Experienced health in older women with rheumatoid arthritis.
This study explored how older women with chronic illness and disability experience their own health. Data were collected in in-depth interviews with ten older women with rheumatoid arthritis. Data analysis and interpretation was carried out within a phenomenological- hermeneutic frame of understanding, which revealed five major themes: health as coping with everyday life, health as freedom, health as absence of inconvenience, health as togetherness and health as mental well-being. For older people with chronic illness and disability, good health found expression in general well-being. It was perceived as a state of equilibrium that the respondents sought to maintain through their own active choices.


Towards unstructured mortality prediction with free-text clinical notes.
Healthcare data continues to flourish yet a relatively small portion, mostly structured, is being utilized effectively for predicting clinical outcomes. The rich subjective information available in unstructured clinical notes can possibly facilitate higher discrimination but tends to be under-utilized in mortality prediction. This work attempts to assess the gain in performance when multiple notes that have been minimally preprocessed are used as an input for prediction. A hierarchical architecture consisting of both convolutional and recurrent layers is used to concurrently model the different notes compiled in an individual hospital stay. This approach is evaluated on predicting in-hospital mortality on the MIMIC-III dataset. On comparison to approaches utilizing structured data, it achieved higher metrics despite requiring less cleaning and preprocessing. This demonstrates the potential of unstructured data in enhancing mortality prediction and signifies the need to incorporate more raw unstructured data into current clinical prediction methods.


Thickness- and Twist-Angle-Dependent Interlayer Excitons in Metal Monochalcogenide Heterostructures.
Interlayer excitons, or bound electron-hole pairs whose constituent quasiparticles are located in distinct stacked semiconducting layers, are being intensively studied in heterobilayers of two-dimensional semiconductors. They owe their existence to an intrinsic type-II band alignment between both layers that convert these into p-n junctions. Here, we unveil a pronounced interlayer exciton (IX) in heterobilayers of metal monochalcogenides, namely, γ-InSe on ε-GaSe, whose pronounced emission is adjustable just by varying their thicknesses given their number of layers dependent direct band gaps. Time-dependent photoluminescense spectroscopy unveils considerably longer interlayer exciton lifetimes with respect to intralayer ones, thus confirming their nature. The linear Stark effect yields a bound electron-hole pair whose separation d is just (3.6 ± 0.1) Å with d being very close to dSe = 3.4 Å which is the calculated interfacial Se separation. The envelope of IX is twist-angle-dependent and describable by superimposed emissions that are nearly equally spaced in energy, as if quantized due to localization induced by the small moiré periodicity. These heterostacks are characterized by extremely flat interfacial valence bands making them prime candidates for the observation of magnetism or other correlated electronic phases upon carrier doping.


[Damage control surgery in multiply traumatised patients].
The results of extensive and prolonged surgical procedures performed in multi trauma patients are often poor. These patients may develop the lethal combination of metabolic acidosis, coagulopathy and hypothermia, which reduces their physiological reserve capacity. The 'damage control surgery' (DCS) approach is known to reduce the mortality rate in multi trauma patients. DCS consists of a short primary operation to control bleeding and prevent contamination. Thereafter, resuscitation is performed in the intensive care unit. Finally, reoperation and definitive repair of lesions are done.


Modified Bidirectional Encoder Representations From Transformers Extractive Summarization Model for Hospital Information Systems Based on Character-Level Tokens (AlphaBERT): Development and Performance Evaluation.
Doctors must care for many patients simultaneously, and it is time-consuming to find and examine all patients' medical histories. Discharge diagnoses provide hospital staff with sufficient information to enable handling multiple patients; however, the excessive amount of words in the diagnostic sentences poses problems. Deep learning may be an effective solution to overcome this problem, but the use of such a heavy model may also add another obstacle to systems with limited computing resources. We aimed to build a diagnoses-extractive summarization model for hospital information systems and provide a service that can be operated even with limited computing resources. We used a Bidirectional Encoder Representations from Transformers (BERT)-based structure with a two-stage training method based on 258,050 discharge diagnoses obtained from the National Taiwan University Hospital Integrated Medical Database, and the highlighted extractive summaries written by experienced doctors were labeled. The model size was reduced using a character-level token, the number of parameters was decreased from 108,523,714 to 963,496, and the model was pretrained using random mask characters in the discharge diagnoses and International Statistical Classification of Diseases and Related Health Problems sets. We then fine-tuned the model using summary labels and cleaned up the prediction results by averaging all probabilities for entire words to prevent character level-induced fragment words. Model performance was evaluated against existing models BERT, BioBERT, and Long Short-Term Memory (LSTM) using the Recall-Oriented Understudy for Gisting Evaluation (ROUGE) L score, and a questionnaire website was built to collect feedback from more doctors for each summary proposal. The area under the receiver operating characteristic curve values of the summary proposals were 0.928, 0.941, 0.899, and 0.947 for BERT, BioBERT, LSTM, and the proposed model (AlphaBERT), respectively. The ROUGE-L scores were 0.697, 0.711, 0.648, and 0.693 for BERT, BioBERT, LSTM, and AlphaBERT, respectively. The mean (SD) critique scores from doctors were 2.232 (0.832), 2.134 (0.877), 2.207 (0.844), 1.927 (0.910), and 2.126 (0.874) for reference-by-doctor labels, BERT, BioBERT, LSTM, and AlphaBERT, respectively. Based on the paired t test, there was a statistically significant difference in LSTM compared to the reference (P<.001), BERT (P=.001), BioBERT (P<.001), and AlphaBERT (P=.002), but not in the other models. Use of character-level tokens in a BERT model can greatly decrease the model size without significantly reducing performance for diagnoses summarization. A well-developed deep-learning model will enhance doctors' abilities to manage patients and promote medical studies by providing the capability to use extensive unstructured free-text notes.


A Syndemic Approach to Explore Factors Associated with Bacterial Vaginosis.
Bacterial vaginosis (BV) is the most common genital infection in women and is associated with an increased risk of sexually transmitted infections and HIV. This study uses a syndemic approach to evaluate factors associated with BV. Non-pregnant, HIV-negative, sexually active, cis-gender women aged 18-45 years living in Miami, Florida were recruited from Nov.2018- Jun.2021. Participants completed a sociodemographic and behavioral questionnaire along with gynecological examinations. BV was diagnosed by Amsel criteria and confirmed by a Nugent score ≥ 4. A syndemic score was calculated as the sum of factors associated with BV. The association between syndemic score and BV was assessed using logistic regression. Of 166 women included, 60.2% had BV. Race, ethnicity, education, vaginal sex, recent cannabis use, and reasons for intravaginal practices were included in the syndemic score. Higher odds of BV were found in women with a score of ≥ 3 compared to women with a score of 0/1. A higher syndemic score was associated with increased odds of having BV. Multilevel interventions to decrease BV are needed to decrease women's risk of acquiring HIV.


Antibacterial Radicicol Analogues from Pochonia chlamydosporia and Their Biosynthetic Gene Cluster.
Chemical investigation of fungus Pochonia chlamydosporia strain 170, derived from rice fermentation sediment samples, afforded seven radicicol analogues, including two new compounds, monocillin VI (1) and monocillin VII (2), and five known compounds, monocillin II (3), monorden D (4), monocillin IV (5), monocillin V (6), and pochonin M (7). The structures of compounds 1-7 were established primarily by analysis of nuclear magnetic resonance data, and the absolute configurations of the secondary alcohol in compounds 1 and 2 were assigned by the modified Mosher method. All seven compounds have modest antibacterial activities, with a minimal inhibitory concentration (MIC) of 25.6 μg/mL for compounds 1 and 3-7 and 51.2 μg/mL for compound 2, on inhibition of the growth of the plant pathogen Xanthomonas campestris (the positive control ampicillin showed a MIC value of 12.8 μg/mL), indicating that the fungus has the potential to control bacterial disease. The biosynthetic gene cluster and putative biosynthetic pathways of these radicicol analogues in the P. chlamydosporia genome were proposed. These findings increase our knowledge of the chemical potential of P. chlamydosporia and may allow us to better utilize the fungus as a biological control agent.


Temporal cavity solitons in a laser-based microcomb: a path to a self-starting pulsed laser without saturable absorption.
We theoretically present a design of self-starting operation of microcombs based on laser-cavity solitons in a system composed of a micro-resonator nested in and coupled to an amplifying laser cavity. We demonstrate that it is possible to engineer the modulational-instability gain of the system's zero state to allow the start-up with a well-defined number of robust solitons. The approach can be implemented by using the system parameters, such as the cavity length mismatch and the gain shape, to control the number and repetition rate of the generated solitons. Because the setting does not require saturation of the gain, the results offer an alternative to standard techniques that provide laser mode-locking.


Cytokine regulation of TNF-alpha mRNA and protein production by unprimed macrophages from C57Bl/6 and NZW mice.
It is well known that bacterial lipopolysaccharide (LPS) induces the synthesis of tumor necrosis factor alpha (TNF-alpha) and other inflammatory cytokines by primary monocytes and macrophages and that the Th1 lymphokines, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), augment this response. We investigated the ability of IL-2 and IFN-gamma to induce the production of TNF-alpha mRNA and protein independently of LPS and the modulation of this response by macrophage colony-stimulating factor (M-CSF) and IL-10. We found that IL-2 and IFN-gamma were both able to induce the accumulation of TNF-alpha mRNA, albeit with slower kinetics than LPS, and that they acted synergistically. However, very little TNF bioactivity was secreted by lymphokine-stimulated macrophages unless LPS was also added. This finding underscores the importance of translational effects in the control of TNF production. M-CSF and IL-10 strongly inhibited TNF production at the level of both mRNA and bioactivity but had no effect on the production of IL-6. Bone marrow-derived or thioglycollate-elicited macrophages from the NZW mouse strain, which have been reported to be deficient in their ability to produce TNF, were at least as responsive to LPS or lymphokines as those taken from the C57Bl/6 strain and were similarly affected by M-CSF and IL-10. Therefore, the genetic defect of NZW mice is not a primary deficiency in TNF production.


Effects of low-dose protocols in endovascular treatment of intracranial aneurysms: development of workflow task analysis during cerebral endovascular procedures.
Reducing radiation exposure through the use of low-dose protocols during cerebral endovascular procedures is recommended, but evaluation of the impact on the procedure itself is difficult and subjective. A workflow task analysis could provide an objective comparison of two different radiation exposure protocols. Twenty endovascular aneurysm treatments were analyzed using a low-dose protocol (reducing radiation exposure by 20%) in 10 cases and a normal-dose protocol in the other 10 cases. The procedure was subdivided into five phases, each comprising a sequence of tasks. Each task was defined as a triplet, associating an action, an instrument, and an anatomic structure. A workflow editor was used to record tasks and phases with a tablet PC. The total duration of the entire procedure, the duration of each task, and the number of task repetitions were isolated and used as the metric. Moreover, the tasks involving x-ray use, essential for navigation and treatment phases, were separated and analyzed. For the microcatheter navigation and treatment phases, no statistically significant difference was found between the two radiation exposure protocols. For guide catheter navigation in cervical vessels, the total phase duration and total and mean time of tasks specifically involving x-ray use increased with age, but there was no difference between the two radiation protocols. Workflow task analysis of endovascular aneurysm treatment shows no difference between low-dose and normal-dose protocols in the guide catheter navigation, microcatheter navigation, or treatment phases.


Elevation of brain-enriched miRNAs in cerebrospinal fluid of patients with acute ischemic stroke.
The purpose of this study was to investigate the potential of cerebrospinal fluid miRNAs as diagnostic biomarkers of acute ischemic stroke using three different profiling techniques in order to identify and bypass any influence from technical variation. Cerebrospinal fluid (CSF) from patients with acute ischemic stroke (n = 21) and controls (n = 21) was collected by lumbar puncture. miRNA analysis was performed with three different methods: 1) Trizol RNA extraction followed by Illumina Next Generation Sequencing (NGS) on all small RNAs, 2) Exiqon RNA extraction protocol and miRNA qPCR assays, and 3) validation of 24 selected miRNAs with Norgen Biotek RNA extraction protocol and Applied Biosystems qPCR assays. NGS detected 71 frequently expressed miRNAs in CSF of which brain-enriched miR-9-5p and miR-128-3p were significantly higher in CSF of stroke patients compared to controls. When dividing stroke patients into groups according to infarct size several brain-enriched miRNAs (miR-9-5p, miR-9-3p, miR-124-3p, and miR-128-3p) were elevated in patients with infarcts >2 cm3. This trend appeared in data from both NGS, qPCR (Exiqon), and qPCR (Applied Biosystems) but was only statistically significant in some of the measurement platforms. Several brain-enriched miRNAs are elevated in the CSF three days after stroke onset, suggesting that these miRNAs reflect the brain damage caused by ischemia. The expression differences seem, however, limited to patients with larger ischemic brain injury, which argues against the use of CSF miRNAs as diagnostic biomarkers of stroke based on current methods.


Evaluating the Effect of Nursing-Performed Point-of-Care Ultrasound on Septic Emergency Department Patients.
Introduction Nursing-performed point-of-care ultrasound (NP-POCUS) studies have been performed on applications such as ultrasound-guided peripheral intravenous line placement and assessing bladder volume. However, research on the use of NP-POCUS in the management of septic patients remains limited. The purpose of this quality improvement study was to investigate how NP-POCUS could impact fluid treatment decisions affecting septic patients in the emergency department (ED) using a focused IVC and lung ultrasound protocol. Methods Nurses received standardized training in POCUS and performed inferior vena cava (IVC) and lung ultrasound scans on septic patients in the ED at predetermined intervals (hours: zero, three, and six). Based on their findings, they were asked to make recommendations on fluid management. Emergency physicians (EPs), both residents and attendings, are providing recommendations for fluid management without the use of ultrasound, which is being compared to the nurse-driven POCUS assessment of fluid management. EPs reviewed the NP-POCUS assessments of patient fluid status to determine nursing accuracy. Results A total of 104 patients were scanned, with a mean age of 60.7 years. EPs agreed with nursing ultrasound assessments in 99.1% of cases. Nursing ultrasound images changed management or increased physician confidence in current treatment plans 83.7% and 96.6% of the time, respectively. Before reviewing saved nursing ultrasound images, EPs underestimated fluid tolerance in 37.5% of cases, overestimated fluid tolerance in 26% of cases, and correctly estimated fluid tolerance (within 500 ml) in 36.5% of cases. Throughout resuscitation, IVCs became less collapsible, the number of cases with B-lines was essentially unchanged, and less fluid was recommended. Conclusion This study demonstrated that nurse-performed POCUS is feasible and may have a meaningful impact on how physicians manage septic patients in the emergency department.


Podocyte Injury at Young Age Causes Premature Senescence and Worsens Glomerular Aging.
As life expectancy continues to rise, age-related diseases are becoming more prevalent. For example, proteinuric glomerular diseases typified by podocyte injury have worse outcomes in the elderly compared to young patients. However, the reasons are not well understood. We hypothesized that injury to non-aged podocytes induces senescence, which in turn augments their aging processes. In primary cultured human podocytes, injury induced by a cytopathic anti-podocyte antibody, Adriamycin, or Puromycin Aminonucleoside increased the senescence-related genes CDKN2A (p16INK4a/p14ARF), CDKN2D (p19INK4d), and CDKN1A (p21). Podocyte injury in human kidney organoids was accompanied by increased expression of CDKN2A, CDKN2D, and CDKN1A. In young mice, experimental FSGS induced by Adriamycin and anti-podocyte antibody increased the glomerular expression of p16, p21, and senescence-associated beta-galactosidase (SA-β-gal). To assess the long-term effects of early podocyte injury-induced senescence, we temporally followed young mice with experimental FSGS through adulthood (12m of age) and middle age (18m of age). p16 and Sudan Black staining were higher at middle age in mice with earlier FSGS compared to age-matched mice that did not get FSGS when young. This was accompanied by lower podocyte density, reduced canonical podocyte protein expression, and increased glomerular scarring. These results are consistent with injury-induced senescence in young podocytes, leading to increased senescence of podocytes by middle age accompanied by lower podocyte lifespan and health span.


Assessment of chronic kidney disease in Nepalese people with hypertension.
Hypertension is one of the leading causes to develop chronic kidney disease (CKD) and could be a risk factor for progression of CKD to end stage renal disease (ESRD).Uncontrolled hypertension worsens CKD. Hypertension control may contribute to prevent CKD in early stages and retards the progression of CKD stages to ESRD. Prevalence of CKD in people with diagnosed and chronic hypertension is known to be high, but little is known about the prevalence of CKD in those with newly diagnosed Hypertension. Present work was undertaken to see the prevalence of CKD among people with newly diagnosed hypertension. In this cross-sectional study, we accessed the CKD in newly diagnosed hypertensive patients and determined the association between hypertension and CKD. CKD was defined as either kidney dysfunction or kidney damage or both as per National Kidney Foundation Guidelines. 106 of newly diagnosed patients and 106 of normotensive controls were recruited in the study. 51.9% of newly diagnosed hypertensive patients and 23.6% of normotensive controls had CKD which was statistically significant (p-value <0.001). Difference in the mean value in eGFR and spot urine ACR (mg/mmol) between hypertensive patients and normotensive controls was statistically significant (p-Value <0.001). Both systolic BP and diastolic BP negative significantly correlated with eGFR (p-Value < 0.001 and 0.024 respectively) and positive significantly correlated with ACR (p-Value 0.003 and 0.003 respectively). The prevalence of CKD is high among people with newly diagnosed hypertension. Those, people might benefit from interventions aimed at preventing development and/or progression of both CKD and hypertension.


Erythroid progenitors in adult chronic pure red cell aplasia: relationship of in vitro erythroid colonies to therapeutic response.
Twenty-two cases of idiopathic chronic pure red cell aplasia (PRCA) in adults have been studied to evaluate their erythroid progenitors in vitro using the plasma clot technique. Three types of culture growth patterns were observed and classified as follows. Type I: showing a normal number of autologous CFU-E; type II: CFU-E and BFU-E were detectable but constantly decreased; type III: CFU-E and BFU-E were undetectable. The results were reproducible when patients were studied on two or more occasions. A strong correlation was found between the in vitro growth of autologous erythroid colonies and the results of immunomodulating therapy in 18 evaluable patients. A constant response to immunomodulating treatment was observed in type I patients. A constant failure of treatment was observed in type III patients, whereas results of therapy were unpredictable in type II patients. Two patients with chronic PRCA associated with thymoma and three with chronic myeloproliferative disorders were also studied. Patients with PRCA and thymoma behaved in vitro like type I patients. Patients with chronic myeloproliferative disorders exhibited very low numbers or no CFU-E or BFU-E (type II or III). These data support the hypothesis that at least two mechanisms are responsible for PRCA--one immunologically mediated and the other resulting from a stem cell defect. Moreover, they suggest that the study of erythroid progenitors in vitro might be useful in predicting the immunosuppressive therapy effect in adult chronic PRCA.


[Pulse synchronous vascular tinnitus: radiologic diagnosis and therapy].
Tinnitus synchronous with the pulse is usually caused by vascular anomalies. In our own patient group we found the most frequent cause to be highly vascularised tumours related to the pretrous bone, the most common being glomus tumours. Pulsatile tinnitus however also is a main symptom of dural arterio-venous malformations with shunts into the transverse and sigmoid sinus. Finally pulsatile tinnitus may be caused by venous deformities, possibly combined with anomalies of the bulb of the jugular vein. While clinical methods give valuable clues to the type of pathological findings, subtle radiological investigations are necessary for the final diagnosis, such as high resolution computer tomography and super-selective angiography. There has been substantial progress in recent years due to technical developments leading to improved diagnosis and treatment by interventional radiology.


Hair Cortisol, Perceived Stress and Dispositional Optimism: A Pilot Study among Adolescents.
Psychological stress is often associated with poor health-related outcomes. One potential biomarker for chronic stress, hair cortisol, is minimally invasive compared to other cortisol collection techniques. This pilot study examined the relationships between hair cortisol and self-reported perceived stress, stressful life events, depressive symptoms, and dispositional optimism among adolescents. This cross-sectional study comprised of a convenience sample of 27 adolescents (age: M=14.96, SD=1.63) recruited from a Southern California after-school program. Along with demographic and hair characteristics (e.g., hair color, type, etc.), participants completed the Perceived Stress Scale, Stressful Life Events checklist, CES-D (depressive symptoms), and Life Orientation Test (optimism). Hair cortisol was measured by analyzing hair samples approximately 1 cm from the scalp representing one month of cortisol exposure. Hair cortisol had a significant inverse association with dispositional optimism (r=-0.44, p<0.05). Hair cortisol was not significantly associated with self-reported perceived stress, stressful life events, or depressive symptoms. Assessment of hair cortisol may prove beneficial as an objective measure in research examining chronic stress-related outcomes among adolescents. Resiliency or protective dispositions, such as optimism, merit attention in relation to this biomarker.


Suppression by phenobarbital of ethionine-induced hepatocellular carcinoma formation and hepatic S-adenosylethionine levels.
An 18-month carcinogenicity study was conducted in male weanling F344 rats (28/group) to examine the effects of the simultaneous feeding of selected concentrations of ethionine and 0.05% phenobarbital in a normal chow diet. The effects of a 1-6-week feeding of phenobarbital and ethionine on the hepatic levels of the related metabolites S-adenosylmethionine, S-adenosylhomocysteine and S-adenosylethionine were also examined. Ethionine at 0.3% or 0.1% induced hepatocellular carcinoma (HCCa) at incidences of 90% (19/21) and 89% (24/27), respectively. Adding phenobarbital to the 0.1% ethionine diet reduced the incidence of HCCa to 36% (10/28) and reduced the number of liver tumor-associated deaths occurring prior to terminal sacrifice from 10/27 to 1/28. No hepatic tumors were observed in rats fed 0, 0.003, 0.01, or 0.03% ethionine. Phenobarbital alone or combined with 0.03% ethionine produced no hepatic tumors. Dietary ethionine at 0.1% reduced the intracellular hepatic level of S-adenosylmethionine to <50% of that seen in control rats. Phenobarbital alone had little effect on either S-adenosylmethionine or S-adenosylhomocysteine levels. The combination of phenobarbital and 0.1% ethionine led to increases in the hepatic levels of S-adenosylmethionine of 40-60% after 3 and 6 weeks of feeding, compared to those seen in rats receiving 0.1% ethionine alone. Ethionine feeding resulted in high levels of S-adenosylethionine in the livers. Combining phenobarbital with ethionine in the diet led to 30-50% reductions in hepatic S-adenosylethionine content. The results indicate that phenobarbital inhibits hepatocarcinogenesis by ethionine, that ethionine may cause HCCa via methyl group insufficiency, and that at levels of < or =0.03% ethionine did not show evidence of tumorigenicity.


Molecular genetical and phenotypical analysis of the gerM spore germination gene of Bacillus subtilis 168.
The gerM gene, encoding a single product of 22.5 kDa, has been identified by subcloning and sequencing of DNA recovered from adjacent to a Tn917 insertion. The gene product has a potential lipoprotein signal sequence, but otherwise has no homology to known sequences. Spores of the gerM mutant were more heat sensitive than wild-type, but their dipicolinic acid content was normal. The level of cortical peptidoglycan in mutant spores is also normal but release at germination of hexosamine-containing fragments, the breakdown products of cortex degradation, is less complete than wild-type. The sporulation, resistance and germination phenotypes of the gerM mutant would be consistent with the gene product having a role, either directly or indirectly, in peptidoglycan synthesis during sporulation.


Interpretations of the patient-therapist relationship in brief dynamic psychotherapy : effects on long-term mode-specific changes.
The authors examined whether persistent analysis of the patient-therapist relationship in brief dynamic psychotherapy favorably affects long-term dynamic change in patients initially deemed suitable for such treatment. As in common practice, 22 highly suitable patients were given a high number of transference interpretations per session. A comparison group of 21 patients with lower suitability received the same treatment, but transference interpretations were withheld. Statistical adjustment for the deliberate nonequivalence in pretreatment suitability indicated a significant negative effect of high numbers of transference interpretations on long-term dynamic changes. Demographic variables, DSM-III diagnoses, additional treatment, life events in the follow-up years, or therapist effects did not explain or obscure the findings.


[Use of the right gastroepiploic artery as a coronary bypass graft. Indications, technique and early results].
435 isolated coronary artery procedures have been performed between January and December 1989 at the HerzZentrum Hirslanden. In 93% of the cases, one or two internal mammary arteries (IMA) and in 7%, saphenous vein grafts only were used as a bypass conduit. In 12 patients, the right gastroepiploic artery (RGE) was used as a free (3) or pedicled (9) graft to the posterior surface of the heart. This group of 12 patients was analyzed in a retrospective study. Postoperative complications in this group included one myocardial infarction and reexploration for intraabdominal bleeding in the same patient. All patients were discharged from hospital after an average of 9.7 days. After a mean follow-up time of 5 months, all patients are in NYHA-functional class I without antiischemic drugs. Postoperative angiography in 7 patients (mean postoperative interval 4 months) showed all 13 IMA-grafts and 5 RGE-grafts patent, 1 RGE-conduit is occluded, 1 RGE-graft could not been assessed for technical reasons. The RGE is an viable additional arterial bypass conduit and an alternative to other grafts. Indications for use of the RGE are lack of sufficient other conduits, calcified ascending aorta, coronary reoperation after vein graft failure and probably young patients with severe hyperlipidemia.


Substance P and somatostatin actions on spinal cord neurons in primary dissociated cell culture.
In this paper, we have demonstrated that two peptides, SP and SRIF, which have been localized to and are released from small DRG neurons, have specific but different actions on mouse spinal cord neurons in PDC culture. SP has been shown to be excitatory by decreasing potassium conductance and to a lesser extent sodium conductance; SP also appeared to evoke release of neurotransmitter. SRIF has been shown to modify neurotransmitter release by a presynaptic action. The extensive experimental control that is possible over neurons in vitro permits precise measurements of specific membrane actions to be made and thus allows hypotheses of cellular mechanisms of peptide actions to be advanced. Predictions made based on these hypotheses should then be tested using intact preparations. A reasonable goal for such studies is a detailed understanding of the cellular and ionic mechanisms underlying actions in the CNS, PNS and gut.


Effects of lincomycin on the immune system.
The effects of lincomycin on the immune system were studied on patients suffering from chronic bronchitis by means of phagocytosis, chemotaxis and natural-killer tests. The tests were performed before and 2, 4, 8, 12 and 24 h after administration of 600 mg lincomycin i.m. in a single dose. The results indicate that lincomycin stimulates phagocytosis, expressed as enhanced superoxide production (O2-), chemotaxis and the activity of natural killer cells, measured on the basis of their ability to perform a lysis on the K562 tumoral target labelled with 51Cr. The stimulating effects on chemotaxis appear already 2 h after the administration of the drug, while the same effect on phagocytosis and natural-killer activity occurs after 4 h. The maximal stimulating activity on all three parameters can be shown at 8 h and disappears at 24 h.


Mesoscopic stoner instability in metallic nanoparticles revealed by shot noise.
We study sequential tunneling through a metallic nanoparticle close to the Stoner instability coupled to parallel magnetized electrodes. Increasing the bias voltage successively opens transport channels associated with excitations of the nanoparticle's total spin. For the current this leads just to a steplike increase. The Fano factor, in contrast, shows oscillations between large super-Poissonian and sub-Poissonian values as a function of bias voltage. We explain the enhanced Fano factor in terms of generalized random-telegraph noise and propose the shot noise as a convenient tool to probe the mesoscopic Stoner instability.


Presystemic glucuronidation of morphine in humans and rhesus monkeys: subcellular distribution of the UDP-glucuronyltransferase in the liver and intestine.
Glucuronyltransferase (GT) activity was measured in the homogenate and in the nuclear, mitochondrial and microsomal fractions of liver and intestinal mucosa from man and rats. In man the average rate of morphine glucuronidation was 0.58 and 0.27 nmol/min per mg protein in the homogenates of the liver and intestinal mucosa, respectively. GT was evenly distributed in the different fractions of liver, whereas the major part of the activity in the intestinal mucosa was associated with the nuclear fraction. There was a larger difference between the GT activities in the microsomal fractions of the liver and intestine (0.68 and 0.06 nmol/min per mg, respectively), than between the homogenates of these organs. Similar results were obtained in the rat. GT activity in homogenates of the liver and intestine differed only three-fold whereas there was an 18-fold difference between the microsomal GT activities in these organs.


STRUCTURAL CHARACTERISTICS AND ANTIHYPERTENSIVE EFFECTS OF ANGIOTENSIN-I-CONVERTING ENZYME INHIBITORY PEPTIDES IN THE RENIN-ANGIOTENSIN AND KALLIKREIN KININ SYSTEMS.
The commercially available synthetic angiotensin-I-converting enzyme (ACE) inhibitors are known to exert negative side effects which have driven many research groups globally to discover the novel ACE inhibitors. Literature search was performed within the PubMed, ScienceDirect.com and Google Scholar. The presence of proline at the C-terminal tripeptide of ACE inhibitor can competitively inhibit the ACE activity. The effects of other amino acids are less studied leading to difficulties in predicting potent peptide sequences. The broad specificity of the enzyme may be due to the dual active sites observed on the somatic ACE. The inhibitors may not necessarily competitively inhibit the enzyme which explains why some reported inhibitors do not have the common ACE inhibitor characteristics. Finally, the in vivo assay has to be carried out before the peptides as the antihypertensive agents can be claimed. The peptides must be absorbed into circulation without being degraded, which will affect their bioavailability and potency. Thus, peptides with strong in vitro IC50 values do not necessarily have the same effect in vivo and vice versa. The relationship between peptide amino acid sequence and inhibitory activity, in vivo studies of the active peptides and bioavailability must be studied before the peptides as antihypertensive agents can be claimed.


Demonstration of human kidney differentiation antigens with monoclonal antibodies.
Six human differentiation antigens (EE24.6, EG9.11, EG14.1, EI16.1, EK8.1, EK17.1) have been defined using monoclonal antibodies obtained from mice immunized with embryonic kidney cells. Their histologic distribution was determined on frozen sections of embryonic, fetal, and adult human kidneys by immunofluorescence assay. EE24.6, an ureteral bud marker, was detected only on the germ layer of mature kidney urothelium. EG9.11 and EG14.1 were detected on the S-shaped bodies and also on the adult proximal convoluted tubule for the former and the glomerular basement membrane for the latter. EI16.1, a marker of condensed mesenchyme, was detected only on epithelial cells of adult proximal convoluted tubule. EK8.1 was found in the mesangium, connective tissue, and with particularly dense labeling in the basement membranes. This labeling pattern was present throughout renal organogenesis. EK17.1 recognized both cell and plasma human fibronectins. Staining for all antibodies was nearly identical in mesonephros and metanephros. These results demonstate that some antigens follow their embryonic destiny. They indicate an antigenic similarity between the mesonephros and the metanephros and, therefore, a very early appearance of these antigens. During differentiation, these antigens concentrate on more defined structures, and staining became increased with an increased degree of differentiation.


KCNV2-associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.
To investigate genotype-phenotype associations in patients with KCNV2 retinopathy. Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants-two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)-and parameters were compared. Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.


Relationship between apatite-forming ability and mechanical properties of bioactive PMMA-based bone cement modified with calcium salts and alkoxysilane.
Polymethylmethacrylate (PMMA)-based bone cement is used for the fixation of artificial joints in orthopaedics. However, the fixation is liable to loosen in the body, because the cement does not bond to living bone. So-called bioactive ceramics bond directly to living bone through the apatite layer formed on their surfaces in the body. We previously revealed that modification using gamma-methacryloxypropyltrimethoxysilane (MPS) and water-soluble calcium salts such as calcium acetate and calcium hydroxide was effective for providing the PMMA-based bone cement with apatite-forming ability in a simulated body fluid (SBF, Kokubo solution) that closely reproduces the body environment. However, the effect of the chemical reaction forming the apatite on the mechanical properties of the cements has not been clarified. The present work aimed to investigate this issue from the viewpoint of the interface structure between the apatite and the cement. The surface of the cement modified with calcium acetate and MPS was fully covered with newly formed apatite after soaking in Kokubo solution within 7 days, while half of the surface area of the cement modified with calcium hydroxide and MPS was covered with the apatite. The bending strength of the modified cements decreased after soaking in Kokubo solution. Porous structure was observed in the region about 50-100 microm in depth from the top surface because of release of the Ca2+ ions by both modified cements after soaking in Kokubo solution. The decrease in bending strength of the modified cements could be attributed to the formation of the pores. In addition, the pores on the top surfaces of the cements were filled with the newly formed apatite. The apatite formation would be effective not only for bioactivity but also for decreasing the reduction of mechanical strength.


Stimulus conflation and tuning selectivity in V4 neurons: a model of visual crowding.
Visual crowding is a fundamental constraint on our ability to identify peripheral objects in cluttered environments. This study proposes a descriptive model for understanding crowding based on the tuning selectivity for stimuli within the receptive field (RF) and examines potential neural correlates in cortical area V4. For V4 neurons, optimally sized, letter-like stimuli are much smaller than the RF. This permits stimulus conflation, the fusing of separate objects into a single identity, to occur within the RF of single neurons. Flanking interactions between such stimuli were found to be limited to the RF. The response to an optimal stimulus centered in the neuron's RF, is suppressed by the simultaneous presentation of flanking stimuli within the RF. The degree of suppression is a function of the neuron's stimulus tuning properties and the position of the flanker within the RF. A single neuron may show suppression or facilitation depending on the detailed stimulus conditions and the relationship to tuning selectivity. Loss of activity in the set of neurons tuned to a particular stimulus alters its overall representation and potential identification, thus forming a basis for visual crowding effects. The mechanisms that determine the outcome of conflation are associated with object identification, and are not some other independent visual phenomena.


Public awareness of risk factors and screening for colorectal cancer in Europe.
Colorectal cancer (CRC) is the commonest site for malignancy in Europe. The Commissioner for Health wishes to promote screening for colorectal, breast and cervical cancer in Europe. The aim of this study was to assess public knowledge of CRC in Europe and likely take up of free screening. To this end 20710 members of the public from 21 European countries were interviewed by means of a regular survey amongst consumers (Omnibus survey) using 13 stem questions. Forty-eight per cent thought the population were at equal risk of CRC, only 57% were aware of age and 54% of family history as risk factors. Although 70% were aware of dietary factors, only 30% knew that lack of exercise might be a risk factor. Only 51% had knowledge of CRC screening but 75% were 'very', or 'quite interested, in taking up faecal occult blood (FOB) screening if offered free. Barriers to screening were lack of awareness of risk (31%), youth (22%) and an un-anaesthetic test (19%). There was a big cultural difference in willingness of the public to discuss bowel symptoms: there was a major barrier in Finland (91%), Britain (84%), Luxembourg (82%), Poland (81%) and Portugal (80%); less of a barrier in Spain (49%), Italy (44%) and Iceland (39%). In conclusion, the challenge of achieving high compliance for CRC screening must be a major objective amongst EU member states and non-aligned countries of Europe in the next decade, because it is known that the non-compliant group are those at greatest risk of death from CRC. This study has shown that awareness of CRC is low in Europe and that an educational programme will be essential to achieve high compliance for CRC screening as a means of reducing deaths from bowel cancer.


A Combined PD-1/C5a Blockade Synergistically Protects against Lung Cancer Growth and Metastasis.
Disruption of the programmed cell death protein 1 (PD-1) pathway with immune checkpoint inhibitors represents a major breakthrough in the treatment of non-small cell lung cancer. We hypothesized that combined inhibition of C5a/C5aR1 and PD-1 signaling may have a synergistic antitumor effect. The RMP1-14 antibody was used to block PD-1, and an L-aptamer was used to inhibit signaling of complement C5a with its receptors. Using syngeneic models of lung cancer, we demonstrate that the combination of C5a and PD-1 blockade markedly reduces tumor growth and metastasis and leads to prolonged survival. This effect is accompanied by a negative association between the frequency of CD8 T cells and myeloid-derived suppressor cells within tumors, which may result in a more complete reversal of CD8 T-cell exhaustion. Our study provides support for the clinical evaluation of anti-PD-1 and anti-C5a drugs as a novel combination therapeutic strategy for lung cancer.Significance: Using a variety of preclinical models of lung cancer, we demonstrate that the blockade of C5a results in a substantial improvement in the efficacy of anti-PD-1 antibodies against lung cancer growth and metastasis. This study provides the preclinical rationale for the combined blockade of PD-1/PD-L1 and C5a to restore antitumor immune responses, inhibit tumor cell growth, and improve outcomes of patients with lung cancer. Cancer Discov; 7(7); 694-703. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 653.


Temporal evolution of neural activity and connectivity during microsleeps when rested and following sleep restriction.
Even when it is critical to stay awake, such as when driving, sleep deprivation weakens one's ability to do so by substantially increasing the propensity for microsleeps. Microsleeps are complete lapses of consciousness but, paradoxically, are associated with transient increases in cortical activity. But do microsleeps provide a benefit in terms of attenuating the need for sleep? And is the neural response to microsleeps altered by the degree of homeostatic drive to sleep? In this study, we continuously monitored eye-video, visuomotor responsiveness, and brain activity via fMRI in 20 healthy subjects during a 20-min visuomotor tracking task following a normally-rested night and a sleep-restricted (4-h) night. As expected, sleep restriction led to an increased number of microsleeps and an increased variability in tracking error. Microsleeps exhibited transient increases in regional activity in the fronto-parietal and parahippocampal area. Network analyses revealed divergent transient changes in the right fronto-parietal, dorsal-attention, default-mode, and thalamo-cortical functional networks. In all subjects, tracking error immediately following microsleeps was improved compared to before the microsleeps. Importantly, post-microsleep recovery in tracking response speed was associated with hyperactivation in the thalamo-cortical network. The temporal evolution of functional connectivity within the frontal and posterior nodes of the default-mode network and between the right fronto-parietal and default-mode networks was associated with temporal changes in visuomotor responsiveness. These findings demonstrate distinct brain-network-level changes in brain activity during microsleeps and suggest that neural activity in the thalamo-cortical network may facilitate the transient recovery from microsleeps. The temporal pattern of evolution in brain activity and performance is indicative of dynamic changes in vigilance during the struggle to stay awake following sleep loss.


Evaluation of hemostatic changes using n thromboelastography after crystalloid or colloid fluid administration during major orthopedic surgery.
The effects of Ringer lactate, 6% hydroxyethyl starch (HES) (130/0.4) or 4% succinylated gelatin solutions on perioperative coagulability were measured by thromboelastography (TEG). Seventy-five patients (ASA I-III) who were to undergo major orthopedic procedures performed under epidural anesthesia were included in the study. Patients were randomly divided into three groups of 25 each for the administration of maintenance fluids: group RL (Ringer lactate), group HES (6% HES 130/0.4), and group JEL (4% gelofusine solution). Blood samples were obtained during the perioperative period before epidural anesthesia (t1, baseline), at the end of the surgery (t2), and 24 h after the operation (t3). TEG data, reaction time (R), coagulation time (K), angle value (α), and maximum amplitude (MA) were recorded. TEG parameters changed from normal values in all patients. In group RL, R and K times decreased compared to perioperative values while the α angle and MA increased (P < 0.05). In group HES, R and K times increased, however, the α angle and MA decreased (P < 0.05). In group JEL, R time increased (P < 0.05), but K time, α angle and MA did not change significantly. In the present study, RL, 6% HES (130/0.4) and 4% JEL solutions caused changes in the coagulation system of all patients as measured by TEG, but these changes remained within normal limits.


A Multi-Centric Comparative Study Between Endoscopy-Assisted Laparoscopic Surgery (EALS) vs Laparoscopic Surgery for the Treatment of Gastric Duplication Cysts in Children.
To compare and analyze the therapeutic effects of endoscopy-assisted laparoscopic surgery (EALS) and laparoscopic surgery (LS) in the treatment of gastric duplication cysts (GDCs). We reviewed the clinical data of children with GDCs who underwent surgical treatment at Hubei Maternal and Child Health Hospital, Yijishan Hospital of Wannan Medical College, and Qingdao Women and Children's Medical Center from September 2014 to November 2022. The study comprised 29 children with GDCs, including 14 in the EALS group and 15 in the LS group. There was no significant difference between the two groups in terms of age, sex, weight, and cyst size characteristics. There was a significant difference between the two groups in terms of average surgical time (P>0.05), which was 1.100 ± 0.833 hours in the EALS group and 1.933 ± 0.159 hours in the LS group. There was a significant difference between the two groups (P<0.05) in average intraoperative blood loss, which was 7.93 ± 3.81 milliliters in the EALS group and 11.80 ± 2.72 milliliters in the LS group. There was a significant difference between the two groups (P<0.05) in average postoperative fasting time, which was 73.79 ± 8.36 hours in the EALS group and 114.1 ± 9.24 hours in the LS group. There was a significant difference between the two groups (P<0.05) in average postoperative hospital stay, which was 10.21 ± 4.25 days in the EALS group and 14.47 ± 4.36 days in the LS group. EALS technology can not only shorten surgical time, accurately locate GDCs, reduce injuries, and decrease the probability of complications but also achieve treatment goals safely and reliably.


Bulimia: a primary care approach.
More common than anorexia and less easily detected, bulimia typically begins as an effort to control weight. Although the prognosis is better than that for anorexia nervosa, a number of medical complications can arise related to the mode of purging. Some of these complications can have profound deleterious sequelae if not diagnosed and treated.


Preparation and stabilization of heparin/gelatin complex coacervate microcapsules.
The aims of this study are to optimize conditions for the preparation, stabilization, and harvesting of heparin/gelatin microcapsules prepared by complex coacervation. Microelectrophoresis and dry coacervate weight were used to determine the optimum conditions of pH and ionic strength for maximum heparin/gelatin coacervate yield. Heparin/gelatin microcapsules were formed by complex coacervation in the presence and absence of poly(1-vinyl-2-pyrrolidone) (PVP), which was used as a stabilizer. The microcapsules were collected using a spray-drying technique. Microcapsule particle size was analyzed using an AccuSizer optical sizer. Optimized conditions for maximum coacervate yield were pH 2.6, ionic strength 10 mM, and a 1:2 heparin/gelatin A ratio. PVP stabilized the heparin/gelatin coacervate droplets and reduced droplet aggregation during spray-drying. The mean particle diameter of the spray-dried coacervate droplets was lower in the presence of PVP and was unaffected by PVP concentration (in the range 0.5-2.0% w/w). Heparin/gelatin microcapsules, prepared under conditions optimized for maximum coacervate yield, were stabilized without the use of chemical cross-linking agents. Stabilization was achieved by a combination of the addition of PVP and spray-drying.


Latency and reactivation of varicella zoster virus infections.
Varicella zoster virus (VZV) is the causative agent of chickenpox (varicella) and shingles (zoster). The study of latency and reactivation has been hampered by the fact that the virus is strictly human and grows to low titres in tissue culture. Molecular biology techniques have opened a new era of VZV research. The site of VZV latency was determined to be sensory ganglia by Southern blotting and later by PCR technology. It was also demonstrated that the entire virus genome is present in the latently infected ganglia and that VZV is latent in multiple ganglia along the entire human neuraxis. Since the amount of latent VZV per cell is very low, the question of which cell type is involved in VZV latency could not be conclusively settled by the use of traditional in situ hybridization studies. However, we have now demonstrated the presence of latent VZV DNA in neurons only, by using a more sensitive method which employs a combination of in situ PCR and in situ hybridization. The transcriptional activity of VZV during latency is still not completely clear. Ganglia are small and the total amount of latent VZV is low, therefore conventional methods to detect latent VZV have proved limited. Nevertheless, the detection of a latent transcript from the SalI C region of the virus was demonstrated by Southern hybridization of cDNA synthesized from RNA isolated from latently-infected ganglia. Further studies have localized this transcript to the open reading frame of VZV gene 21. The study of VZV latency and reactivation has, until now, been dependent on the investigation of post mortem human tissue. However, simian varicella virus seems to be the simian counterpart to human VZV. The 2 viruses exhibit DNA homology as well as similarities in clinical, virological, and immunological features. Further studies of VZV infections may open new and possibly unpredictable opportunities in varicella virus research.


Clinical queries addressed in patients with systemic autoimmune diseases. Can cardiovascular magnetic resonance give the final solution?
To evaluate the potential of cardiovascular magnetic resonance (CMR) to answer queries, addressed in systemic autoimmune diseases (SAD). Thirty-six patients aged 52±6 years, (range 27-71) with SAD and suspected cardiac disease underwent CMR by a 1.5 T, after routine evaluation, including clinical, ECG and echocardiographic examination. Steady-state, free precession cines, STIR T2-W and late gadolinium enhanced (LGE) images were evaluated. Abnormal findings were detected by: clinical evaluation in 14/36, ECG in 17/36, echocardiography in 11/36 and CMR in 30/36 SAD. Clinical, ECG and echocardiographic examination could not assess cardiac disease acuity and lesions'pathophysiology. In contrary, CMR identified cardiac lesions' etiology, acuity, need for catheterization and heart disease persistence, even if SAD was quiescent. Clinical, ECG and echocardiographic abnormalities may suggest, but not always interpret cardiac involvement in SAD. CMR can help to identify both etiology and acuity of cardiac lesions and guide further diagnostic and/or therapeutic approach in these patients.


Cholinergic stimulation of arachidonic acid and phosphatidic acid metabolism in C62B glioma cells.
Glioma C62B cells were incubated for 18 h with [1-14C]arachidonic acid. Most (80%) of the added [1-14C] arachidonic acid was taken into the intracellular pool; less than 1% of the intracellular [1-14C]arachidonic acid remained unesterified; the rest was present in glycerophospholipids. Acetylcholine stimulation of the prelabeled cells resulted in the rapid accumulation of free [1-14C]arachidonic acid, presumably liberated by hydrolysis from phospholipids. Labeled unesterified [1-14C]arachidonic acid peaked by 90 s and returned to basal levels by 5 min. Paralleling the transient increase of unesterified [1-14C]arachidonic acid were increases in level of radioactivity in an unidentified lipoxygenase metabolite of arachidonic acid and of radioactive phosphatidic acid. The release of arachidonic acid induced by acetylcholine or carbachol was blocked by muscarinic but not nicotinic receptor antagonists; adrenergic or histaminergic receptor agonists were ineffective at stimulating arachidonic acid liberation. In contrast to the transient effects of stimulation with cholinergic agonists, stimulation with the divalent cation ionophore A23187 resulted in a linear increase in the accumulation of liberated arachidonic acid for at least 1 h. Furthermore, the pattern of metabolites synthesized from arachidonic acid in response to ionophore stimulation was more complex than that observed following cholinergic stimulation and included also several metabolites derived from cyclooxygenase activity. We conclude that muscarinic receptor agonists rapidly induce specific changes in arachidonic acid and phosphatidic acid metabolism in a glioma cell line and suggest that similar responses may occur in glial cells and play a physiologically significant role in neural metabolism.


Disenfranchised grievers--the GP's role in management.
Disenfranchised grief results from a loss that is not or cannot be openly acknowledged, publicly mourned, or socially supported. This article aims to explain the concept and varying presentations of disenfranchised grief and outlines the importance of the general practitioner's role. Preliminary quantitative results of a study of 15 cross cultural workers re-entering Australia are presented, showing more than half experiencing grief during re-entry and all having some form of disenfranchised grief. Disenfranchised grievers present with various symptoms, however, primary care has focused on mental illness, with little recognition of loss and grief issues, especially disenfranchised grief. Further research is required and currently underway to design and formally test a model that can be implemented within an Australian fee-for-service setting.


Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach.
C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [68Ga]Pentixafor in comparison to 68Ga-DOTA-D-Phe-Tyr3-octreotide ([68Ga]DOTATOC) and 18F-fluorodeoxyglucose ([18F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [68Ga]DOTATOC, [18F]FDG, and [68Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [68Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [18F]FDG revealed sites of disease in 10/12 and [68Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [68Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [68Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.


[Questionnaire methods used in the psychosomatic evaluation of tinnitus].
Tinnitus is a common disorder in ear, nose and throat practice. Not only muscular, vascular, neuronal, odiologic and ear pathologies, also psychological parameters contribute to the formation of tinnitus. Scales which evaluate patients' perception of tinnitus and how they are affected from tinnitus psychosomatically have gained increasing importance. Questionnaire studies are very assisting in terms of showing the degree of anxiety and depression experienced by the patients, diagnosis of the disease, evaluation of treatment efficacy, and patient follow-up. In this study, we reviewed the visual analog scale which measures the level of subjective perception in tinnitus, tinnitus evaluation questionnaires, and questionnaires measuring the level of quality of life and depression.


Biosimulation of drug metabolism--a yeast based model.
Computationally predicting the metabolic fates of drugs is a very complex task which is owed not only to the huge and diverse biochemical network in the living cell, but also to the majority of in vivo transformations that occur through the action of hepatocytes and gastro-intestinal micro-flora. Thus, xenobiotics are metabolised by more than a single cell type. However, the prediction of metabolic fates is definitely a problem worth solving since it would allow facilitate the development of drugs in a way less relying on animal testing. As a first step in this direction, PharmBiosim is being developed, a biosimulation tool which is based on substantial data reduction and on attributing metabolic fates of drug molecules to functional groups and substituents. This approach works with yeast as a model organism and is restricted to drugs that are mainly transformed by enzymes of the central metabolism, especially sugar metabolism. The reason for the latter is that the qualitative functioning of the involved biochemistry is very similar in diverse cell types involved in drug metabolism. Further it allows for using glycolytic oscillations as a tool to quantify interactions of a drug with this metabolic pathway.


AcMNPV enhances infection by ThorNPV in Sf21 cells and SeMNPV in Hi5 cells.
An expression cassette containing the DsRed2 gene, which encodes the red fluorescent protein (RFP), was inserted into the wide-host-range Autographa californica M nucleopolyhedrovirus (AcMNPV) at the polyhedrin locus (vAcDsRed2). An expression cassette containing the enhanced green fluorescent protein (EGFP) gene was inserted at the gp37 locus of the narrow-host-range Thysanoplusia orichalcea MNPV (ThorMNPV) and the p10 locus of Spodoptera exigua MNPV (SeMNPV) to produce vThGFP and vSeGFP, respectively. vThGFP and vSeGFP are poor at infecting Sf21 and Hi5 cells, respectively, whereas vAcDsRed2 is highly infectious to both cell lines. During co-infection, vAcDsRed2 enhanced vThGFP infection in Sf21 cells by approximately 20-fold, and it enhanced vSeGFP infection in Hi5 cells by more than 300-fold, as detected by fluorescence measurements. In contrast, vThGFP reduced vAcDsRed2 infection by 5.4-fold in Sf21 cells, while vSeGFP reduced vAcDsRed2 by 3.2-fold in Hi5 cells. Plaque assay data did not suggest viral recombination, but vThGFP plaques surrounded by vAcDsRed2 plaques were observed. A viral DNA replication assay performed by real-time quantitative PCR suggested that the detected fluorescence correlated with virus replication. Sf21 cells infected with vAcDsRed2 were resistant to superinfection by viruses of the same type expressing EGFP (vAcGFP). These results demonstrated that AcMNPV could enhance replication of ThorMNPV and SeMNPV in non-permissive cells without recombination.


Verification of pedigree information with paternity testing in Karacabey Merino sheep.
Complex tests of DNA sequences, genetic research, and the use of specific DNA polymorphisms as genetic markers have all advanced rapidly in recent years. It is widely used in DNA-based parental testing. Therefore, it has replaced the blood types routinely used in pedigree tests. The study aimed to evaluate the 14 microsatellite loci in the study in terms of paternity test parameters and to investigate the usability of the relevant loci in determining the parentage of the Karacabey Merino breed. In this study, paternity testing was performed on 5 rams of the Karacabey Merino breed and their probable 98 offspring using 14 microsatellite loci. A total of 290 alleles were observed in the study. The observed heterozygosity ratio (Ho) based on loci was between 0.82 and 0.98, and the expected heterozygosity ratio (He) was between 0.87 and 0.93. Individual exclusion probability (PE) values for the loci were calculated to be between 0.596 and 0.761, with combined exclusion probability (CPE) values of 0.99999995. According to the results of the study, paternity tests using 14 microsatellite markers in Karacabey Merino sheep can be used with high accuracy.


Sugar starvation- and GA-inducible calcium-dependent protein kinase 1 feedback regulates GA biosynthesis and activates a 14-3-3 protein to confer drought tolerance in rice seedlings.
Germination followed by seedling growth constitutes two essential steps in the initiation of a new life cycle in plants, and in cereals, completion of these steps is regulated by sugar starvation and the hormone gibberellin. A calcium-dependent protein kinase 1 gene (OsCDPK1) was identified by differential screening of a cDNA library derived from sucrose-starved rice suspension cells. The expression of OsCDPK1 was found to be specifically activated by sucrose starvation among several stress conditions tested as well as activated transiently during post-germination seedling growth. In gain- and loss-of-function studies performed with transgenic rice overexpressing a constitutively active or RNA interference gene knockdown construct, respectively, OsCDPK1 was found to negatively regulate the expression of enzymes essential for GA biosynthesis. In contrast, OsCDPK1 activated the expression of a 14-3-3 protein, GF14c. Overexpression of either constitutively active OsCDPK1 or GF14c enhanced drought tolerance in transgenic rice seedlings. Hence, our studies demonstrated that OsCDPK1 transduces the post-germination Ca(2+) signal derived from sugar starvation and GA, refines the endogenous GA concentration and prevents drought stress injury, all essential functions to seedling development at the beginning of the life cycle in rice.


Using prayer and scripture in a Christian-based stress-coping support group for church attendances: implications for professionals.
This study explored the participants' perceptions of using prayer and scripture in a Christian-based stress-coping support group (CSCSG). Twenty-eight church attendances were recruited from a Presbyterian Church in Taiwan. Based on the finding from qualitative analyses using a modified grounded theory approach, four themes related to the participants' learning experiences emerged. The four themes identified were stressful life events, stress-coping experiences, integration of Christian faith with life, and spiritual connection. A follow-up survey indicated that the participants perceived the experiences gained from the CSCSG as appropriate, important, functional, and constructive in coping with stress. Research questions and implications for church professionals are discussed.


Evaluation of dynamic compliance of lungs and disturbances of breathing mechanics in patients following laryngectomy for carcinoma of the larynx.
The purpose of study was to observe changes which may develop in the mechanics of breathing following laryngectomy in patients with carcinoma of the larynx as compared with the pre-operative conditions. The studies were carried out on a group of 29 patients, performing the measurements twice, i.e. before operation and after laryngectomy and tracheostomy. The measurements were done using a Godart Compliance-Test type 121 apparatus. The value of the coefficient of dynamic compliance of the lungs was determined together with the magnitude and type of work necessary to overcome respiratory resistance. It was found that after the operation the coefficient of dynamic compliance of the lungs increased by 63.7% while the total work of breathing decreased by 38.7% and the work necessary to overcome the elastic resistance of the lungs fell by 33.7% and that for overcoming the non-elastic resistance fell by 49.3%. The most significant changes in breathing mechanics observed after the operation concerned the ratio or breathing work necessary to overcome the non-elastic resistance to the total breathing work. This ratio was 43.35% pre-operatively and 34.11% post-operatively. The obtained results suggest that impairment of laryngeal patency caused by the tumour raises the breathing work and reduces the coefficient of dynamic compliance of the lungs due mainly to an increased non-elastic breathing resistance.


Treatment of painful neuropathy.
With the aging of the population, treatment of painful neuropathies is becoming more and more important for neurological practice. This short review highlights recent findings and current problems. In addition to tricyclic antidepressants and gabapentin, the reliability of which is established, some drugs have more recently been demonstrated to be efficacious: major and minor opioids, pregabalin, and serotonin-noradrenaline-reuptake inhibitors. In contrast, some other drugs have yielded disappointing results: memantine, mexiletine, topiramate, and - very recently - lamotrigine. Three main questions are currently being debated. Notwithstanding their proven efficacy, should opioids be used in chronic noncancer pain? In which patients should serotonin-noradrenaline-reuptake inhibitors be preferred to tricyclic antidepressants? What is the difference between pregabalin and gabapentin? The whole field suffers from important limitations that make evidence-based medical data hard to translate in clinical practice: most clinical trials were and still are focused on two conditions only (diabetic neuropathy and postherpetic neuralgia) and studies on polytherapy are insufficient. A large variety of drugs are being tried in the treatment of painful neuropathy. Neurologists now have a wide choice. Recent publications can help in choosing the best treatment course.


A novel role for methyl CpG-binding domain protein 3, a component of the histone deacetylase complex, in regulation of cell cycle progression and cell death.
Histone deacetylases (HDACs) form HDAC-associated complexes and play an essential role in transcriptional repression. The functional significance of HDAC-associated proteins in the progression of the cell cycle and in cell death remains to be established. Here, we investigated the molecular mechanisms by which methyl CpG-binding domain protein 3 (MBD3), a component of the HDAC complex, modulates these processes via its functional interplay with HDAC. Depletion of MBD3 induced an arrest at the G(2)/M transition and resulted in defective mitosis in cancer cells. These effects appear to be associated with the transcriptional modulation of key cell cycle-regulator genes, including CylinB1, Plk1, and Survivin. Chromatin immunoprecipitation analyses revealed that the transcription of these cell cycle regulators is modulated by MBD3, supporting its direct role in their transcriptional repression. These findings collectively support a role for MBD3 in cell cycle progression and cell death as a modulator of HDAC-mediated transcription.


The action of low- and high-chlorinated biphenyl mixture on prepubertal porcine ovary: steroid secretion and cells apoptosis.
To compare the effects on ovarian function of low chlorinated polychlorinated biphenyls (PCBs) mixture generally distributed at a faster rate and metabolised to a greater extent (Delor 103) with high chlorinated PCBs mixture which are accumulated in large amounts in biological samples (Delor 106). Theca interna and granulosa cells were isolated from prepubertal porcine follicles and initially cultured in M199/CS without test compounds for 24 hrs to allow for cell attachment to the wells. After 24 h, the medium was discarded and 0.3 ml of fresh M199 alone was added to the control culture, while Delor 103 or Delor 106 at concentrations of 0.02, 0.2 or 2 ng/ml medium were added to the cultures. For analysis of steroid levels, the media were collected after 24 hrs (single exposure) or 72 hrs (repeated exposure) and frozen at--20 degrees C. Additionally, after 72 hrs, LDL test was used to show the action of both mixtures on the cell viability and cells were used for the measurement of caspase-3 activity. An increase in testosterone secretion after the single exposure and strong stimulatory action on estradiol secretion was noted after permanent treatment with Delor 103. In Delor 106 treated cultures, antiestrogenic action after the single exposure and strong estrogenic action in permanently treated cells was observed. Both mixtures had no effect on cell viability and apoptosis. By stimulation of estradiol secretion from ovarian follicles in prepubertal animals, PCB mixture could be responsible for premature development of follicles and in consequence, premature sexual maturation.


pH-Triggered Aggregation of Gold Nanoparticles for Enhanced Labeling and Long-Term CT Imaging Tracking of Stem Cells in Pulmonary Fibrosis Treatment.
Gold nanoparticles (AuNPs) pose a great challenge in the development of nanotracers that can self-adaptively alter their properties in response to certain cellular environments for long-term stem cell tracking. Herein, pH-sensitive Au nanotracers (CPP-PSD@Au) are fabricated by sequential coupling of AuNPs with sulfonamide-based polymer (PSD) and cell-penetrating peptide (CPP), which can be efficiently internalized by mesenchymal stem cells (MSCs) and undergo pH-induced self-assembly in endosomes, facilitating long-term computed tomography (CT) imaging tracking MSCs in a murine model of idiopathic pulmonary fibrosis (IPF). Using the CPP-PSD@Au, the transplanted MSCs for the first time can be monitored with CT imaging for up to 35 days after transplantation into the lung of IPF mice, clearly elucidating the migration process of MSCs in vivo. Moreover, we preliminarily explored the mechanism of the CPP-PSD@Au labeled MSCs in the alleviation of IPF, including recovery of alveolar integrity, decrease of collagen deposition, as well as down-regulation of relevant cytokine level. This work facilitates our understanding of the behavior and effect of MSCs in the therapy of IPF, thereby providing an important insight into the stem cell-based treatment of lung diseases.


[Levels of anti-Legionella antibodies in a healthy Neapolitan population].
Legionella pneumophila was firstly recognized as the causative agent of a serious pneumonia about a decade ago. Since then a number of studies was carried out in order to define the epidemiological and clinical features of the microorganism. So far a high variability of the geographic distribution of the infection has been reported, with prevalences up to 50% of healthy populations. Therefore, a seroepidemiological survey was carried out on prevalence of Legionella pneumophila infections among healthy people in Naples. 562 serum specimens were randomly collected and examined by the indirect fluorescent antibody technique for antibodies against serogroups 1 to 6 of Legionella pneumophila, using 1:256 as the cut off titer. An overall prevalence of 23% was observed among the 562 persons tested. 24.5% among males and 21.9% among females had antibodies against Legionella pneumophila. There were no significant differences associated with sex and age, even though an apparent increase with age was observed. The highest prevalence was found for antibodies against serogroup 3 (9.4%). This finding was confirmed in all the age-sex groups, but among males aging between 21 and 40 years and among elderly people, 12.1% of persons tested had antibodies against only one serogroup of Legionella pneumophila, whilst 5.3%, 3.4% and 2.1% of subjects had antibodies against 2, 3 and 4 serogroups respectively. No serologic cross reactivity of Legionella pneumophila groups was found among seropositivities to different serogroups.


Leader Narcissism and Outcomes in Organizations: A Review at Multiple Levels of Analysis and Implications for Future Research.
Narcissists often pursue leadership and are selected for leadership positions by others. At the same time, they act in their own best interest, putting the needs and interests of others at risk. While theoretical arguments clearly link narcissism and leadership, the question whether leader narcissism is good or bad for organizations and their members remains unanswered. Narcissism seems to have two sides, a bright and a dark one. This systematic literature review seeks to contribute to the ongoing academic discussion about the positive or negative impact of leader narcissism in organizations. Forty-five original research articles were categorized according to outcomes at three levels of analysis: the dyadic level (focusing on leader-follower relationships), the team level (focusing on work teams and small groups), and the organizational level. On this basis, we first summarized the current state of knowledge about the impact that leader narcissism has on outcomes at different levels of analysis. Next, we revealed similarities and contradictions between research findings within and across levels of analysis, highlighting persistent inconsistencies concerning the question whether leader narcissism has positive or negative consequences. Finally, we outlined theoretical and methodological implications for future studies of leader narcissism. This multi-level perspective ascertains a new, systematic view of leader narcissism and its consequences for organizations and their stakeholders. The article demonstrates the need for future research in the field of leader narcissism and opens up new avenues for inquiry.


Recurrent respiratory papillomatosis: clinical characteristics and viral genotyping in a Brazilian population.
This study presents 25 cases of recurrent respiratory papillomatosis (RRP) that occurred in Sao Luis, Maranhao State, Northeast region, Brazil, between January 2007 and December 2018. Sociodemographic and clinical profile of patients as well as human papillomavirus (HPV) infection status were evaluated. Clinical and histopathological data were collected from the patients' medical records. For the HPV infection analysis, DNA was extracted and subjected to amplification by a nested polymerase chain reaction. Viral genotyping was performed by automated sequencing. The median age of patients was 12.40 ± 12.6. years, and the juvenile form of the disease (68%) was the predominant form of disease. Female participants were predominant (60%), and they were from cities located in the interior of the State (60%). The most common clinical manifestation was dysphonia; recurrence was observed in most cases (56%), and tracheostomy was necessary in seven patients (26.9%). When comparing the RRP forms, patients in the juvenile-RRP group had higher recurrence rates and need of tracheostomy than those in the adult-RRP group. The viral genotyping analysis revealed that 47.8% of patients had low-risk HPVs, whereas 13.1% had high-risk HPVs, and in 39.1% of patients the viral genotype was not obtained. HPV-6 was the most prevalent type and Juvenile-RRP was more prevalent in our population. HPV was present at a high rate, and HPV-6 was the predominant genotype. This study serves as the basis for further studies to be conducted in the Brazilian population. Our findings aid the better understanding of RRP, possibly suggesting some prognostic factors associated with the disease aggressiveness.


Incidence of injuries among amateur badminton players: A cross-sectional study.
The main aims of this study were, firstly, to investigate the frequency, location, and severity of injuries in amateur badminton players, and then to determine risk factors that may be associated with a higher incidence of injuries.A cross-sectional study, composed of 150 players drawn from the 2018 BWF European Senior Championships, was analyzed. The definitions and types of injury included in the study are based on those published in previous epidemiology studies.Among the 150 players analyzed, 221 injuries were observed, of which the highest proportion (40.3%, n = 89) affected the lower limb. Of these 22.44% were to the knee and 18.3% to the leg. In the upper limb, the shoulder was most frequently affected (11.8%). The mean rate of injuries per 1000 hours of play was 0.134 (standard deviation [SD]: 0.1), with 0.138 (SD: 0.1) among the male players and 0.131 (SD: 0.08) among the female players (P = .981: F = 0.001). The average duration of the injuries suffered exceeded 28 days in 34.5% of the cases.The incidence of injury varied according to sex and age. Most injuries affected the muscles, especially those of the knee (in the lower limbs) and the shoulder (in the upper limbs).


Glucosamine enhances body weight gain and reduces insulin response in mice fed chow diet but mitigates obesity, insulin resistance and impaired glucose tolerance in mice high-fat diet.
This study investigated the potential of glucosamine (GlcN) to affect body weight gain and insulin sensitivity in mice normal and at risk for developing diabetes. Male C57BL/6J mice were fed either chow diet (CD) or a high fat diet (HFD) and the half of mice from CD and HFD provided with a solution of 10% (w/v) GlcN. Total cholesterol and nonesterified free fatty acid levels were determined. Glucose tolerance test and insulin tolerance test were performed. HepG2 human hepatoma cells or differentiated 3T3-L1 adipocytes were stimulated with insulin under normal (5 mM) or high glucose (25 mM) conditions. Effect of GlcN on 2-deoxyglucose (2-DG) uptake was determined. JNK and Akt phosphorylation and nucleocytoplasmic protein O-GlcNAcylation were assayed by Western blotting. GlcN administration stimulated body weight gain (6.58±0.82 g vs. 11.1±0.42 g), increased white adipose tissue fat mass (percentage of bodyweight, 3.7±0.32 g vs. 5.61±0.34 g), and impaired the insulin response in livers of mice fed CD. However, GlcN treatment in mice fed HFD led to reduction of body weight gain (18.02±0.66 g vs. 16.22±0.96 g) and liver weight (2.27±0.1 vs. 1.85±0.12 g). Furthermore, obesity-induced insulin resistance and impaired Akt insulin signaling in the liver were alleviated by GlcN administration. GlcN inhibited the insulin response under low (5 mM) glucose conditions, whereas it restored the insulin response for Akt phosphorylation under high (25 mM) glucose conditions in HepG2 and 3T3-L1 cells. Uptake of 2-DG increased upon GlcN treatment under 5 mM glucose compared to control, whereas insulin-stimulated 2-DG uptake decreased under 5 mM and increased under 25 mM glucose in differentiated 3T3-L1 cells. Our results show that GlcN increased body weight gain and reduced the insulin response for glucose maintenance when fed to normal CD mice, whereas it alleviated body weight gain and insulin resistance in HFD mice. Therefore, the current data support the integrative function of the HBP reflecting the nutrient status of lipids or glucose and further implicate the importance of the pathway in insulin signaling for the regulation of metabolism.


The role of experiential avoidance in the relation between racial discrimination and negative mental health outcomes.
Objective Racial discrimination has been shown to be associated with negative mental health outcomes among people of color (POC), and students of color (SOC) specifically. The current study examines experiential avoidance (EA) as a potential moderator in the relation between discrimination and mental health outcomes. Sample: Two-hundred students of color at a large, public university in Northeastern United States. Methods: We evaluated the associations between racial discrimination frequency and stress appraisal (GEDS and GEDS-A), EA (AAQ), and the Depression, Anxiety, and Stress Scales (DASS). Results: Discrimination frequency and appraised stress were associated with each DASS subscale. EA moderated the relation between GEDS and depression, and between GEDS-A and the stress subscale. Conclusions: Discrimination frequency and appraised stress were positively associated with DASS subscales, and at low EA scores, frequency and appraised stress of discrimination were no longer associated with depressive or stress symptoms, respectively.


Metabolomic mechanisms of gypenoside against liver fibrosis in rats: An integrative analysis of proteomics and metabolomics data.
To investigate mechanisms and altered pathways of gypenoside against carbon tetrachloride (CCl4)-induced liver fibrosis based on integrative analysis of proteomics and metabolomics data. CCl4-induced liver fibrosis rats were administrated gypenoside. The anti-fibrosis effects were evaluated by histomorphology and liver hydroxyproline (Hyp) content. Protein profiling and metabolite profiling of rats liver tissues were examined by isobaric tags for relative and absolute quantitation (iTRAQ) approach and gas chromatography-mass spectrometer (GC-MS) technology. Altered pathways and pivotal proteins and metabolites were searched by integrative analysis of proteomics and metabolomics data. The levels of some key proteins in altered pathways were determined by western blot. Histopathological changes and Hyp content in gypenoside group had significant improvements (P<0.05). Compared to liver fibrosis model group, we found 301 up-regulated and 296 down-regulated proteins, and 9 up-regulated and 8 down-regulated metabolites in gypenoside group. According to integrative analysis, some important pathways were found, including glycolysis or gluconeogenesis, fructose and mannose metabolism, glycine, serine and threonine metabolism, lysine degradation, arginine and proline metabolism, glutathione metabolism, and sulfur metabolism. Furthermore, the levels of ALDH1B1, ALDH2 and ALDH7A1 were found increased and restored to normal levels after gypenoside treated (P<0.05). Gypenoside inhibited CCl4-induced liver fibrosis, which may be involved in the alteration of glycolysis metabolism and the protection against the damage of aldehydes and lipid peroxidation by up-regulating ALDH.


Hypoxia, via stabilization of the hypoxia-inducible factor HIF-1alpha, is a direct and sufficient stimulus for brain-type natriuretic peptide induction.
BNP (brain-type natriuretic peptide) is a cardiac hormone with systemic haemodynamic effects as well as local cytoprotective and antiproliferative properties. It is induced under a variety of pathophysiological conditions, including decompensated heart failure and myocardial infarction. Since regional hypoxia is a potential common denominator of increased wall stretch and myocardial hypoperfusion, we investigated the direct effects of hypoxia on BNP expression, and the role of the HIF (hypoxia-inducible transcription factor) in BNP regulation. Using an RNase protection assay we found a strong hypoxic induction of BNP mRNA expression in different cell lines and in cultured adult rat cardiomyocytes. Systemic hypoxia and exposure to 0.1% CO induced BNP expression in the rodent myocardium in vivo, although this was at a lower amplitude. BNP promoter-driven luciferase expression increased 10-fold after hypoxic stimulation in transient transfections. Inactivation of four putative HREs (hypoxia-response elements) in the promoter by site-directed mutagenesis revealed that the HRE at -466 nt was responsible for hypoxic promoter activation. A functional CACAG motif was identified upstream of this HRE. The HIF-1 complex bound specifically and inducibly only to the HRE at -466 nt, as shown by EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation). siRNA (small interfering RNA)-mediated knockdown of HIF-1alpha, but not HIF-2alpha, interfered with hypoxic BNP mRNA induction and BNP promoter activation, confirming that BNP is a specific HIF-1alpha target gene. In conclusion, BNP appears to be part of the protective program steered by HIF-1 in response to oxygen deprivation. Induction of BNP may therefore contribute to the potential benefits of pharmacological HIF inducers in the treatment of ischaemic heart disease and heart failure.


Using double gloves in surgical procedures: a literature review.
This article will present a critical review of the literature relating to the use of double gloves during surgery in order to identify best practice by using available resources and to improve health care. During surgery there is an increased risk of exposure to blood and, as a result, pathogens can be transferred through contact between the patient and surgical team. Health professionals working in the operating room are prone to frequent exposure to patients' blood and body fluids (Davanzo et al, 2008 ; Au et al, 2008 ; Myers et al, 2008). Several researchers have also demonstrated that the highest incidence of blood and body fluid exposure is in the operating room during surgical procedures (Ganczak et al, 2006 ; Myers et al, 2008 ; Naghavi and Sanati, 2009).


Short communication: Associations of udder edema with health, milk yield, and reproduction in dairy cows in early lactation.
Udder edema (UE) is a common condition of cows around calving, but its effects are not well characterized. The objectives of this study were to determine the associations of UE with the incidence of health disorders and with milk yield and reproduction in dairy cows in early lactation. On 3 commercial farms, UE was scored weekly on 1,346 cows, on a scale of 0 to 3, from 1 wk before calving to 3 wk after calving. Among cows with complete UE scores, 30% never had edema, 12% had edema only prepartum, 11% had it only postpartum, and 48% had edema prepartum and in at least 1 wk postpartum. Udder edema was associated with a greater incidence of clinical mastitis before 30 d in milk (5 vs. 2%). Subclinical ketosis (blood β-hydroxybutyrate ≥1.2 mmol/L) was more prevalent at wk 2 (11 vs. 6%) postpartum among cows with UE. No association was observed of UE with other diseases or culling in early lactation. In a subset of 912 cows with complete UE and 3 test-days of milk yield data, differences were observed in yield at test d 1 among UE categories. Cows with UE only prepartum produced less milk (39.9 kg/d) than cows with UE postpartum only (42.4 kg/d) and cows with UE both prepartum and postpartum (41.6 kg/d), none of which differed from cows without UE (40.9 kg/d). Udder edema was not associated with the prevalence of anovulation, or the time to or probability of pregnancy at first insemination, yet to 300 d in milk, cows that had UE postpartum had a shorter time from calving to pregnancy than cows without UE. The associations of UE with health and productivity are mixed, and the mechanisms underlying UE and its effects merit further investigation.


Physician assistants and bioterrorism preparedness.
Despite the resources dedicated since 2001 to training health providers in emergency and bioterrorism preparedness and response, the literature on the participation of physician assistants (PAs) is very limited. The purpose of this pilot study was to explore the training level and experiences of PAs in the diagnosis and treatment of chemical, biological, radiological, nuclear, and explosive agents that could be used in a bioterrorism attack. The study population consisted of licensed PAs in 37 northern Texas counties. Data were collected through mailed and web-based surveys. Response rate was 36%. More than half of the respondents (58.6%) had not participated in bioterrorism preparedness and response training. Results also indicated that the level of training has not increased since September 11, 2001. However, most respondents were receptive to the idea of participating in both preparedness training and response efforts. It is recommended that state agencies increase training opportunities for PAs in bioterrorism preparedness and response.


[Investigation and analysis on Wenchuan area earthquake trauma to ear, nose and throat].
The epidemic data of Wenchuan area earthquake trauma of ear, nose and throat were investigated. Affected families and sufferers of part of disaster area in Sichuan province in 2008 were investigated with emphasis on severity, cause and treatment of otorhinolaryngologic trauma. Two hundred and twenty-seven cases of otorhinolaryngologic trauma in survival crowd 3 days after earthquake were included in this study. Most of them were minor trauma or complex lesion. There were 185 cases of soft tissue wound in head and face, 13 cases of fracture of the nose, 18 cases of hemorrhage of the nose, 7 cases of fracture of the skull base, 4 cases of lacerated wound of the auricle. Diagnosis and management were carried out by medical aid post and field ambulance on different condition. The methods of treatment included debridement and suture of soft tissue wound and positioning of fracture. If there was serious injury and accompanied complex lesion, the patients should be sent to hospital after emergent treatment. Forty-six cases were treated in medical aid post, except 3 cases of complex lesion by transportation, 43 cases recovered in 5 to 10 days after treatment. One hundred and eighty-one cases were treated in field ambulance, except 3 cases with fracture of skull base by transportation. Among 31 hospitalized patients, 26 recovered and were discharged before 26th of may, 5 were still in ward because of complex lesion. Among 147 cases treated out of wards with soft tissue wound, 146 cases recovered and bone fracture in rehabilitation. 1 case of lacerated wound of auricle was infected with delayed healing. There were no complication in all cases. For earthquake trauma of the ear, nose and throat, emergent management are debridement, suture and positioning of fracture. For seriously injured patient, transportation to hospital in time can decrease complications and death rate.


Applying Quality Function Deployment Model in Burn Unit Service Improvement.
Quality function deployment (QFD) is one of the most effective quality design tools. This study applies QFD technique to improve the quality of the burn unit services in Ghotbedin Hospital in Shiraz, Iran. First, the patients' expectations of burn unit services and their priorities were determined through Delphi method. Thereafter, burn unit service specifications were determined through Delphi method. Further, the relationships between the patients' expectations and service specifications and also the relationships between service specifications were determined through an expert group's opinion. Last, the final importance scores of service specifications were calculated through simple additive weighting method. The findings show that burn unit patients have 40 expectations in six different areas. These expectations are in 16 priority levels. Burn units also have 45 service specifications in six different areas. There are four-level relationships between the patients' expectations and service specifications and four-level relationships between service specifications. The most important burn unit service specifications have been identified in this study. The QFD model developed in the study can be a general guideline for QFD planners and executives.


The Potential of Wine Lees as a Fat Substitute for Muffin Formulations.
The current study evaluates the prospect of wine lees (WL), a costless by-product from Amarone winemaking, as a fat replacer in muffin formulation. WL have elsewhere replaced sunflower oil, allowing the creation of 0, 25, 50, 75, and 100% fat-substituted muffins named ML0, ML25, ML50, ML75, and ML100, respectively. Batter rheology, in addition to the textural and colorimetric characteristics, the pore dimension, and the sensory aspect of the different formulations were evaluated. The batter consistency (K) of fat-replaced muffins was lower than that of the control, while the hardness and chewiness of the end products were higher. ML25 and ML50 samples reached the highest volume, while the baking loss decreased due to WL's fiber components. ML25, ML50, ML75, and ML100 accounted for caloric reductions of 9, 18, 22, and 26%, respectively, compared to full-fat muffins. Muffins with WL showed a darker crust and crumb as lightness (L*) decreased. Moreover, a* parameter increased with the increment of WL in the formulation, leading to a redder and less yellow-hued fat-replaced muffin. In conclusion, WL could effectively replace fat in the 25-50% range in muffins, achieving a final product with reduced calories, a higher dietary fiber content, higher volume, and promising sensory aspects.


A model for the transfer of passive immunity against Newcastle disease and avian influenza in specific pathogen free chickens.
Chicks possess maternally derived antibody (MDA) against pathogens and vaccines previously encountered by the dams. This passive immunity is important in early life, when the immune system is immature and unable to fight off infection. On the other hand, MDA can also affect the development of the immune system and interfere with vaccination against avian diseases such as Newcastle disease (ND) and avian influenza (AI). The effect of MDA is generally investigated by studying the progeny of vaccinated dams, which is time-consuming, poorly flexible and expensive. Moreover, the antibody titres obtained are not homogeneous. In this study, a model was developed to offer a faster, more reproducible and cheaper way to study passive immunity in specific pathogen free chickens by injection of a polyclonal serum into the egg yolk at embryonic day 14, combined with an intraperitoneal injection at day 1. A satisfactory model, with consistent, homogeneous antibody titres, as well as persistence close to natural passive immunity, could be obtained for ND virus. On the other hand, the application of this optimized protocol in an H5 AI context induced only a low artificial passive immunity compared with that described in the literature for the progeny of AI vaccinated dams. This artificial model should facilitate future studies regarding the effect of passive immunity on vaccine efficacy at a young age and its effect on immune system development.