Prognostication in advance cancer: nurses' perceptions of the dying process.
To determine how experienced nurses describe the dying process of patients with advanced cancer. Fifteen nurses, experienced in the care of patients with advanced cancer, employed by a midsize midwestern hospice or academic inpatient oncology unit. Individual interviews using structured and semi-structured questions. Responses were content-analyzed using Krippendorff's techniques. Dying process in cancer. Nurses view the dying process as a weeks-to-months-long, multidimensional process that encompasses physical, psychosocial, and spiritual/existential domains. Impending death is recognized and monitored. Common clinical signs include declining interest in life, increased weakness, somnolence, and changes in respiratory, circulatory, and cognitive status. Active (or acute) dying processes are recognized and monitored by nurses; the complexities and patterns of the phenomenon remain unarticulated. Future research could explore both empirical and contextual aspects of acute dying processes. Nurses are in a position to develop useful knowledge about acute dying processes in cancer.


Dosimetric characteristics of the MammoSite RTS, a new breast brachytherapy applicator.
A new device has been developed with the goal of making breast-conserving therapy more widely available, by making breast brachytherapy as monotherapy simpler and more accurate. This is the first published report on the dosimetric characteristics of this device. The experience of a single institution participating in a multi-institutional trial is reported. Twelve patients were enrolled, of whom 8 were treated. Computed tomography scans of all 12 patients were obtained before initiation of treatment. A commercial three-dimensional planning system was used for retrospective detailed analysis of dosimetry, including dose-volume histograms and, in selected patients, skin dose distributions. These data were compared to those of a similar group of patients, analyzed previously, that was treated with interstitial high-dose-rate brachytherapy. Compared with interstitial brachytherapy, the MammoSite device resulted in a treatment dose that was less uniform, with a mean dose homogeneity index of 0.77 vs. 0.93. Coverage and reproducibility were improved, with a mean D90 (minimum dose to 90% of target volume) of 90.0% of prescribed dose (SD 0.5, range: 89.2-90.8%) vs. 69.8% (SD 7.3, range: 61.1-83.5%) for interstitial brachytherapy. Reproducible placement was easily achieved in this very early experience, indicating a much smaller "learning curve" than for interstitial brachytherapy. Because skin doses can be increased with the use of this device, caution is indicated, although simple maneuvers can significantly reduce skin dose.


Norharman-induced motoric impairment in mice: neurodegeneration and glial activation in substantia nigra.
The beta-carboline norharman is present in cooked food and tobacco smoke and show structural resemblance to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. C57BL/6 mice were injected subcutaneously with norharman (3 and 10 mg/kg) twice per day for five consecutive days. Eighteen hours after the last dose an increased expression of glial fibrillary acidic protein and fluoro-jade staining were demonstrated whereas the number of tyrosine hydroxylase positive cells were unchanged in the substantia nigra. Two weeks after the last treatment a decreased motor activity was observed whereas cognitive functions remained intact. In cultured PC12 cells norharman treatment induced mitochondrial dysfunction and increased the number of caspase-3 and TUNEL-positive cells. The results demonstrate that norharman induced apoptosis in cultured cells as well as early neurodegeneration, glial activation and sustained motor deficits in mice and suggest that exposure to norharman may contribute to idiopathic Parkinson's disease.


Cystoid macular edema occurring 13 years after cataract extraction.
Thirteen years after cataract extraction, a patient complained of diminished visual acuity. In the interim visual acuity was 6/6 (20/20), or 6/7.5 (20/25+2). Fluorescein angiography demonstrated cystoid macular edema. Except for vitreous adherence to the inner surface of the cataract wound, no ocular cause for the macular edema was apparent.


Impact of radiofrequency ablation on the management of patients with hepatocellular carcinoma in a specialized centre.
Radiofrequency ablation (RFA) has been used increasingly in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to investigate changes in the treatment pattern of primary HCC following the implementation of RFA in a specialized surgical centre. This was a retrospective analysis of all 894 patients admitted for treatment of primary HCC over 36 months. There was no difference in the age, sex ratio, liver function according to Child-Pugh grade, serum alpha-fetoprotein concentration, hepatitis B surface antigen status and tumour size among patients before and after the introduction of RFA therapy. Fifty-one patients (10.6 per cent) with primary HCC received RFA treatment after its implementation. There was a 6.8 per cent reduction in the number of patients who had supportive treatment (P = 0.041) and a 3.2 per cent reduction in surgical treatment. The hospital mortality rates for RFA and surgery were 2.0 and 4.9 per cent respectively. The overall survival rates at 6, 12 and 18 months for patients treated with RFA were 92.2, 73.4 and 61.2 per cent respectively. The corresponding survival rates for the 213 patients who had surgery were 88.0, 77.0 and 71.5 per cent. These values were no different from those in patients who had RFA (P = 0.718). Patients treated with RFA or surgery survived longer than those who had other treatments. RFA had a significant impact on the management of primary HCC, increasing the number of patients suitable for liver-directed therapy and leading to survival benefit. RFA may become the treatment of choice for patients with irresectable HCC.


The long-term pharmacokinetics and safety of adding low-dose ritonavir to a nelfinavir 1,250 mg twice-daily regimen in HIV-infected patients.
To evaluate the long-term pharmacokinetics and safety of adding ritonavir 100 mg twice-daily to a nelfinavir 1250 mg twice-daily regimen in HIV-infected patients. This was a prospective, randomized, open-label, controlled 24-week study. Sixteen patients receiving a nelfinavir 1250 mg twice-daily regimen with plasma viral load <1000 HIV-1 RNA copies/mL were randomized to continue treatment or to have ritonavir 100 mg twice-daily added. Safety, including fasting lipid levels, was evaluated at weeks 4, 12 and 24. Patients who were randomized to have ritonavir added (n=9) participated in three 12-h pharmacokinetic evaluations at baseline, week 4 and week 24. Increases in median nelfinavir steady-state plasma concentrations at 12 h (C(12)) from 512 to 773 ng/mL [median difference 450 ng/mL; 95% confidence interval (CI) 116--1510 ng/mL] and in median active nelfinavir metabolite M 8 C(12) from 107 to 603 ng/mL (median difference 545 ng/mL; 95% CI 370--891) were seen after the addition of low-dose ritonavir (baseline to week 24). There were no differences between the nelfinavir or M 8 pharmacokinetic parameters at weeks 4 and 24. No significant changes or differences in the concentration of fasting total cholesterol, low-density lipoprotein (LDL) cholesterol or total triglycerides or in the occurrence of adverse events were observed within or between the two groups. Nelfinavir and especially M 8 concentrations are increased when low-dose ritonavir is added to a nelfinavir-containing regimen. The combination seems to be safe and the nelfinavir/ritonavir regimen could be an option in patients with low nelfinavir+M 8 concentrations.


Recall of residential history and dietary habits during pregnancy and lactation in the distant past: reliability of questionnaire-based radiation doses for persons exposed in utero and early life.
This study evaluates the reliability of information obtained by standardized questionnaires used in by personal interviews for estimation of radiation thyroid doses of 1065 individuals in the Belarusian cohort of individuals who were exposed in utero and early life following the Chernobyl accident in April 1986. Data from two interviews conducted in 2012-2017 and in 2018-2022 with mothers, who were pregnant or gave birth shortly after the Chernobyl accident, were analysed. The most reliable answers dealt with various attributes related to residential history. In contrast, the reliability of answers regarding consumption rates of milk from privately owned cows or trade network was moderate, while the agreement in responses for consumption of milk products and leafy vegetables was fair. Information from the two interviews was used to calculate thyroid doses received by the cohort members. Specifically, 'model-based' thyroid doses due to 131I were estimated using input data on individual residential history and food consumption reported during the personal interviews and ecological data (131I ground deposition in the corresponding settlements). In addition, for a subset of cohort subjects (n = 205) whose mothers were measured for 131I thyroid activity, 'measurement-based' thyroid doses were calculated by adjusting the model-based dose using a scaling factor that is defined as the ratio of measured 131I thyroid activity to model-based 131I thyroid activity calculated for the date of measurement. A moderate agreement was observed for total (prenatal and postnatal) model-based thyroid doses due to 131I intake, the arithmetic mean ± standard deviation for the Jaccard similarity coefficient ([Formula: see text]) was 0.45 ± 0.34 (median = 0.39), while measurement-based doses showed a much better agreement with a [Formula: see text] of 0.78 ± 0.29 (median = 0.93). For model-based thyroid doses from external irradiation and from ingestion of 134Cs and 137Cs, [Formula: see text] was 0.82 ± 0.23 (median = 0.90) and 0.84 ± 0.24 (median = 0.96), respectively. Measurement-based doses due to ingestion of radiocaesium isotopes resulted in an almost perfect agreement, [Formula: see text] was 0.91 ± 0.19 (median = 1.0). The present findings suggest that long-term memory recall can be reliable, if a person is asked about unique or important life events, such as pregnancy and childbirth occurring around the time of a nuclear reactor accident. However, the substantial difference (more than 10 times) observed for model-bases doses calculated using the two questionnaires represents an important source of human factor uncertainties that needs to be considered in any dose response analyses. Other lessons learned from this study are that (i) individual measurements of radionuclides in the human body are the most valuable source of information for estimating radiation doses, and (ii) whenever a radiation accident occurs, a sample of affected people should be asked to keep a diary, if at all possible.


Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Exhibits High Predicted Binding Affinity to ACE2 from Lagomorphs (Rabbits and Pikas).
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic COVID-19. The virus infects human cells by binding of the virus spike to the cell receptor ACE2. The crystal structure of SARS-CoV-2 spikes in complex with human ACE2 has recently been solved, and the main amino acid residues involved in the virus-receptor complex have been detected. To investigate the affinity of ACE2 of lagomorphs to the SARS-CoV-2 spike, ACE2 sequences from rabbits and American pikas were compared with human ACE2 and with ACE2 from mammals with different susceptibility to the virus. Models of the complex formed by SARS-CoV-2 spike and ACE2 from lagomorphs and from other mammals were created for comparative studies. ACE2 of lagomorphs showed fewer substitutions than human ACE2 in residues involved in the ACE2-SARS-CoV-2 spike complex, similar to cats. Analysis of the binding interface of the simulated complexes ACE2-SARS-CoV-2 spike showed high affinity of the ACE2 of lagomorphs to the viral spike protein. These findings suggest that the spike of SARS-CoV-2 could bind the ACE2 receptor of lagomorphs, and future studies should investigate the role of lagomorphs in SARS-CoV-2 epidemiology. Furthermore, the risks to humans coming into close contacts with these animals should be evaluated.


Increased frequency of IgD-CD27hiCD38hi B cells and its association with the renal involvement in ANCA-associated vasculitis.
B cells have been highlighted in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by the identification of activated B cells in granulomatous lesions and the efficacy of B cell depletion in treatment of AAV patients in the current study; we aimed to investigate the frequency of a specific B cell subset, IgD-CD27hiCD38hi B cells in AAV patients, and its association with the disease severity of AAV. Blood samples of patients with AAV in active stage and in remission were collected. The frequency of IgD-CD27hiCD38hi B cells was detected by flow cytometry, and its correlation with clinicopathological parameters was analyzed. Our results showed a significant increase of circulating IgD-CD27hiCD38hi B cells in AAV patients in active stage compared with patients in remission and healthy donors, and the frequency of IgD-CD27hiCD38hi B cells correlated with the severity of renal involvement, including serum creatinine, estimated glomerular filtration rate, and percentages of total crescents in renal biopsies. The results indicated that IgD-CD27hiCD38hi B cells could reflect disease severity of renal involvement in AAV.


Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia.
The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.


Gender identity change in a female adolescent transsexual.
Two years of individual and milieu therapy are described of a 14 1/2-year-old girl who had presented with the persistent request to have a sex-change operation since age 12. Her past history was obtained from her parent and the records of the child guidance clinic which evaluated her at 3 years of age. She gives a history of remarkable tomboyism during her latency years and increasing withdrawal from peers and family during early adolescence. The patient's personal and family dynamics are explored, and these major therapeutic themes are discussed. The individual and milieu therapy are described and discussed with some speculation about the reasons for her positive response to psychotherapy. It would appear that this is a rare case of postpubertal female transsexual reported to have made a gender identity change.


Vasopressin injections impair working memory in a delayed matching to sample task in rats.
Effects of vasopressin were measured in a nonspatial working memory task: food-reinforced, delayed matching to sample. Subcutaneous injections of 0.2 microgram of lysine vasopressin (LVP) or saline were alternately administered to Sprague-Dawley rats after the presentation of the sample and compared to the effect of the same treatments given to a yoked control group of rats. Different durations of sample presentation (5 and 30 min) and various retention intervals (10 min, 3 h, 24 h) were selected. The results showed that LVP never facilitated retention performance: there was no improvement under conditions of weak memory (short presentation of the sample and long retention interval); moreover LVP abolished the facilitation normally obtained when either the length of the sample presentation was longer or the duration of the retention interval was shorter. The performance after the injection of the peptide was differentially impaired, according to brightness of the sample which had been presented: after the presentation of the white box, LVP injections lead to more errors and after that of the black one the treatment induced an increase in latencies of response. All these data may suggest that the physiological consequences of hormonal modifications triggered by the LVP injection are processed along with the stimuli of the learning episode and interfere with the learned positive value of the sample.


Fluorescein angiography in retrolental fibroplasia: experience from 1969-1977.
Acute proliferative retrolental fibroplasia (RLF) has been studied in premature infants employing a Zeiss fundus camera and fluorescein angiography. A total of 164 angiograms have been performed on 122 infants. At the present time, angiography is reserved for studying infants with peculiar or puzzling fundus pictures. A dose of 0.1-0.4 cc of 10% sodium fluoresceinate is employed, depending on the age and the weight of the baby. Fluorescein clearly outlines the major arteriovenous shunt in the retina, which is the hallmark of acute RLF. The shunt fills with fluorescein and leaks it profusely. On regression, a fine brush border of capillaries is seen in the region where the shunt previously had been located. Study of the population susceptible to RLF reveals it to be the smallest sickest babies in the premature nursery.


Immunization with plasmid DNA encoding a truncated, secreted form of the bovine viral diarrhea virus E2 protein elicits strong humoral and cellular immune responses.
The major protective antigen of bovine viral diarrhea virus (BVDV), the E2 protein, is cell-associated and not expressed on the cell surface. In this study we evaluated a DNA vaccine encoding various secreted versions of E2. In vitro analysis demonstrated that deletion of the transmembrane anchor and addition of the signal sequence of bovine herpesvirus-1 (BHV-1) (gDsDeltaE2) resulted in efficient secretion of E2 into the culture medium. In contrast, full-length E2, either without or with gDs (gDsE2), as well as truncated E2 without gDs (DeltaE2), remained entirely cell-associated. Mice immunized with plasmid encoding gDsDeltaE2 developed significantly higher IgG and virus neutralizing antibody titres compared to animals vaccinated with plasmid encoding E2, DeltaE2 or gDsE2. To optimize secretion of E2, the efficiency of gDs was compared with that of the tissue plasminogen activator signal (tPAs) sequence. In addition, the effect of the plasmid backbone was assessed by comparing two vectors. Four plasmids, pMASIA-gDsDeltaE2, pMASIA-tPAsDeltaE2, pSLKIA-gDsDeltaE2 and pSLKIA-tPAsDeltaE2, were constructed and administered intradermally to mice. The mice immunized with pMASIA-tPAsDeltaE2 developed the strongest and most balanced immune responses. Vaccination of cattle confirmed that pMASIA-tPAsDeltaE2 elicited both strong humoral and cellular immune responses and thus could be a candidate DNA vaccine against BVDV.


Effects of biological factors and health condition on mercury and selenium concentrations in the cartilage, meniscus and anterior cruciate ligament.
Due the long-term nature of joint tissue remodeling processes, knee structures including meniscus and anterior cruciate ligament (ACL) can be a model for studying the bioaccumulation of mercury (Hg) and selenium (Se). The accumulation and retention of Hg in human tissues can have a negative effect on the proper functioning of homeostasis-affecting organisms. A factor of chronic poisoning with Hg forms is probably the Se:Hg ratio in tissues. Se:Hg molar ratios below one may increase Hg toxicity potentials, while molar ratios that approach or exceed one effectively may protect against Hg toxicity. Therefore, the aim of the study was to determine total mercury (THg), Se, and Se:THg molar ratios in the cartilage, meniscus and ACL of patients with osteoarthritis (OA) from northwestern Poland. In all studied samples (n=95), we observed higher Se than THg concentration. Taking into consideration the biological factors, we found significantly higher THg levels in the cartilage of women, patients under 65 years of age, patients without hypertension and in the ACL of patients with spinal degenerative disease. We found higher Se levels in the meniscus in women than in men. In all studied parts of the knee joint, we found the Se:THg molar ratio higher than one, which suggests that the joint forming structures are not much exposed to THg. Moreover the results reported here may provide a basis for establishing reference values for the meniscus and ACL in patients with OA who had undergone knee replacement surgery.


Mg-O-F Nanocomposite Catalysts Defend against Global Warming via the Efficient, Dynamic, and Rapid Capture of CO2 at Different Temperatures under Ambient Pressure.
The utilization of Mg-O-F prepared from Mg(OH)2 mixed with different wt % of F in the form of (NH4F·HF), calcined at 400 and 500 °C, for efficient capture of CO2 is studied herein in a dynamic mode. Two different temperatures were applied using a slow rate of 20 mL·min-1 (100%) of CO2 passing through each sample for only 1 h. Using the thermogravimetry (TG)-temperature-programed desorption (TPD) technique, the captured amounts of CO2 at 5 °C were determined to be in the range of (39.6-103.9) and (28.9-82.1) mgCO2 ·g-1 for samples of Mg(OH)2 mixed with 20-50% F and calcined at 400 and 500 °C, respectively, whereas, at 30 °C, the capacity of CO2 captured is slightly decreased to be in the range of (32.2-89.4) and (20.9-55.5) mgCO2 ·g-1, respectively. The thermal decomposition of all prepared mixtures herein was examined by TG analysis. The obtained samples calcined at 400 and 500 °C were characterized by X-ray diffraction and surface area and porosity measurements. The total number of surface basic sites and their distribution over all samples was demonstrated using TG- and differential scanning calorimetry-TPD techniques using pyrrole as a probe molecule. Values of (ΔH) enthalpy changes corresponding to the desorption steps of CO2 were calculated for the most active adsorbent in this study, that is, Mg(OH)2 + 20% F, at 400 and 500 °C. This study's findings will inspire the simple preparation and economical design of nanocomposite CO2 sorbents for climate change mitigation under ambient conditions.


Pre-treatment drug resistance among patients initiating antiretroviral therapy (ART) in Zimbabwe: 2008-2010.
Zimbabwe set up 12 sentinel sites to monitor HIV drug resistance (HIVDR) following the international standards for prevention of HIVDR from 2008 to 2010. Participants were consecutively enrolled. Blood was collected and used for CD4 count, viral load (VL) and pre-treatment DR (PDR) tests besides routine baseline tests. We analyzed the characteristics of participants enrolled into the survey and estimated the point prevalence of PDR and its associated factors among ART initiators in a cross-sectional analysis using the baseline data collected from a prospective cohort in 12 purposefully selected sentinel sites. A total of 1728 participants (96 % response rate) were enrolled and 1610 had complete data. Of the 1610 there were more females (68.7 %) than males (31.3 %). The median CD4 count was 168 cells/mm(3) with males having lower values (P = 0.003). Ninety-six percent of participants had a VL ≥ 1000 copies/ml and the median VL was 128,000. Previous exposure to antiretroviral drugs (ARVs) was mainly through PMTCT (5 % of the participants). Overall, PDR mutations were detected in 6.3 % (95 % CI 5.2-7.7) of the 1480 successfully genotyped participants. However, the prevalence of PDR mutations was double for those with previous exposure (12.1 %) to ARVs compared with those without previous exposure (5.7 %, P = 0.002). The results show a moderate level of PDR prevalence among ART initiators. To maintain the efficacy of the current first-line regimens, there is need to strengthen all HIVDR prevention efforts and to conduct further studies to investigate optimal strategies that can prolong the efficacy of first-line ARV regimens in the country.


Employment of reverse optimization to relax manufacturing tolerances imposed on system constructional parameters associated with complex optical systems.
I describe a practical method for facilitating the construction of a complex optical arrangement that was extremely sensitive to manufacturing defects. I discuss dealing with the actual tolerancing process employed and outline the reverse optimization technique adopted to take the necessary corrective action with regard to the lens to yield the performance specified. The optical design to which the techniques are addressed is that of a high-performance color-corrected scanner lens, capable of resolving 200 line pairs/mm over a 10-mm(2) object.


Walking on eggshells: A life defined by obsessive-compulsive personality disorder.
WHAT IS KNOWN ON THE SUBJECT?: Obsessive-compulsive personality disorder (OCPD), which is experienced by 2.1-7.9% of the population, is characterized by an excessive need for orderliness, neatness and perfectionism. WHAT DOES THE PAPER ADD TO EXISTING KNOWLEDGE?: Existing studies on OCPD commonly focus on the physiological aspects, treatment and/or comparison of features with other disorders. Studies that explore the personal experiences related to OCPD are lacking and so the human element of this condition is missing. This paper contributes to this gap by presenting a glimpse into life with OCPD. The narrative is provided by the daughter of a person who lived with OCPD and presents the ordeals, victories and aspects of everyday life as framed by the condition. Whilst personality disorders such as OCPD are subjected to a high level of stigma, this relative's story shows that love and compassion can be found even in the darkest corridors that OCPD can take one to. As the story shows, behind every disorder there is a human being and the disorder is not the totality of that being. In this view, the paper sheds light on the human element related to the condition. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The paper highlights the need for continuous, hands-on community support to those experiencing OCPD and their significant others. In order to enhance continuity of care, support is ideally centralized and provided by one keyworker who builds a strong therapeutic relationship with the person and their loved ones.


Distribution and disinfection of bacterial loadings associated with particulate matter fractions transported in urban wet weather flows.
Urban runoff is a resource for reuse water. However, runoff transports indicator and pathogenic organisms which are mobilized from sources of fecal contamination. These organisms are entrained with particulate matter (PM) that can serve as a mobile substrate for these organisms. Within a framework of additional treatment for reuse of treated runoff which requires the management of PM inventories in unit operations and drainage systems there is a need to characterize organism distributions on PM and the disinfection potential thereof. This study quantifies total coliform, Escherichia coli, fecal streptococcus, and enterococcus generated from 25 runoff events. With the ubiquity and hetero-dispersivity of PM in urban runoff this study examines organism distributions for suspended, settleable and sediment PM fractions differentiated based on PM size and transport functionality. Hypochlorite is applied in batch to elaborate inactivation of PM-associated organisms for each PM fraction. Results indicate that urban runoff bacterial loadings of indicator organisms exceed U.S. wastewater reuse, recreational contact, and Australian runoff reuse criteria as comparative metrics. All monitored events exceeded the Australian runoff reuse criteria for E. coli in non-potable residential and unrestricted access systems. In PM-differentiated events, bacteriological mobilization primarily occurred in the suspended PM fraction. However, sediment PM shielded PM-associated coliforms at all hypochlorite doses, whereas suspended and settleable PM fractions provide less shielding resulting in higher inactivation by hypochlorite.


Photocatalytic degradation of Acid Red 88 using Au-TiO(2) nanoparticles in aqueous solutions.
Metal loaded semiconductors in general possess greater photocatalytic activity than pure semiconductors. Hence, with an attempt to achieve higher photocatalytic activity, Au-TiO(2) photocatalysts were prepared by deposition-precipitation method and used for the photocatalytic degradation of an azo dye (Acid Red 88; AR88). The materials were characterized by different analytical techniques. A possible mechanism for the photocatalytic degradation of AR88 by Au-TiO(2) in the absence and presence of other oxidizing agents (peroxomonosulfate (PMS), peroxodisulfate (PDS) & hydrogen peroxide (H(2)O(2))) has been proposed. The extent of mineralization of the target pollutant was also evaluated using Total Organic Carbon (TOC) analysis.


Usefulness of electrocardiogram mA modulation during the electrocardiogram-gated CT scan in paediatrics with high heart rate for different helical pitch: a phantom-based assessment study.
We investigated the effect of electrocardiographic (ECG) mA-modulation of ECG-gated scans of computed tomography (CTA) on radiation dose and image noise at high heart rates (HR) above 100 bpm between helical pitches (HP) 0.16 and 0.24. ECG mA-modulation range during ECG-gated CTA is 50-100 mA, the phase setting is 40-60% and the scan range is 90 mm for clinical data during HR for 90, 120 and 150 bpm. Radiation dose and image noise in Housfield units are measured for CT equipment during HR for 90, 120 and 150 bpm between HP 0.16 and 0.24. ECG mA-modulation, dose reduction ratio for HR 90, 120 and 150 bpm are 19.1, 13.4 and 8.7% at HP 0.16 and 17.1, 13.3 and 7.7% at HP 0.24, respectively. No significant differences were observed in image noise between both HP. Dose reductions of 8-24% are achieved with ECG mA-modulation during ECG-gated CCTA scan, which is beneficial even in high HR more than 100 bpm.


The veterinarian's education about the human-animal bond and animal-facilitated therapy.
There is a need to increase curriculum time on the human-animal bond and animal behavior in veterinary medical education. Specific guidelines for veterinarians are described for use of pets in animal-facilitated therapy programs.


ACAOS (Anomalous Coronary Artery From the Opposite Sinus) as Part of a Chaos: 75 Years of Harmonious Occult Coexistence.
It is uncommon for the left anterior descending coronary artery to arise from the contralateral Valsalva sinus, and more of a rarity to see coexistent left main coronary artery anomaly. Our patient reported normal daily physical activity and denied further evaluation (stress test, scintigraphy) or cardiothoracic consultation. She continues to be symptom free at 1-month follow-up.


Lipoprotein lipase activity in cultured macrophage cell line J774(2) and its increase in variants deficient in adenylate cyclase and cyclic AMP-dependent protein kinase.
Three macrophage cell lines, J774(2), CT2 and J7H1 were compared with respect to synthesis and secretion of lipoprotein lipase. The enzyme activity measured was characterized as lipoprotein lipase on the basis of serum dependence and inhibition by 1 M NaCl. Enzyme activity in all three lines increased with time in culture and the highest activity was found in the medium of the CT2 line which is adenylate cyclase deficient while that in the J7H1 line, cyclic AMP-dependent protein kinase deficient, was intermediate. The half life of the enzyme activity in conditioned medium from all three lines was 30-40 min, suggesting that the different levels of activity observed do represent different levels of enzyme production by the cells. About 80% of the lipoprotein lipase activity from all three lines was present in the medium and 50-70% of cellular activity could be released into the medium by a 3-min exposure to heparin. In addition, 24 h incubation with heparin enhanced enzyme secretion in all three lines. To determine the role of cyclic AMP in the regulation of lipoprotein lipase activity use was made of dibutyryl cAMP, methyl isobutylxanthine (IBMX) and cholera toxin. These agents strikingly depressed lipoprotein lipase activity in the J774(2) line but only dibutyryl cAMP was active in the CT2 line (adenylate cyclase deficient). In the J7H1 (protein kinase deficient) line there was no response to dibutyryl cAMP or IBMX over the first 4 h of incubation. Addition of these agents did not affect total cell protein synthesis. The present findings indicate that in the intact cells changes in cyclic AMP levels are associated with a change in the activity of lipoprotein lipase.


Room-temperature and solution-state observation of the mixed-valence cation radical dimer of tetrathiafulvalene, [(TTF)2]+*, within a self-assembled cage.
A mixed-valence state of the cation radical tetrathiafulvalene dimer, [(TTF)2]+*, is generated by the electrochemical oxidation of a stacked TTF dimer accommodated within an organic-pillared coordination cage. This mixed-valence species is remarkably stable (t1/2 = approximately 1 day at room temperature in aqueous solution under air) and clearly characterized by cyclic voltammogram and electronic absorption spectroscopy.


Use of a Bayesian network model to identify factors associated with the presence of the tick Ornithodoros erraticus on pig farms in southern Portugal.
The soft tick Ornithodoros erraticus occurs on pig farms in southern Portugal and Spain and transmits several important pathogens of humans and livestock. Its distribution is patchy and the determinants of its distribution are uncertain. Here, we use a Bayesian network model to explore possible associations between climate, farm management and the presence of O. erraticus. The resulting network confirms previous suggestions that the presence of O. erraticus is more likely in traditionally constructed pig housing, and indicates that carbon dioxide traps are highly effective for the detection of O. erraticus. Our approach also picked up several other intuitively reasonable relationships, including that traditional housing was more likely to be in poor condition and more likely to be out of use, and that buildings which were in use to house pigs were also less likely to be derelict. Neither temperature nor precipitation had any direct effect on the probability of the presence of O. erraticus, suggesting that the distribution of the species is primarily driven by farm management factors.


Evaluating the Effectiveness of Deep Learning Contouring across Multiple Radiotherapy Centres.
Deep learning contouring (DLC) has the potential to decrease contouring time and variability of organ contours. This work evaluates the effectiveness of DLC for prostate and head and neck across four radiotherapy centres using a commercial system. Computed tomography scans of 123 prostate and 310 head and neck patients were evaluated. Besides one head and neck model, generic DLC models were used. Contouring time using centres' existing clinical methods and contour editing time after DLC were compared. Timing was evaluated using paired and non-paired studies. Commercial software or in-house scripts assessed dice similarity coefficient (DSC) and distance to agreement (DTA). One centre assessed head and neck inter-observer variability. The mean contouring time saved for prostate structures using DLC compared to the existing clinical method was 5.9 ± 3.5 min. The best agreement was shown for the femoral heads (median DSC 0.92 ± 0.03, median DTA 1.5 ± 0.3 mm) and the worst for the rectum (median DSC 0.68 ± 0.04, median DTA 4.6 ± 0.6 mm). The mean contouring time saved for head and neck structures using DLC was 16.2 ± 8.6 min. For one centre there was no DLC time-saving compared to an atlas-based method. DLC contours reduced inter-observer variability compared to manual contours for the brainstem, left parotid gland and left submandibular gland. Generic prostate and head and neck DLC models can provide time-savings which can be assessed with paired or non-paired studies to integrate with clinical workload. Reducing inter-observer variability potential has been shown.


Oxidative Potential and Nanoantioxidant Activity of Flavonoids and Phenolic Acids in Sophora flavescens.
In order to further develop and utilize the rutin from Sophora japonica, the contents of total phenolic acids and flavonoids in rutin extracts from different parts of Sophora flavescens were determined, and their antioxidant activities were compared, and the basis of antioxidative activity of Sophora flavescens nanometers was discussed. The experiment found that the total flavonoid content of each extract of Huai Mi was in the range of 5.70-61.55 mg/g, the total phenolic acid content was in the range of 4.07-19.10 mg/g, and the total flavonoid and phenolic acid content of the ethyl acetate extract was significantly higher than other extracts. Its reducing power, light free radicals, DPPH, ABTS+, and scavenging rate are also significantly higher than n-butanol, petroleum ether, and aqueous extracts. ∗ The cleaning ability IC50 values of DPPH· are (0.321 ± 0.0026), (0.213 ± 0.0010), and (0.169 ± 0.0014) mg/mL. The effective components of Sophora japonica are initially separated after the solvent extraction of each phase. The relative content and nanoantioxidant activity of total flavonoids and phenolic acids in the ethyl acetate phase extraction part were significantly stronger than those in the total extract and other extraction parts, and the antioxidant capacity was effectively related to the dose. The flavonoids and phenolic acids in Sophora japonica are closely related to its antioxidant capacity.


The effects of 24 weeks of moderate- or high-intensity exercise on insulin resistance.
This study was designed to investigate the effect of exercise intensity on insulin resistance by comparing moderate- and high-intensity interventions of equal energy cost. Maximum oxygen consumption (VO(2max)), insulin, glucose and triglycerides were measured in 64 sedentary men before random allocation to a non-exercise control group, a moderate-intensity exercise group (three 400-kcal sessions per week at 60% of VO(2max)) or a high-intensity exercise group (three 400-kcal sessions per week at 80% of VO(2max)). An insulin sensitivity score was derived from fasting concentrations of insulin and triglycerides, and insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Data were available for 36 men who finished the study. After 24 weeks, insulin concentration decreased by 2.54+/-4.09 and 2.37+/-3.35 mU l(-1), insulin sensitivity score increased by 0.91+/-1.52 and 0.79+/-1.37, and HOMA-IR decreased by -0.6+/-0.8 and -0.5+/-0.8 in the moderate- and high-intensity exercise groups, respectively. When data from the exercise groups were combined, one-way analysis of variance with one-tailed post hoc comparisons indicated that these changes were significantly greater than those observed in the control group (all P<0.05). Twenty-four week changes in insulin concentration, insulin sensitivity score and HOMA-IR were not significantly different between the exercise groups. These data suggest that exercise training is accompanied by a significant reduction in insulin resistance, as indicated by well-validated surrogate measures. These data also suggest that moderate-intensity exercise is as effective as high-intensity exercise when 400 kcal are expended per session.


Detection of minus-strand hepatitis C virus RNA in tumor tissues of hepatocellular carcinoma.
Recently, the detection of hepatitis C virus (HCV) antibody has been widely performed for clinical serum testing of HCV infection and can be identified in most hepatocellular carcinoma (HCC) cases in Japan. In the current study, the authors detected not only plus-strand but also minus-strand HCV RNA as a template for RNA replication in hepatocytes in the resected tumors of HCC, and they investigated those significant for HCC. The plus-strand and minus-strand HCV RNA were detected using reverse transcription-polymerase chain reaction after the extraction of RNA from the tumor and nontumor tissues of hepatectomized liver, respectively. The detection of HCV RNA in liver tissues from hepatectomized specimens of 20 cases was as follows: in nontumor regions, both of the plus- and minus-strand HCV RNA were detected in 14 cases. Among those cases, plus- and minus-strand HCV RNA were detected in 11 cases, and in another 2 cases, only plus-strand HCV RNA was found in the tumor regions. These results suggest that HCV RNA is able to replicate in tumor tissues of HCC and may be involved in the development of HCC and also that HCV in remnant hepatocytes may cause the recurrence of HCC as secondary carcinogenesis after hepatectomy.


The permeability of bilayer lipid membranes on the incorporation of erythrocyte membrane extracts and the identification of the monosaccharide transport proteins.
1. Extracts of the human erythrocyte membrane have been prepared by five different procedures involving Triton X-100 solubilization and gel chromatography. 2. The extracts have been analysed by gel electrophoresis and incorporated asymmetrically into phosphatidylcholine-cholesterol-n-decane planar bilayers. 3. Removal of excess Triton X-100 from membrane extracts or prolonged storage facilities the proteolysis of membrane extracts with the partial or complete breakdown of band 3 polypeptides (notation of Fairbanks, G., Steck, T.L. and Wallach, D.F.H. (1971) Biochemistry 10, 2606--2616) and the appearance of an enhanced zone 4.5 and low molecular weight material. 4. Incorporation of zone 4.5 polypeptides into bilayer lipid membranes increases their permeability to D-glucose at 27 and 5 degrees C. 5. It is suggested that the components of the monosaccharide system are present in band 3 polypeptides but that they can undergo proteolysis with some retention of transport activity.


Effect of uremic serum on Th17/Treg cell balance and endoplasmic reticulum stress in rats.
The imbalance of T helper 17 (Th17) and regulatory T (Treg) cells exists in the occurrence and development of various diseases. Endoplasmic reticulum stress (ERS) is an important self-protective cellular response to harmful stimuli, such as uremic environment. The objective of this study was to investigate the Th17/Treg cell balance and ERS in a uremic environment and analyze the relationship between them. (1) The rat spleen lymphocytes were extracted and treated with thapsigargin (inducer of ERS) and sodium citrate. The proportion of Th17 and Treg cells were then detected. (2) The uremic serum-cultured lymphocytes were used and divided into three groups: non-uremic serum group, uremic serum group, and uremic serum + sodium citrate group. Afterward, the proportion of Th17/Treg cells and the expression of ERS-related proteins (GRP78 and CHOP) were detected. Thapsigargin had no significant effect on the proportion of Th17 cells within a limited concentration range, but it could reduce the proportion of Treg cells, sodium citrate had a negative influence on the deviation of Th17/Treg cells treated with thapsigargin. Uremic serum treatment reduced the proportion of Treg cells, resulting in an increase of the Th17/Treg ratio. However, sodium citrate had no influence on the deviation of Th17/Treg cells treated by uremic serum. Sodium citrate reduced the elevation of ERS-related proteins induced by uremic serum. Uremic serum can lead to the imbalance of Th17/Treg cells as well as ERS, suggesting that ERS is one of the mechanisms of the imbalance of Th17/Treg cells induced by uremic serum. Sodium citrate can inhibit ERS induced by uremic serum.


Efficacy and safety of ifosfamide in combination with carboplatin and etoposide in small cell lung cancer.
Ifosfamide, a potent alkylating agent, is rarely incorporated into small cell lung cancer (SCLC) treatment. The aim of this study was to assess the efficacy and safety of ifosfamide in combination with carboplatin and etoposide (ICE) in previously untreated patients with SCLC. From January 2002 to January 2014, we consecutively enrolled 69 patients with SCLC who were treated with ICE as initial chemotherapy at Kangbuk Samsung Hospital. The modified ICE regimen consists of ifosfamide 1200 mg/m(2)/day on days 1, 2, and 3 with mesna, etoposide 80 mg/m(2)/day on days 1, 2, and 3, and carboplatin AUC 6 on day 1. Treatment was repeated every 3 weeks and continued for up to nine cycles. Response assessments were performed every three cycles with computed tomography. Among 69 patients with SCLC, the median age was 69 years (range 51-88 years). Sixteen (23 %) patients had limited disease (LD), and 53 (77 %) had extensive disease (ED). The overall response rate was 73 %. Stable disease rate was 20 %. The median overall survival was 11.3 months [95 % confidence interval (CI) 8.9-14.1] in the overall population, 20.6 months (95 % CI 14.2-21.2) for LD and 9.1 months (95 % CI 7.8-11.6) for ED. The median number of administered cycles was 6 (range 1-9). Grade ≥3 hematological toxicities included neutropenia (34 %), anemia (59 %), and thrombocytopenia (31 %). Grade ≥3 non-hematological toxicities included peripheral neuropathy in 2 %. In chemonaïve patients with SCLC, modified ICE is well tolerated and shows favorable efficacy.


N-Acetylcysteine's Renoprotective Effect in Cardiac Surgery: A Systematic Review and Meta-Analysis.
To examine N-acetylcysteine's (NAC's) renoprotective effect in adult cardiac surgeryMethods: PubMed, Ovid Medline, and Embase were searched for randomized controlled trials published between January 1990 and May 2021 that investigated the effect of NAC in preventing acute kidney injury (AKI) in patients undergoing cardiac surgery. The inclusion criterion was studies that assessed the effect of NAC in comparison to placebo by measuring the incidence of AKI. Overall meta-analytic estimates of all 10 included trials showed that NAC did not have a significant effect (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.64-1.10) on AKI. Further subgroup analysis did not show a significant benefit of NAC in preventing AKI. This meta-analysis suggests that NAC does not have a significant effect in reducing the incidence of AKI. However, there is notable heterogeneity among the included studies that could possibly account for the non-significant effect observed. It is worth noting that only one trial administered NAC high dosages perioperatively, and it is the only included trial to show a significant benefit in reducing the incidence of AKI (OR: 0.30, 95% CI: 0.11-0.81). Further studies on this dosage and duration of administration should be conducted to best elucidate the effect of administering NAC.


Poststernotomy arteriovenous fistula of internal mammary origin with pseudoaneurysmal subcutaneous extension.
We describe a very rare subcutaneous pseudoaneurysmal development of an internal mammary arteriovenous fistula supervening after sternal wire closure. The lesion underwent progressive thrombosis and was resected.


Cleft closure (the Bascom cleft lift) for 714 patients-treatment of choice for complex and recurrent pilonidal disease (a cohort study).
Pilonidal disease is a benign condition that affects mainly the young. In existing literature, there is no consensus for best treatment, with multiple operative techniques described, some complex, resulting in a high proportion of failure and/or morbidity. The cleft closure (or cleft lift) described by Bascom and Bascom (Arch Surg, 137, 2002, 1146-50), by comparison, is a simple operation, resulting in healing in the majority and good cosmesis. This is a single surgeon series, with the aim of evaluating outcomes for consecutive patients who underwent cleft closure surgery at two centres (St Mark's Hospital, London, and Queen Alexandra Hospital, Portsmouth) between 1995 and 2021 for either extensive, complex or recurrent pilonidal disease. Primary study outcomes that were measured included rate of primary healing, time to complete healing and rate of recurrence. Some 714 patients had a cleft closure of whom 656 had documented follow-up. Primary healing occurred in 60.7% (n = 398) rising to 88.5% by 12 weeks (n = 562) and 91.8% by 16 weeks. The remaining patients healed over the following weeks with only 19 wounds failing to heal completely (3%), requiring further surgery to achieve healing. After complete healing 5.3% of patients developed recurrent disease at a median of 12 months. Cleft closure is an effective operation for pilonidal disease. Overall, 97% of patients healed without further surgery. A 3% failure rate and 5.3% recurrence rate were observed. This technique could be considered as an alternative procedure to complex flaps or midline excision, in extensive, recurrent and unhealed pilonidal disease.


An electrochemical immunosensor using gold nanoparticles-PAMAM-nanostructured screen-printed carbon electrodes for tau protein determination in plasma and brain tissues from Alzheimer patients.
This work reports a new sensitive strategy for the determination of tau protein, a hallmark of Alzheimer's disease (AD), involving a sandwich immunoassay and amperometric detection at disposable screen-printed carbon electrodes (SPCEs) modified with a gold nanoparticles-poly(amidoamine) (PAMAM) dendrimer nanocomposite (3D-Au-PAMAM) covalently immobilized onto electrografted p-aminobenzoic acid (p-ABA). The capture antibody (CAb) was immobilized by crosslinking with glutaraldehyde (GA) on the amino groups of the 3D-Au-PAMAM-p-ABA-SPCE, where tau protein was sandwiched with a secondary antibody labeled with horseradish peroxidase (HRP-DAb). Amperometry at -200 mV (vs the Ag pseudo-reference electrode) upon the addition of hydroquinone (HQ) as electron transfer mediator and H2O2 as the enzyme substrate was used to detect the immunocomplex formation. The great analytical performance of the immunosensor in terms of selectivity and low limit of detection (LOD) (1.7 pg mL-1) allowed the direct determination of the target protein in raw plasma samples and in brain tissue extracts from healthy individuals and post mortem diagnosed AD patients, using a simple and fast protocol.


Supercapsular Percutaneously Assisted total hip arthroplasty versus lateral approach in Total Hip Replacement. A prospective comparative study.
Supercapsular Percutaneously Assisted total hip arthroplasty (SuperPATH approach) is a relatively new minimal invasive approach which has been associated with encouraging postoperative outcomes. The aim of this study is to compare the minimal invasive (MIS) SuperPATHapproach with the standard modified Hardinge approach at the base of muscle damage due to serum markers, functional results and other perioperative and postoperative data. Forty eight (48) consecutive patients undergone primary total hip arthroplasty (THA) by the same surgeon (GD), were enrolled in our study. From this study population, the modified Hardinge approach was performed in 23 patients and the SuperPATH approach was performed in 25 patients. Soft tissue impairment was studied based on three representative markers, C-reactive-protein (CRP) and two enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH). We measured these markers 10 min after surgery, on 1st and 2nd postoperative day. The levels of the perceived pain were evaluated according to the Visual Analog Scale/Numerical Rating Scale (VAS/NRS) score which was registered 6 h, 12 h, 1 day and 2 days postoperatively. The functional and clinical evaluation of the patients was achieved with Harris Hip Score (HHS), Charnley's Hip score, EuroQol (EQ-5D)-(EQ-100), Patient Health Questionnaire (PHQ-9) and neuropathic pain questionnaire (DN-4) 6 months and 1 year postoperatively. The rest of the collected data included patient's age, gender, body mass index (BMI), other comorbitities, the American Society of Anesthiologists score (ASA), Charlson Index score, the pre-operative diagnosis, implant positioning through radiographic evaluation, the type of anesthesia, the days of hospitalization, the operating time, incision length, blood loss and blood transfusion requirements and complication rates. SuperPATH approach was related with statistically considerable lower levels of CRP at 10 min (p = 0,001) and at 24 h (p = 0,047) postoperatively, as well as lower LDH levels in all time points postoperatively. It was also associated with shorter incision length (p < 0.001), longer operating time (p < 0.001), higher mean cup inclination p < 0.001, decreased postoperative pain levels the first 6 and 12 h (p < 0.001) and relatively better clinical and functional results 6 months after surgery, but not at 12 months. Our study revealed some advantages in favor of the SuperPATH approach comparing with the standard modified Hardinge approach, mainly in terms of less muscle damage and less perceived pain postoperatively. More research is required in order to further elucidate its efficacy.


Prevalence of Otitis Media with Effusion in Children with Hearing Loss.
Otitis media is an inflammation of the middle ear cleft, with or without intact tympanic membrane. Otitis media is known to be one of the most common childhood infections. Middle ear effusions have been recognized to grab increasing attention because of the problems they pose in both the diagnosis and the treatment, and because of the fear that effusion is the cause of learning difficulties, irreversible middle ear disease, or both. To study prevalence of otitis media with effusion in children with hearing loss. Materials and methods: This prospective study was conducted on children with hearing loss ageing between 3 and 15 years presenting to ENT OPD of GURU GOBIND SINGH MEDICAL COLLEGE FARIDKOT with complaint of hearing loss from January 2015 to June 2016. Total of 125 children were taken in study. Detailed history and complete ENT examination was done along with pure tone audiometery and impedence audiometery. Most common complaints of patient were otalgia on ototscopic examination majority of patients had congested tympanic membranes. Otitis media with effusion was most common cause of hearing loss. Majority of children diagnosed with otitis media with effusion were in age group of 6-8 years of age. Patients with mild hearing loss due to otitis media with effusion, on pure tone audiometery was more as compared to moderate hearing loss. B type of tympanogram was found in majority of cases. The potential of otitis media with effusion to cause a series of sequels and complications such as tympanosclerosis, retraction pockets, adhesive otitis media and hearing or speech impairment makes the disease an important public health problem. To prevent delayed diagnosis which leads to development of this disease, parents must be informed about the preventable risk factors and symptoms for the development of otitis media with effusion.


Nutritional knowledge and attitudes of physicians.
A closed-end questionnaire, containing fifty-five knowledge questions and twenty attitude statements, was mailed to physicians on the mailing list of the Nebraska Medical Association who expressed a willingness to participate in this study. The data reported are based on the responses of 292 physicians (22 per cent of the total possible sample). Twelve per cent indicated they had received no nutrition education in medical school, either as a specific course or integrated with other subjects. Eighty-eight per cent had access to a clinical dietitian, with 40 per cent reporting frequent use of this service. Physicians answered 65 per cent of the knowledge questions correctly, with a tendency to score higher on basic nutritional knowledge questions than on those relating to therapeutic nutrition. Attitudes toward nutrition were generally favorable. There was a significant negative, though moderate, correlation (r = -0.188) between years in practice and nutritional knowledge. No significant relationship was found between nutritional knowledge and attitude. The findings of this study suggest that nutrition education should be considered as an area for postgraduate courses for physicians. Also, a need for a greater awareness and utilization by physicians of the dietitian's potential as a nutritional consultant is indicated.


Quinacrine accumulation in pancreatic islet cells of rat and mouse: relationship to functional activity and effects on basal and stimulated insulin secretion.
The fluorescent acridine derivative, quinacrine, was found to accumulate in rat and mouse pancreatic islet cells storing insulin, glucagon, pancreatic polypeptide, or somatostatin. Following administration of large doses of tolbutamide via an oro-gastric tube, the intensity of quinacrine fluorescence of insulin cells was substantially reduced. Similarly, the pancreatic insulin content was lowered. In contrast, the fluorescence intensity of the glucagon, pancreatic polypeptide and somatostatin cells appeared unaffected. Basal plasma insulin levels in the mouse were slightly elevated following quinacrine administration (25%). Glucose-stimulated insulin release was markedly enhanced (51%) in quinacrine-pretreated animals, whereas insulin release induced by cholinergic stimulation was unaffected. The results show that quinacrine accumulates in the various pancreatic islet cells. The drug seems to be confined to the secretory granules and affects the insulin response to glucose but not that to cholinergic stimulation, suggesting that these secretagogues act through different or partly different secretory pathways.


Differences in protein binding and cytokine release from monocytes on commercially sourced tissue culture polystyrene.
Tissue culture polystyrene (TCPS) is a ubiquitous substrate used by many researchers in the biomedical and biological sciences. Different parameters involved in the production of TCPS, including the treatment time and the use of reactive gases and chemical agents, can have a significant influence on the ultimate surface properties achieved. The assumption that they will all yield a consistent and controlled product has not proven to be true. To provide a better insight into the bioactivity differences in TCPS supplied by different manufacturers, TCPS from three different companies (Sarstedt, Wisent Corp., and Becton Dickinson (BD)) were analyzed for their surface properties, protein adsorption characteristics, and interactions with human monocytes. Marked differences were observed in terms of surface wettability and surface chemistry. Furthermore, Wisent TCPS adsorbed more than twice the amount of serum proteins compared with BD and Sarstedt TCPS. Sarstedt showed significantly more cell retention (more DNA) compared with both BD and Wisent TCPS brands over a 7 day culture period. Cytokine release from monocytes adherent on the three different TCPS also differed significantly, suggesting that the differences in the surface properties were sufficient to differentially mediate monocyte activation. These results have important implications for TCPS research use, in terms of appreciating the interpretation of the data when TCPS is used as a control substrate as well as when it is used where a pre-conditioned state would influence the outcome of the study.


Genetic diversity of 15 STR loci in Yunnan Va ethnic minority and the phylogenetic relationships with 26 other populations.
The Va (also called "Wa") people are an ethnic minority living mainly in the southwest of Yunnan Province. This study was conducted to obtain the genetic information and forensic statistical parameters of 15 autosomal short tandem repeat (STR) loci included in the AmpFlSTR®Identifiler™ kit (Applied Biosystems, Foster City, CA) in the Yunnan Va population, with a view to enriching the genetic databases of the Chinese Va population. A total of 508 unrelated Chinese Va individuals were genotyped with this 15 STR kit, the genetic polymorphisms and associated forensic parameters were calculated. The genetic relationships between Chinese Va and 26 other Chinese populations were also evaluated. All of the STR loci reached the Hardy-Weinberg equilibrium after Bonferroni correction. A total of 159 alleles were observed with allele frequencies ranging from 0.000984 to 0.606299. The combined discrimination power (CDP) and the cumulative probability of excluding (CPE) of the 15 STR loci were 0.999 999 999 999 999 988 126 and 0.999 995 734, respectively. Our results indicated that the geographically adjacent or ethnically close populations showed a higher genetic affinity. The results of this study will enrich the forensic databases of the Chinese Va population and could be applied in forensic analysis.


Production and secretion of recombinant soluble CD3 polypeptides by myeloma-derived transfectant clones.
Soluble forms of three human CD3 proteins have been produced by recombinant DNA techniques. The extracellular domain of CD3-gamma, -delta or -epsilon has been linked to the constant region of mouse immunoglobulin kappa light chain to form gamma-kappa, delta-kappa and epsilon-kappa chimaeric proteins. These are secreted by mouse myeloma-derived transfectant cell lines and are immunoprecipitable by CD3- or kappa-specific polyclonal antisera. Yields of 100-500 micrograms secreted recombinant proteins per litre of culture medium were obtained, which could be purified by anti-kappa affinity chromatography. The production of soluble CD3 illustrates the applicability of this technology to a loosely associated protein complex.


"External Iliac Artery Injury After Total Hip Arthroplasty in an Infected Intrapelvic Hemiarthroplasty": A Case Report.
We report a patient with intrapelvic prosthetic protrusion associated with infection after hemiarthroplasty for a fracture neck of the femur. We discuss the challenges involved in the management of this complex case with recommendations to manage a vascular injury. In patients with an intrapelvic prosthesis, thorough preoperative vascular evaluation and vigilant postoperative check are required to prevent a vascular injury. In a suspected vessel injury after primary or revision total hip arthroplasty, it is imperative to get proximal control of the vessel before re-exploration. A combined arterial Doppler and computerized tomography angiogram is more reliable in picking up arterial impingement by acetabular screws.


Does intraoperative quick parathyroid hormone assay improve the results of parathyroidectomy?
Preoperative sestamibi (MIBI) and ultrasonography (US) are used to localize parathyroid tumors in patients with primary hyperparathyroidism (pHPT). The intraoperative quick PTH assay (qPTH) has been recommended to determine whether all hyperfunctioning parathyroid tissue has been removed. We questioned whether qPTH improves the results of parathyroidectomy in patients with pHPT. We analyzed 115 unselected patients with pHPT without a family history or multiple endocrine neoplasia but who had undergone parathyroidectomy. All 115 patients had successful operations without complications. Of these patients, 88 (77%) had solitary adenomas, 13 had double adenomas, 1 had triple adenomas, 12 had hyperplasia, and 1 had carcinoma. Overall, MIBI was correct in 72% (76/106), US in 49% (49/99), and qPTH in 80% (92/115). For preoperative studies showing a single tumor, MIBI was correct in 83% (73/88), US was correct in 71% (45/63), and combined MIBI and US were correct in 95% (37/39). Adding qPTH in this subgroup did not improve the successful focused approach: 70% for MIBI, 65% for US, and 87% for combined MIBI and US. However, adding qPTH improved the overall success of parathyroidectomy (MIBI 92%, US 86%, combined MIBI and US 97%), but at the cost of unnecessary further exploration (MIBI 13%, US 6%, combined MIBI and US 8%). We conclude that when the same solitary tumor is identified by both MIBI and US, a focused exploration can be done with a 95% success rate. Adding qPTH to MIBI or US can improve the success rate but at a significant cost. General exploration of all parathyroid glands, however, has the highest success rate (100%).


Family, anthropometric and biochemical factors affecting birth weight of infants born to GDM women.
Gestational diabetes mellitus (GDM) affects up to 25% of all pregnancies worldwide. If untreated, GDM leads to increased complication rates both, in the mother and the fetus. Early diagnosis and adequate management of GDM are essential to avoid macrosomia. Nonetheless, neonates born to GDM mothers often have high birth weight. The aim of the study was to evaluate selected factors which can affect neonatal birth weight. The study included 152 women with GDM and 58 healthy pregnant controls. Anthropometric data of both parents, maternal biochemical parameters, and neonatal birth weight were collected. The independent factors influencing neonatal birth weight were pregnancy duration, maternal smoking, as well as birth weight and current weight of the father. The risk of delivering a large for gestational age (LGA) infant increases with the diagnosis of GDM, higher maternal pre-pregnancy weight, and higher fasting glycaemia. No correlation between maternal fasting glycaemia, HbA1c, 1,5-AG, lipids and neonatal birth weight was found. Risk factors for LGA include gestational diabetes, high maternal pre-pregnancy weight, and current body weight of the father. Neither HbA1c nor 1,5-AG were reliable predictors of neonatal birth weight and occurrence of LGA in the studied population.


Polymer-supported membranes as models of the cell surface.
Lipid-bilayer membranes supported on solid substrates are widely used as cell-surface models that connect biological and artificial materials. They can be placed either directly on solids or on ultrathin polymer supports that mimic the generic role of the extracellular matrix. The tools of modern genetic engineering and bioorganic chemistry make it possible to couple many types of biomolecule to supported membranes. This results in sophisticated interfaces that can be used to control, organize and study the properties and function of membranes and membrane-associated proteins. Particularly exciting opportunities arise when these systems are coupled with advanced semiconductor technology.


Trophic Position of the Species and Site Trophic State Affect Diet Niche and Individual Specialization: From Apex Predator to Herbivore.
Intra-species variability in isotopic niches, specifically isotopic total niche width (ITNW), isotopic individual niche width (IINW), and isotopic individual specialization (IIS), was studied using an innovative approach without sacrificing the vertebrates. Stable isotopes (δ13C, δ15N) in four body tissues differing in isotopic half-life were analyzed from four freshwater fish species representing different trophic positions. ITNW was widest for the apex predator (European catfish) and narrowest for the obligate predator (Northern pike). IINW exhibited a polynomial trend for the European catfish, Northern pike, and Eurasian perch (mesopredator), decreasing with body mass and increasing again after exceeding a certain species-dependent body mass threshold. Thus, for ectotherms, apex predator status is linked rather to its size than to the species. In herbivores (rudd), IINW increased with body mass. The IIS of predators negatively correlated with site trophic state. Therefore, eutrophication can significantly change the foraging behavior of certain species. We assume that the observed trends will occur in other species at similar trophic positions in either aquatic or terrestrial systems. For confirmation, we recommend conducting a similar study on other species in different habitats.


Ultra violet filters in the urine of preschool children and drinking water.
Benzophenones (BPs) and other ultra violet (UV) filters (UV-filters) are widely used in sunblock and other personal care products, raising concerns about their adverse health risks to human, especially for children. In the present study, BP-type UV-filters and other four widely used UV-filters were evaluated in the child urinary samples (4-6 years, n = 53), tap water and commercial distilled water in Hong Kong. The results suggested that the target chemicals are ubiquitous in the subject. BP1, BP2, BP3 and BP4 in children urine samples contributed closely to the overall children exposure of UV filters, with detection rates above 58% and geometric means ranging from 44.2 to 76.7 ng/mL. As a contrast, BP3 was the major substance found in the tap water and distilled bottle water, with detection rates of 100% and geometric means of 9.64 and 14.5 ng/L, respectively. There were some significant relationships between urinary UV filters and personal characteristics (BMI values, sex, income level, hand washing frequency, and body location usage), but the health risks associated with UV-filters in Hong Kong children might not be concerning. Only two children applied sun creams in this research, indicating that there were other sources to exposure these chemicals.


The haemotoxicity of azathioprine in repeat dose studies in the female CD-1 mouse.
Azathioprine (AZA) is a cytotoxic immunosuppressive drug used in the prevention of rejection in organ transplants and the treatment of auto-immune diseases. However, AZA is haemotoxic causing significant bone marrow depression. The present studies were to characterize the haemotoxicity of AZA in the female CD-1 mouse. In Experiment 1, a dose-ranging study, with AZA gavaged daily for 10 days, clinical evidence of toxicity was evident at 125 mg/kg and above. Experiment 2 was a dose-response study with AZA gavaged daily for 10 days at 40-120 mg/kg. At day 1 after the final dose, AZA induced a dose-related pancytopaenia, reduced femoral marrow cellularity, increases in serum levels of the cytokine fms-like tyrosine kinase 3 ligand, reduction in granulocyte-monocyte colony-forming units and erythroid colonies, and increased bone marrow apoptosis. Histology demonstrated hepatocyte hypertrophy, thymic atrophy, reduced splenic extramedullary haemopoiesis, and reduced cellularity of sternal bone marrow. In Experiment 3, AZA was dosed for 10 days at 100 mg/kg with autopsies at 1, 3, 9, 22, 29, 43 and 57 days postdosing. At 1, 3 and 9 days, haematological parameters reflected changes in Experiment 2. At 22/29 days, many blood parameters were returning towards normal; at 43/57 days, most parameters compared with controls. However, there was some evidence of a persistent (i.e. residual/late-stage) mild reduction in RBC and erythroid progenitor cell counts at day 43/57. We conclude that the CD-1 mouse provides an acceptable model for the haemotoxicity of AZA in man.


Breaking Up Prolonged Sitting Alters the Postprandial Plasma Lipidomic Profile of Adults With Type 2 Diabetes.
Postprandial dysmetabolism in type 2 diabetes (T2D) is exacerbated by prolonged sitting and may trigger inflammation and oxidative stress. It is unknown what impact countermeasures to prolonged sitting have on the postprandial lipidome. In this study, we investigated the effects of regular interruptions to sitting, compared with prolonged sitting, on the postprandial plasma lipidome. Randomized crossover experimental trial. Participants underwent three 7-hour conditions: uninterrupted sitting (SIT); light-intensity walking interruptions (LW); and simple resistance activity interruptions (SRA). Baseline (fasting) and 7-hour (postprandial) plasma samples from 21 inactive overweight/obese adults with T2D were analyzed for 338 lipid species using mass spectrometry. Using mixed model analysis (controlling for baseline outcome variable, gender, body mass index, and condition order), the percentage change in lipid species (baseline to 7 hours) was compared between conditions with Benjamini-Hochberg correction. Thirty-seven lipids were different between conditions (P < 0.05). Compared with SIT, postprandial elevations in diacylglycerols, triacylglycerols, and phosphatidylethanolamines were attenuated in LW and SRA. Plasmalogens and lysoalkylphosphatidylcholines were reduced in SIT, compared with attenuated reductions or elevations in LW and SRA. Phosphatidylserines were elevated with LW, compared with reductions in SIT and SRA. Compared with SIT, LW and SRA were associated with reductions in lipids associated with inflammation; increased concentrations of lipids associated with antioxidant capacity; and differential changes in species associated with platelet activation. Acutely interrupting prolonged sitting time may impart beneficial effects on the postprandial plasma lipidome of adults with T2D. Evidence on longer-term intervention is needed.


Long Term Results and Prognostic Biomarkers for Anti-PD1 Immunotherapy Used after BRAFi/MEKi Combination in Advanced Cutaneous Melanoma Patients.
(1) Background: BRAFi/MEKi are usually offered as a first line treatment for patients requiring rapid response; with elevated lactate dehydrogenase (LDH) activity, large tumor burden, and with brain metastases. The efficacy of second line therapies after BRAFi/MEKI failure is now well defined. (2) Methods: Patients treated with first line target BRAFi/MEKi therapy (vemurafenib plus cobimetinib, dabrafenib plus trametinib or encorafenib plus binimetinib); and for the second line treatment immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors (nivolumab or pembrolizumab) with at least one cycle of second line were analyzed for survival and prognostic biomarkers. (3) Results: There were no statistically significant differences in ORR between the treatment groups with nivolumab and pembrolizumab, as well as median progression free-survival (PSF) and overall survival (OS) since the initiation of second line therapy; on nivolumab OS was 6.6 months, and on pembrolizumab 5.0 months. The greatest clinical benefit with second line immunotherapy was observed in patients with LDH ≤ ULN and <3 organ sites with metastasis at baseline. Longer OS was also noted in patients with time to PD >6 months in first line (slow progression). (4) Conclusions: Second line anti-PD1 immunotherapy is effective in BRAF-mutated melanoma patients after BRAFi/MEKi therapy failure.


Amplification and enhanced expression of the c-myc oncogene in mouse SEWA tumour cells.
SEWA tumour cells are derived from an osteosarcoma induced in an A.SW mouse by infection with polyoma virus. Cytogenetic analyses have revealed three different characteristic chromosomal abnormalities diagnostic for the presence of amplified genes: 'double minutes' (DMs), homogeneously staining chromosomal regions (HSRs) and C-bandless chromosomes (CMs; for review see ref. 2). DMs may undergo fluctuation in number depending on the conditions in which the cells grow. Their number usually increases after injection of cells into a mouse and often is reduced to undetectable levels when the cells are explanted back into tissue culture; when the cells are re-introduced into the mouse, they again acquire multiple DMs. We show here that cells of SEWA lines carrying DMs, HSRs or CMs contain amplified copies of the proto-oncogene c-myc and enhanced levels of c-myc messenger RNA and c-myc protein. DMs or CMs are the sites of c-myc amplification in two different SEWA lines.


Regulatory mechanism of chicken lysozyme gene expression in oviducts examined using transgenic technology.
The use of promoters that strongly express target genes in the chicken oviduct is beneficial for the production of proteinaceous materials into egg white by transgenic chickens. To examine the regulatory mechanisms of chicken lysozyme gene expression in vivo, genetically manipulated chickens that express human erythropoietin under the control of a lysozyme promoter-enhancer were established. By using several deletion mutants of the promoter-flanking region, we found that a -1.9 kb DNase I hypersensitive site (DHS) was essential for oviduct-specific expression in genetically manipulated chickens. The concentration of human erythropoietin in egg white was 14-75 μg/ml, suggesting that the chicken lysozyme promoter containing -1.9 kb DHS is sufficient for the production of pharmaceuticals using transgenic chickens.


Factors influencing adherence to clinical practice guidelines in patients with suspected chronic coronary syndrome: a qualitative interview study in the ambulatory care sector in Germany.
Chronic coronary syndrome (CCS) is a potentially progressive clinical presentation of coronary artery disease (CAD). Clinical practice guidelines (CPGs) are available for prevention, diagnosis, and treatment. Embedded in the "ENLIGHT-KHK" healthcare project, a qualitative study was conducted to identify factors that influence guideline adherence from the perspective of general practitioners (GPs) and cardiologists (CA) in the ambulatory care sector in Germany. GPs and CAs were surveyed via telephone using an interview guide. The respondents were first asked about their individual approach to caring for patients with suspected CCS. Subsequently, the accordance of their approach with guideline recommendations was addressed. Finally, potential measures for assisting with guideline adherence were discussed. The semi-structured interviews were transcribed verbatim and analysed using a qualitative content analysis in accordance with Kuckartz and Rädiker. Factors influencing adherence to CPGs were categorised by assessing whether they (i) inhibited or facilitated guideline adherence, (ii) played a role in patients at risk of CCS or with suspected or known CCS, (iii) were mentioned in implicit or explicit thematic reference to CPGs, and (iv) were declared a practical problem. Based on interviews with ten GPs and five CAs, 35 potential influencing factors were identified. These emerged at four levels: patients, healthcare providers, CPGs, and the healthcare system. The most commonly cited barrier to guideline adherence among the respondents was structural aspects at the system level, including reachability of providers and services, waiting times, reimbursement through statutory health insurance (SHI) providers, and contract offers. There was a strong emphasis on interdependencies between factors acting at different levels. For instance, poor reachability of providers and services at the system level may result in inexpedience of guideline recommendations at the CPG level. Likewise, poor reachability of providers and services at the system level may be aggravated or alleviated by factors such as diagnostic preferences at the patient level or collaborations at the provider level. To assist with adherence to CPGs regarding CCS, promoting measures may be needed that account for interdependencies between barriers and facilitators at various healthcare levels. Respective measures should consider medically justified deviations from guideline recommendations in individual cases. German Clinical Trials Register: DRKS00015638; Universal Trial Number (UTN): U1111-1227-8055.


Brief report: S6 ribosomal protein phosphorylation in autistic frontal cortex and cerebellum: a tissue array analysis.
Few autistic brain samples are available for study, limiting investigations into molecular and histopathological abnormalities associated with this common disease. To facilitate distribution of samples, we have constructed a tissue array containing cerebral and cerebellar cores from 5 autistic children, 1 girl with Rett syndrome, and 5 age-matched controls. To demonstrate the utility of this resource, we examined phosphorylation of the S6 ribosomal protein, a signaling event regulated by the genes mutated in tuberous sclerosis and Cowden disease. We hypothesized that the molecular pathways altered in these inherited conditions associated with autism might be dysregulated in sporadic autistic cases as well. However, no consistent alterations in S6 phosphorylation were detected in autistic tissues compared to controls in the brain regions analyzed.


Ceramide synthase-6 confers resistance to chemotherapy by binding to CD95/Fas in T-cell acute lymphoblastic leukemia.
Ceramide synthases (CERS) produce ceramides which are key intermediators in the biosynthesis of complex sphingolipids and play an important role in cell proliferation, differentiation, apoptosis and senescence. CERS6 is an isoform of ceramide synthases known to generate ceramides with C16 acyl chain (C16-Cer). CERS6 and C16-Cer levels were significantly higher in acute lymphoblastic leukemia (ALL) cells in comparison to peripheral blood mononuclear cells and T lymphocytes derived from healthy human volunteers. We investigated the role of CERS6 in chemo-resistance in T-ALL cell lines. Stable knockdown of CERS6 in CCRF-CEM and MOLT-4 cells resulted in increased sensitivity to ABT-737, a pan-BCL-2 inhibitor, while CCRF-CEM cells with exogenous CERS6 expression showed resistance to ABT-737 relative to the vector control. The cytotoxic activity of ABT-737 in CERS6 knockdown cells was significantly reduced by the addition of a caspase-8 inhibitor Z-IETD, suggesting that CERS6 alters the cytotoxicity via extrinsic pathway of apoptosis. By co-immunoprecipitation of CERS6 in CCRF-CEM cells, we identified CD95/Fas, a mediator of extrinsic apoptotic pathway, as a novel CERS6 binding partner. In Fas pull-down samples, FADD (Fas-associated protein with death domain) was detected at higher levels in cells with CERS6 knockdown compared with control cells when treated with ABT-737, and this was reversed by the overexpression of CERS6, demonstrating that CERS6 interferes with Fas-FADD DISC assembly. CERS6 may serve as a biomarker in determining the effectiveness of anticancer agents acting via the extrinsic pathway in T-ALL.


Magnetic properties of ball-milled SrFe12O19 particles consolidated by Spark-Plasma Sintering.
The room-temperature magnetic properties of ball-milled strontium hexaferrite particles consolidated by spark-plasma sintering are strongly influenced by the milling time. Scanning electron microscopy revealed the ball-milled SrFe12O19 particles to have sizes varying over several hundred nanometers. X-Ray powder-diffraction studies performed on the ball-milled particles before sintering clearly demonstrate the occurrence of a pronounced amorphization process. During sintering at 950 °C, re-crystallization takes place, even for short sintering times of only 2 minutes and transformation of the amorphous phase into a secondary phase is unavoidable. The concentration of this secondary phase increases with increasing ball-milling time. The remanence and maximum magnetization values at 1T are weakly influenced, while the coercivity drops dramatically from 2340 Oe to 1100 Oe for the consolidated sample containing the largest amount of secondary phase.


A prospective multicentre registry of the procedural and long-term clinical and angiographic results of stent implantation using a Dylyn coated coronary stent system.
A prospective registry was performed to evaluate the safety and efficacy of a Dylyn coated coronary stent. Diamond-like nanocomposite (Dylyn) stent coating is thought to be biocompatible, resulting in decreased thrombogenicity and decreased neointimal hyperplasia. In a multicentre, open, prospective, clinical and angiographical registry, the Dylyn-coated stent system was evaluated in patients requiring percutaneous coronary intervention. The primary procedural and angiographical endpoint of the study was the sustained success of stent-implantation using a follow-up catheterisation at six months. The primary clinical endpoint of the study was the composite incidence of death, non-fatal myocardial infarction and revascularisation at six months after stent implantation. 127 Dylyn coated coronary stents were implanted in 121 patients. Procedural success was obtained in 100% of the cases. No episodes of acute stent thrombosis occurred. The number of patients within stent restenosis at six months was 29 (24%). The primary procedural, angiographical endpoint was achieved in 91 (70%) patients. The clinical results at six-month follow-up were favourable with a MACE-rate of 7.4%. A Dylyn coated coronary stent system is well tolerated and has excellent short-term results. The amount of angiographic restenosis at 6 months, however, is considerable, but comparable to other non-drug-eluting stent systems.


Dynamics of pathologic clot formation: a mathematical model.
Recent studies have provided evidence of a significant role of the Hageman factor in pathologic clot formation. Since auto-activation of the Hageman factor triggers the intrinsic coagulation pathway, we study the dynamics of pathologic clot formation considering the intrinsic pathway as the predominant mechanism of this process. Our methodological approach to studying the dynamics of clot formation is based on mathematical modelling. Activation of the blood coagulation cascade, particularly its intrinsic pathway, is known to involve platelets. Therefore, equations accounting for the effects of activated platelets on the intrinsic pathway activation are included in our model. This brings about a considerable increase in the values of kinetic constants involved in the model of the principal biochemical processes resulting in clot formation. The purpose of this study is to elucidate the mechanism of pathologic clot formation. Since the time window of thrombolysis is 3-6h, we hypothesize that in many cases the rate of pathologic clot formation is much lower than that of haemostatic clot. This assumption is used to simplify the mathematical model and to estimate kinetic constants of biochemical reactions that initiate pathologic clot formation. The insights we gained from our mathematical model may lead to new approaches to the prophylaxis of pathologic clot formation. We believe that one of the most efficient ways to prevent pathologic clot formation is simultaneous inhibition of activated factors ХII and ХI.


Ascending aortobifemoral and adjunct carotid bypass grafts.
We describe a case of simultaneous ascending aortobifemoral and right common carotid artery bypass to treat a symptomatic brachiocephalic artery and juxtarenal chronic total occlusion in a 68-year-old female patient with unfavorable characteristics for endovascular and standard aortofemoral procedures. Mid-term follow-up revealed sustained remission of symptoms, quality of life quality of life improvement, and patent bypass grafts. In highly selected patients, this solution can be useful when treating other intrathoracic diseases, as well as allowing the simultaneous revascularization of two remote arterial beds.


Pulmonary embolus presenting as initial manifestation of renal cell carcinoma.
Pulmonary emboli from renal cell carcinoma may be more common than previously suspected. A case is reported of renal cell carcinoma presenting with a massive pulmonary embolus. Pulmonary embolectomy followed by radical nephrectomy with venocavotomy and tumor thrombectomy was successfully performed.


Ammonia-treated N-(1-naphthyl) ethylenediamine dihydrochloride as a novel matrix for rapid quantitative and qualitative determination of serum free fatty acids by matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry.
The blood free fatty acids (FFAs), which provide energy to the cell and act as substrates in the synthesis of fats, lipoproteins, liposaccharides, and eicosanoids, involve in a number of important physiological processes. In the present study, matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) with ammonia-treated N-(1-naphthyl) ethylenediamine dihydrochloride (ATNEDC) as a novel MALDI matrix in a negative ion mode was employed to directly quantify serum FFAs. Multiple point internal standard calibration curves between the concentration ratios of individual fatty acids to internal standard (IS, C17:0) versus their corresponding intensity ratios were constructed for C14:0, C16:1, C16:0, C18:0, C18:1, C18:2, C18:3, C20:4, and C22:6, respectively, in their mixture, with correlation coefficients between 0.991 and 0.999 and limits of detection (LODs) between 0.2 and 5.4μM, along with the linear dynamic range of more than two orders of magnitude. The results indicate that the multiple point internal standard calibration could reduce the impact of ion suppression and improve quantification accuracy in the MALDI mode. The quantitative results of nine FFAs from 339 serum samples, including 161 healthy controls, 118 patients with hyperglycemia and 60 patients without hyperglycemia show that FFAs levels in hyperglycemic patient sera are significantly higher than those in healthy controls and patients without hyperglycemia, and elevated FFA levels are also associated with increased levels of fasting blood glucose (FBG) in hyperglycemic patient sera. Serum FFAs were identified on the basis of the observed accurate molecular masses and reliable isotope distributions obtained by MALDI-FTICR MS.


Dihydromyricetin attenuates cisplatin-induced acute kidney injury by reducing oxidative stress, inflammation and ferroptosis.
Cisplatin is effective against various types of cancers. However, its clinical application is limited owing to its adverse effects, especially acute kidney injury (AKI). Dihydromyricetin (DHM), a flavonoid derived from Ampelopsis grossedentata, has varied pharmacological activities. This research aimed to determine the molecular mechanism for cisplatin-induced AKI. A murine model of cisplatin-induced AKI (22 mg/kg, I.P.) and a HK-2 cell model of cisplatin-induced damage (30 μM) were established to evaluate the protective function of DHM. Renal dysfunction markers, renal morphology and potential signaling pathways were investigated. DHM decreased the levels of renal function biomarkers (blood urea nitrogen and serum creatinine), mitigated renal morphological damage, and downregulated the protein levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. It upregulated the expression levels of antioxidant enzymes (superoxide dismutase and catalase expression), nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream proteins, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, thus eventually reducing cisplatin-induced reactive oxygen species (ROS) production. Moreover, DHM partially inhibited the phosphorylation of the active fragments of caspase-8 and -3 and mitogen-activated protein kinase and restored glutathione peroxidase 4 expression, which attenuated renal apoptosis and ferroptosis in cisplatin-treated animals. DHM also mitigated the activation of NLRP3 inflammasome and nuclear factor (NF)-κB, attenuating the inflammatory response. In addition, it reduced cisplatin-induced HK-2 cell apoptosis and ROS production, both of which were blocked by the Nrf2 inhibitor ML385. DHM suppressed cisplatin-induced oxidative stress, inflammation and ferroptosis probably through regulating of Nrf2/HO-1, MAPK and NF-κB signaling pathways.


Organochlorine pesticides in soil, moss and tree-bark from North-Eastern Romania.
Concentrations of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDE) have been determined in soil, mosses and tree bark samples collected from the same locations in North-Eastern Romania (region of Moldavia). PCBs and PBDEs were under the limit of quantification in all investigated samples. OCPs were the principal pollutants found in the analysed samples. In soil, moss and tree bark samples, DDT together with its metabolites, was the most abundant OCP ranging between 4.4-79, 5.8-95 and 11-440 ng g(-1) in the individual matrices, followed by HCH isomers with levels between 1.1-9.8, 8.9-130 and 12-130 ng g(-1) in soil, moss and bark respectively. To distinguish between the previous and current pollutant input and preferential biodegradation of DDT metabolites, the degradation ratios were calculated between the parent substances and their metabolites (DDT and HCH isomers). The investigation indicates no important pollution sources near sampling sites and reveals that OCPs originate mainly from long-range air transport processes and through atmospheric deposition of isomers volatilised from secondary sources. Discriminant function analysis was performed to determine whether OCPs uptake differ among the three matrices (soil, moss and tree bark). A good separation was observed between tree bark and the other two matrices. The most redundant variable appears to be p,p'-DDE (R(2)=0.336), while the most informative variable seems to be o,p'-DDT (R(2)=0.0361). Significant correlations were found between bark and moss concentrations for most α-HCH and p,p'-DDD (p<0.01). We have also investigated the enantiomeric signature of α-HCH. For bark and moss, EF values suggest preferential degradation of the (-)α-HCH enantiomer.


Effects of thoracic epidural analgesia on glucose homeostasis after cardiac surgery in patients with and without diabetes mellitus.
Even moderate hyperglycaemia increases mortality/morbidity after coronary artery bypass grafting, stroke and myocardial infarction. The goal of this prospective study was to determine if using thoracic epidural analgesia from start of surgery until the end of the third postoperative day would blunt postoperative hyperglycaemia. Forty-four patients had diabetes mellitus, 60 did not; half of each group had an epidural with continuous local anaesthetics. All patients received continuous insulin infusions during the initial 24 h period beginning with surgery. Blood glucose was measured four times daily (fasting or 2-3 h post-prandial) until end of the third postoperative day. For patients without diabetes, the epidural group had lower mean blood glucose and insulin requirements (P < 0.02) than controls during the initial 24 h period beginning with surgery. For patients with diabetes mellitus, thoracic epidural analgesia reduced mean blood glucose (P = 0.017) with unchanged insulin requirements. Epidural did not diminish the increase (vs. preoperative) in fasting blood glucose on the third postoperative day (32% vs. 22%, P < 0.001) for non-diabetics. Epidural analgesia was not able to attenuate hyperglycaemia during the first 3 postoperative days. Epidural analgesia improved glucose homeostasis minimally during the initial 24 postoperative hours but did not attenuate hyperglycaemia during the subsequent 3 postoperative days.


Circulating immune complexes in rats bearing chemically induced tumors. I. Sequential determination during the growth of tumours at various body sites.
Circulating immune complexes were measured in sequential monitoring studies in rats bearing chemically induced tumours at different body sites. The assay employed were based upon radioimmunoprecipitation of serum factors with 125I-C1q or with an indirect test whereby the inhibition of binding of 125I-C1q to IgG aggregates by tumour-bearer sera was measured. 125I-C1q-binding immune complexes were detected at the initial phase of tumour growth and the level of this activity returned to the normal range after tumour excision. With tumour growing at subcutaneous sites or in th peritoneal cavity, serum-borne C1q-binding material, after reaching a maximum level, decreased despite tumour progression and eventually fell into sub-normal ranges at terminal stages of growth. In contrast, following intravenous tumour cell injection, immune-complex levels increased until terminal stages of disease. The present findings indicate that the measurement of C1q-binding serum factors represents a useful method for monitoring the growth and burden of experimental animal tumours.


Correction: Early Fluid Resuscitation by Lactated Ringer's Solution Alleviate the Cardiac Apoptosis in Rats with Trauma-Hemorrhagic Shock.
[This corrects the article DOI: 10.1371/journal.pone.0165406.].


Effect of application technique of luting agent on the retention of three types of fiber-reinforced post systems.
The aim of this study was to evaluate retentive strengths of three adhesive/resin cement/fiber post systems to the apical third of post-space dentin varying the application method of the luting agent. ENA post (Micerium, Avegno, Genova, Italy), FRC Postec Plus (Ivoclar Vivadent, Schaan, Liechtenstein), and Anatomical Post (Dentalica, Milano, Italy) were luted in prepared root canals using the adhesive system and resin cement provided by the respective manufacturer. Each group was randomly divided into three subgroups (n = 10) according to the technique used to place the luting agent into post space: using a lentulo spiral, applying the cement onto the post surface, and injecting the material with a specific syringe. A push-out test was performed on sections from the post-space apical part of each specimen. All fractured specimens were observed using a stereomicroscope. Bond strength values were not significantly affected by the application technique of the luting agent (p > 0.05). The ENA post system showed the highest retentive strengths. The other two post groups exhibited similar bond strengths to each other. Microscopic analysis revealed a prevalence of post/cement and mixed failures.