Analysis and Characterization of 3-(3,4-Dichlorophenyl)-1,1-Dimethylurea (DCMU)-resistant Euglena: I. Growth, Metabolic and Ultrastructural Modifications during Adaptation to Different Doses of DCMU.
Cultures of Euglena gracilis Klebs strain Z Pringsheim were grown photoorganotrophically in the presence of different concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) in the range of 0.05 to 250 micromolar. Cultures were serially transferred and various metabolic parameters were followed for 10 weeks. A process of adaptation occurred which was divided operationally into three phases. A phase of ultrastructural disorganization occurred, succeeded by a recovery phase; their intensity and duration were functions of the dose of DCMU. A stable adaptation phase then ensued. This phase was observed in all cultures except that exposed to the highest DCMU concentration. Adapted cells from all of the DCMU cultures contained twice the protein and half the paramylon of the control cells and thus utilized the carbon source to accumulate cellular reserves with only half the efficiency of controls. DCMU affected cellular metabolism as well as photosynthesis.The energy charge remained at high levels throughout adaptation, although the size of the adenylate pool was half that of controls at the disorganized phase. At this stage the ultrastructure of chloroplasts and mitochondria was considerably modified. The progressive changes of the parameters studied appeared to affect all of the cells in a given culture.


Is Skilled Nursing Facility Financial Status Related to Readmission Rate Improvement?
We examined whether higher skilled nursing facility (SNF) lagged profitability is associated with a lower 30-day all-cause all-payer risk-adjusted hospital readmission rate. Our aim was to provide insight into whether SNFs with limited financial resources are able to respond to incentives to lower their readmission rates to hospitals. We used data from 2012-2016 to estimate a fixed effects (FE) model with a time trend. Our data included financial data from the Centers for Medicare & Medicaid Services Healthcare Cost Report Information System SNF cost reports, facility characteristics including the all-cause all-payer risk-adjusted unplanned 30-day readmission rate from the LTCFocus (Long-Term Care Focus) project at Brown University, and county-level market variables from the Area Health Resource File. We also examined the relationship for a shorter time frame (2012-2015) after stratifying the sample by system membership or ownership. SNFs with an increase in the lagged operating margin showed a statistically significant, small decrease (<.01 percentage point) in the risk-adjusted readmission rate. The results were robust for different time periods and model specifications. Fixed effects model estimates for SNFs in the highest quartile of percentage of Medicaid patients (≥73.9%) had a lagged operating margin coefficient that is almost four times as large as the coefficient of the FE model with all SNFs. SNFs have an important role in achieving the national priority of reducing hospital readmissions. The study findings suggest that managers of SNFs should not see low profitability as an obstacle to reducing readmission rates, which is good news given the low average profitability of SNFs. Further, reductions in profitability due to penalties incurred from the recently implemented Medicare Skilled Nursing Facility Value-Based Purchasing Program may not limit SNFs' ability to lower hospital readmission rates, at least initially. However, policymakers may need to determine whether additional resources to high Medicaid SNFs can lower readmission rates for these SNFs.


32P, 86Rb+ and 45Ca2+ handling by tumoral insulin-secreting cells (RINm5F line).
In perifused tumoral islet cells (RINm5F line), which were prelabelled with either [32P]orthophosphate, 86Rb+ or 45Ca2+, the administration of D-glucose (1.4, 2.8 or 16.7 mM) increased the efflux of 32P, decreased the outflow of 86Rb, increased slightly the efflux of 45Ca from cells perifused in the presence of Ca2+, and decreased modestly the outflow of 45Ca from cells perifused in the absence of Ca2+. D-glucose also stimulated the net uptake of 45Ca2+. When Ba2+ (2 mM) was used, in the absence of Ca2+, instead of D-glucose as an insulin secretagogue, the efflux of 32P was little affected, but the outflow of 45Ca was dramatically increased. These changes are qualitatively similar to those occurring in normal islet cells. Nevertheless, the ionic response to D-glucose appeared, as a rule, less marked in tumoral than normal islet cells. Moreover, the concentration-response relationship was shifted to a lower range of hexose concentrations in the RINm5F cells.


Successful maintenance of body weight reduction after individualized dietary counseling in obese subjects.
The aim of this study was to describe the effectiveness of individualized dietary counseling in obese subjects based on narrative interview technique on the maintenance of body weight reduction, changes in dietary behaviors, including type of cooking and physical activity. One-hundred subjects out of four-hundred patients met the inclusion criteria. Individually, 45-minute educational program with motivation counseling was performed in 0, 6 and 12 weeks of the study. Patients were advised to follow individually well-balanced diet for 12 weeks. The individuals were asked about the changes in their dietary habits (Food Frequency Questionnaire). The mean percentage of body weight changes from the baseline were as follows: in 6th week- 5.9%, in 12th week - 10.9% and in 52th week - 9.7% (P < 0.0001), however there were no statistically significant changes while comparing body weight in 12th and 52th week. The maintenance of body weight reduction was connected with the dietary habits changes, mainly the type of cooking and increased consumption of vegetable oils. In conclusion, individualized dietary counseling, based on narrative interview technique is an effective intervention for obesity treatment that may help maintain body weight reduction and adapt the pro-healthy changes in type of cooking and sources of dietary fat.


Study on Thermodynamic Characteristics and Heat Transfer Method of Uncontrolled Fire in Coal Mine Gangue Mountain Spontaneous Combustion Based on System Dynamics.
Coal fire disaster caused by the spontaneous combustion of coal has always been one of the serious problems that threaten the safety of coal mining. In our study, we first solved the dynamic parameters and mechanical functions of coal gangue using the Achar differential method and Coats-Redfern integral method. Then, based on the flow and heat transfer mechanism of hot rod vapor-liquid two-phase flow, combined with coal spontaneous ignition conditions, influencing factors, coal pile spontaneous combustion temperature field structure distribution, etc., the heat transfer process of the hot rod in the coal pile (coal gangue mountain) was analyzed. Results show the average activation energies of the second stage of different types of coal mine gangue. Upon comparing the characteristic parameters of coal gangue in different regions and ages, it is found that 8# coal gangue has better combustion and burn-out characteristics, and its comprehensive combustion characteristics are second only to those of the coal gangue in Datong and higher than those in Panzhihua, Pingdingshan, and Hancheng. The higher the content of volatile matter and fixed carbon in coal gangue, the lower the ash content, and the better the comprehensive combustion performance of the coal gangue. Under the condition of sufficient oxygen supply combustion, the larger the fuel ratio, the better the burnout performance of the coal gangue. The test of the influence of the hot rod on the temperature field distribution inside the coal pile shows that the maximum cooling rate of a single hot rod to the coal pile during the test period is 33.4°C, and the maximum cooling rate reaches 39.6%. The calculated heat dissipation of the 80 h hot rod is 1.0865, 2.1680, and 3.3649 MJ, respectively.


A device for controlling odorant stimulation and olfactory evoked responses in humans.
We developed a device for odorous stimuli control to record olfactory evoked responses from the human scalp. The characteristics of the apparatus are as follows. Translating the subject's respiration into electric signals with a sensor attached to the nose. The period and timing of odorous stimuli could be adjusted, so that stimuli could be synchronous with respiration. The interstimulus interval could be arbitrarily selected once every 1 to 9 respiration(s) so that adaptation could be prevented. We obtained evoked responses to odorous stimuli using this apparatus from the human scalp, whose positive peak latencies were approximately 350 and 700 msec. Such responses were not recorded if oxygen stimuli were used instead of odorous stimuli or with click sounds produced by the switching electromagnetic valve. Three types of odorant evoked scalp potentials were obtained in normal human subjects. The first type consisted mainly of two positive peaks with a peak latency of about 350 msec (P350) and about 700 msec (P700). The second type and the third type consisted of only one positive peak with a peak latency of about 350 msec and 700 msec, respectively. Such a P350 or P700 peak as that observed in the normal subjects was not detected in anosmic patients.


Production of four identical calves by the separation of blastomeres from an in vitro derived four-cell embryo.
The blastomeres of two in vitro derived four-cell embryos were separated and transferred individually into surrogate zonae pellucidae, then co-cultured with bovine oviductal epithelial cells for five days until blastulation. Pairs of the quarter blastocysts were co-transferred with trophoblastic vesicles into each of four synchronised Holstein heifers, three of which were diagnosed pregnant at 28 days gestation, carrying twin fetuses. Four genetically identical bull calves were delivered by elective caesarean section at term pregnancy. One pregnancy was terminated at 56 days.


The provision of palliative care in nursing homes and residential care homes: a survey of clinical nurse specialist work.
The provision of end-of-life care within nursing and residential care homes is of concern to policy makers and specialist palliative care providers. There is evidence of an increasing number of initiatives involving clinical nurse specialists (CNS) with the care of residents within these care settings, but the extent to which this is occurring in the UK has not been documented. A survey of 730 community CNS in palliative care was undertaken to describe the extent to which these practitioners are involved with the care of residents in nursing and residential care homes and the nature of this work. Although 92% of the CNS surveyed had worked with nursing homes and 80% of the CNS with residential care homes, the responses showed that this work was primarily reactive and undertaken infrequently. The majority of the work undertaken by CNS involved caring for patients with malignant conditions with a clinical focus addressing the management of physical symptoms.


Use of microphotohemolysis to distinguish differences in erythrocyte treatments.
A new microhemolytic assay was used to determine if this assay could distinguish between normal erythrocytes and those which had been experimentally altered. Solutions of erythrocytes (4% hematocrit in buffer with fluorescein isothiocyanate tagged to 150,000 MW dextran, FITC-DEX) were placed in a hemacytometer and epi-illumination with a Leitz fluorescent microscope was used to activate the fluorochrome. The resultant hemolysis that occurred only in the discrete area of activation was dependent on the total light energy used for activation (45-180 J/cm2). It was quantitated by an analysis of the amount of light transmittance through that area. The presence of glucose in the buffers decreased the rate of hemolysis and increased the time to reach 50% of the maximal response (T50). Erythrocytes treated with diamide had up to a fourfold increase in the rate of hemolysis and a 48% decrease in the T50, while chlorpromazine produced a 51% decrease in the T50 but had no effect on the rate of hemolysis. Gluteraldehyde produced a graded suppression of the hemolysis. These results demonstrate that the microphotohemolytic assay can be used with energy response curves to provide a relatively quick, quantitative determination of altered erythrocytes.


Drug delivery to the posterior segment of the eye.
Drug delivery into the posterior segment of the eye is complicated by the existence of the blood-ocular barrier. Strategies for delivering drugs to the posterior segment include systemic administration, modification of the barrier, and local drug delivery (including transcorneal, transscleral, and intravitreal). Recently, new topical treatments have emerged for the treatment of posterior eye disease. Iontophoretic, juxtascleral, and intravitreal routes can be used to achieve therapeutic levels in the posterior segment. Extended-release intravitreal drug delivery systems can achieve sustained therapeutic levels with the goal of providing a prolonged clinical benefit.


Perivascular innervation of the cerebral arteries in spontaneously hypertensive rats--an immunohistochemical study.
Perivascular innervation in cerebral arteries of spontaneously hypertensive rats and of normotensive Wistar-Kyoto rats was studied. Adrenergic nerve fibers and neuropeptide Y-containing nerve fibers, indicative of vasoconstrictor nerves, were denser in all cerebral arteries of spontaneously hypertensive rats than those of Wistar-Kyoto rats. In contrast, cholinergic nerve fibers and vasoactive intestinal polypeptide, substance P-containing nerve fibers, indicative of vasodilator nerves, remained unchanged in all cerebral arteries of spontaneously hypertensive rats, as compared with findings in the Wistar-Kyoto rats. Thus, not only adrenergic nerve fibers but also neuropeptide Y-containing nerve fibers may play an important role in preventing the disruption of the blood-brain barrier and the development of hypertensive encephalopathy in spontaneously hypertensive rats.


Epigenome-Wide Study of Posttraumatic Stress Disorder Symptom Severity in a Treatment-Seeking Adolescent Sample.
Emerging research has demonstrated that psychosocial trauma exposure may elicit epigenetic changes, with downstream effects on the transcriptional regulation of genes. Epigenome-wide association studies (EWAS) offer an agnostic approach to examine DNA methylation (DNAm) associations and are a valuable tool to aid in the identification of biological pathways involved in posttraumatic stress disorder (PTSD). This study represents the first EWAS of PTSD in an adolescent sample, an important group given the significance of this developmental period regarding both DNAm changes and PTSD risk. The sample (n = 39, M age = 15.41 years, SD = 1.27, 84.6% female) comprised adolescents who experienced interpersonal trauma and were enrolled in a treatment study. Participants were assessed using the UCLA PTSD Reaction Index for DSM-IV-Adolescent Version and provided a blood sample at baseline. Genomic DNA was isolated from whole blood and assayed using the Illumina Infinium MethylationEPIC BeadChip. The primary analysis estimated the associations among individual CpG sites and PTSD symptom scores. Of the 793,575 screened probes tested, two were significant at a false discovery rate (FDR) < 10%. Hypomethylation of both sites was associated with increased PTSD symptom scores. Analysis of differentially methylated regions (DMR) identified a DMR associated with PTSD symptom scores at an FDR < 10%. Results from follow-up models are also discussed. Findings from this preliminary investigation suggest the importance of further research conducted in adolescent samples. The analytic pipeline and results are documented for use in future meta-analytic work as more such samples become available.


Can professionalism be taught? Encouraging evidence.
Teaching and assessing the Accreditation Council for Graduate Medical Education (ACGME) competencies of Professionalism and Communication have proven to be a challenge for surgical residency training programs. This study used innovative pedagogic approaches and tools in teaching these two competencies. The purpose of this study was to determine whether the learners actually are assimilating and using the concepts and values communicated through this curriculum. A six-station Objective Structured Clinical Examination (OSCE) was designed using standardized patients to create varying Professionalism and Communication scenarios. The surgical resident learners were evaluated using these OSCEs as a baseline. The faculty then facilitated a specially designed curriculum consisting of six interactive sessions focusing on information gathering, rapport building, patient education, delivering bad news, responding to emotion, and interdisciplinary respect. At the conclusion of this curriculum, the surgical resident learners took the same six-station OSCE to determine if their professionalism and communication skills had improved. The surgical resident learners were rated by the standardized patients according to a strict task checklist of criteria at both the precurricular and postcurricular OSCEs. Improvement in the competencies of Professionalism and Communication did achieve statistical significance (P = .029 and P = .011, respectively). This study suggests that the Communication and Professionalism ACGME competencies can be taught to surgical resident learners through a carefully crafted curriculum. Furthermore, these newly learned competencies can affect surgical resident interactions with their patients positively.


Fetal Protection Policies and Corporate Liability of the US Vinyl Chloride Industry, 1974-1991.
In the late 20th century, fetal protection policies barred women from hundreds of thousands of industrial jobs on the pretext that if women became pregnant, their fetuses might be harmed by workplace exposure to toxic chemicals. Beginning in the 1970s, these policies set off a decades-long contest between the chemical industry, government agencies, and the judicial system over how to balance the uncertain reproductive health risks against sex discrimination. This article revives the subject of reproductive health and workplace protections through a historical case study of fetal protection policies at Firestone Plastics, a leader in the postwar vinyl chloride industry. I use formerly secret industry documents to argue that Firestone used scientific uncertainty and gender essentialism to skirt new regulatory pressures and minimize corporate liability. Ultimately, fetal protection policies stymied innovative regulatory efforts to protect all workers-not just women-from reproductive hazards in the workplace. (Am J Public Health. 2022;112(2):271-276. https://doi.org/10.2105/AJPH.2021.306539).


Cardiomyopathy and other myocardial disorders among hospitalizations for pregnancy in the United States: 2004-2006.
To estimate the rate of pregnancy hospitalizations for women with two groups of myocardial disorders, cardiomyopathy and other myocardial disorders, and report the rate of severe obstetric complications among these hospitalizations in delivery and postpartum periods. We performed a cross-sectional study using 14,323,731 hospitalizations for pregnancy identified from the 2004-2006 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. We reported rates of pregnancy hospitalizations with cardiomyopathy and other myocardial disorders per 1,000 deliveries and rates of severe complications per 1,000 hospitalizations during delivery and postpartum periods by myocardial disease status. We compared these rates by using chi2 tests with adjustment of P values for multiple comparisons using the Bonferroni method. Among all pregnancy hospitalizations, the overall prevalence of hospitalizations with myocardial disorders was 1.33 per 1,000 deliveries. The rate of pregnancy hospitalizations with cardiomyopathy was 0.46 per 1,000 deliveries (0.18 for apparent peripartum cardiomyopathy and 0.28 for other cardiomyopathies). The rate of pregnancy hospitalizations with other myocardial disorders was 0.87 per 1,000 deliveries. Myocardial disorders were rare during delivery hospitalizations (0.01%) but not uncommon among postpartum hospitalizations (4.2%). Among hospitalizations with myocardial disorders, the rate of severe complications ranged from 13.2 for acute myocardial infarction to 128.6 for adult respiratory distress syndrome and from 10.7 for pulmonary edema to 193.0 for fluid and electrolyte disorders per 1,000 delivery and postpartum hospitalizations, respectively. Among hospitalizations without myocardial disorders, the rate of severe complications ranged from 0.07 to 1.9 and from 0.4 to 65.5 for cardiac arrest and for fluid and electrolyte disorders per 1,000 hospitalizations, in delivery and postpartum periods, respectively. Although only a minority of hospitalizations for cardiomyopathy are consistent with peripartum cardiomyopathy, cardiomyopathy and other myocardial disorders are important contributors to severe obstetric complications. III.


Culture matters: A systematic review of antioxidant potential of tree legumes in the semiarid region of Brazil and local processing techniques as a driver of bioaccessibility.
Ethnobotanical studies report that human populations from the Brazilian Caatinga biome use tree legumes (Fabaceae) with medicinal and food purposes. Our study provides a systematic review of the available published information concerning the antioxidant potential of Hymenaea courbaril L. (jatobá), Libidibia ferrea (Mart. Ex Tul.) L.P.Queiroz (jucá), and Dioclea grandiflora Mart. Ex Benth. (mucunã). Furthermore, in this paper, we infer the possible effects of local processing techniques applied to these plants on their antioxidant potential. In order to achieve these goals, we reviewed 52 articles, including studies from ethnobiology (n = 17), chemistry (n = 32), and food studies testing antioxidant activity (n = 17), excluding 14 repetitions. We found that these legume species can inhibit the formation of free radicals and this potential action varies among different parts of the plant. Probably, the presence of phenolic compounds such as phenolic acids and flavonoids, which are not uniformly distributed in the plants, explain their antioxidant activity. Local processing techniques (i.e., roasting, milling) affect the bioaccessibility of antioxidant components of tree legumes, inducing both positive and negative effects. However, studies about the antioxidant potential did not consider local processing techniques in their analyses. Our study highlights that culture is a fundamental driver of nutritional and pharmacological outcomes related to edible resources since it determines which parts of the plant people consume and how they prepare them. Hence, ignoring cultural variables in the analysis of antioxidant activity will produce inaccurate or wrong scientific conclusions.


[Cardiac remodeling in chronic heart failure].
Left ventricular remodeling plays an important role in the progression of chronic heart failure. The early remodeling is an adaptive response to the increased load(i.e. hypertension) and/or the loss of contractile component (i. e. myocardial infarction) in order to maintain the pumping capacity. This process includes cardiac hypertrophy associated with myocyte hypertrophy and myocardial fibrosis. However, the persistence of the inadequate overload results in the decompensation of the adaptive mechanism. Finally, left ventricle is enlarged and the systolic function is impaired.


Local recurrence of rectosigmoid cancer: what about the choice of MRI for diagnosis?
Local recurrence is a frequent event in the natural history of rectosigmoid cancer. The diagnostic possibilities, as well as the limits of computed tomography (CT) and transrectal ultrasonography (TRU), are well known in these conditions. The aim of our study was to define the possible role of magnetic resonance imaging (MRI). We considered 15 examinations carried out in 14 patients, seven of which were obtained before and after Gd-DTPA administration. MRI demonstrated a 93.3% accuracy, 100% sensitivity, and 83.3% specificity in relation to the presence of local recurrence. The presence of pelvic recurrence was suggested on the basis of morphological and signal criteria. The use of paramagnetic contrast gave additional information in four of seven patients. The use of Gd-DTPA may be most beneficial in patients suspected of recurrence, within 6 months of their last treatment, where the diagnosis is more difficult.


Comparisons of the M1 genome segments and encoded mu2 proteins of different reovirus isolates.
The reovirus M1 genome segment encodes the mu2 protein, a structurally minor component of the viral core, which has been identified as a transcriptase cofactor, nucleoside and RNA triphosphatase, and microtubule-binding protein. The mu2 protein is the most poorly understood of the reovirus structural proteins. Genome segment sequences have been reported for 9 of the 10 genome segments for the 3 prototypic reoviruses type 1 Lang (T1L), type 2 Jones (T2J), and type 3 Dearing (T3D), but the M1 genome segment sequences for only T1L and T3D have been previously reported. For this study, we determined the M1 nucleotide and deduced mu2 amino acid sequences for T2J, nine other reovirus field isolates, and various T3D plaque-isolated clones from different laboratories. Determination of the T2J M1 sequence completes the analysis of all ten genome segments of that prototype. The T2J M1 sequence contained a 1 base pair deletion in the 3' non-translated region, compared to the T1L and T3D M1 sequences. The T2J M1 gene showed approximately 80% nucleotide homology, and the encoded mu 2 protein showed approximately 71% amino acid identity, with the T1L and T3D M1 and mu2 sequences, respectively, making the T2J M1 gene and mu2 proteins amongst the most divergent of all reovirus genes and proteins. Comparisons of these newly determined M1 and mu2 sequences with newly determined M1 and mu2 sequences from nine additional field isolates and a variety of laboratory T3D clones identified conserved features and/or regions that provide clues about mu2 structure and function. The findings suggest a model for the domain organization of mu2 and provide further evidence for a role of mu2 in viral RNA synthesis. The new sequences were also used to explore the basis for M1/mu2-determined differences in the morphology of viral factories in infected cells. The findings confirm the key role of Ser/Pro208 as a prevalent determinant of differences in factory morphology among reovirus isolates and trace the divergence of this residue and its associated phenotype among the different laboratory-specific clones of type 3 Dearing.


Looking beyond the myths of aging America.
In today's society, the elderly population is often the most misunderstood group. Many myths, such as all elderly people are poor in both health and income, are simply not always true. There is no longer a "typical" older person. They are much better off physically, financially, and socially than most realize. Healthcare providers and insurers must begin to understand the changing needs of the elderly. They must begin to meet those needs in both the healthcare services and financing alternatives they provide.


Ankyloglossia and effects on breast-feeding, speech problems and mechanical/social issues in children.
This aim of this study was to define the characteristics of the patients who underwent surgery for ankyloglossia. The patients (n = 127) with ankyloglossia underwent surgery between 1987 and 2005. The patients were evaluated for age, gender, complaints, grade, and operative procedures. This study did not cover postoperative evaluation of the procedure. The ages of the children ranged from 20 days to 7 years, and 84% of them were under 1 year of age. Seventy-two percent were boys; 28% were girls. The most common complaint of the parents of infants under one year of age was breast-feeding (35/84). When the tongue movements of the patients were examined, 57 patients (of whom 18 were over one year of age) had limited tongue mobility. The mean frenulum length of the patients was grade 1 in 72 patients and grade 2 in 55 patients. Ankyloglossia was corrected by frenotomy. Three patients had bleeding from their frenotomy site which resolved with local pressure. General anaesthesia was preferred for 77 patients, and there was a need for suturing in 20 patients. The correction of ankyloglossia at an early age reduces the risk of latent complications. In addition, the early correction will mitigate the feeding- and speech-related concerns of parents and doctors alike.


[Physical and colloidal properties picture of gall in patients with hepatitis on background standard diet].
Changes of physical properties and colloidal properties and microscopic picture of gall and liver bladder are detected in patients with virus hepatic B and C. A big number of chrystal elements (cholesterol chrystals gall acids, calcium belirubinates, microlytes) as well as cyllindic epithelium cells are revealed. The revealed changes degree isn't conncted with virus hepatitis ethyology, but proportionate to intensity of expressive changes in liver parenchyma.


A Promoter Variant Within the Aryl Hydrocarbon Receptor Gene Is Associated with an Epithelial Barrier Defect in Smokers with Crohn's Disease.
Smoking worsens Crohn's disease (CD). The aryl hydrocarbon receptor (AhR) is a transcription factor that mediates the toxicity of dioxinlike chemicals. We hypothesized that AHR variants and smoking influence CD. Exon-intron boundaries and coding and promoter regions of AHR gene were sequenced (28 patients with inflammatory bowel disease; 4 healthy controls). Two identified variants (rs7796976 and rs2066853) were studied for an association with intestinal permeability (IP, oral sugar test) in patients with inflammatory bowel disease (stratified according to the smoking status). AHR expression was analyzed by quantitative real-time polymerase chain reaction in colonic biopsies from patients with CD (n = 53). Case-control analysis including a genotype-phenotype correlation was performed for both variants (n = 767 patients with inflammatory bowel disease; n = 466 healthy controls). Sequencing identified a putative promoter variant (rs7796976) and a nonsynonymous variant (rs2066853; Arg554Lys) in AHR, both predicted to be functionally relevant. The major G-allele of rs7796976 increased the risk for disturbed IP (odds ratio 1.9, 95% confidence interval [CI], 1.1-3.2) in CD but not ulcerative colitis. We observed an additive effect of the rs7796976 genotype and smoking on IP (P = 0.005), which was also shown for rs2066853 (P = 0.004; variants not linked). Both variants showed a genotype-dependent AHR expression in colonic biopsies of patients with CD. No overall association with either CD or ulcerative colitis was observed; however, the rs7796976 genotype and smoking increased the risk for the L4 phenotype in CD. Smoking and functionally relevant AHR variants increase IP in CD. Because AhR is known to mediate between smoking and inflammation, these variants might be involved in the deleterious effect of smoking on CD.


Extending the platinum-free interval: The impact of omitting 2nd line platinum chemotherapy in intermediate platinum-sensitive ovarian cancer.
Patients with epithelial ovarian cancer (EOC) recurring between 6 and 12 months after primary platinum chemotherapy have worse prognosis than those recurring in >12 months. Artificially prolonging the platinum-free interval (PFI) with cytotoxic chemotherapy was tested in MITO-8 with poor outcomes. This study aimed to determine the impact of using non-platinum or targeted therapy in 2nd line treatment of EOC patients recurring 6-12 months after completion of primary platinum-based chemotherapy. A multi-institutional retrospective review of 177 patients with recurrent EOC and PFI of 6-12 months following primary chemotherapy was performed comparing platinum versus non-platinum chemotherapy or targeted therapy for 2nd line treatment. PFI1 was defined as the date of last chemotherapy to date of recurrence. PFS2/3 were defined as start of 2nd or 3rd line chemotherapy to start of subsequent line. Of 177 patients, the majority of patients were Caucasian, had serous histology, and underwent primary cytoreductive surgery. Median PFI1 was 8.2 months (95% CI 8-9 months). Second line platinum was omitted in 28% of patients. Bevacizumab was used in 2nd line in 16% of patients; 19% received other targeted therapies. Median PFS2 for platinum chemotherapy was longer than non-platinum (7.1 vs 3 months, p = 0.0114). Median PFS2 was significantly longer for platinum vs. targeted therapy (7.1 vs. 3 months p = 0.0431). Median OS for platinum in 2nd line vs. no platinum was 43.6 vs. 37.6 months (p = 0.0174). Use of non-platinum chemotherapy and even targeted therapy to prolong PFI in patients with EOC recurring between 6 and 12 months leads to worse survival.


Contrast media kinetics in multiparametric magnetic resonance imaging before radical prostatectomy predicts the probability of postoperative incontinence.
To evaluate the role of preoperative multiparametric magnetic resonance imaging (MRI) as predictor of post-prostatectomy incontinence (PPI). We analyzed patients who underwent robot-assisted radical prostatectomy for localized prostate cancer at our institution between July 2015 and April 2017. In these patients, we measured the perfusion quality of the pelvic floor with contrast media kinetics in the preoperative MRI of the prostate and compared the levator ani muscle (region of interest) to the surrounding pelvic muscle structures (reference). Prospectively collected questionnaires regarding urinary incontinence were then evaluated 1 year postoperatively. Outcomes were dichotomized into "continent" (ICIQ-Score = 0-5) and "incontinent" (ICIQ-Score ≥ 6). In each patient, we determined the perfusion ratio of the levator ani muscle divided by the surrounding pelvic muscle structures and compared them among the groups. Forty-two patients were included in the study (n = 22 in "continent", n = 20 in "incontinent" group). The median perfusion ratio from the continent group was significantly higher compared to the incontinent group (1.61 vs. 1.15; 95% CI 0.09-0.81, p = 0.015). The median perfusion ratio in "excellent" (ICIQ-Score = 0) was significantly higher than in "poor" (ICIQ-Score ≥ 11) outcomes (1.48 vs. 0.94; 95% CI 0.04-1.03, p = 0.036). Further, a higher perfusion ratio was negatively correlated with ICIQ-Score (r = - 0.33; 95% CI - 0.58 to 0.03; p = 0.031). Our data demonstrate a promising new strategy to predict PPI through the perfusion quality of pelvic muscle structures with contrast media kinetics. This may facilitate preoperative patient consulting and decision-making.


Otologic manifestations of Wegener's granulomatosis.
To evaluate the clinical features, treatment, and outcomes of otologic manifestations in Wegener's granulomatosis (WG) treated at Hokkaido University Graduate School of Medicine, Sapporo, Japan. We retrospectively reviewed 15 cases of WG with ear involvement. Twenty-five patients with WG were treated at Hokkaido University Graduate School of Medicine between 1992 and 2001. Fifteen of these patients had otologic symptoms. We evaluated the clinical course, method of therapy, and outcomes in all cases. Diagnosis of WG was made when the patients had clinical findings and a positive titer of cytoplasmic pattern antineutrophil cytoplasmic antibodies (c-ANCA), or when there were clear histologic findings. We also present three case reports. In 15 cases, the most frequent finding was chronic otitis media. Sensorineural hearing loss was present in 2 patients. In 7 patients whose otologic manifestations were the primary involvement of WG, all were confirmed positive for c-ANCA and were treated with glucocorticoids and immunosuppressive drugs. Three patients who could be treated within 1 month of symptom onset showed marked improvement. In localized cases, biopsy specimens are often small, and it is frequently difficult to make a histologic diagnosis. The prognosis for hearing was poor when appropriate treatment was not given in the early stages of the disease. Therefore, WG should be included in the differential diagnosis in cases of atypical inflammatory states of the ear. Early diagnosis and appropriate treatment are important to prevent irreversible changes in the middle ear and inner ear.


Long-chain omega-3 fatty acids and women's mental health in the perinatal period and beyond.
Recent research has shown that depression and a range of physical illnesses, including heart disease, metabolic syndrome, and type 2 diabetes, have an inflammatory etiology. The long-chain omega-3 fatty acids (omega-3s) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in fish and fish-oil products, may protect against these illnesses, in part because they lower inflammation. This article reviews the recent research on omega-3s and women's mental health, with a particular focus on the perinatal period. These studies include population studies examining fish consumption and studies testing the efficacy of EPA and DHA as treatments for depression. Although the findings are mixed, the majority of studies indicate that EPA has efficacy in treating depression either alone or in combination with DHA and/or antidepressant medications. The role of DHA alone in mental health is less clear, but it is generally combined with EPA and appears to have a beneficial effect. In moderate doses, EPA and DHA appear safe for pregnant and postpartum women, and they are well tolerated by patients.


Development and Validation of a Chinese Version of a Professional Identity Scale for Healthcare Students and Professionals.
This study was intended to develop a comprehensive and psychometrically adequate professional identity scale for healthcare students and professionals based on Taiwanese cultural contexts. In order to elicit a more consistent result of the psychometric indices of the newly developed scale, the study adopted a combination of exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to examine the consistency of the scale factors. In a pilot study of 562 randomly selected healthcare students and professionals, the EFA yielded a 33-item four-factor model with the terms "professional commitment & devotion" (16 items; 47.33% of variance), "emotional identification & belongingness" (7 items; 9.72% of variance), "professional goals & values" (5 items; 8.17% of variance), and "self-fulfillment & retention tendency" (5 items; 3.38% of variance). The CFA yielded an 18-item four-factor model with good or even excellent fit to the data, where the χ2/df ratio = 1.138, Tucker Lewis index (TLI) = 0.997, comparative fit index (CFI) = 0.997, and root mean square of approximation (RMSEA) = 0.016. The convergent validity and discriminant validities were also conducted to test the feasibility of the Professional Identity Scale for Healthcare Students and Professionals (PIS-HSP) scale. For the EFA model, the Cronbach's alphas for the four factors and the overall scale ranged from 0.84 to 0.96; for the CFA model, the Cronbach's alphas and composite reliabilities were, respectively, in the ranges of 0.78-0.93 and 0.78-0.97, demonstrating satisfactory reliabilities. The results proved that the developed PIS-HSP can be a reliable measurement tool to assess professional identity for healthcare students and professionals.


Phenotypes and natural history of food protein-induced enterocolitis syndrome in the east Mediterranean region.
Background: Food protein-induced enterocolitis syndrome (FPIES) is a rare non-IgE mediated food allergy. Objective: To delineate the differences in the spectrum of culprit foods, remission patterns, and predictors among varying cultures. Methods: We reviewed demographics, culprit foods, outcomes, and predictors in 81 children with a diagnosis of FPIES who were followed up between 2015 and 2020. Results: Eighty-one patients (55.6% boys) were enrolled, including 72 with acute FPIES and 9 with chronic FPIES. Hen's egg was the most common culprit food (36.6%), followed by fish (26.9%), and cow's milk (21.5%). Interestingly, cow's milk was significantly prevalent in chronic FPIES cases (p = 0.006). The most common clinical symptoms were vomiting (100%), pallor (63.4%), and lethargy (55.9%). Emergency department visits were noted in 39 patients (41.9%), of whom 37 (39.8%) were treated with intravenous (IV) fluid. The subjects were followed up for a median (interquartile range) of 19.4 months (12.3-41.2 months), and 26 subjects (32.1%) achieved tolerance. The median (interquartile range) age at tolerance was 2.5 years (2.1-3.2 years). With regard to the culprit foods, hen's egg was observed more frequently in the subjects with resolved FPIES cases (p = 0.008), whereas fish FPIES cases were high in the persistent group (p = 0.001). IgE sensitization of the culprit food was found to be an independent risk factor for the persistence of FPIES (odds ratio 4.855 [95% confidence interval, 1.131-20.844]; p = 0.034). Conclusion: In our cohort, unlike other published series, hen's egg and fish were the two most common culprit foods. Fish differed from other culprit foods, with significantly delayed onset and persistence, and may create a model that allows for the understanding of the disease.


Efficacy in long-term treatment of depression.
Available evidence suggests that antidepressants need to be continued on a long-term basis after the acute response. Premature discontinuation soon after symptomatic response is associated with the return of depression (relapse) in many patients. One efficacy measure of an antidepressant required by many regulatory authorities prior to approval of the agent is the ability of the antidepressant to continue the acute response compared with a placebo control. The reference tricyclic antidepressants (TCAs) amitriptyline and imipramine both have been shown to be effective in this continuation phase, but there is surprisingly little evidence on the efficacy of the other TCAs. The serotonin selective reuptake inhibitors paroxetine, fluoxetine, sertraline, and citalopram, as well as nefazodone, a new antidepressant with a dual mechanism of action that is classified as a serotonin receptor modulator, are effective compared with placebo. Placebo appears to be a good comparator in assessing the long-term efficacy of antidepressants. For example, in an assessment of the long-term efficacy of citalopram, patients who responded while taking placebo and were continued on placebo treatment were compared with patients who responded to drug and were transferred to placebo. The relapse rates in both cases were similar, validating placebo as a useful control. Most studies of long-term efficacy use the discontinuation design in which patients are treated with an active drug until response is obtained and then are either continued on the active drug or switched to placebo in a random and blinded manner. Alternatively, studies with nefazodone have used the double-blind continuation design, which may be preferred because it avoids any confounding effects of the discontinuation of drug in a drug-responsive patient. For example, in acute studies, responders to treatment with nefazodone, imipramine, or placebo were continued on the same treatment under double-blind conditions for 1 year; both antidepressants were effective compared with placebo. This study design may be useful in providing an estimate of long-term efficacy that can be obtained relatively early in a drug development program. The length of treatment in the continuation phase of therapy is also of interest. The separation of drug and placebo efficacy is sharpest in the first 4 months, which is consistent with the recommendation that all treatment for depression should continue for a minimum of 4 to 6 months to prevent relapse after symptomatic response of the acute episode. After the continuation phase (relapse prevention), evolving evidence strongly indicates that antidepressant treatment should be continued in patients at risk for recurrence. Depending on the number of recurrences, lifelong prophylactic therapy may be warranted.


Molecular and cellular interactions in rheumatoid synovium.
There is growing evidence that distinct molecular and cellular interactions in the rheumatoid synovium result in a complex cascade of pathophysiologic events. These interactions finally lead to progressive joint destruction, in a way that is different from all other joint diseases. Keystones are inflammation, proliferation of synovial cells, and attachment and invasion of synovial fibroblasts (in)to adjacent cartilage and bone, mediated by continuous release of matrix-degrading enzymes. Advances in molecular biology have provided numerous new data on the rheumatoid arthritis interaction cascade. Major research topics involve the balance of proinflammatory and inhibitory cytokines, the role of adhesion molecules in attachment of synovial fibroblasts to cartilage, and the localization of various matrix-degrading enzymes in the synovial lining. The results of the research reviewed here also provide a basis for future therapies including gene therapy.


Clinical governance: an educational perspective.
Clinical governance is a novel concept with potentially profound implications for the practice of medicine in the next millennium. What the term might mean from the perspective of patients, and doctors in the health service of the future is explored in this article. All this has significant educational implications and these are considered.


Response to teriparatide in Chinese patients with established osteoporosis: osteocalcin and lumbar spine bone-mineral density changes from teriparatide Phase III study.
Teriparatide is the first anabolic agent for osteoporosis, and this analysis aimed to understand responses to teriparatide in Chinese patients with established osteoporosis in subgroups. In this Phase III study of teriparatide in China, 362 patients were randomized at a 2:1 ratio to receive subcutaneous teriparatide (20 μg/day) or intranasal salmon calcitonin (200 IU/day) for 24 weeks. Teriparatide treatment produced a significantly greater increase in lumbar spine bone-mineral density (LS-BMD) in postmenopausal women than calcitonin at the 24-week end point. The relationship between osteocalcin (OCN) and LS-BMD was evaluated, and the greatest correlation was found between absolute OCN change at week 12 and percentage change in LS-BMD for patients in the teriparatide group (r=0.24, P<0.001). The correlation weakened at week 24 (r=0.16, P=0.02) and was negligibly negative for calcitonin-treated patients. Proportions of patients achieving >10 μg/L absolute OCN change from baseline in the teriparatide- and calcitonin-treated groups were 81% and 6% at week 12, respectively (P<0.001). Proportions of patients with increased LS-BMD ≥3% at week 24 from baseline were 71% and 35% in the teriparatide- and calcitonin-treated groups, respectively (P<0.001). Proportions of patients meeting both criteria were 63% for the teriparatide group and 1% for the calcitonin-treated group (P<0.001). Subgroup analysis suggested that significant increases in LS-BMD and OCN can be achieved in patients receiving teriparatide, regardless of baseline age, LS-BMD, and fracture times. The rate of treatment-emergent adverse events in each subgroup was similar to the overall analysis.


2-Amino-4-(4-chloro-phen-yl)-5,6-dihydro-benzo[h]quinoline-3-carbonitrile-3-amino-1-(4-chloro-phen-yl)-9,10-dihydro-phenanthrene-2,4-dicarbonitrile (1/4).
The asymmetric unit of the 1:4 title co-crystal of 2-amino-4-(4-chloro-phen-yl)-5,6-dihydro-benzo[h]quinoline-3-carbonitrile and 3-amino-1-(4-chloro-phen-yl)-9,10-dihydro-phenanthrene-2,4-dicarbonitrile, 0.2C(20)H(14)ClN(3)·0.8C(22)H(14)ClN(3), has the atoms of the fused-ring system and those of the amino, cyano and chloro-phenyl substitutents overlapped. The fused-ring system is buckled owing to the ethyl-ene linkage in the central ring. There are two independent overlapped mol-ecules in the asymmetric unit. In one independent mol-ecule, the two flanking aromatic rings are twisted by 24.4 (1)° and the ring of the chloro-phenyl substituent is twisted by 87.3 (1)° relative to the amino- and cyano-bearing aromatic ring. In the second mol-ecule, the respective dihedral angles are 26.1 (1) and 57.8 (1)°. The two independent mol-ecules are linked by N-H⋯N hydrogen bonds into dimers.


Acute myeloid leukemias M2 potentially misdiagnosed as M3 variant French-American-Britain (FAB) subtype: a transitional form?
From 1990 to 1994, 3 patients with de novo acute myeloid leukemia (AML) in whom light microscopy and cytochemistry suggested a FAB subtype M3 variant were observed at our Institute. Immunophenotype showed HLA-DR-, CD13+, CD33+, CD2+, CD9+; promyelocytic features were also detected by electron microscopy. However, leukemic cells lacked both translocation t(15;17) and RAR alpha/PML genes rearrangement. These cases were considered to be 'M2 atypical' subtypes and they contribute to point out how cytogenetics and molecular biology are mandatory for a correct diagnosis of acute promyelocytic leukemia (APL) particularly because therapy with all trans retinoic acid (ATRA) is now the best treatment for APL. Nevertheless these 3 cases indicate that the atypical M2 subtype may be confused with the M3v if only cytochemistry, immunophenotype and electron microscopy are used in the defining the FAB subtypes.


Use of the platelet function analyzer to minimize bleeding complications after renal biopsy.
The bleeding time is frequently used to screen primary haemostasis before surgical procedures, although it poorly predicts the risk of hemorrhage. The platelet function analyzer (PFA), which is also used to screen primary haemostasis, has a higher sensitivity and other advantages, like patient friendliness, higher degree of objectivity and analytical reliability, but needs more extensive clinical validation. We compared the predictive values of the PFA-CTs (closure times) and bleeding time for bleeding events after renal biopsy. We prospectively evaluated the complications in patients that underwent a renal biopsy and were screened with PFA in advance (n=170). For comparison we used a historical cohort of patients screened with the bleeding time (n=132). When the PFA-CTs were normal, 26.0% of the patients had a mild bleeding event after the biopsy, which did not differ from the event rate with a normal bleeding time (29.4%). When one or both PFA-CTs were prolonged, 51.3% of the patients had post-biopsy bleeding events independently of the measures to correct the closure time(s), significantly more than with either a prolonged bleeding time (26.7%) or normal PFA-CTs (26.0%). For bleeding events, the PFA has a higher positive and similar negative predictive value compared to the bleeding time. Taken into account the additional advantages of the PFA like patient friendliness and better analytical qualities, we prefer the PFA over the bleeding time as a screening tool for primary haemostasis before performing a renal biopsy.


Father absence and adolescent "problem behaviors": alcohol consumption, drug use and sexual activity.
Among the issues faced by adolescents are problems relating to alcohol consumption, drug use, and sexual behavior. A survey of 813 adolescents found that adolescents are most likely to discuss these problems with peers and least likely to discuss them with parents, especially fathers. However, father absence from the home resulted in greater use of and problems with alcohol, marijuana, and sexual activity. This was the case especially for boys. The results obtained underscore the significance of the father as a key figure in the transmission of values and as a deterrent to certain behaviors. The results point to adolescents from fatherless homes, especially boys, as being at risk for problems in the areas noted. This suggests that community agencies providing services to adolescents should make special efforts to incorporate into their programs specially designed services to meet the particular needs of this group. Aspects of such programs are discussed.


Diverse physiological functions of MKK4 and MKK7 during early embryogenesis.
Mitogen-activated protein kinase kinases (MAPKKs) are important components of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signalling pathway. Two MAPKKs that are crucial transducers upstream of JNK signalling are MKK4 and MKK7. These two MAPKKs directly phosphorylate specific Tyr and Thr residues located in the activation loop of the JNK protein and activate this kinase in response to environmental stress, pro-inflammatory cytokines or developmental cues. Although much is known about the biochemical and structural bases of the catalytic mechanism of the MAPKKs, the regulation and physiological functions of these enzymes during early embryogenesis have remained a mystery until relatively recently. Studies employing a range of animal models have now revealed the essential roles that MAPKKs play in diverse developmental contexts, including in dorsoventral patterning, convergent extension and somitogenesis. Focusing primarily on extensive work done in mouse and zebrafish models, this review summarizes the functional properties of MKK4 and MKK7 during vertebrate and invertebrate development, and the mechanisms by which these kinases regulate multiple steps in the establishment of the body plan of an organism.


Effects in vitro of mercury on rat brain Mg(++)-ATPase.
Mercuric chloride (Hg) in micromolar concentrations inhibited Mg(++)-dependent ATPase activity in rat brain microsomes. Inhibition was higher in oligomycin-sensitive (O.S.) than oligomycin-insensitive (O.I.) Mg(++)-ATPase. Hydrolysis of ATP with 15 and 50 micrograms of microsomal protein for 45 min without and with (2.10(-7M) Hg showed linear rates for 15-20 min. Altered pH vs activity demonstrated comparable inhibitions by Hg in buffered (neutral greater than acidic greater than basic) pH ranges. Inhibition of enzyme activity by Hg was found to be greater at 37 degrees C than at lower temperatures suggesting positive correlation trend. An uncompetitive inhibition with respect to the activation of Mg(++)-ATPase, O.S. Mg(++)-ATPase and O.I. Mg++ ATPase by ATP was indicated by a decrease in apparent Vmax and Km. Mg(++)-activation kinetic studies indicated that Hg causes uncompetitive inhibition of Mg(++)-ATPase and O.I. Mg(++)-ATPase and mixed inhibition of O.S. Mg(++)-ATPase. Inhibition was partially restored by repeated washings. These results indicate that the inhibition of microsomal Mg(++)-ATPase by Hg was pH, temperature, enzyme and Mg++ concentration dependent. Additionally, the data also suggest that O.S. compared to O.I. Mg(++)-ATPase is more sensitive to Hg toxicity.


Proteins of Soybean Seeds: II. Accumulation of the Major Protein Components during Seed Development and Maturation.
Fresh weight and dry weight as well as quantitative and qualitative protein changes in the developing soybean (Glycine max) seed were described from 12 days after flowering until maturity. The seed proteins were separated on sucrose density gradients into three major fractions, having average sedimentation coefficients of 2.2S, 7.5S, and 11.8S. The 2.2S sedimenting proteins predominated at very early stages of development (12 days after flowering) and decreased proportionately throughout maturation. The 7.5S and 11.8S components appeared to be synthesized later in maturity and in larger amounts than the 2.2S proteins. Electrophoretic studies on extracts from whole seeds and on isolated protein fractions confirmed the early abundance of proteins in the 2.2S fraction and revealed temporal differences in the accumulation of three components of the 7.5S fraction. The 11.8S sedimenting fraction appeared throughout seed development as a homogeneous protein which accumulated in the seed with a time course similar to that of the total 7.5S protein fraction.


[Qilin Pills for obstructive azoospermia after ejaculatory duct reconstruction].
To observe the clinical effect of Qilin Pills in the treatment of severe oligozoospermia after microsurgical ejaculatory duct reconstruction for obstructive azoospermia. We retrospectively analyzed 75 cases of obstructive azoospermia treated by ejaculatory duct reconstruction followed by administration of Qilin Pills. The patients were divided into a Qilin group (n=42) and a control group (n=33) postoperatively, treated with Qilin Pills and placebo, respectively. After 3 months of medication, we compared the sperm quality between the two groups of patients. After 3 months' treatment, all the patients experienced remarkable improvement in sperm quality (P<0.05). Compared with the controls, the patients in the Qilin group showed dramatic increases in sperm concentration, from (0.57±0.25) and (0.60±0.18) ×10⁶/ml before medication to (2.83±0.59) and (1.72 ±0.52) ×10⁶/ml after medication, significantly higher in the Qilin than in the control group (P<0.05). The percentage of grade a sperm was increased from (5.52±5.97) and (5.30±6.26)% to (11.56±9.96) and (10.27±6.52)%, that of grade a+b sperm from (9.68±8.63) and (8.64±10.10)% to (23.42 ±14.10) and (20.81±14.70)%, and that of morphologically normal sperm from (2.00±1.27) and (2.31±0.94)% to (3.54±2.47) and (3.47±1.33)%, respectively. No statistically significant differences were observed in sperm motility and normal sperm morphology between the two groups after treatment (P>0.05). The total effectiveness rate was higher in the Qilin group than in the controls (88.1% vs 72.7%), but with no significant difference between the two groups (P>0.05). Qilin Pills are fairly effective in improving the quantity of sperm in obstructive azoospermia patients after ejaculatory duct reconstruction.


Influence of intracanal post on apical periodontitis identified by cone-beam computed tomography.
The determination of the success of endodontic treatment has been often discussed based on outcome obtained by periapical radiography. The aim of this study was to verify the influence of intracanal post on apical periodontitis detected by cone-beam computed tomography (CBCT). A consecutive sample of 1020 images (periapical radiographs and CBCT scans) taken from 619 patients (245 men; mean age, 50.1 years) between February 2008 and September 2009 were used in this study. Presence and intracanal post length (short, medium and long) were associated with apical periodontitis (AP). Chi-square test was used for statistical analyses. Significance level was set at p<0.01. The kappa value was used to assess examiner variability. From a total of 591 intracanal posts, AP was observed in 15.06%, 18.78% and 7.95% using periapical radiographs, into the different lengths, short, medium and long, respectively (p=0.466). Considering the same posts length it was verified AP in 24.20%, 26.40% and 11.84% observed by CBCT scans, respectively (p=0.154). From a total of 1,020 teeth used in this study, AP was detected in 397 (38.92%) by periapical radiography and in 614 (60.19%) by CBCT scans (p<0.001). The distribution of intracanal posts in different dental groups showed higher prevalence in maxillary anterior teeth (54.79%). Intracanal posts lengths did not influenced AP. AP was detected more frequently when CBCT method was used.


[Perioperative Management for Patients Undergoing General Thoracic Surgery with Metabolic or Endocrine Disorders].
By improvement of surgical procedures and advances in perioperative management, the patients with various comorbidity diseases have been able to undergo pulmonary resection. In particular, the patients with endocrine and metabolic disorders are relatively frequent and often underwent pulmonary resection. Most of them are chronic diseases and often controlled for a long time. However, they sometimes have drastic changes due to surgical stress during perioperative periods. Failure to properly perioperative management for them may result in postoperative morbidity or mortality. Therefore, we have to well know perioperative changes by surgical stress for them. Among endocrine and metabolic disorders, following is frequent, diabetes, hyperthyroidism and hypothyroidism, steroid administration. We describe perioperative management of them. When operating on them, it is important to ① proper evaluation before surgery, ② careful postoperative management, and ③ close coordination with the department of endocrinology and anesthesiology.


Chromatographic analysis in bacteriologic diagnostics of blood cultures, exudates, and bronchoalveolar lavages.
This article summarizes our previously achieved and published results. The method for the determination of bacterial volatile fatty acid patterns (VFA) in clinical samples was elaborated. It employs gas chromatography (GC), solvent extraction or head-space solid phase microextraction (SPME). This method was validated by analyses of reference bacterial strains. After cultivation in defined media, aerobic and facultative anaerobic bacteria provided profiles with a low or none acid content, while anaerobic bacteria provided characteristic but medium-dependent profiles with a higher acid content. This method was used for the analyses of clinical samples of total 375 blood cultures, 205 suppurative and apyogenous exudates, and 210 bronchoalveolar lavages (BALs). These analyses enabled within 30 minutes the detection of microbes, probably non-sporulating anaerobes not found by false-negative cultivation, in 11.2% of blood cultures, in 20.0% of exudates, and in 9.0 to 20.0% of BALs. Using the mass spectrometry (MS) methods, a number of other components with unclear diagnostic importance were found in BAL samples, in particular hydrogen cyanide, methanol, ethanol, hexanol, acetone, cyclohexanone, acetonitrile, formaldehyde, acetaldehyde, ethyl acetate, and other esters. Cyclohexanone, occurring mainly in BALs of patients with pneumonia, undergoing intensive care, may originate as a residual solvent from the plastic parts of the ventilation apparatus.


Abundance and spatial-temporal distribution of the shrimp Xiphopenaeus kroyeri (Decapoda: Penaeidae): an exploited species in southeast Brazil.
This study evaluated the abundance and spatial-temporal distribution of the shrimp Xiphopenaeus kroyeri in the coastal region of Macaé, state of Rio de Janeiro, southeastern Brazil. Monthly samples were obtained from March 2008 to February 2010 in six stations located in Inner (5, 10 and 15m depth) and Outer (25, 35 and 45m depth) areas. It was used a commercial fishery boat equipped with an otter-trawl net (3.5 m mouth width, mesh size 20mm and 15mm in the cod end). Water samples were taken for determination of temperature and salinity, and sediment samples for determination of texture and organic matter content. A total of 7146 shrimps were sampled. About 95% of all shrimps were caught in the shallow area, i.e., depths <20m. Greatest abundances were recorded in winter and spring. No significant correlation was observed between sediment (phi) and abundance. The distribution of X. kroyeri in the studied area was closely related to seasonal cold waterfront of the South Atlantic Central Water (SACW) and temperature was the main factor affecting the species abundance.


Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. The Esmolol vs Placebo Multicenter Study Group.
The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).


Severe hypothyroidism following a single topical exposure to iodine in a premature neonate.
A neonate, born at 24 weeks, underwent a patent ductus arteriosus ligation, with previous normal thyroid stimulating hormone (TSH) levels, developed severe hypothyroidism from topical exposure to iodine following a single surgical procedure at 28 days of life. A low free T4 level of 0.05 ng/dL and a high TSH level of 228 mIU/L was detected with an increased urinary iodine excretion level of 178 mg/L (reference range 0.30-1.97 mg/L). The thyroid ultrasound was normal. Levothyroxine was started immediately but thyroid function did not recover fully during admission and levothyroxine was required beyond term corrected. This case highlighted how susceptible extremely preterm infants are to iodine induced hypothyroidism, even short-term topical exposure. Delayed treatment of hypothyroidism can lead to profound neurodevelopmental delay. As surgical advances allow for interventions at earlier gestations, the importance of early thyroid function testing postexposure to iodine is highlighted and ultimately topical iodine should be avoided in these susceptible infants.


Bacillus cereus strains from donor human milk and hospital environment: uncovering a putative common origin using comparative analysis of toxin and infra-red spectroscopy profiles.
Bacillus cereus is reported as a common cause of toxin-induced food poisoning and of contamination in pasteurized human milk donations. As various toxins can be produced by B. cereus, the aim of this work was first to investigate the toxigenic potential and profiles of 63 B. cereus isolates from Amiens Picardie human milk bank. A comparison to the toxigenic profiles of 27 environmental B. cereus isolates harvested in the hospital in which this human milk bank is situated was performed. Toxin gene prevalences were the highest for nhe (ABC) and entFM followed by cytK and hbl(ACD). A 27% prevalence was found for ces human milk isolates, which is higher than previous works reporting on pasteurized milk and dairy products. No significant differences could be found between human milk and environmental isolates regarding toxin gene prevalences and/or toxin gene profiles. The second aim was to establish whether a B. cereus cross-contamination between human milk and the environment could occur. This was achieved with the help of Fourrier-transform infra-red spectroscopy which enabled the discrimination of 2 main clusters of 11 and 8 isolates, each containing human milk and Amiens Picardie human milk bank environmental isolates. For these two clusters, the time sequence showed that human milk isolates were the first to occur and might have contaminated the milk bank environment as well as other human milk donations. Routinely used on B. cereus isolates, Fourrier-transform infra-red spectroscopy could help in rapidly detecting such clusters and in limiting the spread of a B. cereus strain that might generate rejection of pasteurized donation by the human milk bank.


ED becomes 'lean' and cuts LBTC, LOS times.
Lean manufacturing techniques, first developed by Toyota, can be successfully adapted to help improve processes in your ED. St. Luke's Episcopal Hospital in Houston, has used Lean to reduce median length of stay, frequency of diversions, and the percentage of patients who left before treatment was complete (LBTC). Here's why "Lean" can help improve the performance of your ED: It enables you and your staff to see things from the patient's point of view. Lean tools enable you to view the status of your department in real-time and to compare that status with your performance goals. Exercises help identify areas where your processes break down and determine the most likely solutions.


Vacuum-assisted vaginal delivery.
Approximately 5% (1 in 20) of all deliveries in the United States are operative vaginal deliveries. The past 20 years have seen a progressive shift away from the use of forceps in favor of the vacuum extractor as the instrument of choice. This article reviews in detail the indications, contraindications, patient selection criteria, choice of instrument, and technique for vacuum-assisted vaginal delivery. The use of vacuum extraction at the time of cesarean delivery will also be discussed. With vacuum extraction becoming increasingly popular, it is important that obstetric care providers are aware of the maternal and neonatal risks associated with such deliveries and of the options available to effect a safe and expedient delivery.


Individual difference variables that predict response to training in phonological awareness.
The cognitive abilities that predicted growth in response to a 12-week training program in phonological awareness were investigated with a sample of 100 kindergarten children. The children were selected from two elementary schools with historically low achievement in reading. Sixty children received training in both analytic and synthetic awareness skills, and 40 children constituted a no-treatment control group. Pretest measures included assessment of phonological awareness, phonological memory and naming rate, letter knowledge, reading and spelling, and general verbal ability. Growth in phonological awareness was assessed during the middle and at the end of the training period. Hierarchical linear modeling was used to estimate individual growth curves in phonological awareness for children in both the treatment and control groups. Initial comparisons between children in the two groups indicated substantial overall training effects in phonological awareness for children in the treatment group. For children in the training group, the model that best predicted growth in analytic awareness included invented spelling and general verbal ability, while growth in synthetic awareness was predicted best by a combination of invented spelling and rapid automatic naming of digits.


Increase Intensive Care Staff Comfort and Proficiency With Emergent Re-sternotomy in the Post-Open-Heart Patient by Using SynDaver® Simulation.
Simulation training has been used in many avenues such as aeronautics, law enforcement, and healthcare to assist in training personnel to learn a new task and perform highly technical procedures. Simulation training has demonstrated beneficial for providing low-use, high-risk jobs such as landing a plane with a complete engine failure, performing reconstructive surgery, and even emergent lifesaving procedures. Our simulation training group chose to develop our custom hands-on training to perform emergent re-sternotomy on the post-open-heart patient based upon this belief. The goal of this project was to assist the bedside intensive care nurse in their self-perception of being comfortable and proficient in helping the physician with the procedure of an emergent re-sternotomy on the post-surgical open-heart patient. Measurement of self-perception of comfort and proficient was measured with a pre/post-questionnaire. The pre/post-questionnaire results showed improvement ranging from an increase in self-scoring from 1.2 to 1.7, with statistical significance demonstrated with a p <0.05.


Effect of dihydroergotoxine, a cerebral vasodilator, on cognitive deficits induced by prenatal undernutrition and environmental impoverishment in young rats.
The study was conducted on 64 Charles Foster strain albino rats, which were equally distributed into 8 evenly matched groups, following a 2 x 2 x 2 factorial design, by varying three independent factors at two levels: nutrition--normal and undernutrition; environment--enrichment and impoverishment, and drug treatment--vehicle and dihydroergotoxine (3 mg/kg, i.p.). Prenatal undernutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/dihydroergotoxine treatments were given during the postweaning period of the pups. The rats were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. Thereafter, the animals were tested for passive avoidance learning. The results indicate that undernutrition caused significant original and reversal discrimination learning, deficits whereas environmental deprivation attenuated only the original discrimination learning performance. Dihydroergotoxine treatment facilitated the learning performance of rats in both the original and reversal learning tests. Nutritional, environmental and dihydroergotoxine treatments had no effect on the retention of the passive avoidance learning, both at 24 hr and 1 week intervals. Dihydroergotoxine treatment attenuated the learning deficits induced by prenatal undernutrition. The results indicate that dihydroergotoxine is not likely to be useful in cognitive deficits, induced by malnutrition, though it facilitated learning acquisition, since it had no effect on retention.


The role of the serotonergic system in foot shock-induced behavior in mice.
In a foot shock-induced fighting (FSIF) test, serotonergic and antiserotonergic agents were examined. Stimulation of the brain 5-hydroxytryptamine (5-HT) neurons with different serotonergic agents, such as l-tryptophan, 5-hydroxytryptophan, imipramine, fluoxetine, 5-methoxy-tryptamine, quipazine, and fenfluramine, showed the inhibiting role of the 5-HT system in FSIF. At the same time, following the results obtained in FSIF tests and locomotor activity tests, it can be inferred that the 5-HT antagonists used (methysergide, cyproheptadine, metergoline, cinnarizine, and pizotifen) do not act specifically in this model of aggression. P-Chlorophenylalanine effects on mice in FSIF also seem to be partly due to catecholaminolytic action.


Disability and self-rated health among older women and men in rural Guatemala: the role of obesity and chronic conditions.
Unprecedented population aging in poorer settings is coinciding with the rapid spread of obesity and other chronic conditions. These conditions predict disability and poor self-rated health and often are more prevalent in women than men. Thus, gender gaps in obesity and other chronic conditions may account for older women's greater disability and worse self-rated health in poor, rural populations, where aging, obesity, and chronic conditions are rapidly emerging. In a survey of 604 adults 50 years and older in rural Guatemala, we assessed whether gender gaps in obesity and other chronic conditions accounted for gender gaps in disability and self-rated health. Obesity strongly predicted gross mobility (GM) disability, and the number of chronic conditions strongly predicted all outcomes, especially in women. Controlling for gender gaps in body-mass index (BMI) and especially the number of chronic conditions eliminated gender gaps in GM disability, and controlling for gender gaps in the number of chronic conditions eliminated gender gaps in self-rated health. We recommend conducting longitudinal cohort studies to explore interventions that may mitigate adult obesity and chronic conditions among poor, rural older adults. Such interventions also may reduce gender gaps in later-life disability and self-rated health.


Increased angiogenesis and FGFR protein expression indicate a favourable prognosis in bladder cancer.
Compared to other members of the fibroblast growth factor receptor (FGFR) family, only few studies investigate FGFR3 in tumour angiogenesis. We investigated the connection between angiogenesis and FGF/FGFR expression including FGFR3 mutation status in urothelial carcinomas. Immunohistochemistry was performed in invasive and non-invasive urothelial cancers of 61 patients. Protein expression of CD31, factor VIII (FVIII), FGF-1/2, FGFR1, FGFR3 and FGFR4 and FGFR3 mutation status were evaluated. Morphometric assessment of angiogenesis including microvessel count (MVC) and vascular surface area (VSA) was analysed. Correlation and survival analyses (overall survival (OS) and disease-free survival (DFS)) with univariate and multivariate analyses were performed. CD31 values (MVC and VSA) significantly correlated with OS and DFS. OS and DFS were significantly better in patients with FGFR3 overexpression. Multivariate analysis revealed FGFR3 protein expression and tumour grading (WHO classification 2004) as independent prognostic factors of OS and VSA of CD31 and FGFR3 protein expression of DFS. FGFR3 mutation status was correlated with VSA measured by FVIII. FGFR3 may be able to induce a pro-angiogenic phenotype in urothelial carcinomas and significantly influence prognosis. Consequently, FGFR3 is a potential therapeutic target also from the angiogenesis perspective.


Metal-organic architectures of silver(I), cadmium(II), and copper(II) with a flexible tricarboxylate ligand.
Three novel metal-organic architectures, [Ag3(bta)].1.5H2O (1), [Cd3(bta)2(H2O)7].5H2O (2), and [Cu11(bta)6(Hbta)2(H2O)10].29H2O (3), were obtained by reactions of the corresponding metal salts with a flexible tripodal ligand, benzene-1,3,5-triacetic acid (H3bta), and their structures were determined by single-crystal X-ray diffraction studies. The results revealed that, in complexes 1 and 2, the carboxylate groups of the bta3- ligand adopted varied coordination modes to link metal atoms and further to form three-dimensional structures with open channels occupied by water molecules, while in complex 3, for the first time, the flexible H3bta acted as a secondary building unit to generate a novel nanometer-sized metallocage, which is composed of a Cu(II) paddle wheel (square secondary building units) and bta3-/Hbta2- organic links (triangular secondary building units). The photoluminescence properties of complexes 1 and 2 were investigated, and the results showed that 2 exhibited photoluminescence in the solid state at room temperature.


Expression of ZAP-70 protein correlates with disease stage in chronic lymphocytic leukemia and is associated with, but not generally restricted to, non-mutated Ig VH status.
The mutational status of immunoglobulin variable region genes (Ig VH) is a well established prognostic parameter in chronic lymphocytic leukemia (CLL). Recently, a subset of genes with a characteristic expression profile correlating with the mutational status of B-CLLs has been identified. One of the overexpressed genes in the prognostically unfavorable group of CLL patients with unmutated Ig VH genes encodes for the protein tyrosine kinase ZAP-70, which is physiologically involved in T-cell signaling. Since ZAP-70 has been described to be prognostically relevant in CLL, we analyzed the possible relationship of its expression to the mutational status of Ig VH genes as well as to other prognostic factors in CLL and indolent lymphomas. The mutational status of Ig VH genes was analyzed by seminested PCR, direct sequencing and comparison with the sequences of the EMBL databases in 60 samples of patients with B-CLL and 18 samples of patients with indolent B-cell malignancies. ZAP-70 protein expression was assessed in all samples by immunoblotting and for semiquantitative analysis the ratio of ZAP-70 to tubulin expression was calculated. ZAP-70 protein was found to be expressed in all investigated B-cell malignancies. Expression levels varied within a wide range in each entity. The highest mean level of ZAP-70 expression was observed in unmutated B-CLLs, however, with broad expression variability. High levels of ZAP-70 expression correlated with higher stage Binet B or C and with unmutated Ig VH genes. Overall survival rates estimated by Kaplan-Meier curves did not differ among patients with high or low ZAP-70 expression. We conclude that ZAP-70 is associated with the mutational status of Ig VH genes, but this expression pattern is not present in all individual cases. Furthermore, high levels of ZAP-70 correlated with Binet stages B or C indicating an involvement of ZAP-70 in mechanisms promoting growth of B-CLL cells.


Increased cross-linking micelle retention in the brain of Alzheimer's disease mice by elevated asparagine endopeptidase protease responsive aggregation.
Current forms of medication for Alzheimer's disease (AD) provide a symptomatic benefit limited to those with early onset, but there is no single drug available for later stage patients. Given the recent failures of AD drugs in clinical trials, an intensive treatment strategy based on drug combination that is approved is attractive. At present, the greatest difficulty lies in the low accumulation of drugs in the brain. All hydrophilic drugs are limited by the physical and biochemical barriers within the blood-brain barrier and lipophilic drugs are often transported back into the blood by efflux pumps located in the blood-brain barrier. Here, we select elevated asparagine endopeptidase (AEP) as a target to trigger in situ cross-linking of small sized particles to form large sized drug clusters to block the efflux of the brain. Subsequently, responsive cross-linking micelles (RCMs) loaded with the acetylcholinesterase inhibitor, donepezil (DON), the microtubule therapeutic agent, Paclitaxel (PTX), and the glucose metabolism disorder regulator, insulin (INS) are investigated, with a focus on high levels of drug accumulation in the brain in AD. These smart multi-drug delivery RCMs provide a powerful system for AD treatment and can be adapted for other central nervous system (CNS) disorders.


Exploring arising moments and mindfulness in occupational therapists working in diverse clinical practice areas.
An online survey was conducted with 72 Canadian occupational therapists to (1) explore if and how occupational therapists were aware of "arising moments" in clinical practice, which are moments that give rise to emotions, sensations, and thoughts, and (2) to examine therapists' responses to questions related to mindfulness. Participants described arising moments through an open-ended survey question. Framework analysis was used to develop key themes and subthemes. A modified Philadelphia Mindfulness Awareness (PHLMS) subscale with two additional survey questions "understanding of living in the moment and being present, and awareness of mindfulness" (sum = PAM) were used as indicators of mindfulness. There were significant differences in the means of PHLMS mindfulness among therapists working in diverse practice areas (F = 3.63, p = .009). Posthoc analysis revealed that therapists working in mental health had higher mean PHLMS-mindfulness scores than in all other groups. There were no significant differences in PAM mindfulness among the practice areas (ANOVA, F = 2.15, p = .08). However, posthoc tests showed that the participants in the mental health practice area had a significant difference with one group, general physical health. Findings have implications for practice in occupational therapy and education about mindfulness in occupational therapy.


Cancer after total joint arthroplasty: a meta-analysis.
Some epidemiologic and laboratory studies have suggested that total joint arthroplasty could increase the risk of cancer. In this meta-analysis, we attempt to clarify the association of joint arthroplasty with subsequent cancer incidence. We identified population-based studies reporting standardized incidence ratios (SIR) for cancer following large joint arthroplasty. After summing the observed and expected numbers of cases across all qualifying studies, we calculated SIRs for all cancers, and for those at 28 anatomic sites. Latency analysis involving 175,166 patients characterized short-term and long-term cancer associations. The analyses included 1,435,356 person-years of follow-up and 20,045 cases of cancer. Overall cancer risk among patients with arthroplasty was equal to that for the general population. The relative risk of lung cancer, reduced in the first 5 years after arthroplasty, increased significantly over time to approach that of the general population. Risks for all sites in the luminal gastrointestinal tract were significantly reduced by 10% to 20%; with relative risks that were generally stable over time. Increased risks were seen for cancer of the prostate (SIR, 1.12; 95% confidence interval, 1.08-1.16); similar relative risks were seen in each time period after the procedure. For melanoma, relative risks increased with follow-up to a SIR of 1.43 (95% confidence interval, 1.13-1.79) for 10 or more years after arthroplasty. There was a similar delayed emergence of increased risks for cancers of the urinary tract and oropharynx. The relative risk for bone cancer decreased with time after the procedure. There does not seem to be an overall increased risk of cancer following total joint arthroplasty. Although the risks of prostate cancer and melanoma seem to be elevated, there is no obvious mechanism for these associations. Reductions in risk for some malignancies may not be causal.


Factor XIII-A in Diseases: Role Beyond Blood Coagulation.
Multidisciplinary research from the last few decades has revealed that Factor XIII subunit A (FXIII-A) is not only involved in blood coagulation, but may have roles in various diseases. Here, we aim to summarize data from studies involving patients with mutations in the F13A1 gene, performed in FXIII-A knock-out mice models, clinical and histological studies assessing correlations between diseases severity and FXIII-A levels, as well as from in vitro experiments. By providing a complex overview on its possible role in wound healing, chronic inflammatory bowel diseases, athe-rosclerosis, rheumatoid arthritis, chronic inflammatory lung diseases, chronic rhinosinusitis, solid tumors, hematological malignancies, and obesity, we also demonstrate how the field evolved from using FXIII-A as a marker to accept and understand its active role in inflammatory and malignant diseases.


Biological aspects of Schizodon nasutus Kner, 1858 (Characiformes, Anostomidae) in the low Sorocaba river basin, São Paulo state, Brazil.
Four biological aspects of Schizodon nasutus in the low Sorocaba river basin, São Paulo, Brazil were analysed. These were accomplished during the year seasons. The fish diet and the feeding activity were investigated by studying the repletion index, which showed no significant differences between seasons. The food items analysed by frequency of occurrence and dominance showed a predominance of vegetable items in the diet. The reproduction, analysed by using the gonadosomatic index, indicated that the reproductive period occurs during the summer period when temperatures are higher and rainfalls are more intense. The amount of accumulated fat and condition factor varied according to reproduction, especially for females.


Durvalumab activity in previously treated patients who stopped durvalumab without disease progression.
Limited data exist on potential clinical benefit with anti-programmed cell death ligand-1 (PD-L1) retreatment in patients who stop initial therapy for reasons other than disease progression or toxicity and develop disease progression while off treatment. NCT01693562 was a phase I/II study evaluating durvalumab monotherapy in advanced solid tumors. Patients benefiting from treatment were taken off durvalumab at 1 year per protocol and prospectively followed. At disease progression, they were eligible for durvalumab retreatment. Outcomes evaluated during retreatment included best overall response (BOR2), duration of response (DoR2), disease control rate (DCR2), and progression-free survival (PFS2). Of 980 patients enrolled and treated with durvalumab 10 mg/kg every 2 weeks (Q2W) in the dose-expansion cohorts, 168 completed 1 year of initial durvalumab treatment with confirmed BOR1 of complete response in 20 (11.9%), partial response (PR) in 84 (50%), stable disease (SD) in 52 (31%), and disease progression in 12 (7.1%). All 168 patients stopped treatment and were eligible for retreatment at progression; 70 patients (41.7%) representing 14 primary tumor types were retreated and response evaluable. Confirmed BOR2 was PR in 8 patients (11.4%), SD in 42 (60.0%), disease progression in 16 (22.9%), and unevaluable in 4 (5.7%). Median DoR2 was 16.5 months. DCR2 ≥24 weeks (DCR2 24) was 47.1%. PFS2 rate at 12 months was 34.2%, and median PFS2 was 5.9 months. Median overall survival (OS2) was 23.8 months. Response rates, DCR2 24, and median DoR2 were generally greater in patients with high PD-L1 expression than those with low/negative expression. No new safety signals were observed during retreatment. Retreatment restored antitumor activity, resulting in high rates of durable disease control with an acceptable safety profile. This evidence supports retreatment of patients who stop anti-PD-L1 therapy for reasons other than progression or toxicity, and supports further investigation.


Use of paramagnetic chelated metal derivatives of polysaccharides and spin-labeled polysaccharides as contrast agents in magnetic resonance imaging.
Soluble and insoluble polysaccharides were derivatized with diethylenetriaminepentaacetic acid (DTPA) and/or spin-labeled with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). Polysaccharides derivatized with DTPA were prepared via cyanogen bromide activation, coupling to a diamine linker, and to DTPA anhydride. Spin-labeled polysaccharides were also prepared via cyanogen bromide activation. The extent of derivatization for dextran (18 kDa) was about 120 glucose units per DTPA, and for cellulose and starch about 15-30 units per DTPA. For spin-labeled polysaccharides, the average loading ranged from 1 nitroxide per 16 glucose units for starch to 181 for dextran (82 kDa). These derivatized paramagnetic polysaccharides were shown to be more effective relaxants than the small paramagnetic molecules alone. Both soluble and insoluble polysaccharide-linker-DTPA-Gd(III) complexes were effectively cleared from the body (rats) after oral administration. After intravenous administration, the biodistribution of dextran-linker-DTPA-Gd(III) complexes differed significantly from that of GdDTPA. Reduction of the nitroxide by ascorbic acid was retarded in the polysaccharide derivatives, particularly in starch derivatized with both nitroxide and linker-DTPA-Cu(II). These agents showed contrast enhancement in the gastrointestinal tract of rabbits.


May-Thurner syndrome complicated by acute iliofemoral vein thrombosis: helical CT venography for evaluation of long-term stent patency and changes in the iliac vein.
The purpose of this study was to use CT venography to evaluate long-term patency and changes in the iliac veins after stent placement for acute iliofemoral vein thrombosis due to May-Thurner syndrome. From December 1999 to July 2007, 30 patients (22 women, eight men; age range, 30-78 years; mean, 56.7 years) with acute iliofemoral vein thrombosis due to May-Thurner syndrome diagnosed with CT venography were treated with catheter-directed thrombolysis and stent placement. The patients underwent follow-up CT venography at variable intervals according to clinician discretion. The primary objective was to determine the primary patency of the stented segment. The secondary objective was to investigate the potential role of CT venography by analyzing the morphologic features and interval changes in stented iliac veins. Cumulative primary and secondary stent patency rates were calculated by Kaplan-Meier estimation. Four stent occlusions and one stent collapse were found at the first follow-up CT venographic examination within 1 year (mean duration, 129.3 days) after treatment. One stent occlusion and one stent collapse were managed successfully. The primary and secondary patency rates were 83.3% and 90% 1 and 5 years after treatment. The morphologic features of the common iliac vein did not affect stent patency or expanded stent diameter. During sequential CT venographic follow-up, no new in-stent stenosis or occlusion was found. Iliac stents placed for May-Thurner syndrome with acute thrombosis had excellent long-term patency. Restenosis or occlusion occurred early, and initial luminal patency was well maintained during long-term follow-up.


The effect of aligned and random electrospun fibrous scaffolds on rat mesenchymal stem cell proliferation.
The development of combining mesenchymal stem cells (MSCs) with surface modified three-dimensional (3D) biomaterial scaffold provides a desirable alternative for replacement of damaged and diseased tissue. Nanofibrous scaffolds serve as suitable environment for cell attachment and proliferation due to their similarity to the physical dimension of the natural extracellular matrix. In this study the properties of plasma treated poly-C-caprolactone nanofiber scaffolds (p-PCL) and unaltered PCL scaffolds were compared, and then p-PCL scaffolds were evaluated for MSC culture. Aligned and random PCL nanofibrus scaffolds were fabricated by electrospining and their surface modified with O2 plasma treatment to enhance MSC proliferation, adhesion and interaction. Chemical and mechanical characterizations were carried out using scanning electron microscopy (SEM), water contact angle and tensile testing. Cell adhesion and morphology were evaluated using SEM 1 day after culture. Statistical analysis was carried out using one way analysis of variance (ANOVA). The proliferation of MSCs were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide(MTT) assay on day 1, 3, and 5 after cell culture. Results showed that the numbers of cells that had grown on PCL nanofibrous scaffolds were significantly higher than those of control surfaces without nanofibers. Furthermore, the proliferation of MSCs on random nanofiber was significantly higher compared to that on aligned nanofiber. This study showed that while both aligned and random plasma treated PCL nanofibrous scaffold are more suitable substrates for MSC growth than tissue culture plates, random nanofiber best supported the proliferation of MSCs.


Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants.
Serological tests are beneficial for recognizing the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT) is critical. Whether commercial antibody tests have comparable accuracy is unknown. Serum samples were obtained from COVID-19 patients (n = 74), SARS-CoV-2 PCR-negative (n = 179), and suspected healthy individuals (n = 229) before SARS-CoV-2 variants had been detected locally. The convalescent phase was defined as the period after day 10 from disease onset or the episode of close contact. The CRNT using pseudotyped viruses displaying the wild-type (WT) spike protein and a commercial anti-receptor-binding domain (RBD) antibody test were assayed. Serology for the B.1.1.7 and B.1.351 variants was also assayed. Both tests concurred for symptomatic COVID-19 patients in the convalescent phase. They clearly differentiated between patients and suspected healthy individuals (sensitivity: 95.8% and 100%, respectively; specificity: 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titers (r = 0.31, 95% confidence interval [CI] 0.22-0.38). Compared with the WT, lower CRNT values were observed for the variants. Of the samples with ≥100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed ≥50% neutralization against the B.1.1.7 and the B.1.351 variants, respectively. Exceeding 100 U/mL in the anti-RBD antibody test was associated with neutralization of variants (P < 0.01). The CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. Strong positive results with the anti-RBD antibody test can reflect neutralizing activity against emerging variants. IMPORTANCE This study provides a diagnostic evidence of test validity, which can lead to vaccine efficacy and proof of recovery after COVID-19. It is not easy to know neutralization against SARS-CoV-2 in the clinical laboratory because of technical and biohazard issues. The correlation of the quantitative anti-receptor-binding domain antibody test, which is widely available, with neutralizing test indicates that we can know indirectly the state of acquisition of functional immunity against wild and variant-type viruses in the clinical laboratory.


On Developing a Hydrophobic Rubberized Cement Paste.
It is well known that most cement matrix materials are hydrophilic. For structural materials, hydrophilicity is harmful because the absorption of water will induce serious damage to these materials. In this study, crumb rubber was pretreated by partial oxidation and used as an additive to develop a hydrophobic rubberized cement paste. The pretreated crumb rubber was investigated using Fourier-transform infrared spectrometry (FT-IR) to understand the function groups on its surface. The pyrolysis oil adsorbed on the surface of the crumb rubber was observed by FT-IR and nuclear magnetic resonance (NMR) spectroscopy. A colloid probe with calcium silicate hydrate (C-S-H) at the apex was prepared to measure the intermolecular interaction forces between the crumb rubber and the C-S-H using an atomic force microscope (AFM). Pure cement paste, cement paste with the as-received crumb rubber, and cement paste with pretreated crumb rubber were prepared for comparison. FT-IR, X-ray diffraction (XRD), and scanning electron microscopy (SEM) were used to understand the microstructure of the pastes. The static contact angle was used as the index of the hydrophobicity of the pastes. Experimental results showed that the hardened cement paste containing partially oxidized crumb rubber had excellent hydrophobic properties with an insignificant reduction in the compressive strength.