Endogenous synthesis of milk oleic acid in dairy ewes: In vivo measurement using 13C-labeled stearic acid.
The use of stable isotopes is a reliable and risk-free alternative to radioactive tracers for directly examining in vivo fatty acid (FA) metabolism. However, very limited information is available in ruminants, and none is available in sheep. Therefore, we conducted an experiment in dairy ewes to determine, for the first time in this species, the uptake, Δ9-desaturation, and secretion of 13C-labeled stearic acid (SA) into milk with the aim of measuring in vivo endogenous synthesis of milk oleic acid (OA) and stearoyl-CoA desaturase activity. Six lactating Assaf ewes fed a total mixed ration (forage:concentrate ratio = 30:70) received an intravenous injection of 2 g of 13C-labeled SA. At -24, -15, 0, 4, 8, 12, 16, 20, 24, 36, 48, 60, and 72 h postinjection (p.i.), milk yield was recorded and milk samples were collected to examine fat concentration and FA composition, including compound-specific isotope analysis of SA and OA by gas chromatography-combustion isotope ratio mass spectrometry. Over the p.i. period, the SA proportion ranged from 7.6 to 8.3% of total FA, with a maximum 13C enrichment of 1.9%, whereas OA was more abundant (14.3-15.4% of total FA) and had lower 13C enrichments (up to 0.69%). On average, 15% of the isotopic tracer was transferred to milk within 72 h p.i., and 47 to 50% of the SA taken up by the mammary gland would have been desaturated to OA. The proportion of oleic acid being synthesized endogenously was estimated to represent between 48 and 57% of the amount secreted in milk. Further research under different dietary conditions is recommended.


Cysteine-Functionalized Metal-Organic Framework: Facile Synthesis and High Efficient Enrichment of N-Linked Glycopeptides in Cell Lysate.
Cysteine-functionalized metal-organic framework (MOF) was synthesized via a common and facile two-step method of in situ loading of Au nanoparticles on amino-derived MOF followed by l-cysteine (Cys) immobilization. Owing to the large specific surface area and ultrahigh hydrophilicity of this nanocomposite, excellent performance was observed in the enrichment of N-linked glycopeptides in both model glycoprotein and HeLa cell lysate. By using this nanocomposite, 16 and 31 glycopeptides were efficiently extracted from digest of horseradish peroxidase (HRP) and human serum immunoglobulin G (IgG), respectively. The short incubation time (5 min), large binding capacity (150 mg/g, IgG digest to material), good selectivity (1:50, molar ratio of IgG and bovine serum albumin (BSA) digest), high recovery (over 80%), and low detection limit (1 fmol) ensure the effectiveness and robustness of MIL-101(NH2)@Au-Cys in complex HeLa cell lysate. As a result, 1123 N-glycosylation sites corresponding to 1069 N-glycopeptides and 614 N-glycoproteins were identified from the lysate. Compared with those of previously reported hydrophilic methods, to our knowledge, it was the best result. This work paves a new way for fast functionalization of MOF and also provides a novel idea for material design in sample preparation, especially in glycoproteome and related analysis.


Alpha synchronization as a brain model for unconscious defense: An overview of the work of Howard Shevrin and his team.
Howard Shevrin and his team have developed a stringent subliminal priming methodology, which experimentally approximates a situation of an internal, mental triggering of unconscious defense. Through a series of four studies they thus are able to bring evidence for this type of unconscious defense. With event-related potentials, three clinical studies show how synchronization of a specific brain wave, the alpha wave, known for its inhibitory function, is also induced by subliminally presented conflictual subject-specific stimuli. Therefore, alpha synchronization could serve as the brain mechanism of unconscious defense. The results only make sense if we suppose the existence of a dynamic unconscious, which has inherited childhood conflicts, and with privileged connections to neurotic symptom characteristics. Moreover, by showing that the unconscious conflict phrases, inferred by clinicians from clinical interviews, have a similar brain behavior, Shevrin and his team provide evidence that these inferences are not simply clinician-dependent subjective interpretations but also imply some form of independent mental reality. Finally, interpretation of the results has led us to propose two distinct physiological mechanisms for defense: one, unconscious defense, by alpha synchronization in connection with the drive derivatives, and another, repression, based on the indications of reality in connection with the ego.


Calcium concentration-dependent mechanisms through which ketamine relaxes canine airway smooth muscle.
Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation. Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectro-photometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay. In smooth muscle strips stimulated with submaximal (0.1 microM) and maximal (10 microM) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 microM and 850 microM for tissue contracted by 0.1 microM or 10 microM acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+]i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations. Ketamine-induced relaxation of canine airway smooth muscle is associated with a decrease in [Ca2+]i and calcium influx, effects that are not mediated by an increase in cyclic nucleotides; and the sensitivity of the force response to ketamine decreases as the level of preexisting muscle tone increases, an effect that is not explained by differential effects on [Ca2+]i.


Epigenetic mechanisms in the placenta related to infant neurodevelopment.
As the 'third brain' the placenta links the developing fetal brain and the maternal brain enabling study of epigenetic process in placental genes that affect infant neurodevelopment. We described the characteristics and findings of the 17 studies on epigenetic processes in placental genes and human infant neurobehavior. Studies showed consistent findings in the same cohort of term healthy infants across epigenetic processes (DNA methylation, genome wide, gene and miRNA expression) genomic region (single and multiple genes, imprinted genes and miRNAs) using candidate gene and genome wide approaches and across biobehavioral systems (neurobehavior, cry acoustics and neuroendocrine). Despite limitations, studies support future work on molecular processes in placental genes related to neurodevelopmental trajectories including implications for intervention.


Effective and Fast Estimation for Image Sensor Noise Via Constrained Weighted Least Squares.
Noise estimation is crucial in many image processing algorithms such as image denoising. Conventionally, the noise is assumed as a signal-independent additive white Gaussian process. However, for the real raw data of image sensor, the present noise should be practically modeled as signal dependent. In this paper, we propose an effective and fast image sensor noise estimation method for a single raw image. The noise model parameters are estimated via constrained weighted least squares (WLS) fitting on a number of data samples, each of which is generated from a group of weakly textured patches. Specifically, we first design a fast scheme for selecting weakly textured patches, with the guidance of image histogram. To robustly fit the data samples, we then explicitly account for the credibility of each sample by measuring the texture strength of the grouped patches. The image sensor noise estimation is finally formulated as a constrained WLS optimization problem, which can be solved efficiently. Experimental results demonstrate that our method could run much faster than the existing schemes, while retaining the state-of-the-art estimation performance.


Universal testing for COVID-19 in patients undergoing cancer treatment during the second outbreak in Brescia.
The impact of coronavirus disease 2019 (COVID-19) has been overwhelming on patients with cancer, who may be at higher risk of developing severe disease. During the second COVID-19 outbreak in Italy, we planned universal microbiologic screening for patients scheduled for antineoplastic treatment. All patients with planned active treatment at Brescia University Radiation Oncology Department were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA with repeated nasopharyngeal swabs (NPS) from October 31, 2020. Treatment continuation, suspension, or delay was modulated for patients testing positive according to clinical presentation. From October 31, 2020, to February 6, 2021, 636 patients were enrolled and 1243 NPS were performed, of which 28 (2.25%) were positive. The infection rate was 2.52%; 81.3% of the patients with a positive NPS were asymptomatic, 2 had mild disease, and 1 severe disease that led to death. All patients already on treatment with mild or asymptomatic COVID-19 carried on the therapy with no or minimal delay. Median delay for patients with infection detected before treatment start was 16.5 days. Detected incidence of COVID-19 was lower during the second outbreak in our patients (2.52% vs 3.23%), despite the extensive testing schedule, and substantiates the high rate of asymptomatic infections and the low mortality among patients with COVID-19 (6.3% vs 38.5% during the first outbreak). Universal SARS-CoV-2 screening for all patients with planned treatment might allow early identification of patients with COVID-19, resulting in timely management that could improve clinical outcomes and prevent spread of the infection.


[Cat scratch disease - a neglected zoonosis].
Cat scratch disease is a relatively rare infection that is caused by the bacterium Bartonella henselae. This disease occurs after cat scratch or bite. The course of the disease depends on the patients immunity status. In immunocompetent patients, the disease typically runs as a lymph node syndrome. Sometimes, mild general symptoms may appear, or the course can be atypical with a more serious clinical manifestation involving various organs. In immunocompromised patients, Bartonella henselae can cause bacillary angiomatosis or peliosis with a severe course.


Smad1 expands the hemangioblast population within a limited developmental window.
Bone morphogenetic protein (BMP) signaling is an important regulator of hematovascular development. However, the progenitor population that responds to BMP signaling is undefined, and the relative role of downstream mediators including Smad1 is unclear. We find that Smad1 shows a distinctive expression profile as embryonic stem (ES) cells undergo differentiation in the embryoid body (EB) system, with peak levels in cell populations enriched for the hemangioblast. To test the functional relevance of this observation, we generated an ES cell line that allows temporal control of ectopic Smad1 expression. Continuous expression of Smad1 from day 2 of EB culture does not disturb hematopoiesis, according to colony assays. In contrast, a pulse of Smad1 expression exclusively between day 2 and day 2.25 expands the population of progenitors for primitive erythroblasts and other hematopoietic lineages. This effect correlates with increased levels of transcripts encoding markers for the hemangioblast, including Runx1, Scl, and Gata2. Indeed, the pulse of Smad1 induction also expands the blast colony-forming cell (BL-CFC) population at a level that is fully sufficient to explain subsequent increases in hematopoiesis. Our data demonstrate that Smad1 expression is sufficient to expand the number of cells that commit to hemangioblast fate.


High-Resolution Magnetic Resonance Black Blood Thrombus Imaging and Serum D-Dimer in the Confirmation of Acute Cortical Vein Thrombosis.
Cerebral cortical vein thrombosis (CCVT) is often misdiagnosed because of its non-specific diagnostic symptoms. Here, we analyzed a cohort of patients with CCVT in hopes of improving understandings and treatments of the disease. A total of 23 patients with CCVT (confirmed with high-resolution imaging), who had been diagnosed between 2017 and 2019, were enrolled in this cohort study. Baseline demographics, clinical manifestations, laboratory data, radiological findings, treatment, and outcomes were collected and analyzed. Fourteen females and nine males were enrolled (mean age: 32.7 ± 11.9 years), presenting in the acute (within 7 days, n = 9), subacute (8-30 days, n = 7), and chronic (over 1 month, n = 7) stages. Headaches (65.2%) and seizures (39.1%) were the most common symptoms. Abnormally elevated plasma D-dimers were observed in the majority of acute stage patients (87.5%). The diagnostic accuracy of contrast-enhanced magnetic resonance venography (CE-MRV) and high-resolution magnetic resonance black-blood thrombus imaging (HR-MRBTI) in detecting CCVT were 57.1 and 100.0%, respectively. All patients had good functional outcomes after 6-month of standard anticoagulation (mRS 0-1) treatment. However, four CCVT patients that had cases involving multiple veins showed symptom relief after batroxobin therapy (p = 0.030). HR-MRBTI may be a fast and accurate tool for non-invasive CCVT diagnosis. HR-MRBTI combined with D-dimer can also precisely identify the pathological stage of CCVT. Batroxobin may safely accelerate cortical venous recanalization in combination with anticoagulation. Follow-up studies with larger sample sizes are suggested to evaluate the safety and efficacy of batroxobin for treating CCVT.


Seroprevalence of Hepatitis B, and C Viruses and HIV Infections among Antenatal Women in a Secondary Health Facility in Lagos, Nigeria.
Hepatitis B and C viruses and HIV infections contribute a significant proportion to maternal and perinatal morbidity and mortality in low and middle-income countries. While the burden of hepatitis B and C viruses is higher in low and middle-income countries, Nigeria also has the second largest burden of HIV. To determine the seroprevalence of hepatitis B and C viruses and HIV infections among antenatal women who sought care at a secondary health facility in Lagos. This was a retrospective review of patients managed in the antenatal clinic of 68 Nigerian Army Reference Hospital over one year. A study proforma was used to collect relevant data which were entered and analyzed using the IBM Statistical Package for Social Sciences (SPSS Statistics) Version 23. A total of 347 women attended prenatal care during the study period, however, only 329 cases with complete data were included in the final statistical analysis. The prevalence of HIV in our study was 6.4%, while HBV and HCV accounted for 6.2% and 1.8% respectively. Hepatitis B, and hepatitis C viruses and HIV Infections occurred in 3 (0.9%) of our patients, 6 (1.8%) of the women had HIV-HBV co-infection while 1 (0.3%) was infected with HIV-HCV. Our study re-emphasizes the public health importance of HBV, HCV and HIV screening in our antenatal clinics. This knowledge is very important for the implementation of effective prevention and control measures that will further decrease the mother-to-child transmission of these viruses.


Our supramicrosurgical experience of lymphaticovenular anastomosis in lymphoedema patients to prevent cellulitis.
Aim of this paper is to present our reduction of the frequency of cellulitis before and after supramicrosurgical lymphaticovenular anastomosis (s-LVA) in lymphoedema patients, and discuss the possibility to perform this technique outside Japan. 37 patients affected by lymphoedema were enrolled. All patients received preoperative indocyanine green lymphography. Under local anaesthesia s-LVA was performed on all patients. All patients were followed for 1 year. Lymphoedema was staged using the lymphoedema staging classification recommended by the International Society of Lymphology. Cellulitis rate was recorded for all patients the year before and after the s-LVA. A t-test was used to evaluate differences in the frequency of cellulitis the year before surgery and the year following surgery. Cellulitis incidence decreased in all patients, with a mean 1.7 cases the year before s-LVA and 0.1 the year after s-LVA. A significant difference between preoperative and postoperative cellulitis rate was found (p = 0.0012). This study reports our s-LVA case series of lymphoedema patients. With the proper learning curve, s-LVA may be reproduced and lymphoedema patients may gain a better quality of life and a reduced cellulitis rate.


"I hate needles" and other factors impacting on travel vaccine uptake.
Travel vaccines comprise an essential component of pretravel health advice; however, many travelers do not take advantage of this preventive health strategy to decrease their risk of travel-related illness. Factors that impact on a traveler's decision on whether or not to be vaccinated are related to the knowledge, attitudes and beliefs of the traveler regarding travel vaccines, vaccine-preventable diseases, and other factors. Further research is required to increase travelers' awareness of the need for pretravel vaccination and then to translate that awareness into positive attitudes leading to increased travel vaccine uptake.


Lack of effects on fertility and developmental toxicity of a quadrivalent HPV vaccine in Sprague-Dawley rats.
Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases, with approximately half of the HPV-infected people being adolescents and young adults. A recently developed quadrivalent HPV vaccine, GARDASIL((R)), has been shown to be highly effective in the prevention of a number of HPV-mediated diseases. The objective of the present study was to evaluate the potential effects of the vaccine on female fertility and F1 development, growth, behavior, and reproductive performance. In addition, anti-HPV antibodies in the F0 females and F1 offspring were measured during the study. Two groups of 65 virgin Sprague-Dawley rats were administered two or four intramuscular injections of the vaccine (full human dose of 0.5 mL at 5 and 2 weeks prior to mating, on Gestation Day [GD] 6, and Lactation Day [LD] 7; or GD 6 and LD 7 only). Additional groups of rats were administered phosphate-buffered saline or Merck Aluminum Adjuvant (MAA) at the same four times. All females were mated to males of the same stock. Cesarean sections were performed on 22/group on GD 21, 22/group were allowed to deliver, and remaining females used for blood collections or replacements. F0 female fertility parameters were evaluated. An extensive number of prenatal, perinatal, and postnatal parameters were evaluated in the F1 generation. There were no unscheduled deaths during the study. There was no evidence of toxicity in the F0 females given either MAA or vaccine. There were no effects on the fertility or reproductive performance of the F0 females. There was no evidence of developmental toxicity to the F1 generation, including fetal body weight and morphology, postnatal growth and development, behavior, and reproductive performance. The quadrivalent vaccine induced a specific antibody response to the four HPV types in the F0 female rats following one or multiple injections. Antibodies against all four HPV types were transferred to the F1 generation during gestation and/or lactation, likely via the placenta and milk, respectively. The passively transferred antibodies persisted up to Postnatal Day 77 when they were last measured. These results demonstrate that this quadrivalent HPV vaccine had no detectable adverse effects in either the treated F0 female rats or the F1 generation.


Predicting Success in Psychological Statistics Courses.
Many students perform poorly in courses on psychological statistics, and it is useful to be able to predict which students will have difficulties. In a study of 93 undergraduates enrolled in Statistical Methods (18 men, 75 women; M age = 22.0 years, SD = 5.1), performance was significantly associated with sex (female students performed better) and proficiency in algebra in a linear regression analysis. Anxiety about statistics was not associated with course performance, indicating that basic mathematical skills are the best correlate for performance in statistics courses and can usefully be used to stream students into classes by ability.


Molecular analysis of swine hepatitis E virus from north India.
Hepatitis E is the main cause of enterically transmitted non-A, non-B hepatitis in developing countries. In the developed countries such as the USA, Japan and Taiwan, the viruses infecting humans and swine share the same genotype with a high sequence similarity. Genotype 1 circulates in humans whereas genotype 4 in pigs in India. The present study was designed to investigate the presence of anti-HEV antibodies and HEV-RNA in swine population from north India, to investigate the genotype prevalent in it, and to compare it with other swine and human HEV strains from India. A total of 67 serum samples were collected from pigs of age period (1-6 months) from Indian Veterinary Research Institute (IVRI), Izatnagar, Bareily and subjected to anti-HEV IgG and HEV RNA detection. A phylogenetic tree was constructed using the neighbor-joining method and evaluated using the interior branch test method with MEGA 4 software. Anti-HEV IgG and HEV RNA was found in 38.8 and 4.5 per cent of swine samples studied respectively. The above samples were observed to be of genotype 4e. The three new sequences had nucleotide similarity with other swine sequences in genotype 4 ranging from 80-98 per cent. The three sequences observed in the present study showed nucleotide similarity with other swine sequences from southern and western India. The present study suggests that genotype 4 'e' is prevalent in the north India.


Lentic, lotic, and sulfate-dependent waterborne selenium screening guidelines for freshwater systems.
There is consensus that fish are the most sensitive aquatic organisms to selenium (Se) and that Se concentrations in fish tissue are the most reliable indicators of potential toxicity. Differences in Se speciation, biological productivity, Se concentration, and parameters that affect Se bioavailability (e.g., sulfate) may influence the relationship between Se concentrations in water and fish tissue. It is desirable to identify environmentally protective waterborne Se guidelines that, if not exceeded, reduce the need to directly measure Se concentrations in fish tissue. Three factors that should currently be considered in developing waterborne Se screening guidelines are 1) differences between lotic and lentic sites, 2) the influence of exposure concentration on Se partitioning among compartments, and 3) the influence of sulfate on selenate bioavailability. Colocated data sets of Se concentrations in 1) water and particulates, 2) particulates and invertebrates, and 3) invertebrates and fish tissue were compiled; and a quantile regression approach was used to derive waterborne Se screening guidelines. Use of a regression-based approach for describing relationships in Se concentrations between compartments reduces uncertainty associated with selection of partitioning factors that are generally not constant over ranges of exposure concentrations. Waterborne Se screening guidelines of 6.5 and 3.0 μg/L for lotic and lentic water bodies were derived, and a sulfate-based waterborne Se guideline equation for selenate-dominated lotic waters was also developed. Environ Toxicol Chem 2017;36:2503-2513. © 2017 SETAC.


Treatment of reverse oblique trochanteric femoral fractures with proximal femoral nail.
Treatment of reverse oblique trochanteric femoral fractures is still challenging. We present the results of our proximal nailing surgery performed for reverse obliquity intertrochanteric fractures using two lag screws and evaluated the quality of the reduction, operative time, complications and functional status of the patients. Fifteen patients with AO/OTA 31 A-A3 fractures were treated by proximal femoral nailing in our trauma centre. The mean Harris hip score was 74.66 (range 65-96) and the mean Barthel activity score was 15.71 (range 12-20). The mean duration of surgery was 48 minutes and the average consolidation time was 8.6 weeks. No intraoperative complications or postoperative technical failures and no stress shielding as evidenced by the lack of cortical hypertrophy at the level of the tip of the implant were detected. Intramedullary nailing with proximal femoral nails may be a good option in the treatment of reverse obliquity intertrochanteric fractures.


[Treatment choice of locally advanced low and middle rectal cancer after neoadjuvant chemoradiation].
Close observation or local excision have developed to be acceptable choices of managing rectal cancer patients who had a complete or major response to neoadjuvant chemoradiation. Indications of these rectum-preserving strategies, however, remain debatable due to inaccurate tumor staging after chemoradiation, apparent discrepancy between pathological and clinical complete responses, and uncertain lymph node status. Both responses to chemoradiation and original tumor staging must be considered to decide the treatment plan. For patients with major response to chemoradiation and with an original staging of cTis-2, a local excision is now acceptable with close postoperative observation or additive radical surgery according to pathological results. Otherwise, a standard radical surgery is still the treatment of choice. Post-radiation tumor evaluation can be employed for decision on sphincter preservation. A longer waiting time of 6-12 weeks before surgery is suggested.


The Relationship Between Educational Years and Phonemic Verbal Fluency (PVF) and Semantic Verbal Fluency (SVF) Tasks in Spanish Patients Diagnosed With Schizophrenia, Bipolar Disorder, and Psychotic Bipolar Disorder.
Semantic and verbal fluency tasks are widely used as a measure of frontal capacities. It has been well described in literature that patients affected by schizophrenic and bipolar disorders present a worse execution in these tasks. Some authors have also noted the importance of educational years. Our objective is to analyze whether the effect of cognitive malfunction caused by apathology is superior to the expected effect of years of education in phonemic verbal fluency (PVF) and semantic verbal fluency (SVF) task execution. A total of 62 individuals took part in this study, out of which 23 were patients with schizophrenic paranoid disorder, 11 suffered from bipolar disorder with psychotic symptomatology, 13 suffered from bipolar disorder without psychotic symptomatology, and 15 participants were nonpathological individuals. All participants were evaluated with the PVF and SVF tests (animals and tools). The performance/execution results were analyzed with a mixed-model ANCOVA, with educational years as a covariable. The effect of education seems to be more determined by PVF FAS tests than by SVF. With PVF FAS tasks, the expected effect of pathology disappears when the covariable EDUCATION is introduced. With SVF tasks, the effect continues to be significant, even though the EDUACTION covariable dims such effect. These results suggest that SVF tests (animals category) are better evaluation tools as they are less dependent on the patients' education than PVF FAS tests.


Clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease.
There are conflicting reports on the role of azathioprine (AZA) thioguanine nucleotide (TGN) metabolites in optimising therapy for inflammatory bowel disease (IBD). The aim of this study was to investigate TGN intrapatient variation, and the relationship between TGN concentrations and disease activity in IBD patients taking long term constant dose AZA. TGN and methylmercaptopurine nucleotide (MeMPN) concentrations were measured at intervals over a two year period. Disease activity was assessed at each clinic visit using the Crohn's disease activity index or Walmsley simple index for ulcerative colitis. Serial TGNs were measured in 159 patients (3-14 TGN assays, median 6). Intrapatient variation in TGN concentrations was 1-5-fold (median 1.6); the incidence of non-compliance was 13%. At the end of two years, 131 patients were evaluable at TGN steady state. Of this group, patients who remained in remission had significantly higher mean TGN concentrations than those patients who developed active disease (median TGNs 236 v 175, respectively; median difference 44 pmol (95% confidence interval 1-92); p = 0.04). MeMPN concentrations were not related to AZA efficacy or toxicity. This study has shown that lower TGN concentrations were linked to the development of active disease, and that TGNs may act as useful markers of compliance. However, it is clear that repeat TGN measurements are required for an unambiguous index of active metabolite exposure. In view of the high intrapatient variability in TGN production over time, TGN measurements may not be currently advocated for routine clinical use.


Diameter of mammary terminal ducts as an additional tool in evaluation of women with polycystic ovarium disease.
Aim of this study was to show the change of diameter of mammary ducts in relation to polycystic ovaries disease. Women who took part were divided into two groups- the first with polycystic ovaries disease and another second group with no such disease. To both groups a series of laboratory, clinical and ultrasound (u/s) exams were used to diagnose polycystic ovaries disease. Furthermore u/s measurement of mammary ducts was used to define the diameter. In women with polycystic ovaries disease u/s showed an increase in diameter of mammary ducts whereas in the second group we didn't observe such finding. Our study showed that there seems to be a strong relation between the increased diameter of the main terminal lactiferous ducts- the polycystic configuration of the ovaries and the hormonal levels.


Pigmentation of the aortic and pulmonary valves in C57BL/6J x Balb/cByJ hybrid mice of different coat colours.
Neural crest-derived melanocytes have been recorded in several parts of the mammalian heart but not in the pulmonary valve. We report here the presence of melanin-containing cells in the leaflets (cusps) of both the aortic and pulmonary valves. A total of 158 C57BL/6J x Balb/cByJ hybrid mice exhibiting four coat colours, namely black, white, agouti and non-agouti brown, were examined. We sought for any relationship between the presence of melanocytes in the valves and the coat colour of the animals. The pigmentation levels of the leaflets were accomplished using a scale of five pigment intensities. White mice lacked pigment in the heart. In 10.5% of the remaining animals, there were melanocytes in the pulmonary valve leaflets. Thus, this is the first study to report the presence of such cells in the pulmonary valve of mammals. Melanocytes occurred in the leaflets of the aortic valves of 87.2% of mice. The incidence of melanocytes and the pigmentation level of the leaflets did not statistically differ according to the coat colours of the animals. This disagrees with previous observations, indicating that the amount of melanocytes in the heart reflects that of the skin. The incidence and distribution of melanocytes in aortic and pulmonary valves are consistent with the notion that the formation of the arterial valves is mediated by specific subpopulations of neural crest cells. We hypothesize that melanocytes, even not producing melanin, may be more frequent in the heart than previously thought, exerting presumably an immunological function.


Biomechanical behaviour of implant prostheses and adjacent teeth according to bone quality: A finite element analysis.
The contribution of biomechanical factors in the formation of proximal contact loss has been observed, but there is little research on the mechanisms by which they contribute. Using finite element analysis, this study aimed to analyse the impact of bone quality on the biomechanical behaviour of a dentition consisting of implant prostheses and adjacent teeth. The occlusal load was applied on the implant/tooth crown. In the mesiodistal direction, the adjacent natural tooth mesially to the implant denture had the tendency for mesial movement, while the distal adjacent natural tooth had the tendency for distal movement. For the supporting bone around the mesial adjacent tooth, the maximum/minimum principal stress and strain values on the mesial side of the bone were higher than those on the distal side of the bone. Stress and strain values on the mesial side of the supporting bone around the distal adjacent tooth were lower than those on the distal side. With decreasing bone density, displacements of teeth and the implant denture, principal stresses and equivalent strains on tooth supporting bone increased. Studies on biomechanical behaviours of a tooth-implant dentition may provide a deeper understanding of implant-induced dental adaptive processes such as proximal contact loss.


Renal growth after antireflux surgery in infants.
Thirteen children (eleven boys and two girls) with fifteen refluxing ureters have been operated upon during infancy and been followed between five and seven years postoperatively. Kidney growth has been studied by determining renal parenchymal area by planimetry. 14/15 were free from reflux at follow-up. Postoperative vesicoureteric obstruction was found in one infant. In the cases where the kidney had a pronounced parenchymal reduction at presentation poor kidney growth was demonstrated. However, the nine kidneys which had a smaller parenchymal reduction at presentation normal showed growth postoperatively.


A case of membranous proliferative glomerulonephritis type III (Burkholder) with the deposition of both HBeAg and HBsAg.
A case of HB virus associated MPGN type III was described for the first time in a 10 year old Japanese girl. She was followed for a period of 7 years with serial serological work-up and renal biopsy. When she was found seropositive for HBe antigen was stained predominantly in capillary walls, but HBs antigen was also detected in capillary walls and mesangium. The results suggest that both HBe- and HBs antigen antibody immune complexes may play a significant role in the development of HB virus associated nephropathy; HBe antigen for MGN and HBe- and HBs antigens for MPGN type III. Although HB virus associated nephropathy is believed to be a rather benign disorder, the present case warrants a close follow-up because of chronicity of massive proteinuria and renal pathology.


Clinical measures and treatment needs.
Clinically evaluated oral health outcome variables from the ICS-II USA data set were examined in the diverse ethnic groups, for two adult age cohorts (35-44 and 65-74 years). These measures were derived from epidemiological examinations and include the DMFT components, loss of attachment, and an indicator of treatment need--the ratio of decayed teeth over decayed and filled teeth. The ratio of decayed over decayed and filled teeth was used in multivariate analysis, since this measure represents an area where public policy could have an impact if determinants were understood. The most important independent variables were race-ethnicity, educational attainment, no fear of dental visits because of pain, and oral hygiene practices. Having a usual source of dental care and visiting the dentist within the past 12 months did not appear to be as important in predicting unmet needs as these other variables. To bridge the gap between the oral health status of majority and minority populations, health educators in minority communities need to become more accessible, have a pro-active interest in oral health, and also be cognizant of the various socio-cultural issues influencing oral health. The problems regarding Native American adults are more complex and require more careful study.


A Brighter Side to Thalidomide: Its Potential Use in Immunological Disorders.
Thalidomide and its derivatives are immunomodulatory drugs (IMiDs) known for their sedative, teratogenic, anti-angiogenic, and anti-inflammatory properties. Commonly used in the treatment of cancers such as multiple myeloma and myelodysplastic syndrome (MDS), IMiDs have also been used in the treatment of an inflammatory skin pathology associated with Hansen's disease/leprosy. They have also shown promise in the treatment of autoimmune disorders including systemic lupus erythmatosus (SLE) and inflammatory bowel disease (IBD). Recent structural and experimental observations have revolutionized our understanding of these properties by revealing the fundamental molecular events underpinning IMiD activity. We review these findings, their relevance to IMiD therapy in immunological disorders, and discuss how further research might unlock the vast clinical potential of these compounds.


Ulcerative keratitis in contact lens wearers.
To determine the clinical microbiological characteristics of corneal ulcers in contact lens wearers. A retrospective study of 23 patients admitted to our department with contact lens-related corneal ulcers during a 43-month period. Detailed demographic data, the type of contact lens, duration of lens wear, and wearing schedule were derived from a self-administered questionnaire. The severity of the ulcer; cultures of corneal scrapings, storage solutions, and contact lenses; treatment; and final outcome were evaluated. Of the 86 cases of ulcerative keratitis admitted during the study period, 23 (26.74%) were attributed to contact lens use. Most patients were young women from urban areas. All of them were using soft contact lenses for 3 days to 20 years. Five patients used daily-wear lenses as extended-wear lenses. Most ulcers (47.82%) were mild; 30.43% were moderate; and 21.47% were severe. Corneal scrapings for cultures were obtained in 15 of the cases and were positive in 10 (43.47%) of them, whereas in 33.33% of the culture-positive storage solutions and in 66.67% of the culture-positive contact lenses, corneal scrapings were negative. Pseudomonas aeruginosa was the most frequent isolated pathogen (60%). The final visual acuity was 20/40 or better in 60.87% of the cases. Contact lens use is an important risk factor for the development of ulcerative keratitis, with P. aeruginosa remaining the predominant pathogen. It seems important to culture contact lenses and contact lens storage solutions, in addition to the corneal scrapings, and the role of initial therapy for the corneal ulcers remains important.


A practical, single-view alternative to Stenver's for plain radiographic unilateral and bilateral post-cochlear implant position check.
'Stenver's' is the standard plain radiograph view to check the electrode position after cochlear implantation. However, a reproducible alignment for intra-individual comparison of electrode position using a true Stenver's alignment is not always straightforward to achieve, particularly for inexperienced radiographers, or on non-compliant children. In addition, two ionizing exposures in two different positions are required for bilateral cochlear implants. To assess the efficacy of other, more simple, single-exposure radiographs for the assessment of electrode position. Dummy electrodes and receiver units were bilaterally implanted into a cadaver. Plain radiographs in Stenver's views, and plain antero-posterior (AP) midline radiographic single views incorporating both implants were obtained with the tube at a range of angles tilted caudal and cranial to the perpendicular. Five internationally renowned cochlear implant surgeons were each asked if each radiograph gave adequate information for unilateral and for bilateral implants and they were asked to list in order of their favoured top three views. No surgeon thought that a single-exposure Stenver's view was adequate for assessment of the contra-lateral side. Consensus was that all AP views were fit for the purpose, with no preference given between each of the AP views. The ipsi-lateral Stenver's was considered to give better depth of insertion information. There is no apparent advantage of caudal and cranial tilt angles over a straight perpendicular AP. A single-view AP radiograph is an alternative to Stenver's view for a post-unilateral and post-simultaneous bilateral cochlear implant check.


Ultrastructural cytochemical methods in the study of mouse testicular tissue.
Different cytochemical and immunocytochemical techniques employed in processing of mouse testicular tissue at ultrastructural level were compared. Two silver staining procedures applied en block and on ultrathin Lowicryl sections were used to demonstrate acidic argyrophilic nuclear proteins. Both methods give standard results. Silver staining en block gives positivity in the form of fine silver precipitate. Coarser silver aggregates and fine nonspecific reactions of the background result from silver staining on ultrathin sections. The method with alcoholic phosphotungstic acid applied en block was used to demonstrate basic nuclear proteins rich in lysine. The results are confirmed and specified by immunocytochemical demonstration of histones and protamine. Specificity of the reactions is briefly discussed.


[Analysis of misdiagnoses for femoral shaft fracture with ipsilateral femoral neck or femoral fractures].
To analyze the misdiagnoses of femoral shaft fracture combined with ipsilateral femoral neck or femoral fractures. Over the past six years, eight misdiagnosed cases of ipsilateral femoral neck or femoral fractures missed patients, aged 25 to 59 years old (mean: 41.7), were treated at our department. An initial diagnosis of femoral shaft fracture was later revised as ipsilateral femoral shaft with supra-condylar fracture of femoral neck or femur. Femoral shaft fracture was fixed with armor plate, 3-screw hollow compression fixation of femoral neck; two cases of femoral condylar fractures of distal femoral condyle with anatomical plate fixation and 1 case of intraoperative change into the retrograde femoral intramedullary nail fixation. The mean post-operative follow-up was 3.5 years. All fractures healed with excellent hip and knee functions. For those with a strong reverse and torsional violence, femoral shaft fracture combined with ipsilateral femoral neck or femoral fractures may be easily misdiagnosed. A preoperative conventional hip-knee X-ray film is an effective way to avoid a misdiagnosis.


Hepatitis E Virus in Sylvatic and Captive Wild Boar from Portugal.
Hepatitis E virus (HEV) is a zoonotic agent today considered a major Public Health issue in industrialized countries. HEV strains belonging to zoonotic genotype 3 are widely present in swine, being today considered important reservoirs for human disease. Unlike in swine, only scarce data are available on the circulation of HEV in wild boar. This study describes the detection and molecular characterization of HEV in livers from sylvatic wild boar hunted in Portugal and destined for consumption. Additionally, the detection of HEV in stools of a confined wild boar population also destined for consumption is also described. A total of 80 liver samples collected during the hunting season of 2011/2012 and 40 stools collected in February 2012 from a wild boar breeding farm in Portugal were tested by a nested broad-spectrum RT-PCR assay targeting open reading frame (ORF) 1. Twenty livers (25.0%) and 4 stools (10%) were positive for HEV. Phylogenetic analysis showed that all strains clustered with sequences classified as HEV genotype 3 subgenotype e. To our knowledge, this is the first report documenting the occurrence and molecular analysis of HEV in sylvatic and captive wild boar destined for human consumption in Portugal. This report demonstrates for the first time the circulation of HEV in wildlife reservoirs of Portugal adding knowledge to the epidemiology of HEV in wild boar populations.


Assessing the reliability of RNA folding using statistical mechanics.
We have analyzed the base-pairing probability distributions of 16 S and 16 S-like, and 23 S and 23 S-like ribosomal RNAs of Archaea, Bacteria, chloroplasts, mitochondria and Eukarya, as predicted by the partition function approach for RNA folding introduced by McCaskill. A quantitative analysis of the reliability of RNA folding is done by comparing the base-pairing probability distributions with the structures predicted by comparative sequence analysis (comparative structures). We distinguish two factors that show a relationship to the reliability of RNA minimum free energy structure. The first factor is the dominance of one particular base-pair or the absence of base-pairing for a given base within the base-pairing probability distribution (BPPD). We characterize the BPPD per base, including the probability of not base-pairing, by its Shannon entropy (S). The S value indicates the uncertainty about the base-pairing of a base: low S values result from BPPDs that are strongly dominated by a single base-pair or by the absence of base-pairing. We show that bases with low S values have a relatively high probability that their minimum free energy (MFE) structure corresponds to the comparative structure. The BPPDs of prokaryotes that live at high temperatures (thermophilic Archaea and Bacteria) have, calculated at 37 degrees C, lower S values than the BPPDs of prokaryotes that live at lower temperatures (mesophilic and psychrophilic Archaea and Bacteria). This reflects an adaptation of the ribosomal RNAs to the environmental temperature. A second factor that is important to consider with regard to the reliability of MFE structure folding is a variable degree of applicability of the thermodynamic model of RNA folding for different groups of RNAs. Here we show that among the bases that show low S values, the Archaea and Bacteria have similar, high probabilities (0.96 and 0.94 in 16 S and 0.93 and 0.91 in 23 S, respectively) that the MFE structure corresponds to the comparative structure. These probabilities are lower in the chloroplasts (16 S 0.91, 23 S 0.79), mitochondria (16 S-like 0.89, 23 S-like 0.69) and Eukarya (18 S 0.81, 28 S 0.86).


Using ecosystem engineers as tools in habitat restoration and rewilding: beaver and wetlands.
Potential for habitat restoration is increasingly used as an argument for reintroducing ecosystem engineers. Beaver have well known effects on hydromorphology through dam construction, but their scope to restore wetland biodiversity in areas degraded by agriculture is largely inferred. Our study presents the first formal monitoring of a planned beaver-assisted restoration, focussing on changes in vegetation over 12years within an agriculturally-degraded fen following beaver release, based on repeated sampling of fixed plots. Effects are compared to ungrazed exclosures which allowed the wider influence of waterlogging to be separated from disturbance through tree felling and herbivory. After 12years of beaver presence mean plant species richness had increased on average by 46% per plot, whilst the cumulative number of species recorded increased on average by 148%. Heterogeneity, measured by dissimilarity of plot composition, increased on average by 71%. Plants associated with high moisture and light conditions increased significantly in coverage, whereas species indicative of high nitrogen decreased. Areas exposed to both grazing and waterlogging generally showed the most pronounced change in composition, with effects of grazing seemingly additive, but secondary, to those of waterlogging. Our study illustrates that a well-known ecosystem engineer, the beaver, can with time transform agricultural land into a comparatively species-rich and heterogeneous wetland environment, thus meeting common restoration objectives. This offers a passive but innovative solution to the problems of wetland habitat loss that complements the value of beavers for water or sediment storage and flow attenuation. The role of larger herbivores has been significantly overlooked in our understanding of freshwater ecosystem function; the use of such species may yet emerge as the missing ingredient in successful restoration.


[Clinical efficacy of ezetimibe and combined use with statins].
The use of statins is very extensive in patients with some previous cardiovascular complication. However, the new therapeutic objectives of LDL-C, especially in high risk patients, makes it difficult to reach the LDL-C values desired in the daily clinical practice. The appearance of a new inhibitor of the intestinal cholesterol absorption (ezetimibe) noticeably strengthens the actions of the statins in the reduction of LDL-C. Combined use of ezetimibe and statins may make it possible for the vascular high risk patients to reach a greater reduction of LDL-C and achieve the therapeutic objectives more frequently.


Longitudinal Study of Scar Hyperplasia Formation Following Cleft Lip Wound Healing.
The purpose of this study was to observe the hyperplasia trend of scar after the cleft lip surgery in a rabbit animal model, and determine the time-point of the highest hypertrophic degree of scar after cleft lip repair. Forty New Zealand white rabbits from the same offspring were used to establish a cleft lip wound healing model using Millard surgery procedure. The scar volumes were measured and granulation tissues were observed visually in the 2, 3, 4, and 5 weeks after operation. The scar tissues were harvested at the indicated time-points. Immunohistochemical (IHC) and Western Blot analyses were performed to detect the expression level of α-smooth muscle actin (α-SMA) in the scar tissue. The scars shrunk and the volumes reduced at 3 to 4 weeks after surgery; however, at 5 weeks postsurgery, the volumes increased. IHC and Western blot analyses indicated the expression of α-SMA was significantly enhanced 3 to 4 weeks, but reduced in the 5 weeks after surgery. Overall, the degree of scar hyperplasia after cleft lip surgery in rabbits was normally distributed and the scarring was most severe in the 3 to 4 weeks after cleft lip surgery. The study confirms a novel animal model for the assessment of therapies for the treatment of scar hyperplasia of human cleft lip in future.


[Cultural anthropology of traditional Chinese medicine].
Biological, psychological and sociological model of medicine substantializes the old model lacking the social humane attributes. The new medical model makes people take medical anthropology into research and highly evaluate traditional medical system. Cultural anthropology of traditional Chinese medicine (TCM) is part of medical anthropology with three major characteristics: wide research scope, specificity, and integration. It has developed its own research methods, such as field investigation, comprehensive inspection and comparison study. Cultural anthropology provides an efficient research method for TCM, and its application would further develop TCM theory and form comprehensive evaluation on TCM effects.


Comparative antimicrobial activity of no-rub multipurpose lens care solutions in the presence of organic soil.
This study reports the effect of organic soil on the antimicrobial activity of four commercially available multipurpose contact lens care solutions used in no-rub regimens as determined by a modified International Organization for Standardization 14729 (ophthalmic optics-contact lens care products-microbiological requirements for products and regimens for hygienic management of contact lenses) Stand Alone Test procedure. Testing was performed with organic soil consisting of a mixture of heat-killed yeast cells and heat-inactivated bovine serum or these components added separately. The organic soil was mixed with the challenge microorganisms before addition to the solution, added to the solution after addition of the challenge microorganisms, or added to the solution before addition of the challenge microorganisms. A final concentration of 0.4% v/v organic soil and 1 x 105 to 1 x 106 cfu/mL challenge microorganisms was realized in all test cases. The antimicrobial activity of no-rub multipurpose lens care solutions was reduced in the presence of added organic soil. The extent of reduction varied with the type of organic soil, the method of addition of the organic soil to the solution, the challenge organism, and the solution tested. The type of organic soil used and the method of addition of organic soil to the lens care solution may affect antimicrobial activity as determined by the primary criteria of the International Organization for Standardization Stand Alone Test procedure. The overall reduction in antimicrobial activity depends on the solution and organism.


Congenital retinal fold as a sign of dominant exudative vitreoretinopathy.
Four eyes of three patients from two large families with dominant exudative vitreoretinopathy showed an elevated retinal fold extending from the posterior pole toward the inferotemporal periphery of the fundus. A congenital retinal fold (ablatio falciformis congenita) has to be considered as a sign rather than a diagnosis, and can be caused by a few underlying disorders, to which dominant exudative vitreoretinopathy can be added. There are no indications that the hyaloid system is involved in the pathogenesis of a retinal fold in the latter condition. The formation of a retinal fold in dominant exudative vitreoretinopathy is the consequence of a developmental disorder of retinal vasculature during the last few months of intrauterine life, and may even occur after birth. The clinical picture and familial occurrence of many cases of congenital retinal fold described in the literature are suggestive of dominant exudative vitreoretinopathy, which only recently has been recognized as being a rather common condition.


Conjugated Linoleic Acid-Mediated Connexin-43 Remodeling and Sudden Arrhythmic Death in Myocardial Infarction.
Connexin 43 (Cx43) is expressed in the left and right ventricles and is primarily responsible for conducting physiological responses in microvasculature. Studies have demonstrated that NADPH oxidase (NOX) enzymes are essential in cardiac redox biology and are responsible for the generation of reactive oxygen species (ROS). NOX2 is linked to left ventricular remodeling following myocardial infarction (MI). It was hypothesized that conjugated linoleic acid (cLA) treatment increases NOX-2 levels in heart tissue and disrupts connexins between the myocytes in the ventricle. Data herein demonstrate that cLA treatment significantly decreases survival in a murine model of MI. The observance of cLA-induced ventricular tachyarrhythmia's (VT) led to the subsequent investigation of the underlying mechanism in this MI model. Mice were treated with cLA for 12 h, 24 h, 48 h, or 72 h to determine possible time-dependent changes in NOX and Cx43 signaling pathways in isolated left ventricles (LV) extracted from cardiac tissue. The results suggest that ROS generation, through the stimulation of NOX2 in the LV, triggers a decrease in Cx43 levels, causing dysfunction of the gap junctions following treatment with cLA. This cascade of events may initiate VT and subsequent death during MI. Taken together, individuals at risk of MI should use caution regarding cLA consumption.


In-Center Nocturnal Hemodialysis Versus Conventional Hemodialysis: A Systematic Review of the Evidence.
Owing to its longer treatment duration-up to 8 hours per dialysis treatment-in-center thrice-weekly nocturnal hemodialysis (HD) is receiving greater attention. To better understand the evidence for in-center nocturnal HD, we sought to systematically review the literature to determine the effects of in-center nocturnal HD versus conventional HD on clinically relevant outcomes. We searched MEDLINE, Embase, Evidence-Based Medicine Reviews (EBMR), Web of Science, and Scopus from the earliest date in the database to November 2016. Adults receiving in-center nocturnal HD compared with those receiving conventional HD. All quasi-experimental and observational studies were considered; randomized trials were sought but not found. Nocturnal vs conventional in-center HD. Indexes of blood pressure and left ventricular hypertrophy, markers of anemia, measures of bone mineral metabolism, nutrition, quality of life, sleep quality, episodes of intradialytic hypotension, hospitalization, and mortality. Of 2,086 identified citations, 21 met the inclusion criteria, comprising a total of 1,165 in-center nocturnal HD patients and 15,865 conventional HD patients. Although there was substantial heterogeneity in reporting of outcomes, we pooled data for measures of blood pressure, anemia, and mineral metabolism. Though heterogeneity was generally high, in-center nocturnal HD was associated with improved systolic blood pressure (-3.18 [95% CI, -5.58 to -0.78) mm Hg, increased hemoglobin levels (0.53 [95% CI, 0.11-0.94] g/dL), and lower serum phosphate levels (-0.97 [95% CI, -1.48 to -0.46] mg/dL). No randomized trials have been conducted to address the clinical effects of in-center nocturnal HD. The quality of the observational literature contributing to the results of this review was generally poor to moderate. Confounded outcomes are a significant concern. Publication bias and outcome reporting bias remain possibilities. Relative to conventional HD, in-center nocturnal HD was associated with improvements in several clinically relevant outcomes. Other benefits may not have been detected due to small sample sizes of included studies; no prespecified outcome was worse with in-center nocturnal HD.


[Influenza – Not innocuous, but preventable].
Influenza is an infectious disease that can be prevented by a vaccine but the readiness to vaccinate against this recurrent infection is weak in the general population. However, influenza is not always a harmless illness as illustrated in our authentic case report. Individuals with an impaired immune response, particularly pregnant women and the elderly are particularly at risk for a complicated course of influenza. But it is precisely this population, which also has an attenuated immune response to the vaccine. The limited efficacy in this target group is a potential "loss of image" for any flu vaccination campaign. This raises the question whether we should not try to motivate healthy individuals to get vaccinated, particularly if they are living or working next to vulnerable individuals. Epidemiologic data but also recent mathematical models indicate that consistent vaccination of (school-)children results in reduced mortality in elderly people.


Obstructive lung disease after allogeneic bone marrow transplantation.
We report the cases of 3 patients with marked dyspnea and an obstructive ventilation disorder associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation. This disorder was characterized by recurrent pulmonary infections and colonization of the lower respiratory tract by Pseudomonas aeruginosa. Two patients have shown rapidly progressive deterioration with death following due to respiratory failure. Intensive therapy with antibiotics, bronchodilators, high-dose steroids, and azathioprine was not effective in arresting the malignant course of this disorder.


Gene expression of immunomodulatory cytokines induced by Narcissus tazetta lectin in the mouse.
The immunomodulation of Narcissus tazetta lectin (NTL) on the induction of gene expression of cytokines in the mouse was studied using specific cytokine primers, total RNA isolated from mouse splenocytes and macrophages, and reverse transcription-polymerase chain reaction (RT-PCR). For comparison, a fungal antimitogenic lectin from Agaricus bisporus (ABL) was used to test and compare the acute (kinetic) induction of cytokine gene expression. NTL was able to induce the expression of IL-1beta, TNF-alpha, and immunoreactive nitric oxide synthase (NOS) in both splenocytes and macrophages in vivo after 10-day consecutive peritoneal injections of 5 mg NTL x kg(-1) x day(-1) in the mouse. Nevertheless, the expression levels of IFN-gamma and TGF-beta were markedly increased in macrophages, and the levels of IL-2 and IL-4 were up-regulated only in splenocytes. From the kinetic pattern of cytokine induction and gene expression, ABL appeared to induce the up-regulation of IL-1beta and TNF-alpha in splenocytes up to 24 h, whereas NTL showed a more sustained effect on the expression of these cytokines in macrophages. While NTL manifested TGF-beta expression at the onset of 12 and 24 h in macrophages and splenocytes, respectively, ABL induced TGF-beta in neither splenocytes nor macrophages. After injection of NTL, stem-cell factor was clearly down-regulated in macrophages at 24 and 48 h but up-regulated in splenocytes at the end of 24 h. The immunopotentiating effect of NTL is quite similar to that of LZ-8, a fungal immunomodulatory lectin isolated from the Chinese premier medicinal mushroom Ganoderma lucidium. However, the mechanism of immunomodulation of NTL still awaits to be elucidated.


Computer and information literacy in post-qualifying education.
Computer literacy and information retrieval techniques are both skills that are required to undertake further educational study effectively. In the summer of 2000, a group of post-registered nurses and midwives on undergraduate courses in one university department, completed a self-assessment questionnaire to examine their knowledge and competence of computer and information literacy. This paper describes the method and results of this study with the results indicating that these students had deficits in both computer and information literacy. The study also outlines the structural and functional difficulties that need to be resolved around the area of using computers in education for nurses and midwifes.


Accurate measurement of carotid stenosis. Chaos in methodology.
The methods used for measurement of carotid artery stenosis are not uniform. Witness the chaos that developed when the North American Symptomatic Carotid Endarterectomy Trial (NASCET) group changed its classification system from area to linear measurements only to discover that the European Carotid Stenosis Trial (ECST) used still another angiographic definition of degree of stenosis so that the data from the two studies were not comparable. Fortunately, this has been reconciled by recalculation of the data. In still other studies, using unvalidated ultrasound instruments has made it difficult or impossible to compare results. In part, these problems have been the result of misdirected attempts to amalgamate concepts from Doppler and duplex ultrasound with those of arteriography. The former is more precise and accurate than the latter, yet its methodology is harder to apply and has not been generally distributed. Even such anatomical terms as "carotid bulb" are not standard. Ultrasonographers consider it to be the distal common carotid artery, to vascular surgeons it is the carotid sinus, while still others consider it to be both or neither. The present authors advocate a uniform methodology utilizing duplex ultrasound and predict that it plus magnetic resonance angiography will become the standard by which extracranial carotid artery disease is evaluated in the future.


[Telomerase level versus spliced hTERT-specific RNA forms in cervical carcinoma].
An attempt was made to identify molecular markers of different clinical stages of cervical carcinoma caused by papilloma virus (HPV). Presence of viral genome, telomerase level and expression of a gene, which coded the catalytic activity of that enzyme (hTERT), were assayed in 89 patients. HPV (type 16) genome harboring tumors were detected in 73% which was in conformity with the literature and our own data. Telomerase was identified (TRAP) in all tumors and tumor cells cultured in vitro. hTERT-specific RNA was found in all tumor samples, however, increase in its expression was insignificant. As far as the three markers are concerned, no significant differences between clinical stages of tumor were reported.


Follicle profile and plasma gonadotropin concentration in pubertal female ponies.
Twelve female ponies were examined daily for 30 days and classified as ovulating (OV; N = 6; 197 +/- 6 kg) or prepubertal (PP; N = 6; 196 +/- 9 kg). Follicles were detected by ultrasound and gonadotropins quantified by radioimmunoassay. The mean diameter of the largest follicles was significantly larger in OV (38 +/- 1 mm) than in PP (26 +/- 2 mm) but there was no difference between groups in the size of the second largest follicle. There were more small follicles (<24 mm) in the PP than in the OV group, but PP fillies had a smaller number of follicles >29 mm than the OV fillies. Follicle-stimulating hormone (FSH) levels did not differ between groups but PP fillies had lower luteinizing hormone (LH) peak (8 +/- 1 ng/ml) and basal (4 +/- 0.5 ng/ml) levels, lower peak magnitude (2 +/- 0.2 ng/ml) and period average (5 +/- 0.6 ng/ml) than OV fillies (32 +/- 4.5, 8 +/- 1.2, 17.1 +/- 6, and 15 +/- 2.3 ng/ml, respectively). The PP group, in contrast to the OV group, showed no relationship between FSH surge and follicle wave emergence. We conclude that an LH concentration higher than 8 ng/ml is needed for follicle growth to a preovulatory size. Wave emergence and FSH secretion seem to be independent events, probably due to an inhibitory neural system in these PP animals. PP fillies may provide a physiological model for the study of follicle wave emergence which apparently does not depend on gonadotropin levels.


Anaphylaxis during anaesthesia: Indian scenario.
Anaphylaxis during anaesthesia is a rare but serious problem. In contrast to the developed countries where databases of perianaesthetic anaphylaxis are preserved, none exist in India. We conducted a survey amongst Indian anaesthesiologists to study the incidence and aetiology of anaphylaxis during anaesthesia in India. A written questionnaire comprising 20 items was mailed electronically or distributed personally to 600 randomly selected Indian anaesthesiologists. The responses were compiled and analysed. We received responses from 242 anaesthesiologists. One hundred and sixty-two (67%) anaesthesiologists had encountered anaphylaxis during anaesthesia. Anaesthetic drugs led to 40% of reactions, and 60% of reactions were attributed to non-anaesthetic drugs. Opioids were the most common anaesthetic drugs implicated in anaphylaxis during anaesthesia, and non-depolarising muscle relaxants were the second most commonly implicated agents. Colloids, antibiotics and blood transfusion were the common non-anaesthetic agents thought to be responsible for anaphylactic reactions during anaesthesia. There were five deaths due to anaphylaxis during anaesthesia. Only 10% of anaesthesiologists ordered for allergy testing subsequently though 38% of anaesthesiologists had access to allergy testing facilities. Our survey reveals that two-thirds of participating Indian anaesthesiologists had witnessed anaphylaxis during anaesthesia. Commonly implicated anaesthetic drugs were opioids and non-depolarising muscle relaxants while colloids, antibiotics and blood transfusion were the common non-anaesthetic agents causing anaphylactic reactions during anaesthesia. Further, our survey reveals low utilisation and paucity of referral allergy centres to investigate suspected cases of anaphylaxis during anaesthesia.


[Distribution of pulmonary Mycobacterium avium complex (MAC) disease cavities and their course under chemotherapy].
The presence of a cavitary lesion is important factor for pulmonary Mycobacterium avium complex (MAC) treatment. Clarify the location of pulmonary MAC cavities and the changes of these cavities. We observed the location of 56 cavities in 48 patients with pulmonary MAC on computed tomography (CT) images and evaluated the changes in the external diameter of these cavities before and after treatment with a regimen of rifampicin (RFP), ethambutol (EB), and clarithromycin (CAM). These pulmonary MAC cavities were significantly frequently located in segments S2, S3, S9, and S10, and their distribution was different from that of pulmonary tuberculosis at the patients' initial visit. Examination of the external diameters of these cavities after chemotherapy showed that 42.1% of cavities expanded, 0.2% were unchanged, and 56.1% shrank. The mean diameter of the cavities decreased significantly (by 3.1 mm) after chemotherapy. The mean size of the cavities in the upper lobe did not differ from the mean size of the cavities in the lower lobe before chemotherapy; however, the reduction in cavity size was significantly higher in the lower lobe cavities. In 14 cases, the cavities disappeared under the standard chemotherapy regimen in an average of 971 days, and there was a tendency for lower lobe cavities to disappear more rapidly.


Macelignan protects against renal ischemia-reperfusion injury via inhibition of inflammation and apoptosis of renal epithelial cells.
Ischemia-reperfusion injury (IRI) refers to tissue damage that occurs when blood supply returns to tissue after a period of ischemia, anoxia or hypoxia. It occurs frequently during shock, organ transplantation and heart failure. It can cause impairment or even renal failure. Macelignan is a lignin isolated from the seeds of Myristica fragrans. It has been reported to inhibit neuroinflammation and oxidative toxicity. The preventive or therapeutic effects of macelignan on renal IRI has not been reported. The present study investigated the effects of macelignan on renal IRI in rats, and the underlying mechanism(s). Healthy adult male Sprague Dawley rats (n = 50) aged 7 - 9 weeks (mean weight = 220 ± 20 g) were used in this study. The rats were randomly assigned to five groups of 10 rats each: sham treated group, IRI group and 40 mg macelignan/kg body weight (bwt) group, 80 mg macelignan/kg bwt group, and 160 mg macelignan/kg bwt group. Ischemia-reperfusion injury was induced in the rats using standard procedure. The results showed that serum levels of creatinine, blood urea nitrogen (BUN), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and gamma interferon (IFN-γ) were significantly higher in IRI group than in sham treated group, but were significantly and dose-dependently reduced after treatment with macelignan (p < 0.05). The activities of catalase and superoxide dismutase (SOD), and reduced glutathione (GSH) level were significantly reduced in IRI group, when compared with sham treated group, but were significantly and dose-dependently increased after treatment with macelignan (p < 0.05). However, the level of malondialdehyde (MDA) was significantly higher in IRI group than in sham treated group, but treatment with macelignan reduced it significantly and dose-dependently (p < 0.05). Macelignan also significantly and dose-dependently inhibited IRI-induced apoptosis in epithelial cells of renal tubules (p < 0.05). The results of Western blotting showed that IRI significantly upregulated the expressions of bax and caspase-3, and down-regulated the expression of bcl-2 in epithelial cells of renal tubules (p < 0.05). However, treatment with macelignan significantly and dose-dependently down-regulated the expressions of bax and caspase-3 in these cells, but significantly and dose-dependently upregulated the expression of bcl-2. These results show that macelignan confers protection on renal IRI via mechanisms involving inhibition of inflammation and apoptosis, and stimulation of natural antioxidant defense system.


Anti-chemokine therapy for inflammatory diseases.
Chemokines are inflammatory proteins acting via G-protein coupled chemokine receptors that trigger different signaling pathways. Monocyte chemoattractant protein-1 (CCL2/MCP-1) and regulated on activation, normal T expressed and secreted (CCL5/RANTES) are the two major members of the CC chemokine beta subfamily. The roles of RANTES and MCP-1 are emerging in regulating the recruitment of inflammatory cells into tissue during inflammation. The inhibition of MCP-1 and RANTES with corresponding antibodies or other inhibitors may provide benefits in different clinical scenarios including cancer, inflammation, CNS disorders, parasitic disease, autoimmune and heart diseases. RANTES and MCP-1 may represent targets for diagnostic procedures and therapeutic intervention, and may be useful as a prognostic factor in the above diseases.


Acute respiratory distress syndrome triggered by marked cytokine storm in a subject with diabetic ketoacidosis: A case report.
Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury. Many causes of acute direct and indirect lung injury have been described as possible initiators of ARDS. According to the literature data, ARDS could be a rare complication associated with the acute onset of diabetic ketoacidosis (DKA). Moreover, it has been suggested that cytokine release during DKA is involved in the above-mentioned acute clinical complications of DKA. A 48-year-old Japanese woman with a 4-year history of type 1 diabetes mellitus was brought to an emergency room with symptoms of deteriorated consciousness. Three days before, she was diagnosed with influenza A infection. Inflammation markers were markedly elevated and she was under DKA condition. Since her respiratory conditions were suddenly and markedly aggravated 2 days later, we diagnosed her as ARDS and continued systemic management with the ventilator.Interleukin-6 (IL-6) level was markedly elevated at the onset of ARDS, although IL-6 level was high at the onset of DKA. ARDS was suggested to be caused by marked cytokine storm and DKA. We continued to treat her hyperglycemic crises. Moreover, we continued systemic management with the ventilator. Approximately three weeks later, her general conditions were stabilized and ventilator management was stopped. We successfully treated her ARDS and hyperglycemic crises. This case is very important because it shows that DKA can induce cytokine storm, which leads to the onset of ARDS. Therefore, monitoring various cytokines such as IL-6, which are associated with ARDS during the period of treatment of DKA is beneficial.


Efficacy and safety of right and left atrial ablations on the beating heart with irrigated bipolar radiofrequency energy: a long-term animal study.
The Cox maze procedure is the most effective surgical treatment for atrial fibrillation; however, its complexity has limited its clinical utility. The purpose of this study was to simplify the procedure by using an irrigated bipolar radiofrequency ablation device on the beating heart without cardiopulmonary bypass. Six domestic pigs underwent median sternotomy. The pulmonary veins were circumferentially ablated. Electrical isolation was confirmed by pacing. Eight lesions were performed epicardially, and three lesions were performed through purse-string sutures with one of the jaws of the device introduced into the right atrium. After 30 days, magnetic resonance imaging was performed to assess atrial function, pulmonary vein anatomy, and coronary artery patency. Cholinergic stimulation and burst pacing were administered to induce atrial fibrillation. Histologic assessment of the heart was performed after the animal was killed. A modified Cox maze procedure was successfully performed with the irrigated bipolar radiofrequency device with no deaths. In every instance, the pulmonary veins were electrically isolated. Cholinergic stimulation with burst pacing failed to produce atrial fibrillation. Imaging studies revealed tricuspid regurgitation without evidence of pulmonary vein stenosis, coronary artery stenosis, or intra-atrial thrombus. Total atrial ejection fraction was 16.9% +/- 7.5%, a significant reduction. Histologically, 99% of the lesions were transmural, and there was no evidence of coronary sinus injury. Lesions on both the right and left atria can be created successfully on the beating heart with irrigated bipolar radiofrequency. The great majority of lesions with this device were transmural. This device should not be used on valvular tissue.


Screening for intracranial aneurysm in 355 patients with autosomal-dominant polycystic kidney disease.
the association of autosomal-dominant polycystic kidney disease (ADPKD) with intracranial aneurysm (ICAN) is well known but little is known about the characteristics of ICAN in ADPKD. The purpose of this study was to investigate the prevalence and characteristics of ICAN in ADPKD. we screened 355 patients with ADPKD (mean age, 46.5 ± 13.2 years; range, 7 to 87 years) with 3-dimensional time-of-flight MR angiography. Size, location, and morphology of aneurysms were assessed. The prevalence and characteristics of ICAN in patients with ADPKD were evaluated. Patients with ICAN found by MR angiography and moderate renal function subsequently were recommended to undergo digital subtraction angiography for comparison. the prevalence of ICAN in ADPKD was 12.4% (95% CI, 8.95% to 15.82%) with an equal gender distribution. The prevalence increased as age increased, reaching a peak value of 23.3% (95% CI, 16.85 to 29.75%) in the 60- to 69-year age group. The prevalence of ICAN in patients with ADPKD with a positive family history of hemorrhagic stroke or ICAN was higher than patients with ADPKD lacking such family history (relative risk, 1.968; 95% CI, 1.57 to 2.67). The mean diameter of ICAN was 3.85 ± 3.25 mm. The most frequent site of ICAN was the internal carotid artery. The result of digital subtraction angiography of 15 patients with 18 ICANs and moderate renal function corresponded to the detection of MR angiography. the characteristics of ICAN in patients with ADPKD were different from some previous reports. Systematic screening of ICAN with 3-dimensional time-of-flight MR angiography is recommended for patients with ADPKD, particularly for adult patients (≧30 years) or patients with a positive family history of hemorrhagic stroke or ICAN.


Model-based reconstructions for intravoxel incoherent motion and diffusion tensor imaging parameter map estimations.
Intravoxel incoherent motion (IVIM) imaging and diffusion tensor imaging (DTI) facilitate noninvasive quantification of tissue perfusion and diffusion. Both are promising biomarkers in various diseases and a combined acquisition is therefore desirable. This comes with challenges, including noisy parameter maps and long scan times, especially for the perfusion fraction f and pseudo-diffusion coefficient D*. A model-based reconstruction has the potential to overcome these challenges. As a first step, our goal was to develop a model-based reconstruction framework for IVIM and combined IVIM-DTI parameter estimation. The IVIM and IVIM-DTI models were implemented in the PyQMRI model-based reconstruction framework and validated with simulations and in vivo data. Commonly used voxel-wise nonlinear least-squares fitting was used as the reference. Simulations with the IVIM and IVIM-DTI models were performed with 100 noise realizations to assess accuracy and precision. Diffusion-weighted data were acquired for IVIM reconstruction in the liver (n = 5), as well as for IVIM-DTI in the kidneys (n = 5) and lower-leg muscles (n = 6) of healthy volunteers. The median and interquartile range (IQR) values of the IVIM and IVIM-DTI parameters were compared to assess bias and precision. With model-based reconstruction, the parameter maps exhibited less noise, which was most pronounced in the f and D* maps, both in the simulations and in vivo. The bias values in the simulations were comparable between model-based reconstruction and the reference method. The IQR was lower with model-based reconstruction compared with the reference for all parameters. In conclusion, model-based reconstruction is feasible for IVIM and IVIM-DTI and improves the precision of the parameter estimates, particularly for f and D* maps.


Validation of a pediatric population pharmacokinetic model for vancomycin.
Vancomycin is often required to treat serious infections in children, including methicillin-resistant Staphylococcus aureus infections. The pharmacodynamic index that best predicts efficacy with vancomycin use for methicillin-resistant S. aureus infection in adults is the 24-hour area under the curve (AUC) over the minimum inhibitory concentration. Although multiple pediatric population pharmacokinetic (PK) vancomycin models have been published, few use Bayesian optimization. The current standard of care remains measuring vancomycin serum trough concentrations as a surrogate marker of AUC. A prospective validation of a pediatric population PK model of vancomycin was performed. Hospitalized children younger than 18 years receiving vancomycin at Cincinnati Children's Hospital Medical Center were invited to participate. Peak, trough, and random vancomycin serum concentrations were used for Bayesian estimation of individual PK parameters. Model covariates included age, weight, and serum creatinine. To evaluate the predictive performance of the model, precision and bias were measured and compared using the 95% confidence interval. Fifteen subjects were enrolled; 13 subjects had vancomycin serum concentrations drawn per protocol. Of those 13 subjects, the median age was 6 years and 54% were male. Significant medical conditions included cancer (54%), lung disease (23%), neurologic disorders (23%), and prior transplantation (15%). The initial serum creatinine was normal (median, 0.33; interquartile range, 0.23-0.4 mg/dL), and none had underlying renal dysfunction. Equivalence of bias and precision between the original model validation and the Cincinnati Children's Hospital Medical Center validation were found. Pediatric population PK models for vancomycin with Bayesian estimation can be used to reliably predict vancomycin exposure in children. Using AUC instead of trough serum concentrations alone can provide an opportunity to maximally optimize vancomycin administration in children.


Characteristics of challenging behaviours in adults with autistic disorder, PDD-NOS, and intellectual disability.
Challenging behaviours are frequently a problem for people with autism spectrum disorders (ASD) and intellectual disability (ID). A better understanding of which individuals display which behaviours, at what rates, and the relationship of these behaviours to comorbid psychopathology would have important implications. A group of 161 adults with ASD (autistic disorder or Pervasive Developmental Disorder--Not Otherwise Specified [PDD-NOS]) and 159 matched controls with ID only residing in two large residential facilities in Southeastern United States, were studied using the Autism Spectrum Disorders--Behavior Problems for Adults (ASD-BPA). In all four categories of challenging behaviour measured by the ASD-BPA (Aggression/Destruction, Stereotypy, Self-Injurious Behavior, and Disruptive Behavior), frequency of challenging behaviours increased with severity of autistic symptoms. The greatest group differences were found for Stereotypy (repeated/unusual vocalisations/body movements and unusual object play), Self-Injurious Behavior (harming self and mouthing/swallowing objects), Aggression/Destruction (banging on objects), and Disruptive Behavior (elopement). Challenging behaviours in people with ASD and ID are barriers to effective education, training, and social development, and often persist throughout adulthood. Thus, programs designed to remediate such behaviours should continue across the life-span of these individuals.


Premorbid, clinical and cognitive correlates of primary negative symptoms in first-episode psychosis.
Negative symptoms are a core psychopathological dimension of psychotic disorders. Previous research on primary negative symptoms (PNS) mostly focused on chronic samples. Data regarding premorbid, clinical and cognitive correlates of PNS in the early illness course are limited and inconsistent. In this study, we assessed 355 Hong Kong Chinese adult patients presenting with first-episode psychosis (FEP) to early intervention service with an aim to examine the prevalence of PNS and its relationships with premorbid adjustment, clinical and cognitive profiles. PNS was defined as the presence of clinically significant negative symptoms excluding depression, positive symptoms and extrapyramidal signs. Results showed that 14.6% of patients exhibited PNS at service entry. PNS group had poorer premorbid social functioning, lower level of insight, and worse performance in Modified Wisconsin Card Sorting and digit symbol tests than non-PNS group. Logistic regression analysis showed that premorbid social functioning and digit symbol test score were independently associated with PNS. Our findings thus indicate that PNS are frequently observed in FEP patients. Deficits in proceeding speed, alongside impaired premorbid social functioning, might be specifically related to PNS in the early illness stage.


Steroid secretion by the human egg-corona-cumulus complex in culture.
Forty-five oocyte-corona-cumulus complexes ( OCCC ) were obtained from follicles of 13 women undergoing fertilization in vitro. Follicular growth was induced with human menopausal gonadotropin, and follicular aspiration was performed 36 h after an ovulatory injection of hCG. The maturation of these complexes was evaluated by the extent of cumulus mucification and corona cell dispersal. Three main morphological types were characterized: immature OCCCs (6), with a tight and compact corona-cumulus mass surrounding the oocyte; intermediate OCCCs (26), with a dispersed cumulus but only partly dispersed corona layer; and mature complexes (13) with complete dispersal of both cellular components. During a 24-h culture, progesterone secretion by intermediate and mature OCCCs was 30-fold higher (mean +/- SEM, 652 +/- 87 ng/ OCCC X 24 h) than immature OCCCs (19.6 +/- 3.5 ng/ OCCC X 24 h), while estradiol secretion was twice as high (3.8 +/- 1.1 vs. 1.2 +/- 0.6 ng/ OCCC X 24 h). Testosterone secretion was similar in all three types of OCCCs cultured (0.30 ng/24 h). It is suggested that the steroids produced by the OCCC may contribute to the local milieu of the fallopian tube.


Lactate clearance as the predictor of outcome in pediatric septic shock.
Septic shock can rapidly evolve into multiple system organ failure and death. In the recent years, hyperlactatemia has been found to be a risk factor for mortality in critically ill adults. To evaluate the predictive value of lactate clearance and to determine the optimal cut-off value for predicting outcome in children with septic shock. A prospective observational study was performed on children with septic shock admitted to pediatric Intensive Care Unit (PICU). Serial lactate levels were measured at PICU admission, 24 and 48 h later. Lactate clearance, percent decrease in lactate level in 24 h, was calculated. The primary outcome measure was survival or nonsurvival at the end of hospital stay. We performed receiver operating characteristic analyses to calculate optimal cut-off values. The mean lactate levels at admission were significantly higher in the nonsurvivors than survivors, 5.12 ± 3.51 versus 3.13 ± 1.71 mmol/L (P = 0.0001). The cut-off for lactate level at admission for the best prediction of mortality was determined as ≥4 mmol/L (odds ratio 5.4; 95% confidence interval [CI] =2.45-12.09). Mean lactate clearance was significantly higher in survivors than nonsurvivors (17.9 ± 39.9 vs. -23.2 ± 62.7; P < 0.0001). A lactate clearance rate of <10% at 24 h had a sensitivity and specificity of 78.7% and 72.2%, respectively and a positive predictive value of 83.1% for death. Failure to achieve a lactate clearance of more than 10% was associated with greater risk of mortality (likelihood ratio + 2.83; 95% CI = 1.82-4.41). Serial lactate levels can be used to predict outcome in pediatric septic shock. A 24 h lactate clearance cut-off of <10% is a predictor of in-hospital mortality in such patients.


Clinical effectiveness of complex decongestive physiotherapy for malignant lymphedema: a pilot study.
To evaluate the effect of complex decongestive physiotherapy (CDPT) on malignant lymphedema patients. Patients (n=22) with malignant lymphedema of the upper or the lower limb were assigned to this study. CDPT without manual lymphatic drainage (MLD) was used five times per week for two weeks. The main outcome measurements included measurement of the circumference of the limb (proximal, distal, and total) to assess volume changes. We also employed the visual analog scale (VAS) to evaluate pain, and the short form-36 version 2 questionnaire (SF-36) to assess quality of life (QOL). All items were assessed pre and post-treatment for each patient. There was a statistically significant difference in the volume change of the upper limbs (3.7%, p=0.001) and the lower limbs (10.9%, p=0.001). A 1.5 point reduction on the ten-point VAS was noted after CDPT. The scores on the physical and the mental components of the SF-36 showed statistical improvement after treatment (p=0.006, p=0.001, respectively). These results suggest that all components of the CDPT program except MLD are helpful in treating malignant lymphedema in terms of pain reduction and reduction of the volume of the affected upper or lower limb. This treatment regimen also has positive effects on QOL.


A feature-guided, focused 3D signal permutation method for subtomogram averaging.
Advances in electron microscope instrumentation, cryo-electron tomography data collection, and subtomogram averaging have allowed for the in-situ visualization of molecules and their complexes in their native environment. Current data processing pipelines commonly extract subtomograms as a cubic subvolume with the key assumption that the selected object of interest is discrete from its surroundings. However, in instances when the object is in its native environment, surrounding densities may negatively affect the subsequent alignment and refinement processes, leading to loss of information due to misalignment. For example, the strong densities from surrounding membranes may dominate the alignment process for membrane proteins. Here, we developed methods for feature-guided subtomogram alignment and 3D signal permutation for subtomogram averaging. Our 3D signal permutation method randomizes and filters voxels outside a mask of any shape and blurs the boundary of the mask that encapsulates the object of interest. The randomization preserves global statistical properties such as mean density and standard deviation of voxel density values, effectively producing a featureless background surrounding the object of interest. This signal permutation process can be repeatedly applied with intervening alignments of the 3D signal-permuted subvolumes, recentering of the mask, and optional adjustments of the shape of the mask. We have implemented these methods in a new processing pipeline which starts from tomograms, contains feature-guided subtomogram extraction and alignment, 3D signal-permutation, and subtomogram visualization tools. As an example, feature-guided alignment and 3D signal permutation leads to improved subtomogram average maps for a dataset of synaptic protein complexes in their native environment.


Shame and the motivation to change the self.
A central question of human psychology is whether and when people change for the better. Although it has long been assumed that emotion plays a central role in self-regulation, the role of specific emotions in motivating a desire for self-change has been largely ignored. We report 2 studies examining people's lived experiences of self-conscious emotions, particularly shame, in motivating a desire for self-change. Study 1 revealed that when participants recalled experiences of shame, guilt, or embarrassment, shame-and, to some degree, guilt-predicted a motivation for self-change. Study 2 compared shame, guilt, and regret for events and found that although shame experiences often involved high levels of both regret and guilt, it was feelings of shame that uniquely predicted a desire for self-change, whereas regret predicted an interest in mentally undoing the past and repairing harm done. Implications for motivating behavior change are discussed.


Comparing 20 years of national general surgery malpractice claims data: obesity versus morbid obesity.
We hypothesized that the increasing body mass index of the population has affected general surgery malpractice claims. We queried the Physician Insurers Association of America database from 1990 to 1999 (ie, period 1) and 2000 to 2009 (ie, period 2) for claims associated with obesity and morbid obesity. We analyzed the error involved, injury severity, procedure, and outcome. Five hundred seventy-five claims were identified. The percentage of paid claims did not differ by body mass index. Improper performance was the most common alleged error, gastric bypass was the most common procedure, and death was the most common injury. For obesity claims, the case was more likely to be settled in period 1 and withdrawn/dismissed in period 2 (P < .001). The number of morbid obesity claims rose from 9 in period 1 to 249 in period 2. The significant rise in morbid obesity claims between periods is likely caused by the substantial increase in the number of bariatric procedures performed.


[Non-allergic eosinophilic rhinitis. From clinical diagnosis to pathogenic study].
Non allergic rhinitis with eosinophilia syndrome is not an uncommon diagnosis, since eosinophilia in nasal secretions from 20% up to 90% of total cells, is detected in 15% of rhinitis. Nasal symptoms include sneezing paroxysms, profuse watery rhinorrhea, in adults or in children. All immunological tests are negative. Tomodensitometry may detect evolution towards sinusal polyposis, and bronchial challenges with carbamylcholine may detect bronchial hyper-reactivity. We conclude to the possibility for NARES to be a link between common vasomotor rhinitis and nasal polyposis with asthma and intolerance to aspirin. The diagnosis needs to be firmly established by the study of nasal eosinophilia during a nasal challenge with a perennial allergen (house dust mite). The first has to be unchanged, and the second has to be negative. As eosinophils are potent pro-inflammatory cells endowed with cytotoxicity, precise studies upon the characteristics of eosinophils in the nasal secretions and in the pituitary mucosa of patients with NARES, have to be carried on.


"Balancing" the Block Davidson-Liu Algorithm.
We describe a simple modification ("balancing") of the block Davidson-Liu eigenvalue algorithm which allows the norms of the Krylov search directions to decrease naturally as convergence is approached. In the context of integral-direct configuration interaction singles and time-dependent density functional theory, this provides for efficient utilization of density-based screening. Tests within the TeraChem GPGPU code exhibit speedups of ∼2× on systems with up to 1500 atoms, with negligible loss in accuracy.


Using Active Learning for Speeding up Calibration in Simulation Models.
Most cancer simulation models include unobservable parameters that determine disease onset and tumor growth. These parameters play an important role in matching key outcomes such as cancer incidence and mortality, and their values are typically estimated via a lengthy calibration procedure, which involves evaluating a large number of combinations of parameter values via simulation. The objective of this study is to demonstrate how machine learning approaches can be used to accelerate the calibration process by reducing the number of parameter combinations that are actually evaluated. Active learning is a popular machine learning method that enables a learning algorithm such as artificial neural networks to interactively choose which parameter combinations to evaluate. We developed an active learning algorithm to expedite the calibration process. Our algorithm determines the parameter combinations that are more likely to produce desired outputs and therefore reduces the number of simulation runs performed during calibration. We demonstrate our method using the previously developed University of Wisconsin breast cancer simulation model (UWBCS). In a recent study, calibration of the UWBCS required the evaluation of 378 000 input parameter combinations to build a race-specific model, and only 69 of these combinations produced results that closely matched observed data. By using the active learning algorithm in conjunction with standard calibration methods, we identify all 69 parameter combinations by evaluating only 5620 of the 378 000 combinations. Machine learning methods hold potential in guiding model developers in the selection of more promising parameter combinations and hence speeding up the calibration process. Applying our machine learning algorithm to one model shows that evaluating only 1.49% of all parameter combinations would be sufficient for the calibration.


Antibiofilm activity of carboxymethyl chitosan on the biofilms of non-Candida albicans Candida species.
Although most cases of candidiasis have been attributed to Candida albicans, non-C. albicans Candida species have been isolated in increasing numbers in patients. In this study, we determined the inhibition of carboxymethyl chitosan (CM-chitosan) on single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida parapsilosis, Candida krusei and Candida glabrata. Biofilm by all tested species in microtiter plates were inhibited nearly 70%. CM-chitosan inhibited mixed species biofilm in microtiter plates and also on medical materials surfaces. To investigate the mechanism, the effect of CM-chitosan on cell viability and biofilm growth was employed. CM-chitosan inhibited Candida planktonic growth as well as adhesion. Further biofilm formation was inhibited with CM-chitosan added at 90min, 12h or 24h after biofilm initiation. CM-chitosan was not only able to inhibit the metabolic activity of Candida cells, but was also active upon the establishment and the development of biofilms.