Myocardial Work Index: A Novel Method for Assessment of Myocardial Function in South Asian Recreational Athletes.
We used a novel noninvasive method based on speckle-tracking echocardiography to evaluate myocardial performance in South Asian recreational athletes who completed a half marathon. Transthoracic echocardiography was performed on 24 recreational athletes 48 hours before they took part in a half marathon (premarathon), within 2 hours of half marathon completion (postmarathon), and 72 hours after completion. Clinical, laboratory, and echocardiographic variables were collected. Speckle-tracking echocardiography was performed in all subjects to characterize myocardial mechanics. Mean age of participants was 41.8 ± 7.4 years, and 23 (95.8%) were male. No subject had a prior history of coronary artery disease. Significant changes in pre- and postmarathon values suggested myocardial injury, including an increase in mean brain natriuretic peptide (BNP), an increase in left atrial volume, and an overall reduction in peak left ventricular global longitudinal strain. All subjects had a similar value of global work index, the average myocardial work, premarathon. Global work index did not change in 11 patients (Group 1), and global work index increased in 13 patients (Group 2) immediately postmarathon. Group 2 patients were noted to have higher heart rate, lower end-diastolic and end-systolic volumes, and higher BNP levels, suggesting myocardial stress. South Asian athletes completing a half marathon exhibited two different responses to the cardiac stress of the half marathon, as outlined by the use of myocardial work indices, a novel method for assessing cardiac performance.


Night-time blood pressure and target organ damage: a comparative analysis of absolute blood pressure and dipping status.
The prognostic significance of abnormal circadian blood pressure (BP) patterns is well established. Research to date has focused on both nocturnal dipping and absolute night-time BP levels; however, which of these variables should be the primary target for therapy remains unclear. The aim of this study is to determine whether dipping status or absolute night-time BP levels have a stronger association with subclinical target organ damage (TOD). The Mitchelstown Cohort was established to examine cardiovascular health in an adult population sample recruited from primary care. Night-time BP was categorized by dipping status. Subclinical TOD was defined as Cornell Product left ventricular hypertrophy (LVH) voltage criteria on ECG and urine albumin : creatinine ratio (ACR) at least 1.1 mg/mmol. Multivariable logistic regression analysis was used to assess the association between night-time BP and TOD. Of 2047 participants, 1207 (response rate 59%), underwent 24-h ambulatory BP monitoring. We excluded 161 studies due to incomplete data. Of 1046 participants, 178 (17%) had evidence of TOD. Each 10-mmHg rise in night-time SBP increased the odds of TOD. Odds ratio (OR) ACR at least 1.1 mg/mmol 1.5 [95% confidence interval (95% CI) 1.2-1.8] and OR LVH 1.4 (95% CI 1.1-1.8). Absolute BP level rather than dipping status may be a superior early marker of risk associated with night-time BP. Interventional studies are required to determine whether there is a benefit in specifically targeting absolute night-time BP levels to prevent clinically important outcomes.


Proteomic Analysis of Fetal Ovaries Reveals That Primordial Follicle Formation and Transition Are Differentially Regulated.
Primordial follicle formation represents a critical phase of the initiation of embryonic reproductive organ development, while the primordial follicle transition into primary follicle determines whether oestrus or ovulation will occur in female animals. To identify molecular mechanism of new proteins which are involved in ovarian development, we employed 2D-DIGE to compare the protein expression profiles of primordial follicles and primary follicles of fetal ovaries in pigs. Fetal ovaries were collected at distinct time-points of the gestation cycle (g55 and g90). The identified proteins at the g55 time-point are mainly involved in the development of anatomical structures [reticulocalbin-1 (RCN1), reticulocalbin-3 (RCN3)], cell differentiation (actin), and stress response [heterogeneous nuclear ribonucleoprotein K (HNRNPK)]. Meanwhile, at the g90 stage, the isolated proteins with altered expression levels were mainly associated with cell proliferation [major vault protein (MVP)] and stress response [heat shock-related 70 kDa protein 2 (HSPA2)]. In conclusion, our work revealed that primordial follicle formation is regulated by RCN1, RCN3, actin, and HNRNPK, while the primordial follicle transformation to primary follicle is regulated by MVP and HSPA2. Therefore, our results provide further information for the prospective understanding of the molecular mechanism(s) involved in the regulation of the ovarian follicle development.


Efficacy of a coaxial system with a compliant balloon catheter for navigation of the Penumbra reperfusion catheter in tortuous arteries: technique and case experience.
OBJECTIVE The authors describe a method by which they easily and atraumatically navigate a large-bore reperfusion catheter of the Penumbra system to an embolus by using a coaxial system with a compliant balloon catheter in patients with tortuous arteries. METHODS A retrospective review of the prospective endovascular database was performed to identify cases in which a coaxial system with a compliant balloon catheter (Scepter C, MicroVention/Terumo; or TransForm C, Stryker Neurovascular) and a large-bore reperfusion catheter of the Penumbra system (Penumbra, Inc.) was used. The authors achieved a stable guiding sheath position and delivered the coaxial system with a compliant balloon catheter and a large-bore reperfusion catheter. Then, the balloon was inflated somewhat when the distal tip of the balloon was slightly advanced from the tip of the reperfusion catheter, and together the coaxial system was advanced to an embolus over a 0.014-in guidewire, even around the corner. When the distal tip of the balloon catheter reached the embolus, the authors deflated the balloon and navigated the large-bore reperfusion catheter to the embolus. Finally, the aspiration of the embolus with the Penumbra MAX pump was begun. RESULTS Between May 2014 and September 2015, the authors used this technique in 17 cases: 16 cases of middle cerebral artery occlusion (including 5 cases of internal carotid artery occlusion) and 1 case of basilar artery occlusion (age range 36-88 years, mean age 74.7 years, 13 men). For the reperfusion catheter of the Penumbra system, the 5MAX ACE was used in 15 cases, and the 5MAX was used in 2 cases. As a compliant balloon catheter, the Scepter C was used in 16 cases, and the TransForm C was used in 1 case. The technique was successful in 16 cases (94.1%). No parent artery dissections were noted in any cases. Catheter-induced vasospasm was noted in 1 case, but the vasospasm was transient. CONCLUSIONS A coaxial system with a compliant balloon catheter can help safely and easily to navigate the large-bore reperfusion catheter of the Penumbra system to an embolus in patients with tortuous arteries.


Anxiety, stress, depression, and patients' responses to periodontal treatment: periodontists' knowledge and professional behavior.
Anxiety, stress, and depression affect the use of health care services, treatment decision-making, and responses to periodontal treatment. This study explored periodontists' confidence in detecting patient anxiety, stress, or depression, as well as their knowledge concerning the relationships between these factors and patients' pain, use of pain medication, and wound healing after periodontal treatment. In addition, this research surveyed if (and which) special accommodations were offered when treating patients with high levels of anxiety, stress, or depression. Data were collected from 171 members of the American Academy of Periodontology (response rate = 34.41%). Most respondents were male (82.2%), white (88.2%), and practiced in solo practices (60.9%). The respondents were more knowledgeable about the effects of anxiety and stress on pain, the use of pain medication, and wound healing than about the impact of depression on these outcomes. They agreed more strongly with statements that they were more confident in their ability to perceive when patients were anxious and stressed than when they were depressed. They also offered more special accommodations for patients with anxiety and stress than for patients with depression. The respondents were significantly less knowledgeable about the impact of depression on patients' responses to periodontal treatment than about the effect of anxiety and stress. Given the evidence concerning the relationships among depression, pain, pain medication use, and wound healing, it is important to educate periodontists about the role of anxiety and stress and the significance of depression on their patients' responses to periodontal therapy.


Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson's and distinction from Alzheimer disease.
Senile dementia of Lewy body type or Lewy body dementia (LBD), characterized neuropathologically by the presence of Lewy bodies in the brainstem and cortex, and in most cases neocortical senile plaques (but few or no tangles), bears a closer resemblance to Parkinson's (PD) than to Alzheimer disease (AD) in its cholinergic neurochemical pathology. Thus, reductions in the biochemical activity of choline acetyltransferase were generally more extensive in neo- as opposed to archicortical regions in LBD (especially hallucinating cases) and in PD, whereas muscarinic receptor binding was significantly increased in LBD and PD but not in AD. Nerve growth factor receptor (P75) assessed immunocytochemically in the archicortex were decreased in PD and, to a lesser extent, in LBD in conjunction with reductions of neuronal numbers in the nucleus of Meynert (Ch4), but were relatively spared in AD. These observations indicate that although AD is primarily associated with dysfunction of cholinergic axonal input to the cortex, LBD and PD are more likely to involve degeneration of the basal forebrain cholinergic system. Relevance of the findings in terms of aetiopathology and cholinergic treatment strategies is discussed.


Murine T lymphocyte specificity for African trypanosomes. I. Induction of a T lymphocyte-dependent proliferative response to Trypanosoma brucei.
A procedure which results in the specific activation of primed murine T lymphocytes was adapted for the study of T lymphocyte activation by the African trypanosome: Trypanosoma brucei. The assay calls for the in vivo priming of lymphocytes by the subcutaneous administration of parasites, followed by the co-cultivation in vitro of cells taken from the regional draining lymph nodes and the parasite. This co-cultivation results in a marked proliferation of lymphoid cells. The proliferation was shown to be specific for the parasite, and to be dependent on the presence of T lymphocytes and macrophages. Both the in vivo priming and the in vitro activation were shown to require the presence of living parasites. Various factors influencing the magnitude of the proliferative response were analysed. Of special interest is the observation that the time interval between in vivo priming and in vitro culture which results in a substantial proliferative response is quite short when compared to that seen with other antigens. Although lymph node cells from mice primed with T. brucei 1 to 2 weeks previously are able to mount a secondary proliferative response upon stimulation with T. brucei, cells taken 3 weeks after priming are unresponsive to an in vitro challenge with T. brucei. This unresponsiveness may be a result of the generalized immunosuppression seen in African trypanosomiasis. Thus, this method offers the potential for the study of specific T cell responsiveness in African trypanosome infections.


Dopamine-induced inhibition of Na+-K+-ATPase activity requires integrity of actin cytoskeleton in opossum kidney cells.
The present study evaluated the importance of the association between Na+-K+-ATPase and the actin cytoskeleton on dopamine-induced inhibition of Na+-K+-ATPase activity. The approach used measures the transepithelial transport of Na+ in monolayers of opossum kidney (OK) cells, when the Na+ delivered to Na+-K+-ATPase was increased at the saturating level by amphotericin B. The maximal amphotericin B (1.0 microg mL-1) induced increase in short-circuit current (Isc) was prevented by ouabain (100 microM) or removal of apical Na+. Dopamine (1 microM) applied from the apical side significantly decreased (29 +/- 5% reduction) the amphotericin B-induced increase in Isc, this being prevented by the D1-like receptor antagonist SKF 83566 (1 microM) and the protein kinase C (PKC) inhibitor chelerythrine (1 microM). Exposure of OK cells to cytochalasin B (1 microM) or cytochalasin D (1 microM), inhibitors of actin polymerization, from both cell sides reduced by 31 +/- 4% and 36 +/- 3% the amphotericin B-induced increase in Isc and abolished the inhibitory effect of apical dopamine (1 microM), but not that of the PKC activator phorbol-12,13-dibutyrate (PDBu; 100 nM). Colchicine (1 microM) failed to alter the inhibitory effects of dopamine. The relationship between Na+-K+-ATPase and the concentration of extracellular Na+ showed a Michaelis-Menten constant (Km) of 44.1 +/- 13.7 mM and a Vmax of 49.6 +/- 4.8 microA cm-2 in control monolayers. In the presence of apical dopamine (1 microM) or cytochalasin B (1 microM) Vmax values were significantly (P < 0.05) reduced without changes in Km values. These results are the first, obtained in live cells, showing that the PKC-dependent inhibition of Na+-K+-ATPase activity by dopamine requires the integrity of the association between actin cytoskeleton and Na+-K+-ATPase.


Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity.
Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a significant damage of cholinergic neurons concomitant with increased amyloid precursor protein (APP) expression in the cerebral cortex. However, the sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP expression in the damaged MBN are still elusive. Hence, we performed multiple-labeling immunocytochemistry for choline-acetyltransferase (ChAT), neuron-specific nuclear protein (NeuN) and APP 4, 24, and 48 h after NMDA infusion in the MBN. Whereas all cholinergic neurons were immunoreactive for NeuN, this neuronal marker also labeled a population of ChAT-immunonegative non-cholinergic neurons. Both neuron populations exhibited a similar degree of sensitivity to NMDA excitotoxicity that became evident as early as 4 h post-lesion. Cholinergic MBN neurons showed abundant APP immunoreactivity (approximately 90%), while only a fraction (approximately 20-30%) of non-cholinergic neurons expressed the protein. Remarkably, cholinergic but not non-cholinergic neurons retained their APP immunoreactivity after NMDA infusion. In conclusion, cholinergic MBN neurons are not preferentially sensitive to short-term excitotoxicity, but are one of the major sources of APP in the basal forebrain.


Acute effects of resistance training with local vibration.
The aim of this study was to verify the acute effects of the application of local vibration on upper limbs during resistance training on the number of maximum repetitions, metabolic and hormonal responses. 32 volunteers performed a maximum voluntary contraction test during a lat pulldown exercise. After the test, all volunteers underwent one conventional resistance training session and one resistance training session with local vibration. In both interventions, volunteers performed 4 sets with the highest possible number of repetitions of the lat pulldown exercise at 55% of maximum voluntary contraction. During the vibratory resistance training intervention, vibration was locally applied (20-Hz and 12-mm). During the conventional resistance training, volunteers performed the same procedures without vibration. Blood samples were taken at each experimental session before and 5 min after the end of each intervention. No significant differences were observed in number of maximum repetitions between the series of vibratory and conventional training. Serum testosterone, cortisol and lactate were significantly increased after 2 interventions. Vibratory resistance training induced greater increases in testosterone and lactate concentrations. No significant changes were found in creatine kinase, creatinine or urea concentration. These data indicate that local vibration increases the metabolic and anabolic response to the resistance training, without changing the training volume.


The cafeteria diet as a tool for studies of thermogenesis.
The cafeteria diet involves feeding experimental animals a choice of palatable human food items to stimulate energy intake, and has been used extensively to study diet-induced thermogenesis. In a recent commentary Moore has argued that this feeding regime is inappropriate for such studies because the nutrient composition cannot be controlled, many of the effects seen are due to protein or nutrient deficiency and accurate measurements of energy intake are difficult to achieve. We argue that all of these criticisms can be overcome by careful use of the feeding regime and well-controlled experiments. Gross nutrient composition of cafeteria diets can be modified over a wide range, and such studies demonstrate that the effects of protein deficiency can be clearly dissociated from those of hyperphagia. There is no experimental evidence for nutritional deficiency in cafeteria-fed animals even over very long periods of time. Furthermore, the alternatives suggested by Moore, i.e., presenting sucrose solutions to drink or high fat diets, suffer the same drawbacks of altered and often uncontrolled nutrient intake and yet produce little or no increase in energy intake. Criticism of the cafeteria diet is not justified simply because of its misuse by nutritionally naive experimenters. The value and validity of this feeding regime is further supported by the enormous impact it has made on our understanding of energy balance regulation and thermogenesis.


Monoamine oxidase inhibitory activities of heterocyclic chalcones.
Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values <1 μM for the inhibition of MAO-B, with all compounds exhibiting higher affinities for MAO-B compared to the MAO-A isoform. The most potent MAO-B inhibitor (4h) displays an IC50 value of 0.067 μM while the most potent MAO-A inhibitor (4e) exhibits an IC50 value of 3.81 μM. It was further established that selected heterocyclic chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders.


The effect of botulinum toxin A on the vocal symptoms of spastic dysarthria: a case study.
The vocal symptoms of spastic dysarthria and spasmodic dysphonia have many similar features. Botulinum toxin has been used effectively to treat spasmodic dysphonia. This study was designed to determine what vocal changes occur in an individual with spastic dysarthria following Botulinum toxin A injection into the thyroarytenoid muscles. Measures were obtained preinjection and three times postinjection. Acoustic and aerodynamic results were comparable to those reported for individuals with spasmodic dysphonia. The most marked change was increased DC airflow. Despite persistent breathiness, the participant reported great satisfaction with the result, particularly because of her more appropriate loudness. In addition, everyday listeners perceived significantly less listener burden and more relaxed and pleasant vocal quality postinjection.


[Extramedullary plasmacytoma with multiple metastasis following a maxillary plasmacytoma].
A 67-year old man noticed swelling of left maxillary in October 1992. Surgical biopsy of the left maxillary tumor revealed the plasmacytoma at the department of oral surgery. The Tumor disappeared after radiation therapy. He was admitted with dizziness and tarry stool in June 1994. We found left cervical and abdominal paraaortic lymph node swellings by the computer tomography. He died inspite of chemotherapy in December. Autopsy showed that plasma cells diffusely and nodularly invased in all alimentary tract with multiple ulcerations. Invasion was also observed in the liver, lungs, thyroid, heart, kidneys, and adrenals. The plasma cells in the liver showed IgG kappa type by tissue immunostain. Diffuse invasion of extramedullary plasmacytoma is very rare in alimentary tract and many other organs. This case may be value to delineate the nature of this disease.


Endoscopic ultrasonography-guided bi-lateral biliary drainage: A case series study.
Biliary obstruction is preferentially managed by endoscopic retrograde cholangiopancreatography (ERCP). However, after ERCP failed, alternatives include percutaneous transhepatic drainage, surgery and more recently, endoscopic ultrasonography (EUS)-guided hepaticogastrostomy. The limitation of this technique is that the drainage is restricted to the left side. The aim of this study is to describe a new method of drainage of both hepatic ductal systems by hepaticogastrostomy in patients with hilar obstruction. Nine prospectively patients were included, all with hilar obstruction (metastasis of a pancreatic adenocarcinoma n = 4, cholangiocarcinoma n = 1, gallbladder cancer n = 2 and metastasis from a pancreatic neuroendocrine tumor n = 2). A total of four patients had previously Whipple surgery and the others five had duodenal involvement by the tumor. The topography of the stenosis varied from Bismuth type 2 (n = 7) and hilar infiltration in the others two. All of them were submitted a three-step drainage. The first one consisted in a transgastric EUS-guided puncture of the left-side bile duct with a 19 gauge needle, insertion of a 0.0035 inch guide wire which was positioned at the right biliary tree crossing the bile bifurcation. After a dilatation with 6 Fr cystotome, a non-covered self-expandable metal stent was placed communicating the right and left biliary ducts. Finally, a second stent, partially covered, was inserted at the left biliary duct, with the distal part inside the previously stent and the proximal edge positioned at the stomach. Successful drainage was observed in seven patients, two of them presented abdominal pain during the first 72 h. One patient developed sepsis and death 7 days after the procedure and the other one had drainage failure. Jaundice was reduced significatively in seven patients and a chemotherapy was started in 6/7 patients. This pilot study shows the feasibility of this new technique to drain the right biliary duct in patients with hilar obstruction, with few major complications rates.


Long-term efficacy and safety of tamsulosin for benign prostatic hyperplasia.
The treatment approach for recent benign prostatic hyperplasia has changed since the recent introduction of medical therapies with evidence-based efficacy. The choice of treatment to achieve symptom relief must take into account factors such as clinical benefits, potential for morbidity, probable long-term efficacy, and costs. alpha(1)1-Adrenergic receptor antagonists are the primary therapy for patients with benign prostatic hyperplasia presenting with lower urinary tract symptoms and are used by 80% of physicians as the first-line agent to treat this common condition in the aging male. Tamsulosin has been available in the United States since 1997 and has demonstrated its efficacy. Of patients completing 6 years of treatment, 80.7% demonstrated consistent positive response with extremely low incidence of orthostasis, the response being greatest during the first year and largely maintained over the following 5 years.


An Introduction to the North American Clinical Trials Network for Spinal Cord Injury Special Edition: Reflections on Accomplishments and a Look to the Future.
The North American Clinical Trials Network (NACTN) has been established as a network of translational clinical research centers focused on traumatic spinal cord injury (SCI) with the goals of facilitating clinical translational research, promotion of enhanced clinical care protocols including the principle of early surgery for SCI, and improving outcomes for individuals with acute SCI. Since its foundation in 2004 by Dr. Robert Grossman, NACTN has evolved into a powerful multi-stakeholder consortium of eight neurosurgical department faculties at university-affiliated institutions in the United States and Canada, a data management center, and a pharmacological center. To date, high-quality data from more than 1000 patients have been prospectively collected, providing us with a strong body of evidence surrounding SCI epidemiology, the natural history, and complications of acute and subacute SCI management. Key accomplishments of NACTN are summarized in this Focus issue. They include the launch, in collaboration with AO Spine, of the international, multi-center, placebo-controlled, Phase III Riluzole in Acute Spinal Cord Injury Study (RISCIS) that recruited 192 patients. While the primary analyses did not achieve the predetermined endpoint of efficacy for Riluzole, likely related to insufficient power, pre-planned secondary analyses demonstrated that all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with Riluzole showed significant gains in functional recovery. The Focus Issue also includes a detailed analysis of the pharmacokinetics and pharmacodynamics of riluzole in the setting of acute SCI (RISCIS-PK study). Additional achievements include key contributions to the evidence supporting the role of early surgery in acute SCI, and a better understanding of the impact of complications on the outcomes of SCI. Future directions of NACTN will build on past accomplishments and focus on enhanced collaborations with other SCI networks, advanced analytics to examine large datasets, and a greater focus on chronic SCI.


Antibody engineering toward high-sensitivity high-throughput immunosensing of small molecules.
Clinical and environmental analyses often require immunochemical detection and quantification of small molecules (haptens) that are available as biomarkers. However, the affinity ceilings of conventional anti-hapten antibodies, which are produced by immunizing animals, prevent subfemtomole-range determinations with competitive immunoassay formats. "Sandwich-type" noncompetitive (immunometric) assays allow for sensitive determinations of macromolecules (subattomole-range) and the direct relationship between analyte amount and signal intensity provides higher accessibility to modern high-throughput sensing systems. Unfortunately, sandwich-type assays require that analytes have at least two epitopes, and thus are not applicable to haptens. Antibody engineering, i.e., genetic manipulation of antibody molecules, could provide artificially improved reagents that enable us to overcome these limitations. In this review, we summarize recent successful developments and applications of engineered antibodies for sensitive and high-throughput hapten sensing.


Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C.
Some NK cell subpopulations may be involved in the modulation of fibrogenesis in the liver. The aim of the study was to evaluate the relationship between the number and phenotype of NK cell subsets in peripheral blood (PB) and total NK cell percentage, population density and the degree of liver fibrosis of patients infected with hepatitis C virus (HCV+). The study group consisted of 56 HCV+ patients, divided into two subgroups: patients with mild or moderate fibrosis and patients with advanced liver fibrosis or cirrhosis (F ≥ 3 in METAVIR classification). The preparations were stained with H-E and AZAN staining. NK cells were targeted with anti-CD56 antibody and identified automatically in situ using the DakoVision system. Assessment of different NK cell subsets in PB was performed with the flow cytometry technique. In the PB of HCV+ patients with advanced liver fibrosis, there was a lower proportion of CD62L+; CD62L+/CD94++; CD27+; CD127+/CD27+ and CXCR3+/CD27+ NK subsets, as compared to patients with mild/moderate liver fibrosis. The results also showed no association between total PB NK cell level and total intrahepatic NK cell population density between patients with mild/moderate fibrosis and with advanced liver fibrosis. However, positive correlations between the PB levels of CD94+ and CD62L+ NK cell subsets and the intrahepatic total NK cell percentage and population density in the liver, irrespectively to the extent of fibrosis, were observed. Additionally, positive correlation was found between the PB CXCR3+/CD94+ NK cell percentages and intrahepatic NK cell percentages in patients with advanced hepatic fibrosis. Lower blood availability of specific NK subsets in patients with chronic type C hepatitis might be a cause of progression of liver fibrosis via insufficient control over hepatic stellate cells.


Relationships between metal compartmentalization and biomarkers in earthworms exposed to field-contaminated soils.
Partitioning tissue metal concentration into subcellular compartments reflecting toxicologically available pools may provide good descriptors of the toxicological effects of metals on organisms. Here we investigated the relationships between internal compartmentalization of Cd, Pb and Zn and biomarker responses in a model soil organism: the earthworm. The aim of this study was to identify metal fractions reflecting the toxic pressure in an endogeic, naturally occurring earthworm species (Aporrectodea caliginosa) exposed to realistic field-contaminated soils. After a 21 days exposure experiment to 31 field-contaminated soils, Cd, Pb and Zn concentrations in earthworms and in three subcellular fractions (cytosol, debris and granules) were quantified. Different biomarkers were measured: the expression of a metallothionein gene (mt), the activity of catalase (CAT) and of glutathione-s-transferase (GST), and the protein, lipid and glycogen reserves. Biomarkers were further combined into an integrated biomarker index (IBR). The subcellular fractionation provided better predictors of biomarkers than the total internal contents hence supporting its use when assessing toxicological bioavailability of metals to earthworms. The most soluble internal pools of metals were not always the best predictors of biomarker responses. metallothionein expression responded to increasing concentrations of Cd in the insoluble fraction (debris + granules). Protein and glycogen contents were also mainly related to Cd and Pb in the insoluble fraction. On the other hand, GST activity was better explained by Pb in the cytosolic fraction. CAT activity and lipid contents variations were not related to metal subcellular distribution. The IBR was best explained by both soluble and insoluble fractions of Pb and Cd. This study further extends the scope of mt expression as a robust and specific biomarker in an ecologically representative earthworm species exposed to field-contaminated soils. The genetic lineage of the individuals, assessed by DNA barcoding with cytochrome c oxidase subunit I, did not influence mt expression.


Pendant-Type Helicene Oligomers with p-Phenylene Ethynylene Main Chains: Synthesis, Reversible Formation of Ladderlike Bimolecular Aggregates, and Control of Intramolecular and Intermolecular Aggregation.
Pendant-type (P)-helicene oligomers with p-phenylene ethynylene main chains up to a tetramer were synthesized by a building block method. The (P)-tetramer reversibly formed a ladderlike bimolecular aggregate upon cooling and disaggregated upon heating in (trifluoromethyl)benzene. Two bis(tetramer)s, in which two (P)-tetramers were connected by hexadecamethylene linkers, were also synthesized. The head-to-tail bis(tetramer) formed an intramolecular aggregate, and the head-to-head bis(tetramer) formed an intermolecular aggregate in toluene. The results suggest the antiparallel aggregation structure of the pendant-type (P)-tetramers. The structure of the linker was proven to be effective in controlling intramolecular and intermolecular aggregations.


Deregulation of the HOXA9/MEIS1 axis in acute leukemia.
HOXA9 is a homeodomain transcription factor that plays an essential role in normal hematopoiesis and acute leukemia, in which its overexpression is strongly correlated with poor prognosis. The present review highlights recent advances in the understanding of genetic alterations leading to deregulation of HOXA9 and the downstream mechanisms of HOXA9-mediated transformation. A variety of genetic alterations including MLL translocations, NUP98-fusions, NPM1 mutations, CDX deregulation, and MOZ-fusions lead to high-level HOXA9 expression in acute leukemias. The mechanisms resulting in HOXA9 overexpression are beginning to be defined and represent attractive therapeutic targets. Small molecules targeting MLL-fusion protein complex members, such as DOT1L and menin, have shown promising results in animal models, and a DOT1L inhibitor is currently being tested in clinical trials. Essential HOXA9 cofactors and collaborators are also being identified, including transcription factors PU.1 and C/EBPα, which are required for HOXA9-driven leukemia. HOXA9 targets including IGF1, CDX4, INK4A/INK4B/ARF, mir-21, and mir-196b and many others provide another avenue for potential drug development. HOXA9 deregulation underlies a large subset of aggressive acute leukemias. Understanding the mechanisms regulating the expression and activity of HOXA9, along with its critical downstream targets, shows promise for the development of more selective and effective leukemia therapies.


Potassium voltage‑gated channel subfamily E member 4 facilitates the malignant progression of colon cancer by enhancing EGF containing fibulin extracellular matrix protein 2 expression.
Colon cancer is a highly invasive and metastatic cancer with a poor prognosis. The University of Alabama at Birmingham Cancer data analysis portal (UALCAN) database indicates that potassium voltage-gated channel subfamily E member 4 (KCNE4) is highly expressed in colon cancer tissues. UALCAN data also show that KCNE4 expression is positively associated with individual cancer stages and negatively associated with patient survival. Therefore, the aim of the current study was to elucidate the functional role of KCNE4 in the biological behaviors of colon cancer cells and to investigate the underlying molecular mechanism. The gene EGF containing fibulin extracellular matrix protein 2 (EFEMP2) was found to be positively correlated with KCNE4 in colon cancer based on analysis performed using the LinkedOmics database; notably, upregulated EFEMP2 expression has been reported to be closely associated with the malignant phenotypes of colon cancer cells. The differences in the expression levels of KCNE4 and EFEMP2 between human colon cancer and normal colonic mucosa cell lines were assessed via reverse transcription-quantitative PCR and western blot assays. In addition, the proliferation, migration and invasion of colon cancer cells were determined using Cell Counting kit-8, colony formation, would healing and Transwell assays, and a co-immunoprecipitation assay was performed to confirm the interaction between KCNE4 and EFEMP2. The results of the study demonstrated that KCNE4 and EFEMP2 are markedly upregulated in colon cancer cells. In addition, KCNE4 interacted with and bound to EFEMP2. The suppressive effects of KCNE4 knockdown on the proliferation, colony formation, migration and invasion of colon cancer cells were attenuated by EFEMP2 overexpression. On the basis of these findings, it may be concluded that KCNE4 acts as an oncogene in colon cancer via the promotion of EFEMP2 expression.


Mulberry (Morus alba) leaves as human food: a new dimension of sericulture.
Mulberry leaf is commonly used for sericulture in almost every part of the world but its potential to be utilized for human consumption is not well recognized. This paper deals with development of mulberry leaf powder and its use with wheat flour to develop paratha, the most common food item of breakfast and dinner in the Indian diet. The optimum ratio of the mulberry leaf powder and wheat flour (MLP-WF) mix for preparation of paratha on the basis of sensory quality was found to be 1:4. The protein quality of the MLP-WF mix was estimated by measuring the Protein Efficiency Ratio, and was found to be 1.82 against a casein diet for which a value of 2.44 was observed. The in vivo toxic effect of mix was studied and no adverse effect on the growth of internal organs of rats (heart, liver, kidney and testes) was found. The storage stability of the mix was estimated for a period of 2 months in polyethylene bags at room temperature. A non-significant difference was observed between paratha prepared from fresh and stored mix. This indicated that mix can be stored for a period of 2 months at room temperature without loss of quality.


A novel role for Mms2 in the control of spontaneous mutagenesis and Pol3 abundance.
Mms2 is a ubiquitin E2-variant protein with a very well-documented function in the tolerance pathway that protects both human and yeast cells from the lethal and mutagenic effects of DNA damage. Interestingly, a high expression level of human MMS2 is associated with poor survival prognosis in different cancer diseases. Here we have analyzed the physiological effects of Mms2 overproduction in yeast cells. We show that an increased level of this protein causes a spontaneous mutator effect independent of Ubc13, a cognate partner of Mms2 in the PCNA-polyubiquitinating complex responsible for the template switch. Instead, this new promutagenic role of Mms2 requires Ubc4 (E2) and two ubiquitin ligases of HECT and RING families, Rsp5 and Not4, respectively. We have established that the promutagenic activity of Mms2 is dependent on the activities of error-prone DNA polymerase ζ and Rev1. Additionally, it requires the ubiquitination of K164 in PCNA which facilitates recruitment of these translesion polymerases to the replication complex. Importantly, we have established also that the cellular abundance of Mms2 influences the cellular level of Pol3, the catalytic subunit of replicative DNA polymerase δ. Lack of Mms2 increases the Pol3 abundance, whereas in response to Mms2 overproduction the Pol3 level decreases. We hypothesize that increased levels of spontaneous mutagenesis may result from the Mms2-induced reduction in Pol3 accumulation leading to increased participation of error-prone polymerase ζ in the replication complex.


Self-assembled monolayers improve protein distribution on holey carbon cryo-EM supports.
Poor partitioning of macromolecules into the holes of holey carbon support grids frequently limits structural determination by single particle cryo-electron microscopy (cryo-EM). Here, we present a method to deposit, on gold-coated carbon grids, a self-assembled monolayer whose surface properties can be controlled by chemical modification. We demonstrate the utility of this approach to drive partitioning of ionotropic glutamate receptors into the holes, thereby enabling 3D structural analysis using cryo-EM methods.


Can Uremia and Hemodialysis Affect Plasma Levels of Circulating TNF-alpha.
It is well known that uremia is associated with increased susceptibility to infection. In addition, patients on haemodialysis (HD) experience a variety of dialysis associated complications, both acute and chronic, many of them having features similar to acute phase response. Immunoregulatory cytokines such as tumor necrosis factor-a (TNF-a) have been implicated in the pathogenesis of immunological as well as inflammatory diseases. Thus, TNF-a levels could be expected to be high in uremic patients as well as in HD patients. We investigated the plasma levels of TNF-a in 17 patients with renal failure, seven patients with chronic renal failure (CRF) before commencement of HD and 10 patients maintained on regular HD. Eight age matched healthy subjects were studied as normal control. All CRF patients, who were not yet on dialysis, had high plasma levels of TNF-a (mean + SD 71.33 + 33.25 pg/ml). Out of the HD group, TNF-a plasma levels were not detectable in five patients and in the remaining five, TNF-a plasma level (mean + SD 21.06 + 7.72) were comparable to the normal controls (mean + SD 21 + 7.87). Our findings suggest that factors related to uremia, but not to HD, are responsible for high TNF-a plasma levels in these patients and that, HD probably has a beneficial effect by removal and/or neutralising of uremic toxins.


Pharmacokinetics of florfenicol in turkey plasma, lung tissue, and pulmonary epithelial lining fluid after single oral bolus or continuous administration in the drinking water.
Florfenicol (FF) is registered for treatment of bovine and swine respiratory diseases. Although, turkeys often suffer from bacterial respiratory tract infections, there is no registered formulation based on FF for poultry available in Europe. The aim of this study was to evaluate the pharmacokinetic behavior of FF in turkeys in plasma, lung tissue, and pulmonary epithelial lining fluid (PELF).The concentration and pharmacokinetic characteristics of FF in plasma, lung tissue, and PELF in turkeys were determined, either after a single oral bolus (30 mg/kg body weight, BW) or during and after continuous drinking water medication (30 mg/kg BW/d for 5 d). Plasma, lung tissue, and PELF samples were collected at different intervals after administration, and FF was quantified by liquid chromatography-tandem mass spectrometry. After single bolus administration, FF was rapidly absorbed in plasma (the time to maximum concentration, tmax, was 1.02 h) and distributed to the respiratory tract (mean tmax = 1.00 h). The mean t1/2el in plasma and lung tissue was similar, around 6 h, whereas it was slightly higher in PELF, namely, 8.7 hours. After oral bolus dosing, the mean maximum concentration in plasma was twice as high as in the lung tissue, 4.26 μg/mL and 2.64 μg/g, respectively, while in PELF it was much lower, 0.39 μg/mL. During continuous drinking water medication, lung FF concentrations were slightly higher than plasma concentrations, with lung/plasma ratios of 2.01 and 1.27 after 24 h and 72 h, respectively. FF was not detected in PELF during continuous drinking water medication.


Participation of membrane adenylyl cyclase in heparin-induced capacitation in cryopreserved bovine spermatozoa.
The aim of this work was to study the participation of membrane adenylyl cyclase in heparin-induced capacitation in cryopreserved bovine spermatozoa. Sperm suspensions were incubated in Tyrode's albumin lactate pyruvate medium in the presence of heparin (10 IU ml(-1) ) or forskolin (1-75 μm), a well-known membrane adenylyl cyclase activator. The participation of membrane adenylyl cyclase was confirmed using a specific inhibitor, 2',5'-dideoxyadenosine (6-25 μm). Spermatozoa capacitated with forskolin (25 μm) were incubated with bovine follicular fluid to evaluate their ability to undergo acrosome reaction. Capacitation percentages were determined by the fluorescence technique with chlortetracycline, and true acrosome reaction was determined by trypan blue and differential interferential contrast. The forskolin concentrations employed had no effect on progressive motility or sperm viability. Capacitation values induced by 25-μm forskolin treatment (27.80 ± 2.59%) were significantly higher respect to the control (4.80 ± 1.30%). The inhibitor 2',5'-dideoxyadenosine prevented forskolin-induced capacitation and significantly diminished capacitation induced by heparin. Follicular fluid induced physiological acrosome reaction in spermatozoa previously capacitated with 25-μm forskolin (P < 0.05). Forskolin acts as a capacitation inducer and involves the participation of membrane adenylyl cyclase as part of the intracellular mechanisms that lead to capacitation in cryopreserved bovine spermatozoa.


Abrupt response of chemical weathering to Late Quaternary hydroclimate changes in northeast Africa.
Chemical weathering of silicate rocks on continents acts as a major sink for atmospheric carbon dioxide and has played an important role in the evolution of the Earth's climate. However, the magnitude and the nature of the links between weathering and climate are still under debate. In particular, the timescale over which chemical weathering may respond to climate change is yet to be constrained at the continental scale. Here we reconstruct the relationships between rainfall and chemical weathering in northeast Africa for the last 32,000 years. Using lithium isotopes and other geochemical proxies in the clay-size fraction of a marine sediment core from the Eastern Mediterranean Sea, we show that chemical weathering in the Nile Basin fluctuated in parallel with the monsoon-related climatic evolution of northeast Africa. We also evidence strongly reduced mineral alteration during centennial-scale regional drought episodes. Our findings indicate that silicate weathering may respond as quickly as physical erosion to abrupt hydroclimate reorganization on continents. Consequently, we anticipate that the forthcoming hydrological disturbances predicted for northeast Africa may have a major impact on chemical weathering patterns and soil resources in this region.


Imprinted polymer layer for recognizing double-stranded DNA.
A method of preparing a thin polymer layer able to recognize double-stranded DNA (dsDNA) was developed by using 2-vinyl-4,6-diamino-1,3,5-triazine (VDAT) as a functional monomer for creating a DNA-imprinted polymer. The formation of hydrogen bonds between VDAT and A-T base pairs in dsDNA was confirmed by measuring the effects of VDAT on the melting point and the NMR and CD spectra of dsDNA. An imprinted polymer that can recognize dsDNA of the verotoxin gene was prepared by polymerizing VDAT, acrylamide, a crosslinking agent, and the template verotoxin dsDNA on a silanized glass surface. The specificity of this polymer layer for binding verotoxin dsDNA was investigated by using fluorescent-labelled dsDNAs. The fluorescence intensity of the polymer layer after binding verotoxin dsDNA was twice as high as after binding oligo(dG)-oligo(dC), indicating that verotoxin dsDNA was preferentially bound to the polymer imprinted with verotoxin dsDNA. The kinetics of verotoxin dsDNA binding to the imprinted polymer were analyzed by surface plasmon resonance measurements. The dissociation constant (KD) was low, of the order of 10(-9)M.


Multidisciplinary surgical treatment of presacral meningocele and teratoma in an adult with Currarino triad.
Currarino syndrome (CS) is a rare genetic condition that presents with the defining triad of anorectal malformations, sacral bone deformations, and presacral masses, which may include teratoma. Neurosurgeons are involved in the surgical treatment of anterior meningoceles, which are often associated with this condition. The accepted surgical treatment is a staged anterior-posterior resection of the presacral mass and obliteration of the anterior meningocele. This case involved a 36-year-old female who presented with late onset of symptoms attributed to CS (e.g., presacral mass, anterior sacral meningocele, and sacral agenesis). She successfully underwent multidisciplinary single-stage approach for treatment of the anterior sacral meningocele and resection of the presacral mass. This required obliteration of the meningocele and closure of the dural defect. One year later, her meningocele had fully resolved. While late presentations with CS are rare, early detection and multidisciplinary treatment including single-state anterior may be successful for managing these patients.


Relationships between serological groups and deoxyribonucleic acid homology groups in Bacteroides fragilis and related species.
The serological properties of antigens extracted from strains of Bacteroides fragilis and related species belonging to several different deoxyribonucleic acid homology groups were investigated. Antisera prepared against Formalin-treated whole cell suspensions of representative strains were tested against cell suspensions, cell wall preparations, and extracts of homologous and heterologous strains by using agglutination, immunodiffusion, and hemagglutination techniques. Serological results indicated that the species were antigenically distinct, although minor cross-reactions were observed. Homology groups, including the two B. fragilis subgroups, were relatively homogeneous, although the presence of serotypes within each homology group was suggested. Immunodiffusion tests demonstrated, however, that each possessed a mosaic antigen composition; at least 6 antigenic determinants could be demonstrated in B. fragilis 2553, and up to 10 were found in B. fragilis 2393. Hemagglutination tests using antigen extracts also indicate a mosaic of antigens in each strain.


[Giant-cell retinal dysplasia in microphthalmos].
Six-year-old girl presents unilateral moderate microphthalmos. After enucleation ocular histopathological exam shows multiple ocular structures anomalies at both anterior and posterior poles; the most important anomalies were localised at the level of retina, vitreous, and iridocorneal angle, and they were represented by retinal dysplasia with giant cells, persistence of the primitive vitreous, congenital cataract, Rieger syndrome.


[Ways in which new surgical techniques have influenced the increasing use of cardiosurgery].
During the last decade new strategies and equipment have gained popularity in the clinical and experimental setting of cardiac surgery. Little is known about the real impact of these new approaches on the development of heart surgery. The present paper aimed to characterize, through a multicenter evaluation, the state of the art in Italy. A survey of all active heart surgery centers in Italy (both public and private institutions) was conducted through a questionnaire. Diffusion, effectiveness and future perspective of these new surgical techniques were asked. Off-pump coronary artery surgery, myocardial revascularization in patients with low left ventricular ejection fraction, left ventricular surgical remodeling, mitral valve reconstruction, ministernotomic approach in aortic surgery and the use of laser, robots, heart port-access and endoscopy were the strategies under investigation. The use of laser, heart port-access and endoscopy were considered to have a poor impact due to proved ineffectiveness and/or technical complexity. Indications and long-term outcomes of off-pump coronary artery surgery are still under active debate. The introduction of new prosthetic materials has resulted in the widespread diffusion of mitral valve reconstruction approaches with concomitant widening of the indications. Similarly there is wide consensus on myocardial revascularization in patients with low ejection fraction. Ministernotomic strategies and ventricular remodeling are slowly but progressively gaining acceptance. Cardiac surgery in Italy is characterized by a great effort on new research field. Traditional approaches are still preferred unless new techniques have proved effective after strict scientific evaluation.


Trauma transfers and definitive imaging: patient benefit but at what cost?
Many patients undergo computed tomography (CT) scan before transfer to definitive care. Despite this, studies are often repeated on arrival to the trauma center. We evaluated a policy to provide formal in-house interpretation of images performed at outside hospitals. A 3-month retrospective analysis was performed. Two groups were compared. Patients in the in-house interpretation (IHI) group underwent in-house interpretation of outside images. Those images not meeting criteria were placed in the comparison group without in-house radiologic interpretation. Demographics, CT scan data, billing and productivity loss, and extrapolated cancer risk reduction were analyzed. There were no significant differences in demographic or injury data. Fewer total CT scans were performed in the IHI group (223 vs. 320, P = 0.04). The IHI group underwent fewer repeated CT scans (25 vs. 62, P = 0.02; odds ratio [OR], 0.53). Fewer patients were exposed to repeat CT scans (17 vs. 32; OR, 0.48). Total hospital billings decreased by $188,285 ($4,592/patient) in the IHI group. Uncaptured work relative value units totaled 152.19 (3.71/patient) in the IHI group. Radiation exposure decreased by 8 per cent. Use of outside hospital imaging as the definitive evaluation of injured patients is safe and results in an overall decrease in radiation exposure and healthcare cost.


Determination of incidence and risk factors for postsclerotherapy telangiectatic matting of the lower extremity: a retrospective analysis.
Telangiectatic matting are vessels less than 0.2 mm in diameter that may appear after sclerotherapy treatment of varicose or telangiectatic leg veins. It is a complication about which very little epidemiologic data have been formally accrued. Therefore, a retrospective analysis was conducted by reviewing the records of 2120 patients in a private practice setting. The overall incidence of telangiectatic matting in our patient population was 16%. To identify risk factors, in-depth comparative analysis of the databases of 160 of the patients who developed telangiectatic matting and a control group of 160 nonmatting patients was performed. Significantly more patients in the matting group were overweight, on hormones during treatment, and had both a family history and a longer duration of spider veins (p less than 0.05). Additionally, the matting group had a significantly higher proportion of people noting onset of their veins after excess hormonal states, relative to before excess hormonal states, than the nonmatting group. Age and excessive standing did not differ significantly between the two groups. The results of this study provide objective, predictive risk factors for the development of telangiectatic matting.


Trastuzumab not for ductal carcinoma in situ?
Ductal carcinoma in situ (DCIS) is a preinvasive breast lesion accounting for approximately 30% of all newly detected breast cancers in the US. DCIS has been separated into two groups by architecture (comedo versus noncomedo) and nuclear grade. The expression of biological markers in DCIS, however, would reflect the true biologic potential of the lesion. Patients with estrogen receptor (ER)-negative, human epidermal growth factor-2 (HER-2)-positive DCIS pose a treatment challenge. They are not candidates for tamoxifen; trastuzumab has an undetermined role in DCIS. In this report, we present a case of a 45-year-old woman diagnosed with invasive breast cancer and ER-negative/HER-2-positive DCIS who developed recurrence and progression of DCIS as manifested by a new palpable mass while receiving trastuzumab as part of adjuvant treatment for invasive breast cancer. The potential clinical implications are discussed.


[Influence of cancer chemotherapy on conjunctival epithelium and goblet cells].
Evaluation of different types of chemotherapy schemes administered in lung, breast and bowel cancer on conjunctival epithelium and goblet cells morphology. 36 patients (72 eyes) were enrolled to the study. Patients were divided into three groups depending on type of cancer and chemotherapy: group I - patients diagnosed with non- small cells lung cancer treated with PE schema (cisplatin, etoposide), group II - with breast cancer treated with FAC schema (fluorouracil, doxorubicin, cyclophosphamide), group Ill - bowel cancer treated with FU/LV schema (fluorouracil, leucovorin). Examinations were performed before chemotherapy and after Il'th, IV'th, VI'th chemotherapy cycle. Conjuntival specimen were obtained with exfoliative cytology, stained with PAS and hematoxyline. Statistically significant deterioration of conjunctival epithelium and goblet cells in all the groups in each time of examination (p<0.001) was observed. Alterations were aggravated with duration of chemotherapy. Before chemotherapy all the patients had normal epithelium and goblet cells (grade 0 or 1 according to the Nelson's scale). Conjunctival cells status gradually deteriorated and altered from the normal glandular epithelium to the squamous cells epithelium through the process of squamous metaplasia. In further chemotherapy cycles each patient (1,0 fraction) had abnormal morphology of epithelium and goblet cells (grade 2 or 3 of Nelson's scale). Chemotherapy induces squamous metaplasia of epithelium and the reduction of number of conjunctival goblet cells. This abnormalities were time dependent and increased with duration of chemotherapy and were not depended on type of chemotherapy scheme.


Epilepsy in gliomas: recent insights into risk factors and molecular pathways.
The purpose of this review is to discuss the molecular pathways governing the development of seizures in glioma patients. The intrinsic epileptogenicity of the neuronal component of glioneuronal and neuronal tumors is the most relevant factor for seizure development. The two major molecular alterations behind epileptogenicity are the rat sarcoma virus (RAS)/mitogen-activated protein kinase / extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol-3-kinase / protein kinase B / mammalian target of rapamycin (P13K/AKT/mTOR) pathways. The BRAFv600E mutation has been shown in experimental models to contribute to epileptogenicity, and its inhibition is effective in controlling both seizures and tumor growth. Regarding circumscribed astrocytic gliomas, either BRAFv600E mutation or mTOR hyperactivation represent targets of treatment. The mechanisms of epileptogenicity of diffuse lower-grade gliomas are different: in addition to enhanced glutamatergic mechanisms, the isocitrate dehydrogenase (IDH) 1/2 mutations and their product D2-hydroxyglutarate (D2HG), which is structurally similar to glutamate, exerts excitatory effects on neurons also dependent on the presence of astrocytes. In preclinical models IDH1/2 inhibitors seem to impact both tumor growth and seizures. Conversely, the molecular factors behind the epileptogenicity of glioblastoma are unknown. This review summarizes the current state of molecular knowledge on epileptogenicity in gliomas and highlights the relationships between epileptogenicity and tumor growth.


The influence of chest tube size and position in primary spontaneous pneumothorax.
Optimal chest tube position in the pleural cavity is largely unexplored for the treatment of primary spontaneous pneumothorax (PSP). We investigated whether type, size and position of chest tubes influenced duration of treatment for PSP. A retrospective follow-up study of all patients admitted with PSP over a 5-year period. Traumatic, iatrogenic and secondary pneumothoraxes were excluded. Gender, age, smoking habits, type and size of chest tube used (pigtail catheter or surgical chest tube) were recorded from the patients' charts. All chest X-rays upon admittance and immediately following chest tube placement were retrieved and re-evaluated for size of pneumothorax (categorized into five groups) and location of the chest tube tip (categorized as upper, middle or lower third of the pleural cavity). All data were analysed in a Cox proportional hazards regression model. We identified 134 patients with PSP. Baseline characteristics were similar for patients treated with surgical chest tubes and pigtail catheters. Chest tube duration was not significantly influenced by position of the chest tube tip, but was significantly longer in females (P<0.01), patients <30 years (P=0.01), larger pneumothoraxes (P<0.01), use of surgical chest tubes (P=0.03) and a history of previous pneumothorax (P=0.04). Contrary to common belief and guidelines recommendation the position of a chest tube in the pleural cavity did not significantly influence chest tube duration, but it was significantly longer in patients who were treated with a surgical chest tube.


The gastroenterology and endoscopic nursing delegation to China: summary of our professional and cultural experience.
In October 2004, the authors had the opportunity to participate in an international professional and cultural exchange program, coordinated by the People to People Ambassador Programs. A delegation of gastroenterology nurses traveled to China. During the trip, the authors visited hospitals in Beijing, Chongquing, and Kunming. The hospital visits included tours of endoscopy units and other departments within these hospitals. The two groups engaged in dialogue to better understand each other and develop a better understanding of practice standards, education of nurses, and healthcare delivery systems in their respective countries. Formal presentations and informal dialogue were held at each professional exchange and served as the method of discussing the respective professional perspectives on gastroenterology nursing.


Transcriptome-wide analysis of alternative routes for RNA substrates into the exosome complex.
The RNA exosome complex functions in both the accurate processing and rapid degradation of many classes of RNA. Functional and structural analyses indicate that RNA can either be threaded through the central channel of the exosome or more directly access the active sites of the ribonucleases Rrp44 and Rrp6, but it was unclear how many substrates follow each pathway in vivo. We used CRAC (UV crosslinking and analysis of cDNA) in growing cells to identify transcriptome-wide interactions of RNAs with the major nuclear exosome-cofactor Mtr4 and with individual exosome subunits (Rrp6, Csl4, Rrp41 and Rrp44) along the threaded RNA path. We compared exosome complexes lacking Rrp44 exonuclease activity, carrying a mutation in the Rrp44 S1 RNA-binding domain predicted to disfavor direct access, or with multiple mutations in Rrp41 reported to impede RNA access to the central channel in vitro. Preferential use of channel-threading was seen for mRNAs, 5S rRNA, scR1 (SRP) and aborted tRNAs transcripts. Conversely, pre-tRNAs preferentially accessed Rrp44 directly. Both routes participated in degradation and maturation of RNAPI transcripts, with hand-over during processing. Rrp41 mutations blocked substrate passage through the channel to Rrp44 only for cytoplasmic mRNAs, supporting the predicted widening of the lumen in the Rrp6-associated, nuclear complex. Many exosome substrates exhibited clear preferences for a specific path to Rrp44. Other targets showed redundancy, possibly allowing the efficient handling of highly diverse RNA-protein complexes and RNA structures. Both threading and direct access routes involve the RNA helicase Mtr4. mRNAs that are predominately nuclear or cytoplasmic exosome substrates can be distinguished in vivo.


Regulatory T cells and systemic lupus erythematosus.
Regulatory T cells, especially CD4+CD25+ T cells, "natural killer" T cells and gammadelta T cells, are central in the maintenance of peripheral tolerance and the protection from the development of autoimmune diseases. Numerical or functional modifications of these cell populations were demonstrated to lead to the breakdown of tolerance and the emergence of autoimmunity. Involvement of regulatory T cells in the pathogenesis of systemic autoimmune diseases, such as systemic lupus erythematosus, might be of first importance. In murine models and patients with lupus, these regulatory T cells seem to be reduced in number. Functional deficiencies have also been described in a few studies. A better knowledge of regulatory T cell functional properties in systemic autoimmune diseases is essential to manipulate these cells and hopefully to restore immune tolerance.


Barriers and facilitators of physical function, activity, sports and exercise in children and adolescents with spinal pain: a protocol for a systematic review and meta-ethnography.
Spinal pain is one of the leading causes of disability, with the incidence of adolescent back pain estimated at 20%. Multiple barriers influence exercise participation in adolescents. However, there remains a lack of literature surrounding patients' choice to exercise, perceived barriers and facilitators of exercise, and their relationship to participant demographics. The aim of this systematic review with meta-ethnography will be to identify the barriers and facilitators of exercise participation among adolescents with thoracic or lower back pain (LBP). The secondary aim will be to identify any trends in barriers and facilitators of exercise between different demographic groups within children or adolescents under 18 years. The seven-phase process identified by Noblit and Hare's meta-ethnography approach will be used. A comprehensive electronic search of databases (AMED, CINAHLplus, EMBASE, MEDLINE, SCOPUS, Nursing & Allied Health, PubMed, PsycINFO, SPORTDiscus, Social Science Database) will be completed during April 2022. Grey literature using reference lists, websites and search engines will also be searched in accordance with Peer Review of Electronic Search Strategies (PRESS) guidelines. Inclusion criteria include: (A) qualitative studies, (B) participants under 18 years experiencing thoracic or LBP, (C) identification of barriers and facilitators of exercise participation in exercise, sports or physical activity and (D) primary research. This systematic review with meta-ethnography review aims to generate theories of behaviours and interpret significance across multiple studies. This process aims to develop future physiotherapeutic behavioural interventions, inform service provision and identify possible future research questions. No ethical approval was required due to the nature of using previously published work to form a systematic review paper. This systematic review and meta-ethnography will be disseminated through both conference presentations and journal publications. No funding was received for this review. CRD42022314796.


Multidetector CT for Restaging Locally Advanced Esophageal Squamous Cell Carcinoma and Assessing Therapeutic Response to Neoadjuvant Chemotherapy.
Objective To assess the diagnostic accuracy of multidetector CT (MDCT) for restaging of patients with esophageal squamous cell carcinoma (SCC) after neoadjuvant chemotherapy and determine the feasibility of CT for assessing the treatment response and evaluating the prognosis. Methods Totally 135 patients with esophageal SCC who had received neoadjuvant treatment and surgery in Beijing Cancer Hospital from September 2005 to December 2011 were enrolled in this study. TN staging was performed using CT for lesions before and after neoadjuvant treatment by two radiologists,and the tumor regression grade (TRG) and pathological TRG were also assessed. Based on preoperative CT TN restaging results,the patients were defined as responders with T0-2N0 after therapy,non-responders with T3-4N+,and patients with undefined response (T3-4N0 or T0-2NN+). Results The accuracy of T and N restaging using CT was 50%,54% (κ=0.718,P <0.001) and 59%,56% (κ=0.753,P <0.001) by two radiologists,respectively. TRG from CT was predicted correctly in 27% of patients. Pathological TRG was an accurate predictor of survival (χ 2=8.13,P=0.04). There was no significant trend toward better survival for lower CT TRG (χ 2=1.17,P=0.286). Among 135 patients with esophageal cancer,19 patients(14.07%) were responders ,46 patients(34.07%) were non-responders,and 70 patients (50.37%)were patients with undefined response . The overall survival rates of responders,non-responders and patients with undefined response were 71.5%,47.3%,and 18.5%,respectively. The overall survival of responders was better than that of patients with undefined response (χ2=1.518,P=0.63) and non-responders(χ2=12.04,P=0.0016),but the overall survival of patients with undefined response was better than that of non-responders (χ2=14.468,P=0.0003). Conclusion sMDCT restaging after neoadjuvant treatment can not accurately predict pathological stage in esophageal SCC. The CT T and N restaging has certain clinical value in assessing the response to neoadjuvant chemotherapy in patients with esophageal cancer and predicting the prognosis.


A Retrospective Cohort Analysis of Pharmacologic VTE Prophylaxis and Padua Prediction Score in Hospitalized Patients With Chronic Liver Disease.
Coagulopathy resulting from chronic liver disease (CLD) creates uncertainty regarding the risks and efficacy of pharmacologic venous thromboembolism (VTE) prophylaxis (ppx). We aim to describe patient characteristics associated with VTE ppx and the clinical impact of ppx in hospitalized patients with CLD. This retrospective study included patients with CLD, an international normalized ratio (INR) of ≥1.3, and hospital stay of ≥72 hours. Baseline characteristics, incidence of VTE, and major bleeding were compared between patients given ppx and those not given ppx. Of 300 patients with CLD included, 157 (52%) received VTE ppx. Characteristics associated with VTE ppx were lower activated partial thromboplastin time, INR, bilirubin, and Model for End-Stage Liver Disease (MELD) score as well as a higher Padua Prediction Score, hemoglobin, platelet count, and antiplatelet use. VTE occurred in 12 (7.6%) ppx versus 4 (2.8%) non-ppx patients ( P = .07). Major bleeding occurred in 47 (30%) ppx versus 49 (34.3%) non-ppx patients ( P = .46). Ppx was not associated with VTE or bleeding outcomes by multivariate regression. The use of VTE ppx in hospitalized patients with CLD was not associated with a lower risk of VTE nor did it increase the risk of bleeding. Further studies examining the risks and benefits of VTE ppx in this population are needed.


Congenital spinal cord anomalies: a pictorial review.
Development of spinal canal and its contents occurs in a much regulated fashion. Aberration at any stage of development namely gastrulation, primary neurulation, secondary neurulation, and retrogressive differentiation can result in a specific abnormality. Spinal cord anomalies or spinal dysraphism is a heterogeneous group containing some entities that are obvious at birth and many that are discovered only after imaging for neurological symptoms or signs. Congenital spinal tumors are closely related and present either as an external mass or imaging abnormalities. Radiological imaging plays a crucial role in both diagnosis and postoperative evaluation of these patients. Magnetic resonance imaging is the modality of choice. Computed tomography is used in a limited fashion. Plain radiographs are the initial imaging in patients presenting with abnormal curvatures of spine. No other central nervous system abnormality requires as systematic an approach as spinal dysraphism. The authors present a review of both common and rare anomalies that they encountered for a 3-year period in their institute, a tertiary care level hospital.


Demonstration of zero optical backscattering from single nanoparticles.
We present the first experimental demonstration of zero backscattering from nanoparticles at optical frequencies as originally discussed by Kerker et al. [ Kerker , M. ; Wang , D. ; Giles , C. J. Opt. Soc. A 1983 , 73 , 765 ]. GaAs pillars were fabricated on a fused silica substrate and the spectrum of the backscattered radiation was measured in the wavelength range 600-1000 nm. Suppression of backscattering occurred at ~725 nm, agreeing with calculations based on the discrete dipole approximation. Particles with zero backscattering provide new functionality for metamaterials and optical antennas.


Ten-year clinical, developmental, and intellectual follow-up of children with congenital cytomegalovirus infection without neurologic symptoms at one year of age.
This study was undertaken to ascertain whether children with congenital cytomegalovirus (CMV) infection at birth, but without neurologic symptoms at 1 year of age, differed in somatic, neurologic, developmental, or intellectual status from matched control children at long-term follow-up. Congenital CMV infection, as demonstrated by isolation of the virus within the first week of life, was diagnosed in 44 (0.5%) of 9806 infants. From this basic CMV-infected population, children who developed neurologic disturbances including sensorineural deafness before 1 year of age were excluded (n = 7), as were those unwilling to participate (n = 2). Congenitally infected infants (n = 35) and matched control infants (n = 53) were followed up clinically and neurologically. At 21 months, development was assessed with the Griffiths' Developmental Scale and at 7 years of age neurologic status was assessed with the Stott test and intellectual development with the Wechsler Intelligence Scale for Children. As reported previously, 18% (8/44) of the CMV-infected infants manifested symptoms at birth, as compared to 8% (4/53) in the control group. In the congenital CMV group 7% (2/30) children tested had abnormal Stott test results, as compared to 2% (1/43) in the control group. Thirty-two CMV-infected and 51 control group children were assessed with the Griffiths' scale at 21 months of age. The two groups did not differ significantly, either in mean scores (6.3 +/- 2.3 vs 6.1 +/- 1.9) or in the proportion of children with scores below normal (19% [6/32] vs 16% [8/51]). Twenty-five CMV-infected and 41 control group children were assessed with the Wechsler Intelligence Scale for Children at 7 years of age (median 86 months; range, 82 to 90 and 82 to 91, respectively). The two groups did not differ significantly, either in mean scores (5.8 +/- 2.0 vs 6.4 +/- 1.6) or in the proportion of children with scores below normal (12% [3/25] vs 5% [2/41]). Children with congenital CMV infection are unlikely to be at an increased risk of subsequent neurodevelopmental or intellectual impairment if they show normal development at 12 months of age.


Contributions to the taxonomy, identification, and biogeography of Thaumatogelis Schwarz, 1995 (Hymenoptera: Ichneumonidae).
Three species of Thaumatogelis Schwarz, 1995 are described as new: T. megaera Vas sp. nov. from Mongolia, T. alecto Vas sp. nov. from Jordan, and T. tisiphone Vas Schwarz sp. nov. from Sicily, Italy. The identity of the previously misinterpreted T. pilosus (Capron, 1888) is clarified, and is redescribed. An updated identification key to the females of all known Thaumatogelis species is provided. Twelve new records from six countries are reported, some of them significantly expanding the known geographical distribution of certain Thaumatogelis species and that of the genus in the Palaearctic region.


Patient Safety and Workplace Bullying: An Integrative Review.
Workplace bullying is strongly associated with negative nursing outcomes, such as work dissatisfaction, turnover, and intent to leave; however, results of studies examining associations with specific patient safety outcomes are limited or nonspecific. This integrative review explores and synthesizes the published articles that address the impact of workplace nurse bullying on patient safety.


The development and initial evaluation of the survey of readiness for alcoholics anonymous participation.
This article presents 5 studies related to the development and initial evaluation of the Survey of Readiness for Alcoholics Anonymous Participation (SYRAAP). The SYRAAP is a brief, multidimensional, self-administered instrument that assesses beliefs associated with Alcoholics Anonymous (AA) participation. Study 1 generated 239 candidate items for potential inclusion in the instrument. Study 2 assessed the content validity of these items according to 3 criteria and identified a subset of 60 with the highest values on the criteria for further consideration. Study 3 produced a shorter version of the SYRAAP and evaluated its structure, internal reliability, and validity. Study 4 reevaluated the structure and internal reliability of the SYRAAP and yielded findings that were generally consistent with those from Study 3. Study 5 established stability reliability for the instrument. The collective findings indicated the SYRAAP can reliably and validly assess individual-level beliefs associated with AA participation. The potential use of the SYRAAP for researchers and clinicians, along with limitations of the work presented here, are discussed.


[Diverticulitis of the cecum and ascending colon].
Right colon diverticulitis, representing 1-3.6% of cases of diverticular disease is an uncommon cause of right lower quadrant pain. Its presentation is difficult to distinguish from acute appendicitis. Patients are between 35 and 50 years old, have a history of 2-3 days of abdominal pain and few gastrointestinal symptoms. The diagnosis is best confirmed by computed tomography and colonoscopy. Conservative treatment is justified in uncomplicated disease, whereas perforations, abcesses and inflammatory tumors require resection. We describe the cases of six patients treated at our institution from 1991 to 1996. Presentation, geographic variations, diagnostic procedures and management are discussed.


Two latent classes of diagnostic and treatment procedures among traumatic brain injury inpatients.
To characterize latent classes of diagnostic and/or treatment procedures among hospitalized U.S. adults, 18-64 years, with primary diagnosis of TBI from 2004-2014 Nationwide Inpatient Samples, latent class analysis (LCA) was applied to 10 procedure groups and differences between latent classes on injury, patient, hospital and healthcare utilization outcome characteristics were modeled using multivariable regression. Using 266,586 eligible records, LCA resulted in two classes of hospitalizations, namely, class I (n = 217,988) (mostly non-surgical) and class II (n = 48,598) (mostly surgical). Whereas orthopedic procedures were equally likely among latent classes, skin-related, physical medicine and rehabilitation procedures as well as behavioral health procedures were more likely among class I, and other types of procedures were more likely among class II. Class II patients were more likely to have moderate-to-severe TBI, to be admitted on weekends, to urban, medium-to-large hospitals in Midwestern, Southern or Western regions, and less likely to be > 30 years, female or non-White. Class II patients were also less likely to be discharged home and necessitated longer hospital stays and greater hospitalization charges. Surgery appears to distinguish two classes of hospitalized patients with TBI with divergent healthcare needs, informing the planning of healthcare services in this target population.


Design and development of a lanthanide-labeled immunochromatographic strip for simultaneous detection of morphine, methamphetamine and ketamine in hair.
Colloidal gold immunoassay is the most widely used method in the field of drug detection. However, this method often has poor quantitative identification ability and low analytical sensitivity, which is not suitable for the analysis of hair poisoning ingredients. In order to solve these limitations, we developed an immunochromatographic test strip for simultaneously screening multiple drugs in this study. This hand-held test strip used fluorescent nanoparticles loaded with lanthanide chelates as the signal carrier of fluorescence reading, and conducted quantitative testing of various drugs based on the competitive immune reaction between the analyte and antigen. Under the optimal conditions, the competition curves of morphine (MOP), methamphetamine (MET) and ketamine (KET) were obtained on a single band. The detection limit (LOD) of this analytical method was 100-1000 times lower than that of colloidal gold test strips. The detection limits of MOP, MET and KET were 0.06 ng mL-1, 0.1 ng mL-1 and 1.0 ng mL-1, respectively. No cross-reaction was observed when morphine, methamphetamine and ketamine were tested simultaneously with this method. And 184 hair samples were tested simultaneously, and the detected amount was very close to the results of LC-MS. The immunochromatographic strip showed good stability in repeated tests, and the coefficient of variation was less than 15%. Fluorescence immunochromatography strips and handheld strip readers have the characteristics of portability, speed, ease of operation and high sensitivity, and may become powerful tools for screening drug abuse in hair in forensic medicine.


Identification and characterization of peptide: N-glycanase from Dictyostelium discoideum.
Peptide: N- glycanase (PNGase) enzyme cleaves oligosaccharides from the misfolded glycoproteins and prepares them for degradation. This enzyme plays a role in the endoplasmic reticulum associated degradation (ERAD) pathway in yeast and mice but its biological importance and role in multicellular development remain largely unknown. In this study, the PNGase from the cellular slime mold, Dictyostelium discoideum (DdPNGase) was identified based on the presence of a common TG (transglutaminase) core domain and its sequence homology with the known PNGases. The domain architecture and the sequence comparison validated the presence of probable functional domains in DdPNGase. The tertiary structure matched with the mouse PNGase. Here we show that DdPNGase is an essential protein, required for aggregation during multicellular development and a knockout strain of it results in small sized aggregates, all of which did not form fruiting bodies. The in situ hybridization and RT-PCR results show higher level of expression during the aggregate stage. The expression gets restricted to the prestalk region during later developmental stages. DdPNGase is a functional peptide:N-glycanase enzyme possessing deglycosylation activity, but does not possess any significant transamidation activity. We have identified and characterized a novel PNGase from D. discoideum and confirmed its deglycosylation activity. The results emphasize the importance of PNGase in aggregation during multicellular development of this organism.


Capturing and concentrating adenovirus using magnetic anionic nanobeads.
We recently demonstrated how various enveloped viruses can be efficiently concentrated using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate). However, the exact mechanism of interaction between the virus particles and anionic beads remains unclear. To further investigate whether these magnetic anionic beads specifically bind to the viral envelope, we examined their potential interaction with a nonenveloped virus (adenovirus). The beads were incubated with either adenovirus-infected cell culture medium or nasal aspirates from adenovirus-infected individuals and then separated from the supernatant by applying a magnetic field. After thoroughly washing the beads, adsorption of adenovirus was confirmed by a variety of techniques, including immunochromatography, polymerase chain reaction, Western blotting, and cell culture infection assays. These detection methods positively identified the hexon and penton capsid proteins of adenovirus along with the viral genome on the magnetic beads. Furthermore, various types of adenovirus including Types 5, 6, 11, 19, and 41 were captured using the magnetic bead procedure. Our bead capture method was also found to increase the sensitivity of viral detection. Adenovirus below the detectable limit for immunochromatography was efficiently concentrated using the magnetic bead procedure, allowing the virus to be successfully detected using this methodology. Moreover, these findings clearly demonstrate that a viral envelope is not required for binding to the anionic magnetic beads. Taken together, our results show that this capture procedure increases the sensitivity of detection of adenovirus and would, therefore, be a valuable tool for analyzing both clinical and experimental samples.


Kinetics and mechanism for the reaction of hexafluoroacetylacetone with CuO in supercritical carbon dioxide.
A kinetic model and mechanism were developed for the heterogeneous chelation reaction of thin CuO films with hexafluoroacetylacetone (hfacH) in supercritical CO2. This reaction has relevance for processing nanoscale structures and, more importantly, serves as a model system to tune the reaction behavior of solids using supercritical fluids. Precise control over reaction conditions enabled accurate etching rates to be measured as a function of both temperature [(53.5-88.4) +/- 0.5 degrees C] and hfacH concentration (0.3-10.9 mM), yielding an apparent activation energy of 70.2 +/- 4.1 kJ/mol and an order of approximately 0.6 with respect to hfacH. X-ray photoelectron spectroscopy and scanning electron microscopy were used to characterize the CuO surface, and a maximum etching rate of 24.5 +/- 3.1 A/min was obtained. Solvation forces between hfacH and the dense CO2 permitted material removal at temperatures more than 100 degrees C lower than that of the analogous gas-phase process. In the low concentration regime, the etching reaction was modeled with a three-step Langmuir-Hinshelwood mechanism. Small amounts of excess water nearly doubled the reaction rate through the proposed formation of a hydrogen-bonded hfacH complex in solution. Further increases in the hfacH concentration up to 27.5 mM caused a shift to first-order kinetics and an adsorption-limited or Rideal-Eley mechanism. These results demonstrate that relatively modest increases in concentration can prompt a heterogeneous reaction in supercritical CO2 to switch from a mechanism most commonly associated with a low-flux gas to one emblematic of a high-flux liquid.


Autoimmune meningitis and encephalitis in adult-onset still disease - Case report.
Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown cause. Its symptoms usually include persistent fever, fugitive salmon-colored rash, arthritis, sore throat (not specific), but it may also lead to internal organs' involvement, which presents with enlargement of the liver and spleen, swollen lymph nodes, carditis or pleuritis - potentially life-threatening complications. In rare cases, AOSD can cause aseptic meningitis or/and encephalitis. We report a case of 31-year-old male patient, who was referred to neurological department for extending diagnostics of frontal lobes lesions with involvement of adjacent meninges. Abnormalities have been revealed in brain MRI, which was performed due to persistent headaches, visual disturbances, fever, fatigue and cognitive decline. Wide differential diagnosis was performed including laboratory findings, contrast enhanced MRI, MR spectroscopy, flow cytometry and finally brain biopsy to exclude neoplastic or infectious origin. Final diagnosis of autoimmune meningoencephalitis in adult-onset Still disease has been made. Adult-onset Still disease is a rare cause of inflammatory changes in central nervous system, which if diagnosed, may be treated successfully with steroids (commonly available agent), intravenous immunoglobulins or more specific immunomodulating regiments.


Howard: paternity and Pandora's box.
Howard, a young man named in a paternity suit, came to the Chief of the Genetics Clinic at a large teaching hospital to declare the charges against him false and ask for help in mounting evidence for his defense. Howard submitted to HLA testing, as did the mother and child; but in Howard's zeal to prove his innocence, he insisted that his siblings and parents also be tested to show conclusively there was no paternal link between himself and the child in question. The results of the tests solved one problem while creating another. Although the tests showed that Howard was not the father of the child as charged, the tests also indicated that the man Howard believed to be his own father could not, in fact, be his biological parent. The geneticist brought the case to the new ethics committee at a large teaching hospital to ask, "What, if anything, should be done with this information? Does a physician have the right to withhold information that, although acquired accidentally, would have great import for the patient?" In presenting his dilemma regarding Howard's situation, the geneticist also described a related and common problem of who owns the information. For example, a person comes in for genetic counseling about a particular family disorder. In the course of establishing a pedigree, it comes to light that there are relatives who are at high risk of developing a life-threatening disease that is preventable. What is the doctor's obligation to such a person who is not a patient and about whom crucial information has been learned through privileged communication?


Abnormalities in the serum phospholipids fatty acid profile in patients with alcoholic liver cirrhosis - a pilot study.
The fatty acid composition of serum phospholipids were analyzed in 20 patients with alcoholic liver cirrhosis (11 with malnutrition and 9 with acceptable nutritional status); 25 healthy age and sex-matched adults were used as controls. Cirrhotic patients showed higher levels of palmitic acid and total saturated fatty acids than healthy subjects. Total n-6 and n-3 polyunsaturated fatty acids (PUFA), and levels of linoleic, dihomo-gama linolenic, arachidonic, and docosahexaenoic acid were significantly lower (p<0.001) in patients with alcoholic cirrhosis compared to healthy controls. Significant changes were also found between patients stratified according to nutritional status. In particular, the sum of n-3 PUFA was significantly lower (p<0.001) and ratio of n-6/n-3 fatty acids was higher (p<0.01) in malnourished patients when compared to the patients with acceptable nutritional status. Furthermore, important changes in the levels of saturated fatty acids, palmitoleic and oleic acid and long-chain PUFA were found in well-nourished patients with alcoholic cirrhosis as well. Our present data confirmed evidence that malnutrition is one of the factors that led to lower levels of polyunsaturated fatty acids in patients with alcoholic liver cirrhosis. PUFA supplementation in the latter needs further investigation.


Subconductance states in OmpF gating.
Discrepancies were noted in the published conductance of the Escherichia coli porin OmpF. Results from various papers are hard to compare because of the use of different channel preparations, salt types and concentrations, and electrophysiological techniques (black lipid membrane (BLM) vs. patch clamp). To reconcile these data, we present a side-by-side comparison of OmpF activity studied with the two techniques on the same preparation of pure protein, and in the same low salt concentrations (150 mM KCl). The novel aspect of OmpF porin behavior revealed by this comparison is the ubiquitous existence of states of smaller conductance than the monomeric conductance (subconductance states), regardless of the techniques or experimental conditions used, and the drastic enhancement of subconductance gating by polyamines. Transitions to subconductance states have received little attention in previous publications, in particular when BLM electrophysiology was used. Monomeric closures are rare in recordings at clamped potentials, at least at voltages lower than approximately 100-120 mV. Most closing activity is in the form of subconductance gating, which becomes more dominant in the presence of spermine, with a more frequent and prolonged occupation of these substates. A discussion of the molecular basis for this hallmark behavior of porin is presented.


T helper cell-dependent, microbial superantigen-mediated B cell activation in vivo.
We have utilized a severe combined immune-deficient (SCID) mouse adoptive transfer model to explore the in vivo immunostimulatory effects of bacterial superantigens (SAg). B cell reconstituted SCID recipients were treated with the Staphylococcus aureus-derived toxic shock syndrome toxin (TSST-1) alone or in conjunction with syngeneic L3T4+ TSST-1-reactive Th cells. Over several months of study, the repetitive administration of TSST-1 resulted in a prompt, transient increase in serum IgG levels. This response required both biologically active TSST-1 and Th cells. These findings demonstrate that certain bacterial SAgs can promote Th cell-dependent B cell activation and differentiation in vivo. These studies strengthen the analogy between SAg-mediated and allospecific Th-B cell interactions responsible for the autoimmune sequelae of graft-versus-host disease.


Cluster Organic Frameworks Constructed from Heterometallic Supertetrahedral Cluster Secondary Building Units.
The two novel cluster organic frameworks based on heterometallic supertetrahedral cluster secondary building units (SBUs) [Cd4Cu6(L)4(Ac)7(H2O)4](Ac)·7H2O (1) and [Mn4Cu6(L)4(Ac)4.5(H2O)9]CuCN(Ac)3.5·H2O (2), where H3L = 2-(hydroxymethyl)-2-(pyridin-4-yl)-1,3-propanediol and Ac = CH3COO-, have been prepared under solvothermal conditions. 1 and 2 are the first cases of cluster organic frameworks containing Cd-Cu/Mn-Cu heterometallic supertetrahedral cluster SBUs. Furthermore, 1 and 2 show an integration of magnetic properties and adsorption properties from both the heterometallic cluster secondary building units and the framework in a porous material.


Nucleation process in the folding of a domain-swapped dimer.
Nucleation processes are important for the understanding in protein dynamics. To evaluate the effect of nucleation mechanism in dimerization process, a domain-swapped dimer (Esp8) is simulated with the symmetrized Gō model and the classical Gō model. The pathways of the dimerization are analyzed with computational phi -analysis method. It is found out that some nuclei are observed in the kinetic steps of the dimeric association though the whole pathway is a process with multiple intermediate states. The key residues in the nuclei are rather similar to those observed in the monomeric folding. The differences with the monomeric cases are also discussed. These differences illustrate the effects of dimeric feature on the nucleation process. Besides, manual mutations are carried out to illustrate the importance of the interactions related to the nuclei. It is observed that the mutations in the nuclei-related interactions apparently change the dynamics while other mutations have little effect on the kinetics. All of these results outline a picture that the nucleation processes act as the fundamental steps of high-order organization of protein systems.


Digestive response to restricted feeding in migratory yellow-rumped warblers.
Smaller guts and slow initial mass gains at stopover sites have led to the idea that digestive physiology limits refueling rates in migrating birds. We tested the digestive-limitation hypothesis in yellow-rumped warblers using food restriction to simulate infrequent feeding during migration, which may cause a reduction in alimentary tract mass. Restricted birds had small intestine, pancreas, and liver masses 18%-22% lower than ad lib.-fed controls. Total activities of sucrase, maltase, aminopeptidase, and amylase were significantly lower in restricted birds, while those of trypsin and chymotrypsin were not. Only aminopeptidase mass-specific activity was significantly lower in restricted birds. Previously restricted birds were able to feed and digest at a high rate immediately following return to ad lib. feeding. Digestive efficiency did not differ between groups. These results suggest that before migration yellow-rumped warblers have some spare digestive capacity to compensate for declines in their digestive organ masses during migration.


Exploring the Neural Correlates in Adopting a Realistic View: A Neural Structural and Functional Connectivity Study With Female Nurses.
Empathizing leads to positive and negative consequences. To avoid empathy-induced distress, adopting a realistic view (dealing with a situation practically and efficiently independent of one's emotional state) is important. We hypothesized that empathy-demanding professions (e.g., nursing) may require individuals to adopt a realistic view, which may demonstrate modulated neural structure and functional connectivity. We confirmed that female nurses showed a higher tendency, compared to controls, to adopt a realistic view, using the Fantasy subscale of the Interpersonal Reactivity Index (IRI; inverse scale of the realistic view). We then employed voxel-based morphometry (VBM) and resting-state functional magnetic resonance imaging (rs-fMRI) to explore the neural underpinnings related to realistic view adoption. Nurses exhibited significantly lower gray-matter volume (GMV) in the right striatum. In multiple regression analysis, only the Fantasy subscale score showed a significant positive correlation with GMV within the striatum cluster. Moreover, nurses exhibited lower functional connectivity between the right striatum and the right lateral prefrontal cortex (PFC), representing emotional regulation. These findings show that structural differences in the striatum correlated with the realistic view. Furthermore, lower functional connectivity between the striatum and lateral PFC suggests that nurses may use efficient coping strategies that may lessen the recruitment of effortful emotional regulation.