Second trimester septic abortion and the Dalkon shield.
The Dalkon shield was withdrawn from the market in the United States of America last year because of the reports of 11 maternal deaths and 209 cases of septic midtrimester abortions associated with the device in situ. Four cases of late midtrimester septic abortions resulting in neonatal deaths are presented. In one of these, the mother developed septicaemic shock and almost died. The true pregnancy rate with the Dalkon shield is much higher than was initially claimed, particularly if it is inserted in the puerperium. Surveys on the outcome of the pregnancy indicate that 50% end in spontaneous abortion and one in 20 pregnancies are ectopic. A high percentage of the abortions are septic. The Dalkon shield, therefore, has no advantages over other intrauterine contraceptive devices and it remains to be seen whether the recent modification of the device has overcome the disadvantages of the earlier version. If pregnancy is diagnosed with the device in situ, it should be removed if the string is visible. If pregnancy continues with the shield in place, the patient should be observed closely. Should septic abortion occur, active management is indicated and early evacuation of the uterus is recommended.


Modeling the three-dimensional structures of bacterial aminotransferases.
The refined crystallographic structure of the "closed" conformation of chicken mitochondrial aspartate aminotransferase has been used as a template for the construction of models of the two Escherichia coli aminotransferases encoded by the tyrB and aspC genes. The main results are as follows: (1) Only minor changes are required in the coordinates of the backbone atoms to accommodate the large number of substituted side chains. (2) All deletions and insertions required to allow maximum primary sequence alignment are on the solvent-accessible surface. (3) Charged residues are all located on the surface, in contact with solvent, except for certain conserved active site residues. (4) The close packing within the hydrophobic core is maintained. (5) The interactions between the subunits are maintained. (6) Modeling of tyrosine as an external aldimine into the active sites points to several residues that could be involved in determining the substrate specificities of these aminotransferases.


Total and individual kidney function assessment with iodine-123 ortho-iodohippurate.
A simple and reliable method of preparing 123l o-iodohippurate (l-123 OIH) is described. The agent was used to evaluate renal function in 329 patients; its use results in significant dose reduction for those with obstruction, hypertension, or transplant. Images from l-123 OIH provide 2.4 times more detectable photons per mCi administered to the patient than images obtained from l-131 OIH. Diagnoses are expected to be more reliable with l-123 OIH due to the decreased random variation of each data point.


Resistin increases monolayer permeability of human coronary artery endothelial cells.
Resistin has been linked to obesity, insulin resistance, atherosclerosis, and the development of cardiovascular disease. Nevertheless, the effects and the molecular mechanisms of resistin on endothelial permeability, a key event in the development of atherosclerosis, inflammation, and vascular disease, are largely unknown. In order to determine the effect of resistin on endothelial permeability, human coronary artery endothelial cells (HCAECs) were treated with clinically relevant concentrations of resistin and the endothelial permeability was measured using the Transwell system with a Texas-Red-labeled dextran tracer. The permeability of HCAEC monolayers treated with resistin (80 ng/mL) was 51% higher than the permeability of control monolayers (P<0.05). The mRNA levels of tight junction proteins zonula occludens-1 (ZO-1) and occludin in resistin-treated cells were 37% and 42% lower, respectively, than the corresponding levels in untreated cells. The protein levels of these molecules in resistin-treated cells were significantly reduced by 35% and 37%, respectively (P<0.05), as shown by flow cytometry and Western blot analysis. Superoxide dismutase (SOD) mimetic MnTBAP effectively blocked the resistin-mediated reduction of ZO-1 and occludin levels in HCAECs. In addition, superoxide anion production was increased from 21% (untreated cells) to 55% (cells treated with 40 ng/mL resistin), and 64% (resistin, 80 mg/mL) (P<0.05). The natural antioxidant Ginkgolide A effectively inhibited resistin-induced increase in permeability and the increase in superoxide anion production in HCAECs. Furthermore, resistin treatment significantly activated p38 MAPK, but not ERK1/2. Pretreatment of HCAECs with a p38 inhibitor effectively blocked resistin-induced permeability. These results provide new evidence that resistin may contribute to the vascular lesion formation via increasing endothelial permeability through the mechanism of oxidative stress and the activation of p38 MAPK.


[Chemotherapy of malignant solid tumors].
In the chemotherapy of malignant solid tumours, also in form of the adjuvant chemotherapy, the results to be yielded are less favourable than in the diseases of the hemopoietic system. By a consequently performed poly-chemotherapy it is, nevertheless, possible to achieve remissions. By polychemotherapy we achieved in 13 metastatasized carcinomas of the mamma 4 partial and one complete remission, in 15 inoperable lung tumours we achieved four times a standstill of the growth and a complete remission over two years, whereas the tumours of the gastro-intestinal tract could be influenced less clearly. Treatments with only one medicament in each case were without any effect in solid epidermic tumours. The therapy is to be used effectfully only then, when indication, dosage and control of the patients are performed critically and exactly.


The MedSafer Study: A Controlled Trial of an Electronic Decision Support Tool for Deprescribing in Acute Care.
Polypharmacy is common, costly, and harmful for hospitalized older adults. Scalable strategies to reduce the burden of potentially inappropriate medications (PIMs) are needed. We sought to leverage medication reconciliation in hospitalized older adults by pairing with MedSafer, an electronic decision support tool for deprescribing. This was a nonrandomized controlled before-and-after study. The study took place on four internal medicine clinical teaching units. Subjects were aged 65 years and older, had an expected prognosis of 3 or more months, and were taking five or more usual home medications. In the baseline phase, patients received usual care that was medication reconciliation. Patients in the intervention arm also had a "deprescribing opportunity report" generated by MedSafer and provided to their in-hospital treating team. The primary outcome was ascertained at the time of hospital discharge and was the proportion of patients who had one or more PIMs deprescribed. A total of 1066 patients were enrolled, and deprescribing opportunities were present for 873 (82%; 418 during the control and 455 during the intervention phases, respectively). The proportion of patients with one or more PIMs deprescribed at discharge increased from 46.9% in the control period to 54.7% in the intervention period with an adjusted absolute risk difference of 8.3% (2.9%-13.9%). Not all classes of drugs in the intervention arm were associated with an increase in deprescribing, and new PIM starts were equally common in both arms of the study. Using an electronic decision support tool for deprescribing, we increased the proportion of patients with one or more PIMs deprescribed at hospital discharge as compared with usual care. Although this type of intervention may help address medication overload in hospitalized patients, it also underscores the importance of powering future trials for a reduction in adverse drug events. NCT02918058. J Am Geriatr Soc 67:1843-1850, 2019.


Occurrence of Hematological Malignancy in Long-term Survivors With Advanced Thymic Cancer.
Limited information is available on the occurrence of synchronous malignancy in patients with advanced thymic cancer (TC) who have achieved long-term survival due to sequential chemotherapy. Here, we present two cases of hematological malignancies in long-term survivors with advanced TC. A 56-year-old man underwent surgical resection following the diagnosis of TC with a histological indication of squamous cell carcinoma. He received sequential chemotherapy, including carboplatin plus paclitaxel, amrubicin, and S-1, due to multiple pulmonary metastases. After >4 years of first-line chemotherapy, he developed consistent myelosuppression and a definite diagnosis of acute promyelocytic leukemia was made following bone marrow analysis. A 49-year-old man with advanced TC received carboplatin plus paclitaxel with amrubicin as second-line therapy due to recurrence. Amrubicin was administered for 54 cycles but T-cell lymphoblastic lymphoma without recurrence of TC was confirmed following transbronchial nodal biopsy due to marked lymphadenopathy. Physicians should be alert to the occurrence of hematological malignancy in patients with thymic cancer.


Myocardial Hypertrophic Remodeling and Impaired Left Ventricular Function in Mice with a Cardiac-Specific Deletion of Janus Kinase 2.
The Janus kinase (JAK) system is involved in numerous cell signaling processes and is highly expressed in cardiac tissue. The JAK isoform JAK2 is activated by numerous factors known to influence cardiac function and pathologic conditions. However, although abundant, the role of JAK2 in the regulation or maintenance of cardiac homeostasis remains poorly understood. Using the Cre-loxP system, we generated a cardiac-specific deletion of Jak2 in the mouse to assess the effect on cardiac function with animals followed up for a 4-month period after birth. These animals had marked mortality during this period, although at 4 months mortality in male mice (47%) was substantially higher compared with female mice (30%). Both male and female cardiac Jak2-deleted mice had hypertrophy, dilated cardiomyopathy, and severe left ventricular dysfunction, including a marked reduction in ejection fractions as assessed by serial echocardiography, although the responses in females were somewhat less severe. Defective cardiac function was associated with altered protein levels of sarcoplasmic reticulum calcium-regulatory proteins particularly in hearts from male mice that had depressed levels of SERCA2 and phosphorylated phospholamban. In contrast, SERCA2 was unchanged in hearts of female mice, whereas phosphorylated phospholamban was increased. Our findings suggest that cardiac JAK2 is critical for maintaining normal heart function, and its ablation produces a severe pathologic phenotype composed of myocardial remodeling, heart failure, and pronounced mortality.


Common Use of Electroconvulsive Therapy for Chinese Adolescent Psychiatric Patients.
Little is known about the use of electroconvulsive therapy (ECT) for adolescent psychiatric patients in China. This study examined the frequency of ECT and the demographic and clinical correlates of adolescent psychiatric patients hospitalized in a tertiary psychiatric hospital in China. This was a retrospective chart review of 954 inpatients aged between 13 and 17 years treated over a period of 8 years (2007-2013). Sociodemographic and clinical data were collected from the electronic chart management system for discharged patients. The rate of ECT use was 42.6% in the whole sample (46.5% for patients with schizophrenia, 41.8% for major depressive disorder, 57.8% for bipolar disorders, and 23.9% for other diagnoses). Use of ECT was independently and positively associated with older age, high aggression risk at time of admission, and use of antipsychotics and antidepressants. Compared with patients with schizophrenia, those with other psychiatric diagnoses were less likely to receive ECT. The above significant correlates explained 32% of the variance of ECT use (P < 0.001). Limitations of this study included the lack of data regarding the efficacy and side effects of ECT. Furthermore, the high rate of ECT applied only to 1 setting which limits the ability to extrapolate the implications of the results to other populations. The use of ECT was exceedingly high in adolescent patients treated in a tertiary clinical centre in China. It is unlikely that such a high rate of ECT use is found across China or that such practice reflects standard of care for psychiatrically ill adolescents. The underlying reasons for the high use of ECT at this center warrant urgent investigations.


Investigation of Extra-Uterine Tumor Dissemination of Endometrial Cancers with Myometrial Invasion Less Than 50% According to Histologic Subtypes.
This study aims to investigate the rates of extra-uterine metastases of non-endometrioid endometrial tumors limited to the half of the myometrium. Patients operated for endometrial cancer between 2005-2015 in two gynecologic oncology centers were screened from clinical archives. The inclusion criteria were serous, clear cell, undifferentiated or carcinosarcoma histologies and less than half myometrial invasion. Each histological type was analyzed for adnexal metastasis, lymph node metastasis (pelvic/paraaortic) and omental metastasis. A total of 116 patients with the median age of 64 (34-72) were examined. Of the patients, 57 were serous (49.1%), 29 were clear cell (25.0%), 27 were carcinosarcoma (23.3%) and 3 (2.6%) were undifferentiated histologic type. Adnexal metastasis (over/tuba) was detected in 15 patients (12.9 %), nodal metastasis in 10 patients (8.6%), and omental metastasis in 15 patients (12.9%). The rates of adnexal metastases were calculated as 14% for serous type, 10% for clear cell type and 11% for carcinosarcoma. Omental metastasis rates were 11% for serous type, 17% for clear cell type and 15% for carcinosarcoma. The rates of extra-peritoneal nodal metastases were calculated as 12% for serous type, 7% for clear cell type and 4% for carcinosarcoma. According to the findings obtained in this study, the rates of extra-uterine metastasis are high for serous, clear cell or carcinosarcoma types even in the early period. However, the lymph node metastasis in the carcinosarcoma seems to be lower. A comprehensive staging surgery should be planned for these patients, regardless of the depth of myometrial invasion.


Agricultural Waste.
The management and disposal of agricultural waste are drawn more and more attention because of the increasing yields and negative effects on the environment. However, proper treatments such as converting abundant biomass wastes into biogas through anaerobic digestion technology, can not only avoid the negative impacts, but also convert waste into available resources. This review summarizes the studies of nearly two hundred scholars from the following four aspects: the characterization, reuse, treatment, and management of agricultural waste.


Generation and characterization of a competitive antagonist of human hepatocyte growth factor, HGF/NK1.
Our previous studies have suggested that a derivative of hepatocyte growth factor (HGF), HGF/NK2, containing the coding sequences for the N-terminal hairpin and first two kringle domains, is sufficient to mediate high affinity binding to the HGF receptor. Here, we wished to test directly whether HGF/NK1 (N-terminal hairpin and first kringle domains) could bind the receptor and/or mediate receptor signaling. HGF/NK1 was expressed in Escherichia coli and purified to homogeneity using heparin-affinity and fast protein liquid cation-exchange chromatography. Biological characterization of HGF/NK1 showed that it can compete for binding to the HGF receptor on human lung carcinoma A549 cells and to a soluble form of the HGF receptor. HGF/NK1 is inefficient at promoting autophosphorylation of the HGF receptor, although some activity was detected at very high concentrations. HGF/NK1 fails to exhibit mitogenic properties even at very high concentrations. However, HGF/NK1 can act as a potent competitive antagonist in this assay. Our data demonstrate directly that a receptor binding determinant of HGF is located within the N-terminal 32-212 residues of HGF. HGF/NK1 will serve as a powerful tool for (i) generating neutralizing antibodies, (ii) in determining x-ray crystallographic and nuclear magnetic resonance structures, and (iii) for in vivo studies as an HGF antagonist.


Sun Protection Counseling at the Pharmacy: A German Qualitative Study on Status Quo, Potential Deficits, and Sources of Information.
The sale of sunscreen products is lucrative for pharmacies, and many people buy sunscreen in pharmacies because they expect to receive good advice on sunscreen use and sun protection. However, little is known about the knowledge level of pharmacists and pharmacy technicians in the field of skin cancer prevention. By conducting a qualitative study in Germany, we aimed to explore what pharmacy personnel know about sun protection and the proper use of sunscreens, where they get their information from, and where they see deficits concerning these topics. We found that there is a need for education regarding the terms skin type and sun protection factor, both of which can be helpful tools when advising customers on sun protection. In addition, participants wished for more independent information from health authorities because sunscreen manufacturing companies, which offer product-specific information, are often the only source of information. Overall, it seems reasonable that pharmacy staff should be educated more about sun protection behavior and the proper use of sunscreen to be able to advise their customers correctly. Our findings offer a starting point for strengthening the role of pharmacies in skin cancer prevention. It seems to make sense to develop and offer tailored handouts for customer counseling. Since sunscreen products are perceived as seasonal products, an educational leaflet can help refresh knowledge about the use of sunscreen and the concepts of skin type and sun protection factor in early summer.


Pump Up the Jam: Granular Media as a Quasi-Hydraulic Fluid for Independent Control Over Isometric and Isotonic Actuation.
Elastomer-granule composites have been used to switch between soft and stiff states by applying negative pressure differentials that cause the membrane to squeeze the internal grains, inducing dilation and jamming. Applications of this phenomenon have ranged from universal gripping to adaptive mobility. Previously, the combination of this jamming phenomenon with the ability to transport grains across multiple soft actuators for shape morphing has not yet been demonstrated. In this paper, the authors demonstrate the use of hollow glass spheres as granular media that functions as a jammable "quasi-hydraulic" fluid in a fluidic elastomeric actuator that better mimics a key featur of animal musculature: independent control over i) isotonic actuation for motion; and ii) isometric actuation for stiffening without shape change. To best implement the quasi-hydraulic fluid, the authors design and build a fluidic device. Leveraging this combination of physical properties creates a new option for fluidic actuation that allows higher specific stiffness actuators using lower volumetric flow rates in addition to independent control over shape and stiffness. These features are showcased in a robotic catcher's mitt by stiffening the fluid in the glove's open configuration for catching, unjamming the media, then pumping additional fluid to the mitt to inflate and grasp.


[What new knowledge has automated perimetry with the Octopus brought on glaucomatous visual field changes?].
The results of studying patients with glaucomatous field defects over a 5-year period using the Octopus automated perimeter are summarized. This instrument relies on a retest logic and problem-orientated adaptation of the test points as well as of the software is possible with it. Automated perimetry offers significant advantages over conventional field testing and has increasing our understanding of glaucoma considerably. (1) The probability of detecting glaucomatous field defects is substantially greater than with manual perimetry; (2) the results of a visual field examination can be treated mathematically and statistically, especially when Bebie and Fankhauser 's Delta program is used; (3) the evaluation of progressive field loss is only possible using threshold perimetry, as supra-threshold stimuli are too crude; (4) increased fluctuations around the normal age-corrected threshold represent the earliest detectable changes in glaucoma; (5) loss of sensitivity is reversible in early relative scotomata; (6) the depth of relative scotomata cannot be sharply defined on account of rapid fluctuations in sensitivity; (7) early visual field changes probably represent late changes in the course of chronic simple glaucoma.


Basal-cell carcinoma of the eyebrow region.
Five women (21 to 43 years of age), each with a basal-cell carcinoma involving the eyebrow region, are presented. The implications of the clinical situation in terms of therapy and reconstruction are discussed.


[A case of hepatocellular carcinoma( Vp3)-planned radiotherapy after extended right hepatectomy].
The patient was a 57-year-old man who was diagnosed as having hepatocellular carcinoma (HCC). The tumor, 13 cm in diameter, occupied almost the entire right lobe and directly permeated the gallbladder. In addition, invasion of the portal vein umbilical region was seen from an inside area progress department. Because of the small remnant liver volume due to 3 procedures for right area excision and because liver failure was a concern after the operation, we decided to perform extended right hepatectomy for which we retained one S4 Glisson's capsule. Radiotherapy was planned for portal vein tumor thrombus after the operation. We started radiotherapy( 2.0 Gy×25) on postoperative day 14, and the patient was discharged without complications on postoperative day 55. We initiated the internal administration of tegafur-uraci(l UFT 400 mg/day) on postoperative day 44 and continued the treatment for half a year; however, metastasis was frequently noted in the lungs on computed tomography (CT) at 9 months after the operation. We administered low-dose 5-fluorouracil plus cisplatin( FP, intravenous) therapy combined with sorafenib( 800 mg/day), and the patient is being followed up. No recurrence has been noted in the liver at 16 months after the operation.


Rearrangements of bicyclic nitrones to lactams: comparison of photochemical and modified Barton conditions.
The rearrangement of nitrones to lactams can be carried out by photochemical activation or by treatment with Tf(2)O followed by KOH-promoted rearrangement (a modification of conditions originally introduced by Barton). Substrates in which the nitrone is part of a fused bicyclic ring system have traditionally proven problematic for this kind of reaction. In this study, a series of mono-, bi-, and tricyclic ring-fused nitrones were prepared to investigate the dependence of products on nitrone ring size and tether length. Results indicated that photochemical rearrangement of nitrones in benzene afforded reasonably good yields (30-68%) of lactams, while the two-step nonphotochemical process provided slightly better average yields (30-95%) of the same targets.


Inflammatory effects of Salmonella typhimurium porins.
The inflammatory activity of porins purified from Salmonella typhimurium has been investigated. Porins (0.3 to 30 micrograms) injected into the rat paw induced a dose-related edema that was not due to lipopolysaccharide contamination and did not appear to be dependent on the activation of the complement system. The edema induced by 30 micrograms of porins was comparable to that caused by 1 mg of carrageenin and was inhibited by indomethacin (5 mg/kg) and dexamethasone (0.1 mg/kg). Porins (1 to 10 micrograms/ml) induced a concentration-related release of histamine from rat peritoneal cells. These results are discussed in the light of the possible pathogenic role of porins in infections.


Impact of Childhood Abuse on Physical and Mental Health Status and Health Care Utilization Among Female Veterans.
To determine whether childhood abuse predicts health symptoms and health care use among female veterans. Participants were 369 female patients at Veterans Affairs hospitals in New England who completed a mail survey. Multiple regression analyses were conducted to determine the differential impact of childhood physical abuse and childhood sexual abuse on health symptoms and health care use, while accounting for age, race, military branch, and military sexual trauma (MST). In our sample, 109 (29%) female veterans reported experiencing childhood abuse. After adjusting for age, race, military branch, childhood sexual abuse, and MST, childhood physical abuse was predictive of poorer physical health, and greater depressive and post-traumatic stress disorder symptoms. No significant association was found between childhood sexual abuse and poor physical or mental health status. After adjusting for other factors, childhood physical abuse was associated with more frequent use of medical health care. Childhood sexual abuse was not a predictor for health care use. Childhood physical abuse remains an important contributor to physical health and mental health, even after adjusting for the more proximate experience of MST. Screening for adverse childhood experiences may facilitate access to appropriate physical and mental health treatment among female veterans.


Clinical studies with misonidazole.
The preliminary details of a randomized clinical trial of misonidazole for the radiotherapy of Grades 3 and 4 cerebral astrocytoma are described. Plasma concentrations of misonidazole and its O-demethylated metabolite, determined by high-pressure liquid chromatography analysis, are reported for 8 patients with astrocytoma, 1 with carcinoma of the bronchus and 1 with carcinoma of the breast. In the latter case, tumour concentrations are also presented.


Assessment of Undergraduates' Real-World Outcomes of Critical Thinking in Everyday Situations.
Critical thinking is a kind of "good" thinking that integrates a set of cognitive skills and dispositions to use those skills with knowledge to increase the chances of success in academic settings, job market, and daily life. The impact of critical thinking on life events, in face of everyday decisions and challenges, is still unclear, and further research is needed. In this exploratory study, a sample of 230 first-year students of a Bachelor's Degree or a Master's Degree in Portugal completed an experimental Portuguese version of the Real-World Outcomes, a self-report inventory measuring everyday negative life events that are mediated by a lack of critical thinking. Based on exploratory factor analysis results and theoretical premises, changes were made to the Portuguese version of the inventory that was administered, and items were aggregated into six dimensions, creating a new version that is more familiar to Portuguese young adults in college. This original proposal of the inventory presents six types of negative life events resulting from a lack of critical thinking: health neglect, mismanagement, slackness, poor impulse control, academic negligence, and rashness. Both limitations and future potentialities of this version are presented.


Notes on the taxonomy of poorly known Gryllacrididae (Stenopelmatoidea) from Brunei Darussalam, Borneo.
Gryllacrididae, or raspy crickets, belong to the monophyletic clade Stenopelmatoidea, and have complex taxonomy. Many genera require revision, including the ones from Southeast Asia. Orthopteran surveys in Kuala Belalong, Brunei Darussalam, Borneo led to the discovery of a new species of apterous gryllacridid from Brunei Darussalam: Melaneremus? bellus sp. nov. We also redescribe Phlebogryllacris venosa (Walker, 1869) and provide images of this species of both live and preserved specimens. In the process of describing, specimens from morphologically similar genera were also examined. We provide some notes on these genera to aid future taxonomic studies.


Balance between plasma levels of tumor necrosis factor-alpha and interleukin-10 in rheumatic mitral stenosis.
The study population consisted of 16 patients with rheumatic mitral stenosis undergoing percutaneous transluminal mitral valvuloplasty (group 1). The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in the femoral vein and the right and left atria before valvuloplasty were determined by ELISA. Additionally, we measured plasma concentrations of TNF-alpha and IL-10 in the venous blood obtained from 19 control patients, including 12 healthy volunteers in sinus rhythm (group 2) and 7 patients in permanent lone atrial fibrillation (group 3). The venous plasma levels of TNF-alpha were significantly elevated in group 1 patients compared with group 2 patients (p < 0.002). Correlation analysis demonstrated that there was a significantly direct relationship between the plasma TNF-alpha and IL-10 concentrations in the left atrial, right atrial and peripheral venous blood (p < 0.008, r = 0.640; p < 0.04, r = 0.538; p< 0.03, r = 0.571, respectively). In conclusion, the plasma concentrations of TNF-alpha of patients with rheumatic mitral stenosis were significantly higher than those of healthy volunteers. In addition, there was a significantly direct relationship between the soluble TNF-alpha and IL-10 concentrations in the atrial and peripheral venous blood, indicating a balance between circulating TNF-alpha and IL-10 levels in patients with rheumatic mitral stenosis.


Surgical relief of post-herpetic pain by excision of scarred skin.
This paper deals with the problems of post-herpetic pain. The various modes of treatment which have been tried for its relief are discussed as is our experience of excision of the scarred area of skin. The procedure has been found to offer worthwhile pain relief to a significant number of patients.


Size-dependent assemblies of nanoparticle mixtures in thin films.
Hybrid nanoparticle (NP) arrays based on particles of different sizes and chemistries are highly desirable to obtain tunable properties for nanodevices. A simple approach to control the spatial organization of NP mixtures within supramolecular frameworks based on NP size has been developed. By varying the ratio of the NP size to the periodicity of the block-copolymer-based supramolecule, a range of hybrid NP assemblies in thin films, ranging from 1D chains to 2D lattices and 3D arrays and networks of NPs, can be readily generated.


Surgery or assisted reproduction? A decision analysis of treatment costs in male infertility.
Assisted reproductive technology (ART), including in vitro fertilization and intracytoplasmic sperm injection, is routinely used to treat male factor infertility. Because of the success of ART, the optimal method to achieve pregnancy with male infertility is controversial. Two examples in which ART competes with traditional male infertility treatments are varicocelectomy and vasectomy reversal. We used formal decision analysis to estimate and compare the cost-effectiveness of surgical therapy and ART for varicocele and vasectomy reversal. Decision analysis models were created for infertile men seeking paternity with varicocele and with post-vasectomy obstruction. Outcome probabilities applied to the model were derived from institutional and published sources. Costs of interventions were calculated from institutional data. Sensitivity analyses determined which elements were most important and, thus, were used to calculate threshold values. Vasectomy reversal is as cost-effective as ART if bilateral vasovasostomy can be performed. However, if unilateral or bilateral vasoepididymostomy is required, sperm retrieval/intracytoplasmic sperm injection may be more cost-effective due to lower patency rates. Vasectomy reversal is more cost-effective across all pregnancy rates provided that patency rates are greater than 79%. Surgical repair of varicocele is more cost-effective when the postoperative pregnancy rate is greater than 14% in men with a preoperative total motile sperm count of less than 10 million sperm and greater than 45% in men with greater than 10 million total motile sperm. A decision analysis based comparison of ART and classic surgical therapy suggests that varicocelectomy and vasectomy reversal are the most economical treatments in many cases of infertility due to these lesions. Tailoring the decision models to individual centers permits more accurate comparisons using specific costs as well as the surgical outcomes and results of ART.


Haemoglobin M Hyde Park occurring as a fresh mutation: diagnostic, structural, and genetic considerations.
Hb M Hyde Park disease was detected in a girl who for several years was thought to have cyanotic heart disease. The problems of recognizing the condition are outlined and clues to diagnosis are discussed. Evidence for heme loss from the aberrant beta chains of Hb M Hyde Park and production of an unstable molecule is presented. The normal haematological findings in the patient's parents, as well as their blood groups and isozymes, suggest that the occurrence of her Hb M Hyde Park was the result of a fresh mutation.


Osteolipoma of the nasopharynx.
Osteolipomas of the head and neck are very rare, and there is no reported case of osteolipoma of the nasopharynx in the literature. Here, we present a case of osteolipoma of the nasopharynx in a 21-year-old male who was referred for a nasopharyngeal mass causing a defect in the left half of the soft palate. The well-demarcated, firm tumor was excised through transnasal endoscopic and transpalatal approaches, and the defect of the soft palate was repaired by a superiorly based pharyngeal flap. Osteolipomas should be kept in mind in the differential diagnosis of nasopharyngeal mass as an extremely rare benign lesion.


Density functionals for static, dynamical, and strong correlation.
In this work, our exact-exchange-based static + dynamical correlation density functional [A. D. Becke, J. Chem. Phys. 122, 064101 (2005)] is generalized to include "strong" correlation, i.e., accurate computations on dissociating chemical systems without breaking space or spin symmetries and without using multi-determinantal reference states. Also, we introduce a strong-correlation benchmark set composed of space- and spin-symmetrized open-shell atoms on which the generalized functional is tested. Initial results are very promising.


Evaluation of the Risk of Relapse in Classical Hodgkin Lymphoma at Event-Free Survival Time Points and Survival Comparison With the General Population in British Columbia.
Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC). The BC Cancer Agency Lymphoid Cancer Database was screened to identify all patients age 16 to 69 years diagnosed with cHL between 1989 and 2012 treated with the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (or equivalent). We compared the observed mortality to the general population using age-, sex-, and calendar period-generated expected mortality rates from BC life-tables. Relative survival was calculated using a conditional approach and expressed as a standardized mortality ratio of observed-to-expected deaths. One thousand four hundred two patients were identified; 749 patients were male (53%), the median age was 32 years, and 68% had advanced-stage disease. The median follow-up time was 8.4 years. Seventy-two percent of relapses occurred within the first 2 years of diagnosis. For all patients, the 5-year risk of relapse from diagnosis was 18.1% but diminished to 5.6% for patients remaining event free at 2 years. For advanced-stage patients who were event free at 2 years, the 5-year risk of relapse was only 7.6%, and for those who were event free at 3 years, it was comparable to that of limited-stage patients (4.1% v 2.5%, respectively; P = .07). Furthermore, international prognostic score ≥ 4 and bulky disease were no longer prognostic in patients who were event free at 1 year. Although the relative survival improved as patients remained in remission, it did not normalize compared with the general population. Patients with cHL who are event free at 2 years have an excellent outcome regardless of baseline prognostic factors. All patients with cHL had an enduring increased risk of death compared with the general population.


Spontaneous inelastic Rayleigh scattering in optical fibers.
Rayleigh scattering (RS) adds noise to signals that are transmitted over optical fibers and other optical waveguides. This noise can be the dominant noise source in a range between 10 Hz and 100 kHz from the carrier and can seriously degrade the performance of optical systems that require low close-in noise. Using heterodyne techniques, we demonstrate that the backscattered close-in noise spectrum in optical fibers is symmetric about the carrier and grows linearly with both input power and fiber length. These results indicate that the RS is spontaneous and is due to finite-lifetime thermal fluctuations in the glass.


[Giant form of infantile myofibromatosis located on the jaw].
Infantile myofibromatosis is a rare fibrovascular-like tumour, characterized by the development of single or multiple nodular lesions arising from cutaneous, subcutaneous, muscular bone or visceral structures, diagnosed before 2 years. We report a case of infantile myofibromatosis located on the jaw, which is unique because of its large size (12 cm), its location and its neonatal presentation. It was a voluminous proliferate tumour with an ulcerated centre, located on the left jaw. Surgical excision was complete and the diagnosis was maded on histological examination. Recovery was uncomplicated with no recurrence on follow up. Diagnosis of infantile myofibromatosis is difficult because of the clinical heterogeneity and the histopathological appearance. The histological diagnosis relies on identification of two separate components, fascicular myofibroblastic at the periphery and hemangiopericytome in the centre. The most freqaent treatment is conservative surgical excision, because recurrence rates are low and there is a possibility of spontaneous regression. Some authors recommend conservative management of very large or multiple lesions particularly if excision will result in significant functional or cosmetic morbidity.


Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition.
Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this "unmasking" of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.


Video tracking algorithm of long-term experiment using stand-alone recording system.
Many medical and behavioral applications require the ability to monitor and quantify the behavior of small animals. In general these animals are confined in small cages. Often these situations involve very large numbers of cages. Modern research facilities commonly monitor simultaneously thousands of animals over long periods of time. However, conventional systems require one personal computer per monitoring platform, which is too complex, expensive, and increases power consumption for large laboratory applications. This paper presents a simplified video tracking algorithm for long-term recording using a stand-alone system. The feature of the presented tracking algorithm revealed that computation speed is very fast data storage requirements are small, and hardware requirements are minimal. The stand-alone system automatically performs tracking and saving acquired data to a secure digital card. The proposed system is designed for video collected at a 640 x 480 pixel with 16 bit color resolution. The tracking result is updated every 30 frames/s. Only the locomotive data are stored. Therefore, the data storage requirements could be minimized. In addition, detection via the designed algorithm uses the Cb and Cr values of a colored marker affixed to the target to define the tracked position and allows multiobject tracking against complex backgrounds. Preliminary experiment showed that such tracking information stored by the portable and stand-alone system could provide comprehensive information on the animal's activity.


Isolation of human immunodeficiency virus from a Japanese hemophilia B patient with AIDS.
Human immunodeficiency virus (HIV) was isolated from a Japanese hemophilia B patient with AIDS. This isolate, HIV[GUN-1], was infectious to several mature T-cell lines. Proteins with apparent molecular weights of 160, 55 and 25 kilodaltons were detected. Restriction enzyme cleavage patterns of the proviral genome indicated that HIV[GUN-1] is related to but clearly different from HTLV-III or ARV-2.


The use of vibroacoustic stimulation during the abnormal or equivocal biophysical profile.
To determine whether vibroacoustic stimulation during the biophysical profile can change the fetal behavioral state and thus improve the score without increasing the false-negative rate of the test. Eighty-one patients whose biophysical profile scores were 6 or lower after 15 minutes of observation had an electronic artificial larynx applied to the maternal abdomen in the region of the fetal head for 3 seconds, followed by continued observation for fetal movement, tone, and breathing for 15 minutes. We compared the obstetric and neonatal outcomes of 41 patients whose biophysical profile scores improved to normal after vibroacoustic stimulation with those of 283 patients whose scores were normal without vibroacoustic stimulation. Vibroacoustic stimulation did improve an abnormal or equivocal biophysical profile score to normal in 67 of 81 cases (82%). No antepartum stillbirths or perinatal deaths occurred. There was no increase in the obstetric and neonatal complication rates of cesarean delivery for fetal distress, meconium staining of the amniotic fluid, and the incidence of small for gestational age infants. Vibroacoustic stimulation improved the biophysical profile scores in most cases, an effect seen throughout the third trimester. Vibroacoustic stimulation did not appear to increase the false-negative rate of the biophysical profile and may reduce the incidence of unnecessary obstetric intervention.


[Counterimmunoelectrophoresis in the serologic diagnosis of cysticercosis in cattle].
Over the years 1983 to 1984 two-hundred and sixty-five bulls were examined during mass occurrence of bovine cysticercosis in one farm; out of this number 67 animals (25.3%) were confirmed autopsically as infected with cysticercosis. Counterimmunoelectrophoresis was used to examine the serum of slaughtered animals by help of two antigens--Taenia saginata and Taenia crassiceps. With T. saginata the sensitivity amounted to 44.8% and the specificity to 86.4%, with T. crassiceps to 28.3% and to 89.9%.


Cortical characterization of the perception of intelligible and unintelligible speech measured via high-density electroencephalography.
High-density electroencephalography was used to evaluate cortical activity during speech comprehension via a sentence verification task. Twenty-four participants assigned true or false to sentences produced with 3 noise-vocoded channel levels (1--unintelligible, 6--decipherable, 16--intelligible), during simultaneous EEG recording. Participant data were sorted into higher- (HP) and lower-performing (LP) groups. The identification of a late-event related potential for LP listeners in the intelligible condition and in all listeners when challenged with a 6-Ch signal supports the notion that this induced potential may be related to either processing degraded speech, or degraded processing of intelligible speech. Different cortical locations are identified as neural generators responsible for this activity; HP listeners are engaging motor aspects of their language system, utilizing an acoustic-phonetic based strategy to help resolve the sentence, while LP listeners do not. This study presents evidence for neurophysiological indices associated with more or less successful speech comprehension performance across listening conditions.


Conversion of graded to binary response in an activator-repressor system.
Appropriate regulation of gene expression is essential to ensure that protein synthesis occurs in a selective manner. The control of transcription is the most dominant type of regulation mediated by a complex of molecules such as transcription factors. In general, regulatory molecules are of two types: activator and repressor. Activators promote the initiation of transcription whereas repressors inhibit transcription. In many cases, they regulate the gene transcription on binding the promoter mutually exclusively and the observed gene expression response is either graded or binary. In experiments, the gene expression response is quantified by the amount of proteins produced on varying the concentration of an external inducer molecules in the cell. In this paper, we study a gene regulatory network where activators and repressors both bind the same promoter mutually exclusively. The network is modeled by assuming that the gene can be in three possible states: repressed, unregulated, and active. An exact analytical expression for the steady-state probability distribution of protein levels is then derived. The exact result helps to explain the experimental observations that in the presence of activator molecules the response is graded at all inducer levels, whereas in the presence of both activator and repressor molecules, the response is graded at low and high inducer levels and binary at an intermediate inducer level.


Radiologic Findings in Gabapentin-Induced Myositis.
Throughout recent years, Gabapentin has become increasingly used for the treatment of neuropathic pain. We report on a case of a 31 year old female who presented to the emergency department with unilateral leg pain, weakness, and swelling after increasingly titrating her Gabapentin dosage over three weeks. Magnetic resonance imaging confirmed the presence of myositis confined to the left thigh and the patient's symptoms and laboratory abnormalities resolved following Gabapentin cessation. While Gabapentin-induced myositis and rhabdomyolysis is a rare entity, it should be a diagnostic consideration for radiologists, particularly in the absence of infection or trauma.


Cloning, sequence analysis, and expression in Escherichia coli of a gene coding for an enzyme from Bacillus circulans K-1 that degrades guar gum.
A 2,048-bp nucleotide sequence containing a gene coding for an enzyme that degraded guar gum from Bacillus circulans K-1 was identified by polymerase chain reaction walking. This G-gene consisted of 1,551 nucleotides coding for a protein with Mr 55,242. The enzyme was overexpressed in Escherichia coli JM109 cells by the cloning the G-gene downstream of the lac Z promoter of pUC19. The molecular mass of recombinant G-enzyme estimated by SDS-PAGE was 62 KDa, close to that from strain K-1. Analysis of the recombinant enzyme showed GalNAc, Xyl, GlcNAc, Man, Glc, and Gal to account for 1.7%, 14.4%, 6.1%, 3.2%, 54.2%, and 10.4%, respectively, of the total monosaccharides. Polyacrylamide gel electrophoresis of this enzyme with staining gave a red band. The results suggested that the sugars accounted for the differences in the molecular masses. The recombinant enzyme had two kinds of N-terminal sequences, Thr-Met-Ile-Thr-Pro-Ser-Phe-Ala-Ser-Gly-Phe-Tyr-Val-Ile and Ile-Thr-Pro-Ser-Phe-Ala-Ser-Gly-Phe-Tyr-Val-Ile-Gly-Thr. Comparison of these sequences with the deduced N-terminal sequence coded for the G-gene showed that the amino acid, first Met, of the lac Z gene or the next residues Thr-Met in the recombinant enzyme were absent in the native enzyme. Methionines near and at the N-terminus of the mature protein probably were digested by methionine aminopeptidases of E. coli after translation. The properties of recombinant G-enzyme were similar to those of the enzyme from K-1 cells.


[Is a new therapeutic class justified in the treatment of type 2 diabetes?].
Type 2 diabetes is responsible for various micro and macro-vascular complications, appearing early in the course of the disease. The UKPDS results clearly demonstrate the interest of an early and intensive treatment of hyperglycaemia to reduce theses microvascular complications and, to a lesser extent, macrovascular complications. The UKPDS also demonstrate the limits of the current management of type 2 diabetes: delayed diagnosis when several complications already exist, difficulties to maintain an adequate glucose control over the time, particularly with monotherapy, need for an intensive combination treatment policy, unwanted effects of this intensive treatment (weight gain, hypoglycaemias). The 3 classes of oral antidiabetic agents currently available (sulfonylureas and meteglinide analogues, metformin, a-glucosidase inhibitors) imperfectly cover the current therapeutic needs. Thus, the new class, the thiazolidinediones, acting on key physiopathological components, appears as a welcome addition to the treatment of type 2 diabetes. The association of metformin (or a sulfonylurea) and a thiazolidinedione should permit to obtain early a better glycaemic control without the hypoglycaemic risk associated with intensive therapy at an early stage of type 2 diabetes.


Assessing influence of experimental parameters on formation of PCDD/F from ash derived from fires of CCA-treated wood.
Ash residues from fires of radiata pine timber, both untreated and treated with chromated copper arsenate (CCA), were analyzed for the presence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F). Fire conditions were simulated using a cone calorimeter. The sensitivity of the magnitude and profile of PCDD/F in the ash under controlled experimental conditions were examined to gain an insight into the formation of PCDD/F in a system containing CCA. The total amount of PCDD/F increased from 2.0 ng/kg of ash (0.05 ng of TE/kg of ash, using WHO-TEF) for untreated radiata pine to a maximum of 2700 ng/kg of ash (78 ng of TE/kg of ash) for 0.94% CCA. Ash containing CCA showed a distinct preference for formation of PCDFs, particularly the tetrachloro homologue. It is concluded that PCDD/F formation predominantly occurred via de novo synthesis during smoldering of the char rather than during the initial flaming and pyrolysis. Furthermore, the composition of the CCA constituents present in the timber was controlled to assess whether the physical presence of Cu, a known catalyst in PCDD/F production, was sufficient to account for the formation of PCDD/F in fires of timber impregnated with CCA.


A compassion-based treatment for couples with the female partner suffering from current depressive disorder: A randomized-controlled trial.
Studies have shown that depression and interpersonal relationships are interdependently connected and that including the intimate partner in treatment for depression has beneficial effects. Given evidence that compassion is both an interpersonal quality and a promising treatment target, the goal of this study was to examine the effects of a compassion-based, contemplative treatment for couples employing a multi-method approach for evaluation. In a pre-post-follow-up design, n = 53 different-sex couples including women with current depression were randomly assigned to a 10-week-long CBCT®-fC (Cognitively-Based Compassion Training/intervention for couples) or treatment-as-usual (TAU) condition. Multi-level linear regression models and post-hoc contrasts were calculated to determine changes in depressive symptoms, mindfulness and self-compassion, interpersonal functioning and neuroendocrine markers collected during a partnership appreciation task (PAT) in the laboratory before and after CBCT-fC treatment. While CBCT-fC led to a comparable decrease of depressive symptoms as TAU, the training specifically increased self-compassion and mindfulness versus TAU. Interestingly, interpersonal functioning did not improve, which was also reflected in participants' preferred self-focus in-between-session practices, instead of practices with interpersonal focus. There were no group-specific changes in psychobiological stress-marker reactivity. CBCT-fC was effective in decreasing current depressive symptomatology and increasing mindfulness, and self-compassion. Especially the motivation to participate, such as improving interpersonal functioning, should be addressed and intrinsic motives of the partners to be involved. In highly burdened individuals, self-regulation may need to be improved before co-regulation can be addressed, which would requiring longer treatments. Facilitating factors for engaging in the practice between-sessions seem meaningful.


Sulindac reversal of 15-PGDH-mediated resistance to colon tumor chemoprevention with NSAIDs.
Non-steroidal anti-inflammatory drugs prevent colorectal cancer by inhibiting cyclooxygenase (COX) enzymes that synthesize tumor-promoting prostaglandins. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a tumor suppressor that degrades tumor-promoting prostaglandins. Murine knockout of 15-PGDH increases susceptibility to azoxymethane-induced colon tumors. It also renders these mice resistant to celecoxib, a selective inhibitor of inducible COX-2 during colon neoplasia. Similarly, humans with low colonic 15-PGDH are also resistant to colon adenoma prevention with celecoxib. Here, we used aspirin and sulindac, which inhibit both COX-1 and COX-2, in order to determine if these broader COX inhibitors can prevent colon tumors in 15-PGDH knockout (KO) mice. Unlike celecoxib, sulindac proved highly effective in colon tumor prevention of 15-PGDH KO mice. Significantly, however, aspirin demonstrated no effect on colon tumor incidence in either 15-PGDH wild-type or KO mice, despite a comparable reduction in colonic mucosal Prostaglandin E₂ (PGE₂) levels by both sulindac and aspirin. Notably, colon tumor prevention activity by sulindac was accompanied by a marked induction of lymphoid aggregates and proximal colonic inflammatory mass lesions, a side effect seen to a lesser degree with celecoxib, but not with aspirin. These findings suggest that sulindac may be the most effective agent for colon cancer prevention in humans with low 15-PGDH, but its use may also be associated with inflammatory lesions in the colon.


Antioxidant activity, delayed aging, and reduced amyloid-β toxicity of methanol extracts of tea seed pomace from Camellia tenuifolia.
There is a growing interest in the exploitation of the residues generated by plants. This study explored the potential beneficial health effects from the main biowaste, tea seed pomace, produced when tea seed is processed. DPPH radical scavenging and total phenolic content assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as in vivo model to evaluate the beneficial health effects, including antioxidant activity, delayed aging, and reduced amyloid-β toxicity. Among all soluble fractions obtained from the extracts of tea seed pomace from Camellia tenuifolia, the methanol (MeOH)-soluble fraction has the best in vivo antioxidant activities. The MeOH-soluble extraction was further divided into six fractions by chromatography with a Diaion HP-20 column eluted with water/MeOH, and fraction 3 showed the best in vitro and in vivo antioxidant activities. Further analysis in C. elegans showed that the MeOH extract (fraction 3) of tea seed pomace significantly decreased intracellular reactive oxygen species, prolonged C. elegans lifespan, and reduced amyloid-β (Aβ) toxicity in transgenic C. elegans expressing human Aβ. Moreover, bioactivity-guided fractionation yielded two potent constituents from fraction 3 of the MeOH extract, namely, kaempferol 3-O-(2″-glucopyranosyl)-rutinoside and kaempferol 3-O-(2″-xylopyranosyl)-rutinoside, and both compounds exhibited excellent in vivo antioxidant activity. Taken together, MeOH extracts of tea seed pomace from C. tenuifolia have multiple beneficial health effects, suggesting that biowaste might be valuable to be explored for further development as nutraceutical products. Furthermore, the reuse of agricultural byproduct tea seed pomace also fulfills the environmental perspective.


Clostridium difficile disease: Diagnosis, pathogenesis, and treatment update.
Clostridium difficile infections are the leading cause of health care-associated infectious diarrhea, posing a significant risk for both medical and surgical patients. Because of the significant morbidity and mortality associated with C difficile infections, knowledge of the epidemiology of C difficile in combination with a high index of suspicion and susceptible patient populations (including surgical, postcolectomy, and inflammatory bowel disease patients) is warranted. C difficile infections present with a wide spectrum of disease, ranging from mild diarrhea to fulminant colitis or small bowel enteritis and recurrent C difficile infections. Early implementation of medical and operative treatment strategies for C difficile infections is imperative for optimal patient outcomes. National and international guidelines recommend early operative consultation and total abdominal colectomy with end ileostomy and preservation of rectum. Diverting loop ileostomy and colonic lavage followed by intravenous metronidazole and intracolonic vancomycin administered via the efferent limb of the ileostomy should be considered as an alternative to total colectomy in selected patients. New and emerging strategies for C difficile infection treatment include monoclonal antibodies, vaccines, probiotics, biotherapeutics, and new antibiotics. A successful C difficile prevention and eradication program requires a multidisciplinary approach that includes early disease recognition, implementation of guidelines for monitoring adherence to environmental control, judicious hand hygiene, evidence-based treatment and management strategies, and a focused antibiotic stewardship program. Surgeons are an important part of the clinical team in the management of C difficile infection prevention and treatment.


Observations on health services research and health policy analysis.
The importance of mutual communication between researchers and policy makers cannot be overestimated. Although economists are presumed to have an advantage, more interdisciplinary health services research is needed. The case for government support of research and use of its findings is not based solely on government spending for health care. The interests of the federal programs are not well served by a declining access to data or by ambiguous distinctions between research and policy analysis.


[Localization of protease inhibitors in the chorionic villi of the human placenta, by means of the immunoperoxidase technic].
Alpha-1-antitrypsin and alpha-1-antichymotrypsin have been studied in human placentas, from the first trimester to term pregnancy, by immunohistochemical method. Both proteinase inhibitors were localized to the cytoplasm of the villous syncytiotrophoblast, with a decreasing intensity of staining towards term pregnancy. The Hofbauer cells were intensely positive for intracellular alpha-1-antitrypsin and alpha-1-antichymotrypsin at all gestational ages. According to data of the literature we suggest that the existence of the proteinase inhibitors in the placental barrier possibly represents an important part in the defence mechanism of the placenta and may play a particular role in modifying the maternal immune response towards the foetus.


Central nervous system and vertebral malformation resembling the Arnold-Chiari syndrome in a Simmental calf.
Multiple congenital anomalies were identified in a stillborn calf, including severe cerebellar hypoplasia and central nervous system abnormalities resembling the Arnold-Chiari syndrome of malformation of calves. The Arnold-Chiari malformation occurs sporadically and has little economic impact, whereas cerebellar hypoplasia implies the presence of BVD virus in the herd.


Tapered fiber radiation sensor based on Ce/Tb:YAG crystals for remote γ-ray dosimetry.
A novel tapered fiber-optic radiation sensor (TFRS) based on cerium (Ce) and terbium (Tb) co-doped YAG scintillation crystals is demonstrated for the first time. Using the CO2 laser-heated method, a Ce/Tb:YAG crystal is well embedded into silica glass cladding without any cracks. The scintillation light emitted from the YAG scintillation crystal can be directly coupled into the derived silica optical fiber by the tapered region. The loss of the derived optical fiber is 0.14 dB/cm, which is one order of magnitude lower than the 1.59 dB/cm of the YAG crystal in the TFRS. Subsequently, strong photo- and radio-luminescence of Tb3+ (5D4→7F5) ions in TFRS are achieved under ultraviolet light and high-energy ray excitation, respectively. In particular, a prominent remote radiation response of the TFRS is presented under excitation by γ-rays through fusion splicing with multimode optical fibers. The response is approximately four times larger than that of a plastic scintillation fiber (BCF-12) sensor. Furthermore, the results possess high stability as well as a good linearity between the radiation dose rate and the response intensity. The TFRS in combination with an all-silica fiber system is a promising candidate for remote radiation detection.


Optimization of resolution and sensitivity of 4D NOESY using multi-dimensional decomposition.
Highly resolved multi-dimensional NOE data are essential for rapid and accurate determination of spatial protein structures such as in structural genomics projects. Four-dimensional spectra contain almost no spectral overlap inherently present in lower dimensionality spectra and are highly amenable to application of automated routines for spectral resonance location and assignment. However, a high resolution 4D data set using conventional uniform sampling usually requires unacceptably long measurement time. Recently we have reported that the use of non-uniform sampling and multi-dimensional decomposition (MDD) can remedy this problem. Here we validate accuracy and robustness of the method, and demonstrate its usefulness for fully protonated protein samples. The method was applied to 11 kDa protein PA1123 from structural genomics pipeline. A systematic evaluation of spectral reconstructions obtained using 15-100% subsets of the complete reference 4D 1H-13C-13C-1H NOESY spectrum has been performed. With the experimental time saving of up to six times, the resolution and the sensitivity per unit time is shown to be similar to that of the fully recorded spectrum. For the 30% data subset we demonstrate that the intensities in the reconstructed and reference 4D spectra correspond with a correlation coefficient of 0.997 in the full range of spectral amplitudes. Intensities of the strong, middle and weak cross-peaks correlate with coefficients 0.9997, 0.9965, and 0.83. The method does not produce false peaks. 2% of weak peaks lost in the 30% reconstruction is in line with theoretically expected noise increase for the shorter measurement time. Together with good accuracy in the relative line-widths these translate to reliable distance constrains derived from sparsely sampled, high resolution 4D NOESY data.


Expression of immunomodulatory genes in human monocytes induced by voriconazole in the presence of Aspergillus fumigatus.
We assessed the effect of voriconazole (VRC) on the expression and release of selected cytokines and chemokines in the THP-1 human monocytic cell line in response to Aspergillus fumigatus hyphal fragments (HF) by cDNA microarray analysis, reverse transcriptase (RT) PCR, and enzyme-linked immunosorbent assay. Stimulation of THP-1 cells by HF alone caused a significant up-regulation of CCL4 (MIP1B) and CCL16, while CCL2 (MCP1) was down-regulated. By comparison, in the presence of VRC, a large number of genes such as CCL3 (MIP1A), CCL4 (MIP1B), CCL5 (RANTES), CCL7 (MCP3), CCL11 (EOTAXIN), CCL15 (MIP1Delta), CXCL6, and CXCL13 were strongly up-regulated in THP-1 cells challenged by HF, whereas CCL20 (MIP3A) and CCL21 (MIP2) were down-regulated. Among five genes differentially expressed in THP-1 cells, IL12A, IL12B, and IL-16 were down-regulated whereas IL-11 and TGFB1 were significantly up-regulated in the presence of VRC. The inflammation-related genes IFNgamma, IL1R1, and TNFA were also up-regulated in THP-1 cells exposed to HF only in the presence of VRC. RT-PCR of four selected genes validated the results of microarrays. The release of interleukin 1beta (IL-1beta) and IL-12 was significantly increased from monocytes stimulated either by HF alone (P < 0.05) or in the presence of VRC (P < 0.01 and P < 0.05, respectively). In contrast, tumor necrosis factor alpha release from monocytes was enhanced only in the presence of VRC (P < 0.01). The chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1beta were decreased under both conditions (P < 0.01). These results demonstrate that in the presence of VRC, HF induces a more pronounced profile of gene expression in THP-1 cells than HF alone, potentially leading to more-efficient host resistance to A. fumigatus.


Retinal pigment epithelial tear in polypoidal choroidal vasculopathy.
To study the clinical characteristics of tears of the retinal pigment epithelium (RPE) in eyes with polypoidal choroidal vasculopathy (PCV). The authors report eight eyes of eight patients with PCV that had tears of the RPE. These were examined with angiography and tomography. Eight eyes of eight patients (seven men and one woman) had RPE tears at the margin of a serosanguineous pigment epithelial detachment (PED) associated with PCV. Tears of the RPE were detected at the initial visit in one eye and during follow-up without any treatment in five eyes. In two eyes, the RPE tears were detected 3 months and 6 months, respectively, after photodynamic therapy. In all eyes, the RPE tears were detected at the side opposite to the polypoidal lesions of the PEDs, and the fovea was not involved in the RPE tear. Visual acuity in the seven eyes without RPE tears on presentation ranged from 20/100 to 20/16 (median, 20/32). During follow-up, three of these eyes lost three or more lines of vision. At the final examination, while three of these eyes had visual acuity of 20/25 or better, the other four had visual acuity of 20/200 or worse. In eyes with PCV, RPE tears can occur at the margin of serosanguineous PEDs-either spontaneously or after photodynamic therapy.


Postmortem lung weight/body weight standards for term and preterm infants.
Assessment of lung development is a crucial component of the perinatal autopsy, especially in preterm infants. In current pathology practice, the diagnosis of lung hypoplasia in very premature infants (<28 weeks of gestation) is based on a lung weight/body weight ratio (LW/BW) of 1.5% or less. While useful to confirm the presence of marked pulmonary hypoplasia, the 1.5% threshold may be too stringent to detect more subtle degrees of pulmonary hypoplasia, as seen in association with rupture of membranes. The aim of this study was to establish reference values for postmortem LW/BW in preterm and term infants. To this end, we performed a retrospective analysis of fetuses and newborns (16-41 weeks of gestation) without known risk factors for pulmonary hypoplasia. Mean LW/BW ranged between 2.98-3.15% between 16-27 weeks, and decreased to 2.55% by 28-36 weeks and 1.79% at term. The 10th percentile for LW/BW was significantly higher in preterm infants (2.24% between 20-23 weeks, and 2.59% between 24-27 weeks) than in term infants (1.24% at >or=37 weeks, P < 0.01). We then correlated LW/BW of infants with risk factors for pulmonary hypoplasia with the newly established reference values. As expected, mean LW/BW of infants with congenital diaphragmatic hernia or severe renal anomalies was <1.5% (0.98% and 1.40%, respectively). Mean LW/BW of infants with prolonged (> 1 week) rupture of membranes (PROM) was 2.08%. Three of 12 (25%) preterm infants with PROM had pulmonary hypoplasia according to the traditional criteria (LW/BW <1.5%). However, an additional 4/12 (33%) infants with PROM had a LW/BW between 1.5% and the 10th percentile for age (2.2%), indicative of more subtle but potentially relevant pulmonary underdevelopment. In conclusion, we determined LW/BW reference values for preterm and term infants. Correlation of LW/BW with age-matched reference values at postmortem examination represents an invaluable additional tool to evaluate lung growth, particularly in preterm infants.


Bridged bis(4-thiazolidinones) and related compounds with antibacterial activity.
Condensation of 4,4'-diaminobiphenyl ether (1) and 4,4'-diaminobiphenyl methane (6) with various aldehydes gave diarylidenebiphenyl ethers 2a-d and diarylidenebiphenyl methanes 7a-c, respectively, which on cyclocondensation with merceptoacetic acid yielded 3,3'-[oxy-bis(4,1-phenylene)]-bis[(2-substituted phenyl)-4- thiazolidinones] 3a-d and 3,3'-[methylene-bis(4,1-phneylene)]-bis[2-substituted phenyl)-4-thiazolidinones] 8a-c. A series of 2,2'-[oxy-bis(4,1-phenylenenitrilo)]-bis[3- (substituted)-4-thiazolidinones] 5a and b and 2,2'-[methylene-bis(4,1-phnylenenitrilo)]-bis[3-(substituted)-4- thiazolidinones] 10a and b were synthesized from 4,4'-diaminobiphenyl ether (1) and 4,4'-diaminobiphenyl methane (6) via the corresponding dithiocarbamide biphenyl ethers 4a and b and dithiocarbamide biphenyl methanes 9a and b by cyclocondensation with monochloroacetic acid. The structures of compounds 2-10 are supported by elemental analysis and spectral data (IR, 1H NMR, 13C NMR). The specific rotation of compounds 3c, 8b and 8c was measured.


Structural and Functional Evidence for Testosterone Activation of GPRC6A in Peripheral Tissues.
G protein-coupled receptor (GPCR) family C group 6 member A (GPRC6A) is a multiligand GPCR that is activated by cations, L-amino acids, and osteocalcin. GPRC6A plays an important role in the regulation of testosterone (T) production and energy metabolism in mice. T has rapid, transcription-independent (nongenomic) effects that are mediated by a putative GPCR. We previously found that T can activate GPRC6A in vitro, but the possibility that T is a ligand for GPRC6A remains controversial. Here, we demonstrate direct T binding to GPRC6A and construct computational structural models of GPRC6A that are used to identify potential binding poses of T. Mutations of the predicted binding site residues were experimentally found to block T activation of GPRC6A, in agreement with the modeling. Using Gpr6ca(-/-) mice, we confirmed that loss of GPRC6A resulted in loss of T rapid signaling responses and elucidated several biological functions regulated by GPRC6A-dependent T rapid signaling, including T stimulation of insulin secretion in pancreatic islets and enzyme expression involved in the biosynthesis of T in Leydig cells. Finally, we identified a stereo-specific effect of an R-isomer of a selective androgen receptor modulator that is predicted to bind to and shown to activate GPRC6A but not androgen receptor. Together, our data show that GPRC6A directly mediates the rapid signaling response to T and uncovers previously unrecognized endocrine networks.


[The current state of obesity in Mexico].
Excess weight (overweight and obesity) is currently recognized as one of the most important challenges of public health in the world, given its size, speed of growth, and the negative effect on the population who suffers it. Overweight and obesity increases significantly the risk of chronic non-communicable diseases, and premature mortality, as well as the social cost of health. Today, Mexico has the second global prevalence of obesity in the adult population (30 %), which is ten times higher than Korea's or Japan's (4 %). Until 2012, 26 million Mexican adults were overweight, and 22 million, obese. This implies a major challenge for the health sector. Mexico needs to plan and implement strategies and cost-effective actions for the prevention and control of obesity in children, adolescents, and adults. Global experience shows that proper care of obesity and overweight demands to formulate and coordinate efficient multi-sectoral strategies for enhancing protective factors to health, particularly to modify individual behavior, family and community.


The cheek of a cheater: Effects of posing the left and right hemiface on the perception of trustworthiness.
Our cognitive mechanisms are designed to detect cheaters in social exchanges. However, cheater detection can be thwarted by a posed smile, which cheaters display with greater emotional intensity than cooperators. The present study investigated the role of hemifacial asymmetries in the perception of trustworthiness using face photographs with left and right cheek poses. Participants (N = 170) observed face photographs of cheaters and cooperators in an economic game. In the photographs, models expressed happiness or anger and turned slightly to the left or right to show their left or right cheeks to the camera. When the models expressed anger on their faces, cheaters showing the right cheek were rated as less trustworthy than cooperators (irrespective of cheeks shown) and cheaters showing the left cheek. When the models expressed happiness, trustworthiness ratings increased and did not differ between cheaters and cooperators, and no substantial asymmetries were observed. These patterns were replicated even when the face photographs were mirror-reversed. These results suggest that a cheater's fake smile conceals an uncooperative attitude that is displayed in the right hemiface, ultimately disguising cheater detection.


Characterization of plant aquaporins.
Plants have been reported to contain a large set of aquaporins (38 for Arabidopsis), which has been divided into four subfamilies on the basis of similarities in their amino acid sequences. They belong to the large superfamily of major intrinsic proteins (MIP), which was the basis for the nomenclature PIP, TIP, and NIP, also indicating the subcellular localization plasma membrane, tonoplast, and nodule of the respective founding member. The fourth subfamily of small and basic intrinsic proteins is not well characterized so far. The increasing number of reports dealing with various aspects of plant aquaporins is starting to advance our understanding of aquaporin biology in plants. Fundamental questions include: what is the basic function of the different plant aquaporins, what is their primary substrate, and what is the consequence of function/malfunction of a particular aquaporin for the overall function of the plant? Biochemical and biophysical techniques can be employed to get information on the basic functional characteristics of plant aquaporins. An impressive set of techniques has been used to study aquaporin function on molecular, subcellular, and cellular levels in plants, as well as in heterologous expression systems. The physiological role of aquaporins in plants is much less well understood, but reports unraveling the physiological role of aquaporins, mainly employing genetic techniques and functional measurement on the whole plant level, are emerging. The goal of this chapter is to give an overview on the applied methods, together with some exemplary findings.


Analysis of vector models in quantification of artifacts produced by standard prosthetic inlays in Cone-Beam Computed Tomography (CBCT)--a preliminary study.
Cone-beam computed tomography (CBCT) is a relatively new, but highly efficient imaging method applied first in dentistry in 1998. However, the quality of the obtained slices depends among other things on artifacts generated by dental restorations as well as orthodontic and prosthetic appliances. The aim of the study was to quantify the artifacts produced by standard prosthetic inlays in CBCT images. The material consisted of 17 standard prosthetic inlays mounted in dental roots embedded in resin. The samples were examined by means of a large field of view CBCT unit, Galileos (Sirona, Germany), at 85 kV and 14 mAs. The analysis was performed using Able 3DDoctor software for data in the CT raster space as well as by means of Materialise Magics software for generated vector models (STL). The masks generated in the raster space included the area of the inlays together with image artifacts. The region of interest (ROI) of the raster space is a set of voxels from a selected range of Hounsfield units (109-3071). Ceramic inlay with zirconium dioxide (Cera Post) as well as epoxy resin inlay including silica fibers enriched with zirconium (Easy Post) produced the most intense artifacts. The smallest image distortions were created by titanium inlays, both passive (Harald Nordin) and active (Flexi Flange). Inlays containing zirconium generated the strongest artifacts, thus leading to the greatest distortions in the CBCT images. Carbon fiber inlay did not considerably affect the image quality.


Cost-efficacy of MR-guided neurointerventions.
This article summarizes the available data on the cost-efficacy of interventional MR imaging and discusses its potential future role in the diagnosis and management of neurologic diseases and disorders.


Clinical and prognostic significance of a reverse dipping pattern on ambulatory monitoring: An updated review.
Reverse or inverted dipping (ie, the phenomenon characterized by higher nighttime compared with daytime blood pressure values) is an alteration of circadian blood pressure rhythm frequently documented in hypertension, type 2 diabetes mellitus, chronic kidney disease, and sleep apnea syndrome, and generally regarded as a harmful condition. Available literature on the clinical and prognostic implications of reverse dipping is scanty. The present article will review a number of relevant issues concerning reverse dipping, in particular: (1) its possible mechanisms; (2) prevalence and clinical correlates, (3) concomitant cardiac and extracardiac subclinical organ damage; (4) association with acute and chronic cardiovascular diseases; (5) prognostic value in predicting cardiovascular events and mortality; and (6) therapeutic interventions aimed at reverting this abnormal circadian blood pressure rhythm.


Efficacy and safety of thrombectomy for acute ischaemic stroke in patients with pre-stroke mRS scores of 2-3: Real-world evaluation from an open-label, prospective, multicentre, observational study.
This study assessed the efficacy and safety of thrombectomy for acute ischaemic stroke in a population with pre-stroke modified Rankin scale (mRS) scores of 2-3 using real-world data. Our sample set included 2313 consecutive patients enrolled in the Kanagawa Registry of Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry between January 2018 and June 2020 in 40 stroke centres in Kanagawa Prefecture, Japan. Patients treated with intravenous tissue plasminogen activator (t-PA), thrombectomy, or both were included. Patients with pre-stroke mRS scores of 4-5 and those treated only with intra-arterial thrombolysis were excluded. The primary outcome of this study was an mRS score of 0-3 at 90 days after onset to assess the efficacy of thrombectomy for pre-stroke disabled individuals. We performed multivariate logistic regression analyses to investigate independent factors for a 90-day mRS score of 0-3. We also performed nearest-neighbour within-calliper matching between thrombectomy and t-PA only. After excluding patients meeting the exclusion criteria, we analysed data of 2136 consecutive patients, of which 315 (14.7%) had pre-stroke disabilities (mRS score 2-3). A 90-day mRS score of 0-3 was achieved by 33.3% of patients with pre-stroke mRS scores of 2-3. According to multivariate analysis, the National Institutes of Health Stroke Scale (NIHSS) score was an independent factor. Furthermore, after propensity-score matching, thrombectomy showed considerable superiority for achieving a 90-day mRS score of 0-3. Intravenous t-PA and especially thrombectomy were safe and effective for the population with pre-stroke disabilities, particularly for patients with low NIHSS scores.


Soil Application of Metarhizium anisopliae JEF-314 Granules to Control, Flower Chafer Beetle, Protaetia brevitarsis seulensis.
Root-feeding Scarabaeidae, particularly white grubs are considered among the most harmful coleopteran insect pests in turfgrass. In this work, sixteen entomopathogenic fungal species were assayed against flower chafer beetle, Protaetia brevitarsis (Coleoptera: Scarabaeidae) and Metarhizium anisopliae JEF-314 showed high virulence. The control ability of the isolate JEF-314 has been in detail tested for a model insect flower chafer beetle. Further analyses showed insect stage-dependent virulence where the fungal virulence was the highest against smaller instar larvae. Additionally, we confirmed that millet-based solid cultured granule was effective against the soil-dwelling larval stage. The isolate also showed a similar ability for a representative pest (Popillia spp.) in laboratory conditions. Our results clearly suggest a high potential of M. anisopliae JEF-314 to control the flower chafer beetle, possibly resulting in controlling of root-feeding white grubs in turfgrass. Based on the insect life cycle and susceptibility to the fungus, late spring and summer time would be the optimum time to apply JEF-314 granules for an effective control. Further characterization of the efficacy of the fungus under field conditions against the Scarabaeidae beetles might provide an efficient tool to control this beetle in an environment-friendly way.


Review. The strength and genetic basis of reproductive isolating barriers in flowering plants.
Speciation is characterized by the evolution of reproductive isolation between two groups of organisms. Understanding the process of speciation requires the quantification of barriers to reproductive isolation, dissection of the genetic mechanisms that contribute to those barriers and determination of the forces driving the evolution of those barriers. Through a comprehensive analysis involving 19 pairs of plant taxa, we assessed the strength and patterns of asymmetry of multiple prezygotic and postzygotic reproductive isolating barriers. We then reviewed contemporary knowledge of the genetic architecture of reproductive isolation and the relative role of chromosomal and genic factors in intrinsic postzygotic isolation. On average, we found that prezygotic isolation is approximately twice as strong as postzygotic isolation, and that postmating barriers are approximately three times more asymmetrical in their action than premating barriers. Barriers involve a variable number of loci, and chromosomal rearrangements may have a limited direct role in reproductive isolation in plants. Future research should aim to understand the relationship between particular genetic loci and the magnitude of their effect on reproductive isolation in nature, the geographical scale at which plant speciation occurs, and the role of different evolutionary forces in the speciation process.


Deep Learning Analysis of Mammography for Breast Cancer Risk Prediction in Asian Women.
The purpose of this study was to develop a mammography-based deep learning (DL) model for predicting the risk of breast cancer in Asian women. This retrospective study included 287 examinations in 153 women in the cancer group and 736 examinations in 447 women in the negative group, obtained from the databases of two tertiary hospitals between November 2012 and March 2022. All examinations were labeled as either dense breast or nondense breast, and then randomly assigned to either training, validation, or test sets. DL models, referred to as image-level and examination-level models, were developed. Both models were trained to predict whether or not the breast would develop breast cancer with two datasets: the whole dataset and the dense-only dataset. The performance of DL models was evaluated using the accuracy, precision, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC). On a test set, performance metrics for the four scenarios were obtained: image-level model with whole dataset, image-level model with dense-only dataset, examination-level model with whole dataset, and examination-level model with dense-only dataset with AUCs of 0.71, 0.75, 0.66, and 0.67, respectively. Our DL models using mammograms have the potential to predict breast cancer risk in Asian women.


Fixation methods can differentially affect ciliary protein immunolabeling.
Primary cilia are immotile, microtubule-based organelles present on most cells. Defects in primary cilia presence/function result in a category of developmental diseases referred to as ciliopathies. As the cilia field progresses, there is a need to consider both the ciliary and extraciliary roles of cilia proteins. However, traditional fixation methods are not always suitable for examining the full range of localizations of cilia proteins. Here, we tested a variety of fixation methods with commonly used cilia markers to determine the most appropriate fixation method for different cilia proteins. Mouse inner medullary collecting duct and human retinal pigmented epithelial cells were grown to confluence, serum starved, and fixed with one of the following fixation agents: paraformaldehyde-sucrose, paraformaldehyde-PBS, methanol, cytoskeletal buffer followed by methanol, or three variations of cytoskeletal buffer-paraformaldehyde fixation. Each cell type and fixation method combination was probed with the following ciliary markers: acetylated α-tubulin, detyrosinated tubulin, polyglutamylated tubulin, β-tubulin, adenylyl cyclase 3 (AC3), ADP-ribosylation factor-like protein 13b (Arl13b), centrosome and spindle pole associated protein 1 (CSPP1), or intraflagellar transport protein 20 (IFT20). Intraflagellar transport protein 88 (IFT88) and GM130 (Golgi marker) were also used. We assessed actin (via phalloidin) and microtubule integrity, centrioles, cilia, and two extraciliary sites (mitotic figures and Golgi). For the cilia markers examined, paraformaldehyde fixation preserved cilia immunolabeling of cilia-membrane proteins (AC3 and Arl13b), but failed to reveal cilia immunostaining of axonemal proteins (CSPP1 and IFT20). Methanol revealed cilia labeling for some axonemal proteins, but not others, and this depended on cell type. Generally, any method that first included a wash in cytoskeletal buffer, before fixing, revealed more distinct cilia immunolabeling for axonemal proteins (CSPP1, IFT20, and IFT88), but resulted in the loss of cilia labeling for cilia-membrane proteins (AC3 and Arl13b). All three different post-translational modifications of tubulin antibodies positively immunolabeled cilia in all fixation methods tested. Ultimately, we found that fixing cells in a solution of paraformaldehyde prepared in cytoskeletal buffer allowed for the preservation of cilia immunolabeling for most cilia proteins tested and allowed visualization of two extraciliary sites (mitotic figures and Golgi). Some general patterns were observed to guide in the choice of a fixation agent. Cilia-membrane proteins generally benefit from quick fixation with no prior permeabilization, whereas axonemal proteins tend to benefit from permeabilization and use of cytoskeletal buffer.


Stability of cataplexy over several months--information for the design of therapeutic trials.
Twenty-seven narcoleptic patients severely affected with cataplexy completed four symptom diaries over a 4-month period in order to clarify some of the controversies surrounding assessment of anticataplectic medications. The home diary method was found to be a viable model for the assessment of anticataplectic activity. Assessment of reliability in 1-, 2-, 3-, 4-, 5- and 10-day intervals indicated that reliability increases with the number of days included. A 10-day design was found to be optimal. Reliability decreased, however, with each successive diary over the 4-month period. Power analysis indicates that two groups of 30-40 subjects in a parallel design, or one group of 30-40 subjects in a crossover design, would be sufficient to demonstrate a significant therapeutic anticataplectic effect in most cases. A "first diary effect" was observed, suggesting that a training period prior to the actual trial might improve reliability. Whether the patient was treated or untreated with stimulant medications did not affect severity or fluctuation of cataplexy, suggesting that both groups of patients could be included in therapeutic trials. No time-of-day fluctuation was observed in the daily distribution of cataplexy attacks. Sudden increases in cataplexy were often, although not always, caused by unusual emotional events or sleepiness. The finding of a long-lasting "precataplectic" feeling or "aura" pointed to the need to carefully clarify the symptom prior to beginning a therapeutic trial.


Effects of magnetic field on the antioxidant enzyme activities of suspension-cultured tobacco cells.
Effects of magnetic fields (MFs) on the activities of antioxidant enzymes of suspension-cultured tobacco cells were investigated. Compared with the control cells, exposure of the cells to static MF with the magnitudes of 10 and 30 mT for 5 days, 5 h each day, increased the activity of superoxide dismutase (SOD). In contrast, the activity of the catalase (CAT) and ascorbate peroxidase (APX) was decreased by MF, compared with those of the control cells. Level of lipid peroxidation was also increased by MF. It suggests that MF could deteriorate antioxidant defense system of plant cells.


Tumor-Targeted and Clearable Human Protein-Based MRI Nanoprobes.
Biocompatibility, targeting, and clearance are key challenges in the design of new MRI contrast agents. Herein, we report on a tumor-targeting, gadolinium biomineralized human transferrin (Tf) protein-based nanoparticle (Gd@Tf NP) for MRI use. As compared to the conventionally used gadolinium chelates, the resultant Gd@Tf NPs possess outstanding chemical stability and exhibited superior longitudinal relaxation. More importantly, our MR images show that Gd@Tf indeed retained the natural tumor targeting ability and the subsequent tumor retrieval biofunctions of Tf. Thus, such Tf protein-based MR NPs integrate T1 signal amplification, precise tumor targeting, and systematic clearance capabilities. They offer a new approach to design biocompatible multifunctional MRI contrast agents for a wide range of clinical imaging and treatment applications.


[Detection of anti-Lassa antibodies in the Western Forest area of the Ivory Coast].
Lassa fever is an African viral hemorrhagic fever (VHF) known to be endemic in a number of West African countries including Nigeria, Sierra Leone, Liberia and Guinea. Despite having common borders with Liberia and Guinea, Côte d'Ivoire has never reported any cases of Lassa fever. In March 2000, as part of a research project on VHF--mainly yellow fever, Lassa fever and Ebola fever--in Guinea and Cote d'Ivoire, an exploratory survey was conducted to assess knowledge about VHF and immunological status against Lassa virus among forest workers in the Duekoue and Guiglo regions. One hundred and sixty-three male forest workers were interviewed using a questionnaire designed to assess risk factors for VHF exposure and personal medical history over the last 12 months. Detection of IgG antibodies against Lassa virus was performed by immunofluorescence assay with Lassa virus antigens from the Josiah and Las/AV strains. The overall prevalence of IgG antibodies was 26% (42/161). Among the Lassa IgG positive subjects, 38.5% were loggers including 20% that were positive at a serum dilution of 1/40 and 46.7% were national park workers or forest rangers including 69% that were positive at a dilution of 1/40 and more. Forty-one percent of subjects had heard of VHF including 14% who attributed it to animals and 2% who attributed it to plants. Contact with rodents was frequent and more than 50% of subjects had either eaten or skinned rodents. Although the prevalence of anti-Lassa IgG antibodies seemed high in the study population, no conclusion can be about level of exposure to Lassa virus.


Comprehensive Analysis of CDC27 Related to Peritoneal Metastasis by Whole Exome Sequencing in Gastric Cancer.
The peritoneum is the most common metastatic site of gastric cancer and is associated with a dismal prognosis. However, there is no reliable biomarker for predicting peritoneal metastasis (PM). Whole-exome sequencing (WES) was performed on formalin-fixed, paraffin-embedded (FFPE) samples from 63 patients with stage I-III gastric cancer and circulating tumor DNA (ctDNA) samples from 10 patients with stage IV gastric cancer. Differentially expressed genes (DEGs) were identified between the PM and non-PM groups and analyzed by multiple bioinformatics analyses. Univariate and multivariate Cox regression analyses were used to identify the risk factors for PM and a risk score model was developed. The number of mutant genes and the tumor mutation burden (TMB) in the PM group were higher than those in the non-PM group (p < 0.05). There was a significant positive correlation between the number of mutant genes and the TMB (R2 = 0.9997). The risk of PM was significantly higher in the high TMB group than in the low TMB group (p = 0.045). Forty-nine DEGs were identified as associated with PM in gastric cancer. CDC27 mutations were associated with a higher risk for PM and poor survival. The CDC27 mutations were located in the Apc3 region, the TPR region, and the phosphorylation region, and new mutation sites were not included in the TCGA database. Multivariable Cox regression analysis demonstrated that pathological T stage, poor tumor differentiation, Borrmann type, and CDC27 mutations were independent predictive factors of PM. A risk score model was constructed that demonstrated good performance. Through WES, we identified 49 DEGs relevant to PM in gastric cancer. CDC27 mutations were independently associated with PM by statistical and bioinformatics analyses. A risk score model was built and was demonstrated to effectively discriminate gastric cancer patients with and without PM.


Conflict and criterion setting in recognition memory.
Recognition memory requires both retrieval processes and control processes such as criterion setting. Decision criteria were manipulated by offering different payoffs for correct "old" versus "new" responses. Criterion setting influenced the following late-occurring (1,000+ ms), conflict-sensitive event-related brain potential (ERP) components: the stimulus-locked late posterior negativity (LPN) and the response-locked error-related negativity (ERN). The LPN-ERN were most negative to hits under conservative payoff conditions involving conflict between the correct old response and the payoff for new responses. This same conservative-hit condition was most frequently associated with response reversals when fast initial judgments were followed by slower judgments. Postresponse ERP activity may index conflict-sensitive processes underlying postretrieval cognitive control mechanisms involved with assessing responses to current items and updating response criteria on later trials.


Expression Analysis of Long Non-Coding RNA HAR1A and HAR1B in HBV-Induced Hepatocullular Carcinoma in Chinese Patients.
To determine the clinical relevance of long noncoding RNA (lncRNA) HAR1A and HAR1B expression in hepatocellular carcinoma (HCC). In this study, we enrolled 50 cases of chronic hepatitis B (CHB) without cirrhosis, 50 cases of CHB and liver cirrhosis (LC), and 100 cases of HBV and HCC. The expression profiles of lncRNA HAR1A and HAR1B were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of HAR1A and HAR1B were significantly lower in the HCC group, compared with the CHB and LC groups (P <.01). HAR1A and HAR1B were negatively associated with histologic grade and TNM (tumor/nodes/metastasis) stage (all P <.05). Univariable multivariable analysis showed that decreased HAR1A (HR = 0.753, P = .02) and HAR1B (HR = 0.551, P = .01) levels were independent predictors for shorter overall survival (OS) in HCC. Decreased HAR1A and HAR1B expression in HCC indicates poor prognosis.


Upper eyelid reconstruction with a hard palate mucosa-lined bipedicled myocutaneous flap.
The upper eyelid is very difficult to reconstruct because smooth opening and closure of the eyelid must be maintained. A patient is presented in whom a hard palate mucosa-lined bipedicled myocutaneous flap containing innervated orbicularis oculi was used to successfully reconstruct a subtotal upper eyelid defect. Good functional and aesthetic results were achieved. This method may be a good alternative for reconstruction of large upper eyelid defects.