vs. 43.2% [CI, 29.5% to 56.9%]) and were less likely to have a hemoglobin A(1c)level greater than or equal to 9.5%. Persons taking insulin were more likely than those who were not to have annual dilated eye examination (72.2% [CI, 66.3% to 78.1%] vs. 57.6% [CI, 53.7% to 61.5%]) and foot examination (67.3% [CI, 61.4% to 73.2%] vs. 47.1% [CI, 43.2% to 51.0%]) but were also more likely to have poor glycemic control (24.2% [CI, 18.3% to 30.1%] vs. 15.5% [CI, 11.6% to 19.4%]). According to U.S. data collected during 1988-1995, a gap exists between recommended diabetes care and the care patients actually receive. These data offer a benchmark for monitoring changes in diabetes care.


Arsenic speciation and mobilization in CCA-contaminated soils: influence of organic matter content.
A laboratory incubation experiment was conducted to investigate the influence of organic matter content on arsenic speciation and mobilization in chromated copper arsenate (CCA)-contaminated soils. The study was performed with four synthetic CCA-contaminated soils, with a range of organic matter content (mixture of peat moss and poultry manure) varying between 0.5% and 15% (w/w), under unsaturated and aerobic conditions for 40 days. Changes in water-soluble arsenic speciation (As(V), As(III), MMAA, DMAA) were monitored over time in soil extracts by HPLC-ICP-MS and in the soil solid phase (As(III), As(V)) by a solvent extraction method. Irrespective of organic matter content, As(V) was the predominant soil bound and aqueous phase arsenic species. However, over 40 days, a high soil organic matter content (7.5% and 15%) was able to entail formation of soil bound As(III). Moreover, total water-soluble arsenic was positively correlated with dissolved organic carbon (r(2)=0.88). However, the organic matter content did not influence arsenic speciation in the soluble fraction; neither As(V) reduction nor arsenic biomethylation occurred within 40 days. An increase in dissolved organic carbon content promoted both As(V) and As(III) solubilization in soils. Also, over time, organic matter contents of 7.5% and 15% entailed the persistence of soluble As(V), likely due to the high content of dissolved organic compounds which prevented its sorption onto soil. Based on this data, the environmental risk of aerobic CCA-contaminated soils rich in organic matter may be due to an enhanced availability of soluble As(V) over time, rather than to the formation of the more toxic and more mobile As(III).


Uptake and predictors of post-mastectomy reconstruction in women with breast malignancy--systematic review.
There is enormous range in the reported rates of breast reconstruction. This study explored reasons for this variation by reviewing the published literature to examine rates of reconstruction, factors associated with uptake, and possible barriers. A systematic review of the literature was performed. Eligible studies reported rates of breast reconstruction and variables associated with uptake in women undergoing mastectomy for early invasive or in situ breast malignancy. Twenty-eight eligible studies were included, reporting 159,305 cases of breast reconstruction in 940,678 women. In these studies 16·9% of women underwent immediate or delayed reconstruction (range 4·9-81·2%, median 23·3%). Variables associated with reconstruction were: patient/tumour factors (early stage, no adjuvant therapy, young age, white race, private insurance, higher education/income), surgeon/hospital factors and psychological/other factors (including patient choice). Rates of breast reconstruction were highly variable. Reconstruction appeared to be offered to a minority of women; around half took up the offer. The main reasons reported for no reconstruction included patient-related and adjuvant therapy-related factors. Clinicians' beliefs about reconstruction may be an important factor. Rates of reconstruction could be increased with early discussion of the options when mastectomy is chosen or required.


The diagnostic accuracy of neck ultrasound, 4D-Computed tomographyand sestamibi imaging in parathyroid carcinoma.
Our aim was to investigate the accuracy of available imaging modalities for parathyroid carcinoma (PC) in our institution and to identify which imaging modality, or combination thereof, is optimal in preoperative determination of precise tumor location. All operated PC patients in our institution between 2000 and 2015 that had at least one of the following in-house preoperative scans: neck ultrasonography (US), neck 4D-Computed Tomography (4DCT) and 99mTc Sestamibi SPECT/CT (MIBI). Sensitivity, specificity and accuracy of PC tumor localization were assessed individually and in combination. 20 patients fulfilled the inclusion criteria and were analysed. There were 18 US, 18 CT and 9 MIBI scans. The sensitivity and accuracy for tumor localisation of US was 80% (CI 56-94%) and 73% respectively, of 4DCT was 79% (CI 58-93%) and 82%, and of MIBI was 81% (CI 54-96%) and 78%. The sensitivity and accuracy of the combination of CT and MIBI was 94% (CI 73-100%) and 95% and for the combination of US, CT and MIBI was 100% (CI 72-100%) and 100% respectively. The wash-out of the PC lesions, expressed as a percentage change in Hounsfield Units from the arterial phase to early delayed phase was -9.29% and to the late delayed phase was -16.88% (n=11). The sensitivity of solitary preoperative imaging of PC patients, whether by US, CT or MIBI, is approximately 80%. Combinations of CT with MIBI and US increase the sensitivity to 95% or better. Combined preoperative imaging of patients with clinical possibility of PC is therefore recommended.


Community based hematological reference intervals among apparently healthy adolescents aged 12-17 years in Mekelle city, Tigrai, northern Ethiopia: A cross sectional study.
Hematological reference intervals are important in clinical and diagnostic management for the assessment of health and disease conditions. Hematological reference intervals are better to be established based on gender and age differences as these are among the main affecting factors. The aim of this study was to establish hematological reference intervals among apparently healthy adolescents aged 12-17 years in Mekelle City, Tigrai, Northern Ethiopia, 2019. A community-based cross-sectional study was conducted in 249 adolescents aged 12-17 years from December 2018 to May 2019. About 4ml of blood sample was collected from each study participant using vacutainer tube containing K2EDTA. Hematological parameters were analyzed using Sysmex KX-21N hematology analyzer (Sysmex Corporation Kobe, Japan). Data were entered and analyzed using SPSS version 23. Both parametric and non-parametric analyses were used to calculate the median and 95% of reference intervals. The 97.5th and 2.5th percentiles were calculated using descriptive statistics for the upper and lower reference limits of the study participants. Differences in reference intervals between male and female participants were evaluated using the Mann-Whitney U test. Among the 249 participants 122 (49%) were males and 127 (51%) were females with the median age of 14.5 (range 12 to 17) years were recruited in this study. The median and the 95% reference intervals of hematological parameters were determined. The 95% RIs were: Red blood cells (1012/Liter) 4.6-5.9 (Males) and 4.3-5.6 (Females), White blood cells (109/Liter) 2.9-9.6 (Males) and 3.4-10.2 (Females), Hemoglobin (g/dl) 12.6-17.1 (Males) and 12-15.4 (Females), Platelets (109/Liter) 138-364 (Males) and 151-462 (Females). Almost all of the hematological parameters showed significant differences (p<0.05) across gender. The hematological reference intervals established in this study showed a difference based on gender. We suggest preparing and using distinct local reference intervals for males and females separately.


Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension.
The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved. The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH. In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia. A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients. Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.


[Placental pathology of uteroplacental vascular deficiency].
The indications of the pathological examination of the placenta are mainly represented by uteroplacental vascular deficiency. The clinical context is often evocative, but it can sometimes be solely an intra-uterine growth retardation or an unexplained in utero fetal death. So, the pathological lesions of this uteroplacental vascular deficiency must be well-known to be correctly interpreted, for none of these lesions is truly specific. The pathological diagnosis is based on a group of macroscopic and microscopic arguments. Various physiopathological mechanisms, often imperfectly known, can be at the origin of an uteroplacental vascular insufficiency, but in the current position, the pathological examination does not allow etiopathogenic orientation. The development of the trophoblastic biopsies gives us access to a new material which, in parallel with the cytogenetic analysis, often allows us, in front of an unexplained intra-uterine growth retardation, to direct the diagnosis towards uteroplacental vascular insufficiency. The histological analysis of the chorionic villous sampling taken precociously during pathological pregnancies is thus a major diagnostic contribution. But especially, this analysis gives access to new information which, in the near future, will enable us to better define the pathological evolution of the lesions of hypoxic chorionic villous and to contribute to a better knowledge of this pathology which, under many aspects, still conceals many mysteries.


[Timing of surgical treatment for gallstone pancreatitis].
To evaluate the timing of surgery in the treatment of gallstone pancreatitis (GP). The records of 53 patients with GP were retrospectively analysed. The morbidity and mortality of early surgical treatment (less than 48 hours after admission) were 29.20% and 9.30%, respectively, in contrast to 3.50% and 0 in patients who underwent delayed surgical treatment (more than 48 hours after admission) (P < 0.05). In mild gallstone pancreatitis (APACHE-II <or= 8), timing of surgery appeared to have little effect on outcome. However, the rates of common bile duct exploration and the morbidity were 91.70% and 11.10% in the patients receiving early surgery, significantly higher than those (62.10% and 0) in the patients receiving delayed surgery. In severe gallstone pancreatitis patients (APACHE-II > 8), the timing of surgery was related to the morbidity and mortality, namely, they were higher in early surgery than in delayed surgery. We suggest delayed surgical treatment for mild gallstone pancreatitis, and delayed and selective surgery for severe gallstone pancreatitis.


Successful Aging in Older US Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study.
To identify the current prevalence, and sociodemographic, military, health, and psychosocial correlates of successful aging in older US veterans. Data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 3,001 US veterans aged greater than or equal to 60 years (mean = 73). Multiple regression and relative importance analyses were conducted to identify key factors associated with successful aging. A total 79% of older veterans rated themselves as aging successfully. Physical and mental health difficulties emerged as the strongest correlates of successful aging (71% variance explained), while psychosocial factors, most notably perceived resilience, purpose in life, and positive expectations about emotional aging, explained 29% of the variance in this outcome. Nearly 4 of 5 US veterans rate themselves as successful agers. Prevention and treatment efforts designed to mitigate physical and mental health difficulties, and promote protective psychosocial factors may help bolster successful aging in this population.


Intravenous immunoglobulin prevents peripheral liver transduction of intrathecally delivered AAV vectors.
Gene therapy using neurotropic adeno-associated virus vectors represents an emerging solution for genetic disorders affecting the central nervous system. The first approved central nervous system-targeting adeno-associated virus gene therapy, Zolgensma®, for treating spinal muscular atrophy is administered intravenously at high doses that cause liver-associated adverse events in 20%-30% of patients. Intrathecal routes of vector administration, such as the intra-cisterna magna route, provide efficient gene transduction to central nervous system cells while reducing off-target liver transduction. However, significant levels of liver transduction often occur upon intra-cisterna magna vector delivery in preclinical studies. Using vectors expressing monoclonal antibody transgenes, we examined whether passive transfer of adeno-associated virus-neutralizing antibodies as intravenous immunoglobulin before intrathecal adeno-associated virus delivery improved the safety of viral gene therapy targeting the central nervous system in mice and nonhuman primates. We used intracerebroventricular and intra-cisterna magna routes for vector administration to mice and nonhuman primates, respectively, and evaluated transgene expression and vector genome distribution. Our data indicate that pretreatment with intravenous immunoglobulin significantly reduced gene transduction to the liver and other peripheral organs but not to the central nervous system in both species. With further refinement, this method may improve the safety of adeno-associated virus-based, central nervous system-targeting gene therapies in clinical settings.


Correction notice for Westerdahl et al. The Effectiveness of a Preoperative Lifestyle-Based Weight Loss Program on Postoperative Outcomes in Bariatric Patients: A Secondary Data Analysis. Curr Dev Nutr 2021;5 (Supp_2):1256.
[This corrects the article DOI: 10.1093/cdn/nzab055_066.].


1 H, 15 N, and 13 C backbone and side chain resonance assignments of the cold shock domain of the Arabidopsis thaliana glycine-rich protein AtGRP2.
AtGRP2 (Arabidopsis thaliana glycine-rich protein 2) is a 19-kDa RNA-binding glycine-rich protein that regulates key processes in A. thaliana. AtGRP2 is a nucleo-cytoplasmic protein with preferential expression in developing tissues, such as meristems, carpels, anthers, and embryos. AtGRP2 knockdown leads to an early flowering phenotype. In addition, AtGRP2-silenced plants exhibit a reduced number of stamens and abnormal development of embryos and seeds, suggesting its involvement in plant development. AtGRP2 expression is highly induced by cold and abiotic stresses, such as high salinity. Moreover, AtGRP2 promotes double-stranded DNA/RNA denaturation, indicating its role as an RNA chaperone during cold acclimation. AtGRP2 is composed of an N-terminal cold shock domain (CSD) followed by a C-terminal flexible region containing two CCHC-type zinc fingers interspersed with glycine-rich sequences. Despite its functional relevance in flowering time regulation and cold adaptation, the molecular mechanisms employed by AtGRP2 are largely unknown. To date, there is no structural information regarding AtGRP2 in the literature. Here, we report the 1H, 15N, and 13C backbone and side chain resonance assignments, as well as the chemical shift-derived secondary structure propensities, of the N-terminal cold shock domain of AtGRP2, encompassing residues 1-90. These data provide a framework for AtGRP2-CSD three-dimensional structure, dynamics, and RNA binding specificity investigation, which will shed light on its mechanism of action.


Absorption and tissue distribution of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in the rat.
A defined mixture of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) was parenterally administered to rats and absorption and tissue distribution were measured: 1) Toluene/DMSO (1 + 2; v/v) proved to be a convenient vehicle for the subcutaneous administration of the various PCDDs and PCDFs. Seven days after application the rate of absorption was 90% of the administered dose or even higher for almost all of the PCDDs/PCDFs in the mixture. In a few cases only (e.g. OCDD) the rate was found to be 84-89%; 2) Seven days after subcutaneous administration all 2378-substituted congeners were found in the liver, whereas only a few non-2378-substituted congeners could be measured in minor quantities. The 2378-substituted congeners also predominated in adipose tissue; however, most of the non-2378-substituted congeners were also detected; 3) The amount deposited within the liver as percentage of the administered dose differed for the various 2378-substituted PCDDs and PCDFs, ranging from less than 10% for OCDD or 2378-T4CDF, and between 60 and close to 100% for 12378-P5CDD or the H6CDDs. Therefore, the concentration ratio (liver/adipose tissue) was also found to be very different, ranging from less than 3 in the case of 2378-T4CDD or 2378-T4CDF to greater than 40 in the case of 1234678-H7CDD, 23478-P5CDF, 123678-H6CDF, or 1234678-H7CDF; 4) Studies performed at the time period of ongoing absorption (13-14 h after injection) provided the first evidence that some of the non-2378-substituted congeners do reach substantial concentrations in hepatic tissue shortly after administration; 5) Subsequent to intraperitoneal injection of the same PCDD/PCDF mixture the concentrations within the liver were found to be almost identical with that found after subcutaneous injection. In contrast, much higher concentrations of the congeners were found in (abdominal) adipose tissue; 6) In the liver of untreated rats of the same strain no T4CDDs/T4CDFs or P5CDDs/P5CDFs were detectable under our experimental conditions.


Prognostic Factors for Survival of Stage IB Non-small Cell Lung Cancer Patients: A 10-Year Follow-Up Retrospective Study.
This study aimed to determine the prognostic factors for the long-term outcome of stage IB non-small cell lung cancer (NSCLC). Surgically resected patients with stage IB NSCLC diagnosed (based on TNM 8th edition) between April 2008 and December 2013 were retrospectively reviewed. The prognosis and possible risk factors among the stage IB NSCLC patients were evaluated. Of the 349 patients identified for the study, 80 (22.9%) received post-surgery adjuvant chemotherapy (ACT). The median follow-up time after surgery was 123.3 months. The 10-year overall survival (OS) rate was 69.6%, and the 10-year recurrence-free survival (RFS) rate was 62.8%. The patients in this cohort were divided into three groups (T1 with visceral pleural invasion [VPI], T2a without VPI, and T2a with VPI), and no significant differences in OS or RFS were found among the groups. Furthermore, survival analysis indicated that the absence of ground-glass opacity (GGO) components portends an adverse long-term OS and RFS. In a subgroup of patients with solid nodules, age older than 65 years (hazard ratio [HR] 1.987; 95% confidence interval [CI] 1.312-3.010; p = 0.001) and ACT (HR 0.392; 95% CI 0.225-0.684; p < 0.001) were independent prognostic factors for OS, whereas lymphovascular invasion (HR 1.792; 95% CI 0.995-3.227; p = 0.052) should be considered as an independent unfavorable prognostic factor for RFS. As an upstaging factor, VPI did not further stratify prognosis for the stage IB patients in our cohort. The presence of GGO components had a notable impact on a favorable prognosis in stage IB NSCLCs.


Effect of atorvastatin on tumor necrosis factor alpha serum concentration and mRNA expression of adipose in hypercholesterolemic rabbits.
Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine involved in atherogenesis. Adipose tissue is an important source of endogenous TNFalpha production. The aim of this study was to evaluate the effect of atorvastatin on TNFalpha serum concentration and mRNA expressions of subcutaneous adipose in hypercholesterolemic rabbits. Sixteen rabbits fed with a high-cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) the high-cholesterol group (n=8) was maintained on a high-cholesterol diet for 6 weeks; (2) the atorvastatin group (n=8) had the same high-cholesterol diet plus atorvastatin (2.5 mg/kg/d) for 6 weeks. A control group (n=5) was fed with a normal diet for 14 weeks. Subcutaneous adipose was collected for mRNA analysis. Additionally, the direct effect of atorvastatin on TNFalpha release and mRNA expression was assayed in primary rabbit adipocytes. TNFalpha levels in serum and adipocyte culture supernatant were measured by ELISA. RT-PCR was used to evaluate TNFalpha mRNA expression in adipose and adipocytes. Serum TNFalpha concentration was significantly associated with serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) (both P<0.01). Compared with the control group, rabbits fed with a high-cholesterol diet showed higher levels of TNFalpha serum concentration and mRNA expression of adipose, both of which were significantly reduced by atorvastatin treatment (both P<0.05). TNFalpha mRNA expressions of adipose were significantly correlated with circulating TNFalpha levels among the 3 groups (r=0.51, P<0.05). Atorvastatin dose-dependently inhibited lipopolysaccharide (LPS)-induced TNFalpha secretion and mRNA expression in cultured adipocytes. In conclusion, atorvastatin can directly inhibit TNFalpha expression and secretion in adipocytes. Atorvastatin reduced TNFalpha serum concentration in hypercholesterolemic rabbits, which might be because of its cholesterol-lowering effect and direct inhibition of TNFalpha expression in adipose.


Comparison of Three Renal Function Formulas for Ganciclovir/Valganciclovir Dose Individualization in CMV-Infected Solid Organ Transplantation Patients Using a Population Approach.
The gold standard treatment of established cytomegalovirus infection or prevention in solid organ transplantation is the intravenous administration of ganciclovir (GCV) or oral administration of valganciclovir (VGCV), both adjusted to the renal function. In both instances, there is a high interindividual pharmacokinetic variability, mainly owing to the wide range of variation of both the renal function and body weight. Therefore, accurate estimation of the renal function is crucial for GCV/VGCV dose optimization. This study aimed to compare three different formulas for estimating the renal function in solid organ transplantation patients with cytomegalovirus infection, for individualizing antiviral therapy with GCV/VGCV, using a population approach. A population pharmacokinetic analysis was performed using NONMEM 7.4. A total of 650 plasma concentrations obtained after intravenous GCV and oral VGCV administrations were analyzed, from intensive and sparse sampling designs. Three different population pharmacokinetic models were built with the renal function given by Cockcroft-Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease EPIdemiology Collaboration (CKD-EPI) formulas. Pharmacokinetic parameters were allometrically scaled to body weight. The CKD-EPI formula was identified as the best predictor of between-patient variability in GCV clearance. Internal and external validation techniques showed that the CKD-EPI model had better stability and performed better compared with the others. The model based on the more accurate estimation of the renal function with the CKD-EPI formula and body weight as a size metric most used in the clinical practice can refine initial dose recommendations and contribute to GCV and VGCV dose individualization when required in the prevention or treatment of cytomegalovirus infection in solid organ transplantation patients.


Treatment of bilateral severe eyelid burns with skin grafts: an odyssey.
Eyelid burns occur in about 10% of thermal injuries and pose a considerable challenge for the reconstructive surgeon. A consensus on a treatment regime has not been reached and plastic surgeons are divided on the subject. A case of severe bilateral eyelid burns was treated with full- and split-thickness skin grafts. The patient was first operated at 2 years post-injury, and a total of 5 operations in 5 years were necessary to address recurrent ectropion of both upper and lower eyelids.


Susceptibility of Hydrotaea aenescens (Wiedemann) (Diptera: Muscidae) to selected insecticides and its importance in integrated fly management.
The doses lethal to 50% of the insects (LD50 values) obtained for a strain of Hydrotaea aenescens (Wiedemann) adults from a layer farm revealed higher sensitivity to 16 insecticides than those recorded for the susceptible WHO/SRS strain of the housefly. Because H. aenescens adults are about half the size of the housefly, the chemical compounds used for adult control may jeopardize the survival of Hydrotaea populations released in animal confinement houses. An efficient and economical combined application of biological and chemical control methods is possible only if the local management conditions and the dissimilar behavior of the adults of the two species are taken into consideration during the use of insecticides. Other suggestions and implications are further discussed.


Real-time prediction of acute cardiovascular events using hardware-implemented Bayesian networks.
This paper presents a decision support system that aims to estimate a patient׳s general condition and detect situations which pose an immediate danger to the patient׳s health or life. The use of this system might be especially important in places such as accident and emergency departments or admission wards, where a small medical team has to take care of many patients in various general conditions. Particular stress is laid on cardiovascular and pulmonary conditions, including those leading to sudden cardiac arrest. The proposed system is a stand-alone microprocessor-based device that works in conjunction with a standard vital signs monitor, which provides input signals such as temperature, blood pressure, pulseoxymetry, ECG, and ICG. The signals are preprocessed and analysed by a set of artificial intelligence algorithms, the core of which is based on Bayesian networks. The paper focuses on the construction and evaluation of the Bayesian network, both its structure and numerical specification.


The Genetic and Molecular Analyses of RAD51C and RAD51D Identifies Rare Variants Implicated in Hereditary Ovarian Cancer from a Genetically Unique Population.
To identify candidate variants in RAD51C and RAD51D ovarian cancer (OC) predisposing genes by investigating French Canadians (FC) exhibiting unique genetic architecture. Candidates were identified by whole exome sequencing analysis of 17 OC families and 53 early-onset OC cases. Carrier frequencies were determined by the genetic analysis of 100 OC or HBOC families, 438 sporadic OC cases and 1025 controls. Variants of unknown function were assayed for their biological impact and/or cellular sensitivity to olaparib. RAD51C c.414G>C;p.Leu138Phe and c.705G>T;p.Lys235Asn and RAD51D c.137C>G;p.Ser46Cys, c.620C>T;p.Ser207Leu and c.694C>T;p.Arg232Ter were identified in 17.6% of families and 11.3% of early-onset cases. The highest carrier frequency was observed in OC families (1/44, 2.3%) and sporadic cases (15/438, 3.4%) harbouring RAD51D c.620C>T versus controls (1/1025, 0.1%). Carriers of c.620C>T (n = 7), c.705G>T (n = 2) and c.137C>G (n = 1) were identified in another 538 FC OC cases. RAD51C c.705G>T affected splicing by skipping exon four, while RAD51D p.Ser46Cys affected protein stability and conferred olaparib sensitivity. Genetic and functional assays implicate RAD51C c.705G>T and RAD51D c.137C>G as likely pathogenic variants in OC. The high carrier frequency of RAD51D c.620C>T in FC OC cases validates previous findings. Our findings further support the role of RAD51C and RAD51D in hereditary OC.


Insertional mutagenesis in Chlamydomonas reinhardtii: An effective strategy for the identification of new genes involved in the DNA damage response.
The formation of double-strand breaks in DNA represents a serious stress for all types of organisms and requires a precisely regulated and organized DNA damage response (DDR) to maintain genetic information and genome integrity. Chlamydomonas reinhardtii possesses the characteristics of both plants and animals and is therefore suitable for the identification of novel genes connected to a wide spectrum of metabolic pathways, including DDR. One very effective tool for the detection and subsequent characterization of new mutants in C. reinhardtii is insertional mutagenesis. We isolated several insertion mutants sensitive to DNA-damaging agents that had disrupted or completely deleted genes with putative functions in the DDR. In most of the analysed mutants, we identified various changes at both ends and even inside the inserted cassette. Using recent information from databases, we were also able to supplement the characteristics of the previously described mutant with a pleiotropic phenotype. In addition, we confirmed the effectiveness of hairpin-PCR as a strategy for the identification of insertion flanking sites and as a tool for the detection of changes at the site of insertion, thus enabling a better understanding of insertion events.


Phase-I trial of combination therapy with continuous-infusion MMPR and continuous-infusion 5-FU.
Fourty-four evaluable patients were treated with 6-methylmercaptopurine riboside (MMPR) at a dose of 20 mg/m2/day X 5 by continuous IV infusion (days 1-5 and 5-fluorouracil (5-FU) on an escalating dose schedule of 300-1519 mg/m2/day X 5 by continuous IV infusion (days 2-6). Dose-limiting oral mucositis occurred at a 5-FU dose of 1,381 mg/m2/day; other toxicities included nausea, vomiting, diarrhea, skin rash, and occasional myelosuppression. A partial and a complete response were observed in two previously untreated patients with metastatic colon carcinoma given the highest 5-FU doses (1,381 and 1,519 mg/m2/day). Bone marrow phosphoribosyl pyrophosphate (PRPP) levels monitored after 24 h of MMPR treatment indicated increases of 7.8- and 9.2-fold those found prior to therapy.


Effect of beta-adrenergic stimulation on experimental canine anaphylaxis in vivo.
We studied beta-adrenergic modulation of antigen-induced release of histamine and changes in lung function in natively allergic, anesthetized dogs. After thoracotomy and bilateral cervical vagotomy, samples of peripheral lung frozen in situ were obtained for measurement of adenosine cyclic 3',5'-monophosphate (cAMP) and histamine. In 11 dogs with beta-adrenergic blockade (propranolol), subsequent Ascaris suum antigen (intravenous) decreased lung tissue histamine 21.5% +/- 5.3% (mean +/- SE), with marked physiologic changes of anaphylaxis. In six other dogs, with no pharmacologic treatment before antigen, A. suum decreased lung tissue histamine only 11.5% +/- 1.9%. In six other dogs, terbutaline (1 mg/kg, i.v.) increased concentration of cAMP in peripheral lung, indicating stimulation of beta-adrenergic receptors, and inhibited response to A. suum. When a beta-adrenergic agonist was given 15 sec prior to A. suum, cAMP doubled and inhibition was incomplete. When a beta-agonist was given 150 sec prior to A. suum, cAMP increased fivefold and inhibition was complete.


Specific detection of metastasized human tumor cells in embryonic chicks by the polymerase chain reaction.
We have established a highly sensitive method for specific detection of metastasized human tumor cells in embryonic chicks using the polymerase chain reaction (PCR). The cells (HT-1080 or KMST-6) were inoculated into the chorioallantoic membrane vein of the chick embryo and DNA of each embryonic organ was extracted. Then, a human beta-globin-related sequence (576 bp) in the DNA from the embryonic liver and lung was specifically amplified and detected by gel electrophoresis and by a specific oligonucleotide probe. The amplified fragments from the liver DNA samples increased gradually from 2 h to 7 days after HT-1080 inoculation. On the other hand, with inoculation of non-tumorigenic human embryonal fibroblast KMST-6 cells, the DNA from the embryonic liver 7 days after inoculation did not show the PCR-amplified product. This detection technique can contribute significantly to the precise detection of microscopic metastasis.


[Ligament reconstruction for trapeziometacarpal joint instability].
Restoring stability and preventing subluxation/dislocation of the trapeziometacarpal (first carpometacarpal = CMC-I) joint while preserving mobility. Posttraumatic, acquired or congenital instability of the CMC-I joint. Existence of osteoarthritis of the CMC-I joint. Neurogenic or muscular origin dysfunction of thenar muscles and other contractures the CMC-I area. Infections. Radiopalmar approach to the CMC-I joint, reduction, and transosseous ligament reconstruction with a distally pedicled tendon strip from the abductor pollicis longus muscle. Splint immobilization for 5 weeks. This procedure generally results in good or very good outcomes. Of 24 patients, only one patient experienced rupture of the ligament reconstruction. Ligament reconstruction for the carpometacarpal joint of the thumb relieves pain and restores stability while preserving functional range of motion in patients with chronic instability.


Nodal factors predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma.
Lymph node (LN) metastasis of oral cavity squamous cell carcinoma (OSCC) is associated with survival outcomes. However, the relationship between different metastatic nodal factors and treatment outcomes requires further elucidation. This study examined nodal factors predictive of recurrence and survival in patients with OSCC. This prospective observational study included 157 patients with OSCC who underwent surgery between 2010 and 2015. Clinicopathological and follow-up information were recorded. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with recurrence-free survival, disease-specific survival and overall survival. Sixty-five of 157 patients (41.4%) had neck metastasis. During a median follow-up of 46 months, any recurrences and all deaths occurred in 43 (27.4%) and 43 (27.4%) of cases, respectively. All nodal factors (LN classification, size, number and ratio) and extra-nodal extension were significantly associated with all survival outcomes (P < .001). Multivariate analyses indicated that a tumour size >2 cm and LN ratio were independently associated with all survival (P < .05). Patients with LN ratio >0.05 had sixfold higher recurrence and mortality rates than other patients (P < .001). Lymph node ratio is an independent and predictive determinant of post-treatment recurrence and survival.


Immunocytochemical localization of gamma-glutamyltranspeptidase, GP-2 and amylase in the rat exocrine pancreas: the concept of zymogen granule membrane recycling after exocytosis.
We localized gamma-glutamyltranspeptidase (GGT) in the rat pancreas by immunocytochemistry using the protein A-gold technique. The enzyme was found in the apical and zymogen granule (ZG) membranes of the pancreatic acinar cell. With ZG at the onset of exocytosis, labeling was seen over membrane, whereas content was unreactive. In the acinar lumen, the enzyme was generally associated with small vesicles previously described as "pancreasomes." This observation corroborates a recent proposal that a membrane-shedding process is associated with exocytosis in the exocrine pancreas. It also implies that some elements of the ZG membrane are not recycled after exocytosis. The cellular distribution of GGT was compared with GP2, another glycoprotein component of the ZG membrane, and differences in localization indicate different fates for these two proteins. Indeed, GP2 shows a strong signal with the basolateral membrane, whereas in the case of GGT the signal is barely detectable. The reverse situation is observed on the apical plasma membrane, GGT producing a much stronger signal than GP2. The failure to detect GGT in lysosomal structures, combined with the fact that some endocytic-like vacuoles in the vicinity of the apical plasma membrane give a positive reaction, supports the view that some GGT molecules are recycled in the ZG membrane after exocytosis. Our observations clearly demonstrate that a fraction of the protein components of the ZG membrane are not recycled after exocytosis, raising new questions regarding the concept of membrane recycling associated with regulated secretion.


Terfenadine and fexofenadine reduce in vitro ICAM-1 expression on human continuous cell lines.
Epithelial cells and fibroblasts play an important role in allergic inflammation. Modulation of surface expression of adhesion molecules on epithelial cells by antiallergic drugs has been shown by both in vivo and in vitro studies. The aim of the study was to evaluate the effect exerted by terfenadine and fexofenadine on adhesion molecules expression (CD54/ICAM-1 and CD29) of a human continuously cultured conjunctival epithelial cell line (WK) and a fibroblast cell line (HEL). By means of flow cytometry analysis, we evaluated ICAM-1 and CD29 expression by WK and HEL epithelial cells in basal condition (at baseline) or after IFN gamma or TNF alpha stimulation in the presence or in the absence of terfenadine and fexofenadine. We also performed immunoenzymatic assays in order to evaluate soluble ICAM-1 released by WK cells and procollagen type I and III and IL6 released by HEL cells. Terfenadine and fexofenadine significantly reduced ICAM-1 basal expression on WK cells at the concentration of 1 microg/mL and 50 microg/mL, respectively. In addition, both terfenadine and fexofenadine were able to decrease soluble ICAM-1 levels in IFN gamma-stimulated WK cells. On HEL fibroblasts, fexofenadine only was able to inhibit ICAM-1 upregulation induced by IFN gamma. Concerning the release of fibroblast products, we observed a dose-dependent decrease of spontaneous IL6 release only in the presence of fexofenadine. This study shows that terfenadine and fexofenadine exert a biologic effect directly on epithelial cells and fibroblasts reducing ICAM-1 expression and partially reducing soluble ICAM-1 release.


[Low molecule and middle molecule metabolites with haemodynamic activity in the ultrafiltrate from uraemic patients (author's transl)].
Substances causing blood pressure changes and myocardial damage in rats were first detected in the ultrafiltrate obtained from patients on long-term haemodialysis by means of size separation, high-voltage electrophoresis and thin-layer chromatography. Of the 100 to 140 fractions produced by Sephadex G 15 chromatography at least 3 raised the blood pressure when administered in doses of 2 to 10 mg/0.1 to 0.2 ml 0.9% NaCl, that is the high molecular fraction 18 to 23 and the low molecular fractions 71 to 72 and 73 to 74. The fractions 96 to 98 and 97 to 106 showed high toxicity. Less than 1 mg/0.1 to 0.2 ccm 0.9% NaCl produced cardiac arrest. The fractions 35 to 55, which originate from the middle molecules and are retained in regularly uraemia, contain substances which caused a reduction in blood pressure at low dosage and cardiotoxic effects at a dosage of more than 10 mg. Thin-layer chromatography indicates that the substances most probably consist of peptides whose structure contains the amino acids leucine, isoleucine, valine, glutamic acid, aspartic acid, alanine and cystine.


Developing a Portable Device for the Identification of miRNAs in Fluids.
In the present work we describe a novel system for the identification of microRNAs (miRNAs) in fluids. The method is based on combined novel 3D microarray technology using silk as scaffold and total internal reflection fluorescence microscopy (TIRFM), which allows for the rapid identification of miRNAs using a portable device.


Effect of free radical scavenger, edaravone, for patients with carbon monoxide poisoning.
Chronic neurological symptoms after carbon monoxide (CO) poisoning are caused by various biological processes in the damaged brain, with free radicals playing roles as mediators in establishing pathological processes leading to chronic neurological symptoms under CO poisoning. This study aimed to clarify the effects of a free radical scavenger, edaravone, in patients with CO poisoning. We retrospectively compared two groups comprising patients treated with hyperbaric oxygenation alone (Group A, n=25) or edaravone in addition to hyperbaric oxygenation (Group B, n=25). Edaravone was administrated intravenously at 30 mg every 12h for 7 days. Patient characteristics, general conditions on admission, and frequency of chronic neurological symptoms were compared between groups. Among patients showing chronic neurological symptoms, cognitive function and daily activity were also compared between groups. No significant differences in characteristics or general conditions on admission were identified between groups. In Group B, no patients presented with marked complications caused by edaravone. Although chronic persisting symptoms were less frequent in Group B (n=1, 0.04%) than in Group A (n=5, 20%), this difference was not significant. In the 11 patients showing chronic symptoms, scores for cognitive function and daily activity in the chronic phase were better in Group B than in Group A, but no significant differences were apparent. The present results suggest that edaravone represents a tolerable and feasible treatment for CO-poisoned patients. Further studies are needed to clarify whether edaravone can favorably influence chronic neurological symptoms caused by CO poisoning.


Enantioselective degradation of alpha-cypermethrin and detection of its metabolites in bullfrog (rana catesbeiana).
Bullfrog, as a kind of amphibians, can be easily exposed to varied pollutants in the environment for the reason of its habitats and highly permeable skin. We investigated the degradation kinetics and residues of α-cypermethrin in bullfrog by two different methods of administration for the environmental monitoring the behavior of one of the most used pesticides in the amphibians. The oral administration and water exposure of α-cypermethrin on bullfrog was studied in this work. α-Cypermethrin and its main metabolites of cis-3-(2',2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA) and 3-phenoxybenzoic acid (3-PBA), which have been determined that having correlation with a number of epidemic diseases, were detected simultaneously. The method for residue analysis in the bullfrog's organs was validated. The average recoveries for α-cypermethrin were ranged from 71.7% to 100.3% and the limit of quantification was 0.005mg/kg. The average recoveries of its metabolites at levels between 0.002 and 0.5mg/kg ranged between 77.9% and 102.4% with a limit of quantification of 0.002mg/kg. Furthermore, the enantiomers of α-cypermethrin were separated on gas chromatograph (GC) equipped with a chiral column of BGB-172 and the metabolites were detected by gas chromatography (GC) after derivatization. After exposure of α-cypermethrin on bullfrog, the enantioselective degradation behavior was observed and its metabolites were detected in bullfrog tissues. The dynamic trends of α-cypermethrin and its metabolites were fitted to a two-compartment model except 3-PBA fitting to one-compartment model in skin. Concentration of α-cypermethrin and its metabolites in bullfrog's organs increased and reached an equilibrium state during water exposure of α-cypermethrin. Liver and kidney were the major organs for α-cypermethrin and its metabolites retention in both experiments.


Effects of Horse Housing System on Energy Balance during Post-Exercise Recovery.
This study examined the effects of two housing systems (free-range and box stalls) on recovery of energy balance after competition-like exercise in Standardbred horses. Eight adult geldings (mean age 11 years) were used. The study had a change-over design, with the box stall (BOX) and free-range group housing (FreeR) treatments each run for 21 days. The horses were fed forage ad libitum and performed two similar race-like exercise tests (ET), on day 7 and day 14 in each treatment. Forage intake was recorded during the last 6-7 days in each period. Blood samples were collected before, during, and until 44 h after ET. Voluntary forage intake (measured in groups with four horses in each group) was higher in FreeR horses than BOX horses (FreeR: 48, BOX: 39, standard error of the mean (SEM) 1.7 kg (p = 0.003)). Plasma non-esterified fatty acids (NEFA) was lower at 20-44 h of recovery than before in FreeR horses (p = 0.022), but not in BOX horses. Housing did not affect exercise heart rate, plasma lactate, plasma urea, or total plasma protein concentration. Thus the free-range housing system hastened recovery in Standardbred trotters, contradicting anecdotal claims that it delays recovery. The free-range housing also had positive effects on appetite and recovery of energy balance.


Cross-cultural adaptation and psychometric properties of the Turkish version of the Manual Ability Measure-36 (MAM-36) in people with multiple sclerosis.
The Manual Ability Measure-36 (MAM-36) has been used to assess subjective upper limb function in people with several neurological and non-neurological diseases. Besides, the MAM-36 is one of the most commonly used patient-reported outcome measures (PROMs) in people with multiple sclerosis (pwMS). The aim was to translate and conduct cross-cultural adaptation of the MAM-36 into Turkish and investigate its psychometric properties in pwMS. The MAM-36 was translated and culturally adapted into Turkish. Two hundred pwMS were recruited for the psychometric study. Hand skills, handgrip strength, upper limb spasticity, disability level, and quality of life were evaluated by the validated performance-based tests and questionnaires including the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) which is a validated MS-specific PROM to assess upper limb function. MAM-36 was significantly correlated with the performance-based tests and questionnaires, EDSS, age, and disease duration (p < 0.05). MAM-36 and AMSQ were strongly correlated (rs = - 0.90, p < 0.01). PwMS with spasticity had significantly lower MAM-36 scores compared to those without spasticity (p < 0.01). Internal consistency (Cronbach's alpha = 0.97) and test-retest reliability (ICC = 0.97) was high. The Turkish version of MAM-36 has been found as a valid and reliable method for measuring upper limb function in pwMS.


Attention rapidly reorganizes to naturally occurring structure in a novel activity sequence.
Fluent event processing involves selectively attending to information-rich regions within dynamically unfolding sensory streams (e.g., Newtson, 1973). What counts as information-rich likely depends on numerous factors, however, including overall event novelty and local opportunity for repeated viewing. Using Hard, Recchia, and Tversky's (2011) method, we investigated the extent to which these two variables affected viewers' attentional patterns as events unfolded. Specifically, we recorded viewers' "dwell times" as they advanced through two slideshows depicting distinct methods of shoelace tying varying in novelty but equated on other dimensions. Across two experiments, novelty sparked increased dwelling overall, and viewers' dwelling patterns displayed rapid and systematic reorganization to structure within the activity stream after just one viewing of distinctively novel content. As well, increased dwelling positively predicted memory performance. These findings newly illuminate reorganization in attention as relevant information within novel activity sequences is quickly incorporated to guide event processing and support event memory.


Repeatability and reproducibility of determinations of vinyl chloride in foodstuffs.
In the spring of 1978 and the autumn of 1979, two collaborative investigations were carried out with the aim of determining the variability of measurements of the vinyl chloride (VC) content of foodstuffs. The first investigation was a preliminary test on VC standards in N,N-dimethylacetamide. The results of this test were considered to be satisfactory. In a second test, lemonade and oil samples spiked with VC were investigated. The methods used were based on the headspace gas-chromatographic technique. The amount of VC added was 3 micrograms/kg for the lemonade sample and 20 micrograms/kg for the oil sample. The external standard method yielded a reproducibility of 53 and 39% and a repeatability of 18 and 17% for the lemonade and oil, respectively. The corresponding findings with the addition method were a reproducibility of 119 and 40% and repeatability of 33 and 9%.


Sexual harassment: identifying risk factors.
A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.


Judet osteoperiosteal decortication for treatment of non-union: the Cornwall experience.
The treatment of non union can be challenging with a variety of surgical options available to achieve bone consolidation. Robert Judet first described a method of osteo-periosteal decortication in 1963. He stated that by elevating cortical chips that remain attached to the periosteum and overlying soft tissues surrounding the site of non-union, combined with mechanical support, the bone consolidated. Despite excellent results presented in 2008 of 99% union rates with a mean delay of 8 months, the technique has not yet become popularised. We aim to show that Judet's method of decortication can achieve good results in the management of failure of union in a hospital other than Judet's. Retrospective analysis was performed from December 2002 to December 2008 of 40 cases in 39 patients of osteoperiosteal decortication for fracture non-union. Concurrent stabilisation was with internal fixation only. All procedures were performed by one surgeon (MN) using the Judet technique after learning the technique in the originators hospital. A preoperative non union scoring system was also used to assess its use in predicting persistent non-union. Union was successfully achieved in 36 of the 39 surviving cases (92.3%) after a median delay of 8 months (range 3-47, SD 9.2) Twenty-six patients (65%) achieved union following the decortication procedure without subsequent operations. Factors such as open fracture and smoking did not have a statistically significant effect on union. The mean number of procedures following decortication was 0.68 (range 0-4). Metalwork failure occurred in 11 cases (28%), the majority in femoral decortications (n=9, 82%). The femur was the site of all persistent non unions in the series. Three patients had superficial infections and two had deep infections. The pre-operative non union scoring system (0-100) means were noticeably worse for the persistent non union group 42.0 (20-46) compared with the union group 31.0 (range 4-52). Osteoperiosteal decortication remains a highly effective surgical technique in the management of failed fracture union. The non union scoring system is a reliable predictor of persistent non union after this type of surgery. Relevant to general trauma orthopaedic surgeon and specialist orthopaedic surgeons with an interest in fracture non-union.


Fear inoculation among snake experts.
Fear acquisition of certain stimuli, such as snakes, is thought to be rapid, resistant to extinction, and easily transferable onto other similar objects. It has been hypothesized that due to increased survival chances, preparedness to instantly acquire fear towards evolutionary threats has been hardwired into neural pathways of the primate brain. Here, we compare participants' fear of snakes according to experience; from those who often deal with snakes and even suffer snakebites to those unfamiliar with snakes. The Snake Questionnaire-12 (SNAQ-12) and Specific Phobia Questionnaire (SPQ) were administered to three groups of participants with a different level of experience with snakes and snakebites: 1) snake experts, 2) firefighters, and 3) college students. This study shows that individuals more experienced with snakes demonstrate lower fear. Moreover, participants who have suffered a snakebite (either venomous or not) score lower on fear of snakes (SNAQ-12), but not of all other potentially phobic stimuli (SPQ). Our results suggest that a harmless benign exposure might immunize people to highly biologically prepared fears of evolutionary threats, such as snakes.


A New Predictive Model for In-Hospital Major Adverse Cardiac and Cerebrovascular Events in Chinese Patients After Major Noncardiac Surgery.
Prediction tools focused on cardiovascular and cerebrovascular events after noncardiac surgery are lacking, particularly for Chinese patients. We developed and validated what we believe is a new predictive tool for postoperative major cardiovascular and cerebrovascular events (MACCEs) in Chinese patients in this study. Overall, 401 variables derived from 598 patients who received noncardiac surgery at our center were retrospectively analyzed to develop and validate the new predictive model for MACCEs during hospitalization. The 7 strongest predictors for MACCEs in the development cohort were chronic heart failure, age, atrial fibrillation, general anesthesia, history of coronary heart disease, high-risk procedures, and lymphocyte count. The area under the receiver operating characteristic curve was 0.698 (95% confidence interval 0.616 to 0.780) for the new predictive tool with the validation cohort. Receiver operating characteristic curve analysis showed the new predictive tool had better performance than the Revised Cardiac Risk Index and the American College of Surgeons National Surgical Quality Improvement Program scores. This new predictive tool is effective for the prediction of postoperative MACCEs in patients who undergo noncardiac surgery.


Light-activated gating and permselectivity in interfacial architectures combining "caged" polymer brushes and mesoporous thin films.
We demonstrate that "caged" macromolecular building blocks can endow mesoporous thin films with light responsiveness and lead to the creation of functional hybrid ensembles with phototriggered permselective properties.


Nonalcoholic fatty liver disease.
As the hepatic manifestation of the metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of asymptomatic liver enzyme elevations in Western nations. Although it is easy to diagnose NAFLD, a liver biopsy is currently required to diagnose nonalcoholic steatohepatitis (NASH). Patients with NASH are those at greatest risk of progression to cirrhosis and, thus, treatment efforts are targeted to these individuals. Although currently there are no FDA-approved treatments for NASH, a multidisciplinary approach that addresses comorbid conditions and promotes modest weight loss comprises the backbone of therapy.


The effects of motor learning on clinical isokinetic performance of postmenopausal women.
To analyze the effects of motor learning on knee extension-flexion isokinetic performance during clinical isokinetic evaluation of postmenopausal women. One-hundred and twenty postmenopausal women (60.3±3.2 years; BMI=27.6±4.7 kg/m(2)) without knee pain or injury and that never underwent isokinetic testing, were submitted to two bilateral knee extension-flexion (concentric-concentric) isokinetic evaluation (5 repetitions) at 60°/s (Biodex™ Multi-Joint System 3 dynamometer). The tests were first performed in the dominant leg, with a 1-min recovery between them, and after a standardized warm-up that included 3 submaximal isokinetic repetitions. The same procedure was repeated in the non-dominant leg. Peak torque (PTQ) was adjusted for body weight (PTQ/BW), total work (TW), coefficient of variation (CV) and agonist/antagonist (agon/antag) ratio was compared between tests. Subjects showed greater levels (P<0.001) of PTQ, PTQ/BW and TW, and lower CV levels (P<0.01) in test 2 of both legs. Agon/antag ratio did not change significantly between tests. PTQ, PTQ/BW, TW and CV improved in the second knee extension flexion isokinetic testing of postmenopausal women. The results suggests that performing two tests, even with a short period of recovery between them, could be considered for reducing motor learning effects on clinical isokinetic evaluation of knee joint in postmenopausal women.


The Fit-for-Purpose Model: Conceptualizing and Managing Chronic Nonspecific Low Back Pain as an Information Problem.
Chronic nonspecific low back pain (LBP) is a complex and multifaceted problem. The following Perspective piece tries to help make sense of this complexity by describing a model for the development and maintenance of persistent LBP that integrates modifiable factors across the biopsychosocial spectrum. The Fit-for-Purpose model posits the view that chronic nonspecific LBP represents a state in which the person in pain holds strong and relatively intransient internal models of an immutably damaged, fragile, and unhealthy back, and information that supports these models is more available and trustworthy than information that counters them. This Perspective proposes a corresponding treatment framework for persistent pain that aims to shift internal models of a fragile, damaged, unhealthy, and unchangeable self toward the formulation of the back as healthy, strong, adaptable, and fit for purpose and to provide the system with precise and trustworthy evidence that supports this supposition while minimizing information that works against it.


Evidence-based evaluation and current practice of non-operative treatment strategies for lumbar stenosis.
A number of non-operative treatment protocols have been proposed in the literature for lumbar stenosis. However, the available primary research describes inadequately the employed protocol. This causes difficulties in distinguishing which interventions are more effective in reducing symptoms. We reviewed existing studies in order to promote the construction of an evidence-based strategy for non-operative treatment rehabilitation of lumbar stenosis patients. Randomized controlled trials describing insufficiently the non-operative treatment rehabilitation protocols were excluded since the results may not direct this review towards a favorable treatment plan. A protocol has been outlined to inform the clinician and to elucidate the effectiveness of non-operative treatment through randomized controlled trials. The results of this study indicate that a comprehensive exercise and manual therapy protocol is more effective in reducing symptoms than a less intensive exercise program. A comprehensive non-operative treatment comprising of flexion exercises, manual therapy and treadmill exercises appears to be more beneficial in reducing symptoms than a less vigorous program comprising of flexion exercises, treadmill training and home exercise.


Selective Estrogen receptor degraders (SERDs) for the treatment of breast cancer: An overview.
Discovery of SERDs has changed the direction of anticancer research, as more than 70% of breast cancer cases are estrogen receptor positive (ER+). Therapies such as selective estrogen receptor modulators (SERM) and aromatase inhibitors (AI's) have been effective, but due to endocrine resistance, SERDs are now considered essential therapeutics for the treatment of ER+ breast cancer. The present review deliberates the pathophysiology of SERDs from the literature covering various molecules in clinical trials. Estrogen receptors active sites distinguishing characteristics and interactions with currently available FDA-approved drugs have also been discussed. Designing strategy of previously reported SERDs, their SAR analysis, in silico, and the biological efficacy have also been summarized along with appropriate examples.


Dementia presenting as postpartum depression.
Other conditions that can mimic postpartum depression are rare but must be considered. A 37-year-old woman developed mood symptoms as well as progressive hyperphagia, hypersexuality, disinhibition, and impairment of judgment after delivery of her third child. She was unresponsive to multiple treatments for depression and was evaluated for frontal lobe syndromes. Frontotemporal dementia, formerly known as Pick disease, is a primary degenerative dementia for which no cause is clearly established. Family history or genetic abnormalities are found in about 50% of cases. The diagnosis is frequently missed or delayed, as in this case, because it occurs in a younger age group, presents with unusual signs and symptoms, and is far less prevalent than Alzheimer disease.


Prevalence of gallstones in sonographic surveys worldwide.
The use of diagnostic sonography allows determination of the prevalence of gallstones in a representative sample of the general population. The objective of this article is to review the reports of sonographically based studies of gallstone prevalence in the world literature. All available published epidemiologic studies on the prevalence of cholecystolithiasis as determined by diagnostic sonography are summarized. The sonographically based studies published to date confirm that there are significant regional differences in the prevalence of gallstones. Certain risk factors, notably age and heredity, are present worldwide.


Rb selectively inhibits innate IFN-β production by enhancing deacetylation of IFN-β promoter through HDAC1 and HDAC8.
Type I IFN production is tightly controlled by host to generate efficient viral clearance without harmful immunopathology or induction of autoimmune disorders. Epigenetic regulation of type I IFN production in innate immunity and inflammatory disorders remains to be fully understood. Several tumor suppressors have been shown to regulate immune response and inflammation. However, the non-classical functions of tumor suppressors in innate immunity and inflammatory diseases need further identification. Here we report retinoblastoma protein (Rb) deficiency selectively enhanced TLR- and virus-triggered production of IFN-β which thus induced more IFN-α generation in the later phase of innate stimuli, but had no effect on the production of TNF, IL-6 and early phase IFN-α in macrophages. Rb1(fl/fl)Lyz2cre(+) Rb-deficient mice exhibited more resistant to lethal virus infection and more effective clearance of influenza virus. Rb selectively bound Ifnb1 enhancer region, but not the promoter of Ifna4, Tnf and Il6, by interacting with c-Jun, the component of IFN-β enhanceosome. Then Rb recruited HDAC1 and HDAC8 to attenuate acetylation of Histone H3/H4 in Ifnb1 promoter, resulting in suppression of Ifnb1 transcription. Therefore, Rb selectively inhibits innate IFN-β production by enhancing deacetylation of Ifnb1 promoter, exhibiting a previous unknown non-classical role in innate immunity, which also suggests a role of Rb in the regulation of type I IFN production in inflammatory or autoimmune diseases.


Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide.
In patients with acute coronary syndromes (ACS), troponin I (TnI), C-reactive protein (CRP), and B-type natriuretic peptide (BNP) each predict adverse cardiac events. Little is known, however, about the utility of these biomarkers in combination. Baseline measurements of TnI, CRP, and BNP were performed in 450 patients in OPUS-TIMI 16. Elevations in TnI, CRP, and BNP each were independent predictors of the composite of death, myocardial infarction (MI), or congestive heart failure (CHF). When patients were categorized on the basis of the number of elevated biomarkers at presentation, there was a near doubling of the mortality risk for each additional biomarker that was elevated (P=0.01). Similar relationships existed for the endpoints of MI, CHF, and the composite, both at 30 days and through 10 months. In a validation cohort of 1635 patients in TACTICS-TIMI 18, the number of elevated biomarkers remained a significant predictor of the composite endpoint after adjustment for known clinical predictors: patients with one, two, and three elevated biomarkers had a 2.1- (P=0.006), 3.1- (P<0.001), and 3.7- (P=0.001) fold increase in the risk of death, MI, or CHF by 6 months. Troponin, CRP, and BNP each provide unique prognostic information in patients with ACS. A simple multimarker strategy that categorizes patients based on the number of elevated biomarkers at presentation allows risk stratification over a broad range of short- and long-term major cardiac events.


Environmentally relevant impacts of nano-TiO2 on abiotic degradation of bisphenol A under sunlight irradiation.
Understanding the effects of nano-TiO2 particles on the environmental behaviors of organic pollutants in natural aquatic environments is of paramount importance considering that large amount of nano-TiO2 is being released in the environment. In this study, the effect of nano-TiO2 on the degradation of bisphenol A (BPA) in water was investigated under simulated solar light irradiation. The results indicated that nano-TiO2 at environmentally relevant concentration (1 mg/L) could significantly facilitate the abiotic degradation of BPA (also at low concentration) under mild solar light irradiation, with the pseudo first-order rate constant (kobs) for BPA degradation raised by 1-2 orders of magnitude. As reflected by the inhibition experiments, hydroxyl radicals (OHs) and superoxide radical species were the predominant active species responsible for BPA degradation. The reaction was affected by water pH, and the degradation rate was higher at acidic or alkaline conditions than that at neutral condition. Humic acid (HA) also affected the reaction rate, depending on its concentration. At lower concentration (the mass ratio of HA/nano-TiO2 was 0.1:1), HA improved the dispersion and stability of nano-TiO2 in aquatic environment. As a result, the yield of OHs by nano-TiO2 under sunlight irradiation increased and BPA degradation was facilitated. When the HA concentration increased, a coating of HA formed on the surface of nano-TiO2. Although nano-TiO2 became more stable, the light absorption by nano-TiO2 was significantly reduced due to the strong light absorption of the HA coated on the surface. As a consequence, the yield of OH decreased and BPA degradation was depressed. The results imply that nano-TiO2 at low concentration may distinctly mediate BPA degradation, and can contribute to the natural attenuation of some organic pollutants in aquatic environment with low level of HA. However, this process would be significantly reduced in the presence of high level of HA.


Enterotoxic effect of stool supernatant of Cryptosporidium-infected calves on human jejunum.
The clinical pattern of cryptosporidial diarrhea suggests an enterotoxic mechanism. No evidence for this mechanism has been reported thus far. This study aimed to look for enterotoxic effect elaborated by Cryptosporidium. The effects on human intestinal transport of stool supernatant of diarrheal calves infected with Cryptosporidium parvum were examined. Aliquots of centrifuged and filtered stools were added to the mucosal or serosal side of human jejunum obtained from patients undergoing surgery and mounted in Ussing chambers. Electrical parameters were recorded. Stool supernatants of uninfected calves served as a control. The mucosal addition of 2.5 mg protein of fecal supernatant from diarrheal calves induced a prompt and significant increase in short circuit current with no effects on tissue conductance. The serosal addition of this material and the addition of control supernatant to either side did not induce modifications of electrical parameters. The enterotoxic effect was dose-dependent and saturable. It was reversible by withdrawing the supernatant from the incubation medium. The electrical effect was chloride- and calcium-dependent and was sensitive to heating. An enterotoxic activity is present in the stools of Cryptosporidium-infected calves. This activity may be responsible for secretory diarrhea in humans.


Advances in structural analysis and process monitoring of thermoplastic composite pipes.
Thermoplastic composite pipes (TCP) in comparison to other pipes have proven beneficial features due to its flexibility which includes being fit for purpose, lightweight and no corrosion. However, during the manufacturing of TCP which involves the consolidation process, certain defects may be induced in it because of certain parameters, and this can affect the performance of the pipe in the long run as the induced defects might lead to in-service defects. Current techniques used in the industry are facing challenges with on-the-spot detection in a continuous manufacturing system. In TCP manufacturing process, the pipe is regularly monitored. When a defect is noticed, the whole process stops, and the appropriate action is taken. However, shutting down the process is costly; hence it is vital to decrease the downtime during manufacturing to the barest minimum. The solutions include optimizing the process for reduction in the manufacturing defects amount and thoroughly understanding the effect of parameters which causes certain defect types in the pipe. This review covers the current state-of-the-art and challenges associated with characterizing the identified manufacturing induced defects in TCP. It discusses and describes all effective consolidation monitoring strategies for early detection of these defects during manufacturing through the application of suitable sensing technology that is compatible with the TCP. It can be deduced that there is a correlation between manufacturing process to the performance of the final part and selection of characterization technique as well as optimizing process parameters.


Improved Nanopore full-length cDNA sequencing by PCR-suppression.
Full-length transcript sequencing remains a main goal of RNA sequencing. However, even the application of long-read sequencing technologies such as Oxford Nanopore Technologies still fail to yield full-length transcript sequencing for a significant portion of sequenced reads. Since these technologies can sequence reads that are far longer than the longest known processed transcripts, the lack of efficiency to obtain full-length transcripts from good quality RNAs stems from library preparation inefficiency rather than the presence of degraded RNA molecules. It has previously been shown that addition of inverted terminal repeats in cDNA during reverse transcription followed by single-primer PCR creates a PCR suppression effect that prevents amplification of short molecules thus enriching the library for longer transcripts. We adapted this method for Nanopore cDNA library preparation and show that not only is PCR efficiency increased but gene body coverage is dramatically improved. The results show that implementation of this simple strategy will result in better quality full-length RNA sequencing data and make full-length transcript sequencing possible for most of sequenced reads.


[Contribution of anesthesia to workflow operation].
The changes in our health care system caused by the introduction of DRGs make it necessary for us to abandon departmental process structures in favour of total hospital orientated process structures. An interdisciplinary approach is crucial to enable the most effective use of personnel and material resources. Future orientated information technology and organisational structures will enable us to process our patients effectively and efficiently from pre-admission to discharge. Anaesthesia has to be integrated into a patient management system for in- and out-patients. The essential matters for consideration are anaesthesia consulting hours, the common establishment of process structures for preoperative care, operation room management and postoperative patient care. Routine controls and analysis of the required teamwork reveal improvement potential and enable us to use the necessary control elements effectively.


CO Emission from an Impinging Non-Premixed Flame.
Carbon monoxide (CO) results from the incomplete oxidation of hydrocarbon fuels. While CO can be desirable in some syngas processes, it is a dangerous emission from fires, gas heaters, gas stoves, or furnaces where insufficient oxygen in the core reaction prevents complete oxidation of fuel to carbon dioxide and water, particularly when the reaction is interrupted by interaction with relatively cool solid boundaries. This research examines the physico-thermo-chemical processes responsible for carbon monoxide release from a small laminar non-premixed methane/air flame impinging on a nearby surface. We measure the changes in CO emission as correlated with variations in flame structure observed using planar laser induced fluorescence (PLIF of OH and 2-photon CO), and two-line OH PLIF thermometry, as a function of burner-to-plate distance. In particular, this work combines the use of OH and CO PLIF, and PLIF thermometry to describe the relative locations of the CO rich region, the peak heat release zone as indicated by chemiluminescence and OH gradients, and the extended oxidative zone in the impinging flames. The results show that CO release correlates strongly with stagnating flow-driven changes in the location and extent of high concentration regions of OH in surface-impinging diffusion flames.


Carcinogenic nitrosamines: free radical aspects of their action.
NDMA and other nitrosamines may be activated into DNA binding intermediates by a cytochrome P450-dependent formation of alpha-nitrosamino radicals or photochemically. Within the catalytic site of cytochrome P450, these radical intermediates either combine with HO. to form alpha-hydroxynitrosamines or decompose into nitric oxide and N-methylformaldimine. In the presence of phosphate, nutagenic alpha-phosphonooxy derivatives are formed from radicals generated chemically/photochemically. Studies on lipid peroxidation, in vivo and in vitro, have further suggested that radicals are formed as intermediates from N-nitrosodialkylamines. The level of nitrosamine-induced lipid peroxidation parallels hepatocarcinogenicity in rats. These data, although preliminary, provide further evidence that free radical damage and DNA alkylation are involved in carcinogenesis induced by nitrosamines.


Misuse of non-prescription codeine containing products: Recommendations for detection and reduction of risk in community pharmacies.
Misuse of opioid analgesics is an emergent global public health concern. Codeine has an identified abuse liability, given its effect and development of tolerance within a short timeframe on regular or excessive use. Estimation and management of misuse of over the counter (OTC) codeine containing products are hampered by widespread and easy availability and the heterogeneous and hidden nature of misuse. Continued debate around availability centre on increasing evidence of misuse, dependence and adverse health effects associated with presence of non-opioid agents (paracetamol, ibuprofen) in combination products, and lack of evidence of a significant clinical analgesic benefit of combining low dose codeine in OTC products. Limited up scheduling that still enables purchase of codeine products without a prescription, and varied measures of pharmacist intervention at point of sale have not succeeded in curtailing therapeutic and non-therapeutic forms of misuse. This commentary broadly discusses the concepts of medication misuse, codeine's potential for misuse and dependence, characteristics of codeine misuse in general, harms from OTC codeine products in particular, 'unique issues' with OTC codeine products, the problems with scheduling solutions and pharmacy based interventions targeting users, along with the supports needed for these interventions. The recent introduction of new OTC combinations of non-opioid agents which provide greater analgesic efficacy than OTC codeine combination analgesics with no risk of opioid dependence provides a satisfactory alternative to these widely misused products.


Leaching of phthalate acid esters from plastic mulch films and their degradation in response to UV irradiation and contrasting soil conditions.
Phthalate acid esters (PAEs) are commonly used plastic additives, not chemically bound to the plastic that migrate into surrounding environments, posing a threat to environmental and human health. Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) are two common PAEs found in agricultural soils, where degradation is attributed to microbial decomposition. Yet the impact of the plastic matrix on PAE degradation rates is poorly understood. Using 14C-labelled DBP and DEHP we show that migration from the plastic matrix into soil represents a key rate limiting step in their bioavailability and subsequent degradation. Incorporating PAEs into plastic film decreased their degradation in soil, DBP (DEHP) from 79% to 21% (9% to <1%), over four months when compared to direct application of PAEs. Mimicking surface soil conditions, we demonstrated that exposure to ultraviolet radiation accelerated PAE mineralisation twofold. Turnover of PAE was promoted by the addition of biosolids, while the presence of plants and other organic residues failed to promote degradation. We conclude that PAEs persist in soil for longer than previously thought due to physical trapping within the plastic matrix, suggesting PAEs released from plastics over very long time periods lead to increasing levels of contamination.


Burns in the Lebanon War 1982: "the blow and the cure".
There were 70% more burns in the October 1973 war than in the Six Day War of 1967. This increase caused great concern and emphasized the need for better personal and crew protection against burns. Some of these measures were already implemented by the outbreak of the 1982 war in Lebanon. Analysis of the burn injuries of this war is the subject of this short report.