Common features of atopic dermatitis with hypoproteinemia.
The purpose of this study was to identify the causes, symptoms, and complications of hypoproteinemia to prevent hypoproteinemia and provide appropriate treatment to children with atopic dermatitis. Children diagnosed with atopic dermatitis with hypoproteinemia and/or hypoalbuminemia were retrospectively reviewed. The patients' medical records, including family history, weight, symptoms, treatment, complications, and laboratory test results for allergies and skin cultures, were examined. Twenty-six patients (24 boys) were enrolled. Seven cases had growth retardation; 7, keratoconjunctivitis; 6, aural discharges; 5, eczema herpeticum; 4, gastrointestinal tract symptoms; and 2, developmental delays. In 21 cases, topical steroids were not used. According to the blood test results, the median values of each parameter were elevated: total IgE, 1,864 U/mL; egg white-specific IgE, 76.5 kUA/L; milk IgE, 20.5 kUA/L; peanut IgE, 30 kUA/L; eosinophil count, 5,810/μL; eosinophil cationic protein, 93.45 μg/L; and platelet count, 666.5×103/μL. Serum albumin and total protein levels decreased to 2.7 g/dL and 4.25 g/dL, respectively. Regarding electrolyte abnormality, 10 patients had hyponatremia, and 12, hyperkalemia. Systemic antibiotics were used to treat all cases, and an antiviral agent was used in 12 patients. Electrolyte correction was performed in 8 patients. Hypoproteinemia accompanying atopic dermatitis is common in infants younger than 1 year and may occur because of topical steroid treatment continuously being declined or because of eczema herpeticum. It may be accompanied by growth retardation, keratoconjunctivitis, aural discharge, and eczema herpeticum and can be managed through skin care and topical steroid application without intravenous albumin infusion.


Training Family Medicine Residents to Perform Home Visits: A CERA Survey.
Home visits have been shown to improve quality of care, save money, and improve outcomes. Primary care physicians are in an ideal position to provide these visits; of note, the Accreditation Council for Graduate Medical Education no longer requires home visits as a component of family medicine residency training. To investigate changes in home visit numbers and expectations, attitudes, and approaches to training among family medicine residency program directors. This research used the Council of Academic Family Medicine Educational Research Alliance (CERA) national survey of family medicine program directors in 2015. Questions addressed home visit practices, teaching and evaluation methods, common types of patient and visit categories, and barriers. There were 252 responses from 455 possible respondents, representing a response rate of 55%. At most programs, residents performed 2 to 5 home visits by graduation in both 2014 (69% of programs, 174 of 252) and 2015 (68%, 172 of 252). The vast majority (68%, 172 of 252) of program directors expect less than one-third of their graduates to provide home visits after graduation. Scheduling difficulties, lack of faculty time, and lack of resident time were the top 3 barriers to residents performing home visits. There appeared to be no decline in resident-performed home visits in family medicine residencies 1 year after they were no longer required. Family medicine program directors may recognize the value of home visits despite a lack of few formal curricula.


Impact of Vaccination on Distribution of T Cell Subsets in Antiretroviral-Treated HIV-Infected Children.
Antiretroviral therapy (ART) is generally prescribed to patients with human immunodeficiency virus (HIV) infection with vaccination introduced to prevent disease complications. However, little is known about the influence of immunization on T cell subsets' distribution during the course of infection. This study aims to identify the impact of viral replication and immunization on naïve, effector, effector memory, and central memory T cell subpopulations in ART-treated HIV-infected children. Fifty patients were recruited and injected intramuscularly with influenza A (H1N1) 2009 vaccine on the day of enrollment (day 0) and day 28. Blood samples were collected for pre- and postvaccination on days 0 and 56 for analyzing T cell phenotypes by flow cytometry. Phenotypes of all T cell subsets remained the same after vaccination, except for a reduction in effector CD8+ T cells. Moreover, T cell subsets from patients with controllable viral load showed similar patterns to those with virological failure. Absolute CD4 count was also found to have a positive relationship with naïve CD4+ and CD8+ T cells. In conclusion, vaccination and viral replication have a little effect on the distribution of T cell subpopulations. The CD4 count can be used for prediction of naïve T cell level in HIV-infected patients responding to ART.


Constructive and Unproductive Processing of Traumatic Experiences in Trauma-Focused Cognitive-Behavioral Therapy for Youth.
Although there is substantial evidence to support the efficacy of cognitive-behavioral treatments (CBT) for posttraumatic stress disorder (PTSD), there is some debate about how these treatments have their effects. Modern learning theory and cognitive and emotional processing theories highlight the importance of reducing avoidance, facilitating the constructive processing of feared experiences, and strengthening new inhibitory learning. We examined variables thought to be associated with unproductive and constructive processing of traumatic experiences in a sample of 81 youth with elevated PTSD symptoms, who received Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for abuse or traumatic interpersonal loss. Sessions during the trauma narrative phase of TF-CBT were coded for indicators of unproductive processing (overgeneralization, rumination, avoidance) and constructive processing (decentering, accommodation of corrective information), as well as levels of negative emotion. In previous analyses of this trial (Ready et al., 2015), more overgeneralization during the narrative phase predicted less improvement in internalizing symptoms at posttreatment and a worsening of externalizing symptoms over the 12-month follow-up. In contrast, more accommodation predicted improvement in internalizing symptoms and also moderated the negative effects of overgeneralization on internalizing and externalizing symptoms. The current study examined correlates of overgeneralization and accommodation. Overgeneralization was associated with more rumination, less decentering, and more negative emotion, suggesting immersion in trauma-related material. Accommodation was associated with less avoidance and more decentering, suggesting a healthy distance from trauma-related material that might allow for processing and cognitive change. Decentering also predicted improvement in externalizing symptoms at posttreatment. Rumination and avoidance showed important associations with overgeneralization and accommodation, respectively, but did not predict treatment outcomes. This study identifies correlates of overgeneralization and accommodation that might shed light on how these variables relate to unproductive and constructive processing of traumatic experiences.


Volitional and Nonvolitional Responses to Hypnotic Suggestions: Predictors and Subjective Experience.
This investigation combined the data from two studies that used modified scoring of the Harvard Group Scale of Hypnotic Susceptibility (Shor & Orne, 1962) to evaluate deliberate, volitional responses to suggestions. One study also employed subjective ratings of each item of the Harvard Scale, with comparisons of nonvolitional, volitional, and non-responses. Based on the assumption that participants would have marked volitional responses as positive responses using the traditional scale, the traditional scoring method was found to inflate mean hypnotic responsiveness by nearly one point. Two hypothesized correlates of hypnotic performance, rapport with the hypnotist and a phenomenological measure of hypnosis, increased significantly when volitional responses were taken into account. The way in which participants were recruited did not predict volitional responses, but individuals who reported deliberate responses to suggestions from the Harvard Scale were less likely to express willingness to participate in future studies. Some of the volitional responses to the items were rated as subjectively more real compared to no responses, though nonvolitional responses were rated as the most real compared with compliance responses and no responses for all items. More difficult items were more likely to be performed volitionally than easier items. It is suggested that future studies using hypnotic inventories account for volitional responses. The nature of deliberately produced responses should also be examined using qualitative and quantitative data, especially with respect to how a given suggestion may affect the execution of the volitional behavior.


[Day-to day variability of cardiac pressure values in horses measured with right heart catheterization on 3 consecutive days].
In the present study, a right heart catheterisation was carried out on three consecutive days in 17 healthy horses to evaluate the day-to-day variability of cardiac pressure values. Cardiac pressure values were measured in the right atrium, the right ventricle, the pulmonary artery, and the pulmonary capillaries (pulmonary artery wedge pressure). Additionally it was examined wether the cardiac pressure variability was influenced by the heart rate and if there are differences between trained and untrained horses. Beside the coefficient of variances, statistical analysis with assessment of variance components were carried out. Therefore the variation between repeated measurements at one day and within one horse, and the variation between repeated measurements over three days and within the horses (day to day intraindividual variation) as well as the variation between the horses (interindividual variation) were taken into account. The absolute interindividual variance of the pressure values and the heart rate was between 0.4 and 19.6 at all day and for all horses. Between trained and untrained horses the variation of the pressure values and the heart rate was lower than in the trained horses. A significant difference between trained and untrained horses was seen in right atrial mean pressure (p < 0.001) and right atrial diastolic pressure (p < 0.005). The coefficient of variances of the mean heart rate was 11.8%. The coefficient of variances of the different pressure values ranged between 13.1 (mean pulmonary artery pressure) and 46.4% (right ventricular pressure). By splitting the variances, 54.4-78.9% of the variation was caused by the effect of days, 6.2-30.7% of the variation was caused by the effect of horses and 12.5-23% of the variation was caused by the repeated measurements at the different days. In sumary the results shows that nearly all of the pressure values had a low effect of days on the variation, thus cardiac pressure measurements at one day seem to be sufficient.


Preservation of the ureteral blood supply in rat renal transplantation.
A new technique of preserving ureteral blood supply in heterotopic rat renal transplantation is described. This entails leaving an intact gonadal artery in continuity with the donor aortic stump, which is anastomosed to the recipient aorta. Comparison of this technique with conventional methods wherein the spermatic artery is ligated revealed a marked decrease in the incidence of ureteral complications with the former. Preservation of adequate blood supply to the ureter in experimental rat renal transplantation provides more consistent results and lessens the risk of unnecessary animal loss.


Perfusion of the Rotator Cuff Tendon According to the Repair Configuration Using an Indocyanine Green Fluorescence Arthroscope: A Preliminary Report.
The disturbance of rotator cuff tendon perfusion has been connected with the suture-bridge configuration repair (SBCR) technique; however, in vivo assessments of the tendon blood supply have been problematic with other modalities. An evaluation of tissue perfusion by an indocyanine green (ICG) fluorescence arthroscope has been developed to counteract this difficulty. To verify the hindrance of perfusion in SBCR, we used an ICG fluorescence camera to compare parallel-type transosseous repair (PTR) and SBCR in rabbits immediately and at 3 days after rotator cuff repair. Controlled laboratory study. Acute rotator cuff repair was performed on the shoulders of 10 rabbits. Both shoulders were repaired using either PTR or SBCR. For PTR, simple repair was performed through 2 parallel transosseous tunnels created using a microdrill. For SBCR, 2 additional crisscross transosseous tunnels were added to mimic arthroscopic SBCR. Immediately after repair, ICG was injected through the ear vein, and images were recorded using an ICG fluorescence camera. Tendon perfusion was compared by measuring fluorescence intensity using ImageJ software in both methods. At 3 days after rotator cuff repair, a reassessment of ICG fluorescence was performed. In addition, as a subsidiary study, a comparison of each repair method and a healthy tendon was performed (PTR vs healthy tendon and SBCR vs healthy tendon). Six rabbits (3 for each comparison) were included. Immediately after rotator cuff repair, the mean (±SD) grayscale intensity of ICG fluorescence was weaker in SBCR than PTR in 10 specimens (65.9 ± 47.6 vs 84.3 ± 53.4 per pixel, respectively; P = .003). At 3 days after repair, 8 specimens were included in the analysis because suture strands failed in 2 specimens in SBCR. The mean intensity of fluorescence was still weaker in SBCR compared with PTR (52.5 ± 13.7 vs 60.2 ± 22.7 per pixel, respectively; P = .077). The mean fluorescence intensity compared with a healthy tendon was 83.2% ± 9.5% in PTR and 63.2% ± 13.2% in SBCR. Our ICG fluorescence camera system was able to detect ICG fluorescence in an acute rabbit rotator cuff repair model. SBCR showed inferior tendon perfusion immediately after repair. At 3 days after repair, SBCR still showed inferior fluorescence intensity, although it did not reach statistical significance. In this study, SBCR hindered perfusion at the tendon in the compressed area. This finding may affect rotator cuff tendon healing and failure mode.


siRNA-mediated inhibition of hTERC enhances radiosensitivity of cervical cancer.
To investigate the influence of telomerase activity, apoptosis, radiosensitivity of cervical cancer after siRNA-mediated knockdown of telomerase RNA and evaluate in vivo growth with gene interference. We studied siRNA-targeting-telomerase RNA transfection into the Hela cell line. Expression of hTERC mRNA was detected by RT-PCR and telomerase activity was measured by the TRAP assay. Growth inhibition was determined by MTT assay and radiosensitivity of the cervical cancer cells was examined by colony formation assay. In addtion, effects of hTERC inhibition in vivo were studied by injection of siRNA-transfected Hela cells into nude mice. The hTERC siRNA effectively downregulated the expression of hTERC mRNA and also reduced the telomerase activity to 30% of the untreated control vlaue. The viability of hTERC siRNA transfected Hela cells was reduced by 44.7% after transfection. After radiation treatment, the radiosensitivity of Hela cells with hTERC knockdown was increased. In vivo, the tumors developing from the hTERC siRNA-transfected cells were of reduced size, indicating that the hTERT siRNA also depressed the tumorigenic potential of the Hela cells. Our results supported the concept of siRNA-mediated inhibition of telomerase mRNA which could inhibit the expression of hTERC and telomerase activity. Furthermore, radiosensitivity was upregulated after knockdown the hTERC in vivo and in vitro.


Rhythmic control of activity and sleep by class B1 GPCRs.
Members of the class B1 family of G-protein coupled receptors (GPCRs) whose ligands are neuropeptides have been implicated in regulation of circadian rhythms and sleep in diverse metazoan clades. This review discusses the cellular and molecular mechanisms by which class B1 GPCRs, especially the mammalian VPAC2 receptor and its functional homologue PDFR in Drosophila and C. elegans, regulate arousal and daily rhythms of sleep and wake. There are remarkable parallels in the cellular and molecular roles played by class B1 intercellular signaling pathways in coordinating arousal and circadian timekeeping across multiple cells and tissues in these very different genetic model organisms.


Targeted therapy and immunotherapy in advanced melanoma: an evolving paradigm.
Metastatic melanoma is one of the most challenging malignancies to treat and often has a poor outcome. Until recently, systemic treatment options were limited, with poor response rates and no survival advantage. However, the treatment of metastatic melanoma has been revolutionized by developments in targeted therapy and immunotherapy; the BRAF inhibitor, vemurafenib, and anticytotoxic T-lymphocyte antigen 4 antibody, ipilimumab, are the first agents to demonstrate a survival benefit. Despite the success of these treatments, most patients eventually progress, and research into response and resistance mechanisms, rationally designed combination therapies and evaluation of the role of these agents in the adjuvant setting is critically important.


Growth hormone (GH) determinations by RIA and IFA during GH stimulation tests in children with short stature.
Growth hormone deficiency (GHD) as a syndrome comprises multiple pathogenetically distinct entities caused by disorders of secretion or peripherial action of growth hormone (GH). Confirmation of the diagnosis of GH deficiency in children is based on provocative testing for human growth hormone (hGH). Immunofunctional assay (IFA) allows quantitation of only biological active GH forms in circulation. The aim of this study was to compare the results of GH determinations by radioimmunoassay (RIA) and IFA, and to establish cut-off-levels for IFA in insulin tolerance test (ITT). We have investigated 32 children (30 males and 2 females) with short stature. All patients underwent insulin tolerance test (ITT), GH was measured in duplicate by radioimmunoassay (RIA, Seria) and IFA (DSL). Children with peak GH concentration below 10 ng/ml in ITT (by RIA) underwent arginin tolerance test (ATT, arginin 0,5 g/kg). The correlation between the results of growth hormone determination by radioimmunoassay and immunofunctional assay was excellent and cut-off-level in stimulatory test was established for the immunofunctional assay.


Compensation of Horizontal Gravity Disturbances for High Precision Inertial Navigation.
Horizontal gravity disturbances are an important factor that affects the accuracy of inertial navigation systems in long-duration ship navigation. In this paper, from the perspective of the coordinate system and vector calculation, the effects of horizontal gravity disturbance on the initial alignment and navigation calculation are simultaneously analyzed. Horizontal gravity disturbances cause the navigation coordinate frame built in initial alignment to not be consistent with the navigation coordinate frame in which the navigation calculation is implemented. The mismatching of coordinate frame violates the vector calculation law, which will have an adverse effect on the precision of the inertial navigation system. To address this issue, two compensation methods suitable for two different navigation coordinate frames are proposed, one of the methods implements the compensation in velocity calculation, and the other does the compensation in attitude calculation. Finally, simulations and ship navigation experiments confirm the effectiveness of the proposed methods.


Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.
Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B', B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.


More than one kind of inference: re-examining what's learned in feature inference and classification.
Three studies examined how task demands that impact on attention to typical or atypical category features shape the category representations formed through classification learning and inference learning. During training categories were learned via exemplar classification or by inferring missing exemplar features. In the latter condition inferences were made about missing typical features alone (typical feature inference) or about both missing typical and atypical features (mixed feature inference). Classification and mixed feature inference led to the incorporation of typical and atypical features into category representations, with both kinds of features influencing inferences about familiar (Experiments 1 and 2) and novel (Experiment 3) test items. Those in the typical inference condition focused primarily on typical features. Together with formal modelling, these results challenge previous accounts that have characterized inference learning as producing a focus on typical category features. The results show that two different kinds of inference learning are possible and that these are subserved by different kinds of category representations.


New pathways to renal damage: role of ADMA in retarding renal disease progression.
In recent years, increasing evidence has been found that chronic kidney disease (CKD) is a strong cardiovascular risk factor, and therefore, the concept of cardiorenal association is well recognized. One possible factor that could explain this link seems to be endothelial dysfunction. It is widely recognized that endothelial dysfunction plays important roles in both the initiation and progression of atherosclerosis. In addition, we have come to understand that endothelial dysfunction may be a causative factor for proteinuria and/or progression of CKD. Asymmetric dimethylarginine (ADMA) is a naturally occurring L-arginine analogue found in plasma and various types of tissues, acting as an endogenous nitric oxide synthase inhibitor in vivo. Plasma levels of ADMA are elevated in patients with CKD and have been found to be a strong biomarker or predictor for future cardiovascular disease (CVD) as well as the progression of renal injury. These findings suggest that elevation of ADMA-mediated endothelial dysfunction may be a missing link between CVD and CKD. In this review, we discuss the biology of ADMA, especially focusing on its role in the progression of CKD.


Fine mapping of a surface-accessible, immunodominant site on the bluetongue virus major core protein VP7.
The 349-amino-acid major core protein VP7 of bluetongue virus (BTV) is both the most abundant viral structural protein and the major immunogenic serogroup-reactive viral antigen. Previous studies indicated that a conformation-dependent antigenic site, defined by the VP7-specific monoclonal antibody 20E9/B7/G2(20E9), was accessible from the virus surface and that the binding of the monoclonal antibody to this epitope could be blocked specifically by antisera raised against different serotypes of bluetongue virus, suggesting it is a serogroup-specific immunodominant epitope. Using a combination of three different mapping strategies, we have located the 20E9 binding site at the N-terminus of the molecule, between amino acids 30 and 48. The fine mapping of the 20E9 immunodominant epitope will facilitate structure-function analyses of the major core protein and provide new opportunities to improve existing BTV serodiagnosis methods based on this immunogenic site.


CO2 introduced the coagulation-flocculation of oil acidized wastewater: pollutant removal and cost analysis.
It is difficult to adjust the pH of oil acidized wastewater rich in Ca2+, thus hindering the polyacrylamide (PAM) flocculation. This study aims at accelerating the flocculation process by introducing CO2 into the water to induce the formation of CaCO3 nuclei. The order in which CO2 and NaOH were added affected the floc structures. Compared with CO2-NaOH-PAM, the flocs of NaOH-CO2-PAM were more compact and more CaCO3 crystals were formed. The aqueous Ca2+ involved in the reaction reached 20%, and CO2 utilization was enhanced. The settling time was shortened by half (from 20 to 3 min), and NaOH consumption was reduced by one-tenth (from 0.03 to 0.003 mol), hence significantly reducing the costs. Due to the higher settling rate and shorter contact time, the NaOH-CO2-PAM flocs adsorbed less so that the residual oil was 124 mg·L-1, while in the case of CO2-NaOH-PAM it was 88 mg·L-1. As a promising coagulation aid, CO2 can also be used to mineralize pollutants in wastewater.


Atypical disease produced in chickens by Newcastle disease virus isolated from exotic birds.
Chickens were infected with a Newcastle disease virus (NDV) recovered from exotic birds with severe clinical disease and with lesions characteristic of viscerotropic velogenic Newcastle disease (VVND). The infection in chickens was inconsistently lethal, some infected chickens were not clinically affected, and gastrointestinal involvement was only marginally evident. Pathogenicity of the virus for chickens was not detectably altered by laboratory passage in chickens or by limit dilution passage in chicken embryos. The results suggest that the difference between velogenic NDV pathotypes may not always be distinct and that clinical manifestations of VVND in chickens may not always be predictable based on signs and lesions observed in exotic birds.


Stereotactic localization of deep-seated arteriovenous malformations in the functional area.
The authors approached 5 arteriovenous malformations (AVMs) located deep in functional areas of the cortex with major draining veins found in the mesial hemisphere by using the stereotactic method. This procedure is a useful adjunct to total resection of these AVMs. No mortality or significant morbidity was noted after the surgical procedure. The authors believe that direct attack on AVMs in areas of critical function is the procedure of choice in order to preserve neurological function.


Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats.
Gram-negative and gram-positive infections have been considered the most important causes of morbidity and mortality in patients with leukopenia following chemotherapy. However, discrimination between bacterial infections and harmless fever episodes is difficult. Because classical inflammatory signs of infection are often absent and fever is frequently the only sign of infection, the aim of this study was to assess the significance of serum interleukin-6 (IL-6), IL-10, macrophage inflammatory protein-2 (MIP-2), procalcitonin (PCT), and C-reactive protein (CRP) patterns in identifying bacterial infections during start of fever in normal and cyclophosphamide-treated (leukopenic) rats following an injection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP) as a model for gram-negative and gram-positive bacterial infections. We found that, compared to normal rats, immunosuppressed animals exhibited significantly higher fevers and lesser production of all mediators, except IL-6, after toxin challenge. Moreover, compared to rats that received MDP, both groups of animals that received an equivalent dose of LPS showed significantly higher fevers and greater increase in serum cytokine levels. Furthermore, in contrast to those in immunocompetent rats, serum levels of IL-6 and MIP-2 were not significantly changed in leukopenic animals after MDP injection. Other serum markers such as PCT and CRP failed to discriminate between bacterial stimuli in both groups of animals. These results suggest that the use of the analyzed serum markers at an early stage of fever could give useful information for the clinician for excluding gram-negative from gram-positive infections.


Emotional impact of genetic trials in progressive paediatric disorders: a dose-ranging exon-skipping trial in Duchenne muscular dystrophy.
Gene-modifying trials offer hope for improvement in chronic paediatric disorders, but they may also lead to disappointment and have an adverse emotional effect on families. This study aimed to examine emotional impact on participants in a paediatric exon-skipping trial. Nineteen male children with Duchenne muscular dystrophy (DMD), and their parents, taking part in a dose-ranging study of an i.v. administered morpholino splice-switching oligomer (which can restore the reading frame in DMD and induce dystrophin expression) underwent a psychosocial/psychiatric examination at trial entry. Emotional impact was assessed at trial completion using questionnaires. The mean child age was 8.9 years (SD 2.1); 13(68%) were attending mainstream school. Most families were well adjusted psychosocially at trial entry. Post-trial median child emotional impact scores were 5/10 (n= 18), but impact was rated as positive by 6/14 (42%), neutral/mixed by 5 (35%) and negative by 3 (21%). Median post-trial psychosocial/psychiatric change scores in children and parents were minimal. Actual post-trial negative impact was statistically significantly associated with higher expected impact at trial entry, at which time the families of the three children displaying actual negative impact reported higher family stress levels in combination with a variety of other psychosocial risks factors. In carefully selected families with low levels of psychosocial stress/distress at trial entry, and with good support from paediatric research units (including psychiatric input when required), genetic trials in progressive disorders such as DMD can have a predominantly positive or neutral emotional impact. Nevertheless, negative impact is reported by a minority of families and possible psychosocial predictors deserving further scrutiny have been identified.


Applications of robotic surgery in gynecology.
This article reviews the applications of robotic surgery in gynecology and presents a summary of the early studies that have been performed regarding its use for hysterectomy, myomectomy, reproductive surgery, pelvic floor reconstruction, and gynecological cancer staging. Despite significant advances in conventional laparoscopic techniques, the majority of gynecological procedures are still performed through major abdominal incisions, which are associated with higher surgical morbidity. This article addresses the potential that robotic surgery may have in converting more gynecological operations to a minimally invasive approach.


Isolated myocardial abscess causing coronary artery rupture and fatal hemopericardium.
We report a rare case of cardiac tamponade caused by hemopericardium secondary to erosion and rupture of a coronary artery by an adjacent solitary myocardial abscess. The resulting tamponade led to the sudden death of this 46-year-old man. Antemortem blood culture and the postmortem microscopic examination of the myocardial abscess revealed the causative agent to be Staphylococcus aureus. Hemopericardium due to ventricular wall rupture secondary to a myocardial abscess has been infrequently reported, but, to our knowledge, only one other report of hemopericardium due to coronary artery rupture related to myocardial abscess has been published.


Transfer of interferon-induced viral resistance from human leukocytes to other cell types.
Nonsensitized human leukocytes cocultured with various xenogeneic epithelioid and fibroblastic cells produced human leukocyte interferon and shortly thereafter transferred antiviral activity to the xenogeneic cells. Antiviral activity in the cocultured xenogeneic cells was not due to cell-mediated cytotoxicity as measured by specific 51Cr release and staining with vital dyes. The transfer of antiviral activity from leukocytes to xenogeneic cells was blocked by rabbit antiserum to human leukocyte interferon. Transferred viral resistance failed to develop in actinomycin D-treated xenogeneic cells, even though these cells induced human leukocyte interferon. Based on these findings, it appears that interferon made in the cocultures acts on the leukocytes to effect the transfer of interferon-induced viral resistance to the xenogenic cells, possibly by transmission of an inducer for the antiviral state. These studies strongly suggest a new and efficient host defense against virus infection which does not require killing of noninfected or recently infected cells.


[Calcium/protein relation of women on the climacteric].
To evaluate the calcium/protein relation of the diet of climacteric women. In a transversal study the diet was evaluated of 154 women 35-65 years old and matriculated in the Health Clinic of the Climateric Woman of Health Center of Public Health College of the São Paulo University. The food intake of calcium and protein was investigated by "24 hours recall" method. The evaluation of calcium/protein relation was made according to Massey and Heaney (1998), that is 20/1 (mg/g). The mean of intake of calcium was 624.9 mg, the mean of intake of protein was 86.7 g and the calcium/protein relation was 7/1 (624.9 mg/86.7 g). The studied population presents inadequated consumation of the calcium and protein nutrients. It could result in serious risk for health.


Myocardial infarction in the distribution of a patent anomalous left circumflex coronary artery.
Anomalous origin of the left circumflex coronary artery is the most common congenital coronary artery anomaly. Myocardial infarction has been seen in the distribution of this anomalous vessel. This has been noted most typically when the vessel is atherosclerotic. Sudden death and myocardial infarction, however, also have been seen in a case without atherosclerotic involvement. This is a case report of a 45-year-old man who suffered a myocardial infarction after strenuous and sustained physical effort and who was found to have nonatherosclerotic coronary arteries with an anomalous left circumflex coronary artery arising from the right sinus of Valsalva.


Determination of carbamate insecticides in Chinese medicinal herbs by gas chromatography with a nitrogen-phosphorus detector.
A simplified method for determining carbamate insecticides (including metolcarb, isoprocarb, fenobucarb, carbofuran, pirimicarb, and carbaryl) in Chinese medicinal herbs (White Peony Alba, Red Peony Root, and Baical Skullcap Root) is described. Standards were fortified into Chinese medicinal herbs at 3 levels (0.05-0.5 mg/kg). The carbamates were extracted with dichloromethane in a Soxhlet apparatus and analyzed by gas chromatography with a nitrogen-phosphorus detector. The results showed average recoveries between 80.77 and 104.56%. The method evidenced good robustness, accuracy, and precision for monitoring carbamates in Chinese medicinal herb samples, and it is a suitable alternative to replace the currently dedicated analytical systems. The minimum detectable amount ranged from 3.0 x 10(-10) to 5.0 x 10(-10)g, and the limit of quantification was 0.05 mg/kg. The method is rapid, simple, sensitive, and reproducible, and it can be conveniently used as a low-cost, rapid method for measuring the carbamate insecticide contamination of Chinese medicinal herbs.


Pathological changes and myocardial remodelling related to the mode of shunting following surgical palliation for hypoplastic left heart syndrome.
The modification of placing the shunt from the right ventricle to the pulmonary arteries, also known as Sano procedure, has allegedly improved results over the short term in surgical palliation of hypoplastic left heart syndrome with the Norwood procedure. With this in mind, we reviewed autopsied specimens from neonates and children who did not survive after either a classic arterio-pulmonary shunt, or the modified procedure with the shunt placed from the right ventricle to the pulmonary arteries, so as to evaluate the pathological substrates of the remodelling of the systemic right ventricle, assessing any differences induced by the 2 techniques. We obtained the hearts from 11 patients with neonatal diagnosis of hypoplastic left heart syndrome who died after the first or second stages of the Norwood sequence of operations, comparing them with 6 normal hearts matched for age and weight. Macroscopic, microscopic and morphometric analysis were performed on each specimen, evaluating the diameter of the myocytes, extracellular matrix remodelling in terms of fibrosis and type of collagen, and vascularization in terms of capillary density. Hypertrophy of the myocytes was significantly increased in the hearts from patients having either a classic arterio-pulmonary or the ventriculo-pulmonary modification of the shunt compared to controls (p < 0.05). Myocardial fibrosis was increased in those having a shunt placed from the right ventricle to the pulmonary arteries when compared to the other 2 groups. The ratio of collagen I to collagen III was similar in those undergoing a classic arterio-pulmonary shunt compared to controls (0.94), but was lower in those having a shunt placed from the right ventricle to the pulmonary arteries (0.61), with an increase in collagen type III. The density of capillaries was lower in those who had undergone a classic arterial shunt when compared to the others. We have shown greater remodelling of the ventricular myocardial extracellular matrix in patients having a shunt from the right ventricle to the pulmonary arteries when compared to those having a classic arterio-pulmonary shunt, with this remodelling progressing even after the neonatal period. This may influence a later suboptimal ventricular performance.


Functional MRI in Neuro-Oncology: State of the Art and Future Directions.
Since its discovery in the early 1990s, functional MRI (fMRI) has been used to study human brain function. One well-established application of fMRI in the clinical setting is the neurosurgical planning of patients with brain tumors near eloquent cortical areas. Clinical fMRI aims to preoperatively identify eloquent cortices that serve essential functions in daily life, such as hand movement and language. The primary goal of neurosurgery is to maximize tumor resection while sparing eloquent cortices adjacent to the tumor. When a lesion presents in the vicinity of an eloquent cortex, surgeons may use fMRI to plan their best surgical approach by determining the proximity of the lesion to regions of activation, providing guidance for awake brain surgery and intraoperative brain mapping. The acquisition of fMRI requires patient preparation prior to imaging, determination of functional paradigms, monitoring of patient performance, and both processing and analysis of images. Interpretation of fMRI maps requires a strong understanding of functional neuroanatomy and familiarity with the technical limitations frequently present in brain tumor imaging, including neurovascular uncoupling, patient compliance, and data analysis. This review discusses clinical fMRI in neuro-oncology, relevant ongoing research topics, and prospective future developments in this exciting discipline.


Hepatitis B virus infection in dentists.
To evaluate viral hepatitis as a hazard in general dentistry, we surveyed participants in an annual health-screening program at the 1972 American Dental Association session. Of 1245 practitioners, 0.9 per cent were positive for hepatitis B surface antigen, and 12.7 per cent were antibody positive. Of those who had had clinical hepatitis while studying or practicing dentistry, 43 per cent were seropositive. The frequency of evidence for prior infection with hepatitis B virus increased uniformly with increasing years of professional experience. The proportion of seropositive dentists did not vary with geographic region of the United States, or size of community. Only 10.5 per cent recognized illicit self-injection among patients, and their infection rate was not increased. These data indicate an increased frequency of infection with hepatitis B virus among general dentists, and are compatible with relatively uniform endemicity of subtype/ad strans of that agent in the general population for several decades.


Rhinoplasty for Sinonasal Deformities in Granulomatosis with Polyangiitis: A Systematic Review and Meta-Analysis.
Granulomatosis with polyangiitis (GPA) is a vasculitis that affects respiratory and kidney vessels. It primarily involves the nose and sinuses but can progress systemically. Granulomatosis with polyangiitis causes severe nasal deformities, impacting aesthetics and breathing. Literature focuses on rhinoplasty for saddle nose deformities in non-GPA patients, but its suitability for GPA patients remains uncertain. Our study aims to assess the effectiveness and safety of rhinoplasty in GPA patients by analyzing the existing literature. Four databases were searched; 2 reviewers independently screened the retrieved references, then relevant data for our study were extracted. Categorical outcomes were analyzed using pooled proportions and 95% CI. Statistical heterogeneity was assessed using the I2 statistics χ 2 test with a P -value lower than 0.1 indicating heterogeneity. In our systematic review and meta-analysis, we incorporated 16 studies encompassing 136 patients who underwent nasal reconstruction as part of their treatment for GPA. The collective findings indicate a favorable success rate for rhinoplasty, with a pooled ratio of 89% (95% CI: 84%, 95%). The rate of revision surgeries was relatively low, with a pooled rate of 19% (95% CI: 12%, 26%). Furthermore, rhinoplasty demonstrated comparatively lower rates of recurrence (pooled rate: 22%, 95% CI: 3%, 42%) and complications (pooled rate: 12%, 95% CI: 7%, 18%). Rhinoplasty benefits GPA patients with saddle nose deformity and septal perforation with high success rates and low recurrence, revision, and complication outcomes. However, more research is needed for validation and refinement.


Afrotropical Sarcophagidae in a carrion fly community.
Collections of Afrotropical Sarcophagidae were made at a single locality. Seventeen species in two genera were found: Heteronychia with two species, and Sarcophaga with fifteen species. All male flies were identified, together with a few females, wherever possible. The number of male flies collected exceeded that of females. A small proportion of females captured were gravid.


Myotrophin-kappaB DNA interaction in the initiation process of cardiac hypertrophy.
To investigate how cardiac hypertrophy and heart failure develop, we isolated and characterized a candidate initiator, the soluble 12-kDa protein myotrophin, from rat and human hearts. Myotrophin stimulates protein synthesis and myocardial cell growth associated with increased levels of hypertrophy marker genes. Recombinant myotrophin from the cloned gene showed structural/functional motifs, including ankyrin repeats and putative phosphorylation sites for protein kinase C (PKC) and casein kinase II. One repeat, homologous with I kappaB, interacts with rel/NF-kappaB in vitro. We analyzed the interaction of recombinant myotrophin and nuclear extracts prepared from neonatal and adult cardiomyocytes; gel mobility shift assay showed that myotrophin bound to kappaB DNA. To define PKC's role in myotrophin-induced myocyte growth, we incubated neonatal rat myocytes (normal and stretch) with specific inhibitors and found that myotrophin inhibits [3H]leucine incorporation into myocytes and different hypertrophic gene expression in neonatal myocytes. Using confocal microscopy, we observed that a basal level of myotrophin was present in both cytoplasm and nucleus under normal conditions, but under cyclic stretch, myotrophin levels became elevated in the nucleus. Myotrophin gene levels were upregulated when myocytes underwent cyclic stretch or were treated with tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta and also when excised beating hearts were exposed to high pressure. Our data showed that the myotrophin-kappaB interaction was increased with age in spontaneously hypertensive rats (SHRs) only. Our data provide evidence that myotrophin-kappaB DNA interaction may be an important step in initiating cardiac hypertrophy.


Novel Tumor-specific Mutations in Receptor Tyrosine Kinase Subdomain IX Significantly Reduce Extracellular Signal-regulated Kinase Activity.
The identification of additional therapeutic targets by clinical molecular profiling is necessary to expand the range of molecular-targeted cancer therapeutics. This study aimed to identify novel functional tumor-specific single nucleotide variants (SNVs) in the kinase domain of receptor tyrosine kinases (RTKs), from whole-exome sequencing (WES) data. SNVs were selected from WES data of multiple cancer types using both cancer-related databases and the index reflecting molecular evolution. Immunoblotting and luciferase assay were performed to assess the function of selected SNVs. Among the seven selected SNVs, two, namely neurotrophic receptor tyrosine kinase 1 (NTRK1) V710A and fms related tyrosine kinase 3 (FLT3) K868N, detected in kinase subdomain IX, were investigated. These SNVs inhibited the autophosphorylation of the respective RTKs, thereby reducing the activity of extracellular signal-regulated kinases. RTK subdomain IX is a promising target for the molecular design of kinase inhibitors.


Association of torovirus with acute and persistent diarrhea in children.
To study the etiologic role of toroviruses as a cause of gastroenteritis in humans. The design was a case-control study. We compared the rate of torovirus detection in fecal specimens from a selection of children with acute or persistent diarrhea and controls without diarrhea from a study of childhood diarrhea in an urban Brazilian slum. Stool samples were coded and tested in a blinded fashion for the presence of torovirus antigen by enzyme-linked immunosorbent assay, other enteropathogens, toxins and fecal leukocytes. Thirty-three children with acute diarrhea, 41 children with persistent diarrhea and 17 controls were enlisted in the study. Torovirus antigen was detected in 9 (27%) samples from children with acute diarrhea, 11 (27%) samples from children with persistent diarrhea and none of the samples from controls (P < 0.05). In addition the presence of enteroaggregative E. coli was associated with persistent diarrhea and the presence of Cryptosporidium oocysts was common although not significant (P = 0.08); torovirus and Cryptosporidium occurred in different subsets of samples, whereas torovirus and enteroaggregative Escherichia coli were commonly found in combination. These data indicate that toroviruses, alone or in combination with enteroaggregative E. coli, may play a pathogenic role in acute and possibly persistent diarrhea. Further studies are warranted to determine the etiologic role of toroviruses in gastroenteritis.


Effects of Helicobacter pylori infection on genetic instability, the aberrant CpG island methylation status and the cellular phenotype in Barrett's esophagus in a Japanese population.
Genetic or epigenetic alterations in Barrett's esophagus (BE) with/without Helicobacter pylori (H. pylori) infection remain unclear. We examined the effects of H. pylori infection on genetic instability (GIN), the CpG island methylation status and a biomarker related to BE carcinogenesis. We analyzed 113 Japanese individuals with endoscopically suspected BE. The patients included, Group CLE (n = 25): no specialized intestinal metaplasia (SIM) in a columnar lined epithelium (control); Group BE (n = 88): all had SIM. Microsatellite instability and a loss of heterozygosity as GIN, the methylation status at hMLH1, E-cadherin, p16 and APC, and immunoreactivity using a monoclonal antibody (mAb) Das-1, which specifically reacts with BE, were evaluated. Nine additional patients with BE were prospectively followed up for 2 years after successful H. pylori eradication. The frequency of GIN, methylation at E-cadherin and APC, and mAb Das-1 reactivity in Group BE was significantly higher than that in Group CLE (p < 0.0001, p < 0.0001 and p < 0.005, and p < 0.0001, respectively). Furthermore, GIN, E-cadherin methylation and mAb Das-1 reactivity showed a significantly higher incidence in patients with H.pylori infection than in those without H. pylori infection (p < 0.01, p < 0.005, and p < 0.01, respectively). Interestingly, the patients from Group BE were observed to change to a stable state of molecular alterations in 60% for GIN, 42.9% for E-cadherin methylation and 55.6% for APC methylation, or a reduction of mAb Das-1 reactivity was noted in 25% following eradication. H. pylori infection may therefore affect these molecular alterations associated with the pathogenesis of BE, to some degree, in the Japanese population.


[Effect of electromagnetic radiation on discharge activity of neurons in the hippocampus CA1 in rats].
In order to explore effect of electromagnetic radiation on learning and memory ability of hippocampus neuron in rats, the changes in discharge patterns and overall electrical activity of hippocampus neuron after electromagnetic radiation were observed. Rat neurons discharge was recorded with glass electrode extracellular recording technology and a polygraph respectively. Radiation frequency of electromagnetic wave was 900 MHZ and the power was 10 W/m2. In glass electrode extracellular recording, the rats were separately irradiated for 10, 20, 30, 40, 50 and 60 min, every points repeated 10 times and updated interval of 1h, observing the changes in neuron discharge and spontaneous discharge patterns after electromagnetic radiation. In polygraph recording experiments, irradiation group rats for five days a week, 6 hours per day, repeatedly for 10 weeks, memory electrical changes in control group and irradiation group rats when they were feeding were repeatedly monitored by the implanted electrodes, observing the changes in peak electric digits and the largest amplitude in hippocampal CA1 area, and taking some electromagnetic radiation sampling sequence for correlation analysis. (1) Electromagnetic radiation had an inhibitory role on discharge frequency of the hippocampus CA1 region neurons. After electromagnetic radiation, discharge frequency of the hippocampus CA1 region neurons was reduced, but the changes in scale was not obvious. (2) Electromagnetic radiation might change the spontaneous discharge patterns of hippocampus CA1 region neurons, which made the explosive discharge pattern increased obviously. (3) Peak potential total number within 5 min in irradiation group was significantly reduced, the largest amplitude was less than that of control group. (4) Using mathematical method to make the correlation analysis of the electromagnetic radiation sampling sequence, that of irradiation group was less than that of control group, indicating that there was a tending to be inhibitory connection between neurons in irradiation group after electromagnetic radiation. Electromagnetic radiation may cause structure and function changes of transfer synaptic in global, make hippocampal CA1 area neurons change in the overall discharge characteristic and discharge patterns, thus lead to decrease in the ability of learning and memory.


Example of a physical system with a hyperbolic attractor of the Smale-Williams type.
A simple and transparent example of a nonautonomous flow system with a hyperbolic strange attractor is suggested. The system is constructed on the basis of two coupled van der Pol oscillators, the characteristic frequencies differ twice, and the parameters controlling generation in both oscillators undergo a slow periodic counterphase variation in time. In terms of stroboscopic Poincaré sections, the respective 4D mapping has a hyperbolic strange attractor of the Smale-Williams type. Qualitative reasoning and quantitative data of numerical computations are presented and discussed, e.g., Lyapunov exponents and their parameter dependencies. A special test for hyperbolicity based on analysis of distributions of angles between stable and unstable subspaces of a chaotic trajectory is performed.


Finite element modeling of blast lung injury in sheep.
A detailed 3D finite element model (FEM) of the sheep thorax was developed to predict heterogeneous and volumetric lung injury due to blast. A shared node mesh of the sheep thorax was constructed from a computed tomography (CT) scan of a sheep cadaver, and while most material properties were taken from literature, an elastic-plastic material model was used for the ribs based on three-point bending experiments performed on sheep rib specimens. Anesthetized sheep were blasted in an enclosure, and blast overpressure data were collected using the blast test device (BTD), while surface lung injury was quantified during necropsy. Matching blasts were simulated using the sheep thorax FEM. Surface lung injury in the FEM was matched to pathology reports by setting a threshold value of the scalar output termed the strain product (maximum value of the dot product of strain and strain-rate vectors over all simulation time) in the surface elements. Volumetric lung injury was quantified by applying the threshold value to all elements in the model lungs, and a correlation was found between predicted volumetric injury and measured postblast lung weights. All predictions are made for the left and right lungs separately. This work represents a significant step toward the prediction of localized and heterogeneous blast lung injury, as well as volumetric injury, which was not recorded during field testing for sheep.


Mammalian somatic hybrids and human gene mapping.
Somatic cell hybridization, as an aid in the study of human map, has made large strides during the past several years. Rodent-human hybrids are readily obtained, and selective systems are available to select hybrid cells to the exclusion of parenteral cells. Various species-specific genetic markers can be studied in the hybrids, and correlation of the expression of these markers with each other and with specific human chromosomes retained allows synteny analysis and chromosome assignment. Methods to determine the relative order of genes and their regional localization are also available. Using these methods, more than 60 human genes have been assigned to 22 human chromosomes.


Hypoxic marker CA IX and adhesion mediator β-catenin are downregulated by lymphocytic choriomeningitis virus persistent infection.
Renal cell carcinoma is one of the most frequent cancer diseases with high resistance to radio- and chemotherapy. Mutation of VHL gene is frequent in these tumors leading to simulation of hypoxic conditions. Lymphocytic choriomeningitis virus, belonging to RNA viruses, is a neglected human pathogen and teratogen. We have found that infection of renal cell carcinoma cells by lymphocytic choriomeningitis virus strain MX causes a decrease of carbonic anhydrase IX protein and RNA level. Lower expression of carbonic anhydrase IX on the cell surface provides less target for carbonic anhydrase IX-targeted immunotherapy. What more, reduced levels of adhesion mediating protein β-catenin as well as E-cadherin, as a consequence of infection, suggest a possible increase in metastatic potential of cells infected by lymphocytic choriomeningitis virus strain MX. These results might help elucidate differences in patients susceptibility to immunotherapy directed against carbonic anhydrase IX or in developing new therapeutical strategies. Our data indicate that presence of infection can significantly affect patient response to cancer therapy.


BMP induced inflammation: a comparison of rhBMP-7 and rhBMP-2.
Concern has been raised because of reports of inflammatory swelling following the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human bone morphogenetic protein-7 (rhBMP-7). The purpose of this study is to compare the inflammatory action of rhBMP-7 with those of rhBMP-2. ELISA assays (IL-6, TNF-α) were used to measure the cytokine response to different concentrations of rhBMP-7 and -2. Recombinant human BMP-7 was absorbed into absorbable collagen sponges and different amounts were implanted either subcutaneously (SC) or intramuscularly (IM) into the backs of rats. Using MRI and MIPAV software, we measured the degree of soft tissue edema at 3 h and at 2, 4, and 7 days postoperatively. After sacrificing rats on day 7 the inflammatory zone and mass were measured and the tissue examined histologically. Soft tissue edema after rhBMP-7 and rhBMP-2 implantation was dose-dependent and peaked at 3 h for the subcutaneous implants and at 2 days for the intramuscular implants. RhBMP-7 was associated with a significantly smaller soft tissue edema volume than was rhBMP-2 only at the highest dose (20 µg/ml). Both rhBMP-2 and rhBMP-7 triggered dose-dependent inflammatory reactions. Compared to rhBMP-2, rhBMP-7 is associated with somewhat smaller soft tissue edema volumes. Although rhBMP-7 is associated with an inflammatory reaction leading to soft tissue edema, at high doses this response is significantly less than that seen with rhBMP-2. Our animal model can be used to test materials that could ameliorate this reaction.


Treatment of disseminated cytomegalovirus infection with 9-(1,3 dihydroxy-2-propoxymethyl)guanine: evidence of prolonged survival in patients with the acquired immunodeficiency syndrome.
Disseminated cytomegalovirus (CMV) infection is a common complication of the acquired immunodeficiency syndrome (AIDS) and contributes significantly to its morbidity and mortality. Dihydroxypropoxymethyl guanine, DHPG, is an antiviral agent that has been shown to inhibit CMV replication and to provide clinical benefit in patients with CMV infections, especially retinitis. In this study, the clinical characteristics, results of diagnostic evaluations, and survival were compared in 11 AIDS patients with disseminated CMV infections who were seen between August 1981 and October 1984 and were not treated with DHPG, and in 18 AIDS patients seen since that time who were treated with DHPG. The study groups were similar though the untreated group was somewhat more tissue depleted. Survival from diagnosis was significantly prolonged with DHPG therapy based upon life table analysis (p = 0.001). Therapy improved the quality of life, as 12 of 18 treated patients and only 2 of 11 untreated patients could be discharged from the hospital. Progression of CMV infection did not appear to play a role in the mortality of patients who died during DHPG therapy. We conclude that DHPG prolongs survival in patients with AIDS who have disseminated CMV infections.


Controlling Fundamental Fluctuations for Reproducible Growth of Large Single-Crystal Graphene.
The controlled growth of graphene by the chemical vapor deposition method is vital for its various applications; however, the reproducibility remains a great challenge. Here, using single-crystal graphene growth on a Cu surface as a model system, we demonstrate that a trace amount of H2O and O2 impurity gases in the reaction chamber is key for the large fluctuation of graphene growth. By precisely controlling their parts per million level concentrations, centimeter-sized single-crystal graphene is obtained in a reliable manner with a maximum growth rate up to 190 μm min-1. The roles of oxidants are elucidated as an effective modulator for both graphene nucleation density and growth rate. This control is more fundamental for reliable growth of graphene beyond previous findings and is expected to be useful for the growth of various 2D materials that are also sensitive to trace oxidant impurities.


Giant papillary conjunctivitis following cataract extraction.
Out of a series of 600 cataract extractions, 14 patients were found to have giant papillary conjunctivitis (GPC) due to 10-0 nylon sutures. When renewed conjunctival irritation appears weeks or months after surgery, GPC should be suspected and confirmed by eversion of the upper eyelid at the slit lamp. Free edges of protruding corneoscleral nylon sutures should be looked for. Signs and symptoms of GPC disappear within one to four weeks after removal of the offending suture.


Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology.
The Japan Society of Obstetrics and Gynecology collects and analyzes annual data on gynecologic cancers from member institutions. Here we present the Treatment Annual Report for 2007. Data on the prognosis of 3381 patients with cervical cancer, 3681 with endometrial cancer, and 2367 with ovarian cancer for whom treatment was initiated in 2007 were analyzed in the Treatment Annual Report. In the 2007 Treatment Annual Report, stage I accounted for 53.1%, stage II for 24.4%, stage III for 14.2%, and stage IV for 8.3% of all patients with cervical cancer. Stage I accounted for 64.8%, stage II for 8.2%, stage III for 20.2%, and stage IV for 6.9% of all patients with endometrial cancer. Stage I accounted for 41.4%, stage II for 9.9%, stage III for 30.6%, and stage IV for 8.6% of all patients with ovarian cancer. The 5-year overall survival rates for patients with cervical cancer were 91.8% for stage I, 71.5% for stage II, 53.0% for stage III, and 23.7% for stage IV; those for patients with endometrial cancer were 95.3%, 89.8%, 75.6%, and 29.1%, and those for patients with ovarian surface epithelial-stromal tumors were 91.5%, 76.1%, 46.9%, and 31.3%, respectively.


Predicting disease progression in Alzheimer's disease: the role of neuropsychiatric syndromes on functional and cognitive decline.
Patients with Alzheimer's disease (AD) have heterogeneous rates of disease progression. The aim of the current study is to investigate whether neuropsychiatric disturbances predict cognitive and functional disease progression in AD, according to failure theory. We longitudinally examined 177 memory-clinic AD outpatients (mean age = 73.1, SD = 8.1; 70.6% women). Neuropsychiatric disturbances at baseline were categorized into five syndromes. Patients were followed for up to two years to detect rapid disease progression defined as a loss of ≥ 1 abilities in Activities of Daily living (ADL) or a drop of ≥ 5 points on Mini-Mental State Examination (MMSE). Hazard ratios (HR) were calculated with Gompertz regression, adjusting for sociodemographics, baseline cognitive and functional status, and somatic comorbidities. Most patients (74.6%) exhibited one or more neuropsychiatric syndromes at baseline. The most common neuropsychiatric syndrome was Apathy (63.8%), followed by Affective (37.3%), Psychomotor (8.5%), Manic (7.9%), and Psychotic (5.6%) syndromes. The variance between the observed (Kaplen Meier) and predicted (Gompertz) decline for disease progression in cognition (0.30, CI = 0.26-0.35), was higher than the variance seen for functional decline (0.22, CI = 0.18-0.26). After multiple adjustment, patients with the Affective syndrome had an increased risk of functional decline (HR = 2.0; CI = 1.1-3.6), whereas the risk of cognitive decline was associated with the Manic (HR = 3.2, CI = 1.3-7.5) syndrome. In conclusion, specific neuropsychiatric syndromes are associated with functional and cognitive decline during the progression of AD, which may help with the long-term planning of care and treatment. These results highlight the importance of incorporating a thorough psychiatric examination in the evaluation of AD patients.


Hypothalamic-pituitary-adrenal axis activity, dehydroepiandrosterone sulphate and their relationships with aggression in early and late alcohol withdrawal.
The study aims at investigating the relationship between hypothalamic-pituitary-adrenal (HPA) axis alterations and aggression level in alcoholic patients during early and late alcohol withdrawal. Serum levels of basal cortisol and dehydroepiandrosterone sulphate (DHEAS) were measured three times, and cortisol and DHEAS response to dexamethasone twice during the early and late withdrawal periods in alcohol dependent males (n=30) and once in healthy control males (n=20). Abnormal cortisol non-suppression response to dexamethasone in dexamethasone suppression test (DST) was observed in some proportion of the patients in early withdrawal, which normalized in late withdrawal. The study revealed reduced basal DHEAS levels and reduced DHEAS response to dexamethasone in late withdrawal. When the patients were assessed in two separate groups as high- and low-aggressives, in the high-aggression group abnormality in DST was observed during both early and late withdrawal periods, in the low-aggression group it was observed only in early withdrawal. While basal DHEAS levels were low in the high-aggression group only in early withdrawal, it was reduced in the low-aggression group during late withdrawal period. Some alterations of the HPA axis during alcohol withdrawal might be associated not only with alcohol use per se but also with aggressivity tendency of alcoholic patients.


Preferences of cancer patients regarding the disclosure of bad news.
To understand patients' preferences regarding the disclosure of bad news is important in the clinical oncology setting. The aim of this study was to clarify descriptively the preferences of cancer patients. Five hundred and twenty-nine Japanese cancer outpatients were surveyed regarding their preferences regarding the disclosure of bad news, and several psychosocial and medical demographic variables were analyzed. In a descriptive analysis, more than 90% of the patients strongly preferred to discuss their current medical condition and treatment options with their physician and to have their physicians take the feelings of their family into consideration as well. While half of the patients preferred to receive information regarding their life expectancy, 30% preferred not to receive it. Multiple regression analyses indicated the preferences showing interindividual variations were associated with the level of education and the mental adjustment to cancer scores. A factor analysis revealed four preferences factors: method of disclosure of the bad news, provision of emotional support, provision of additional information, and setting. These four factors had good internal consistency reliability (Cronbach's alpha = 0.93-0.77). Providing emotional support, including the desire for the physician to show consideration for the patient's family, and understanding an individual's communication preferences may be useful for promoting patient-physician communication.


Safety and efficiency of the fifth generation Woven EndoBridge device: technical note.
The treatment of wide neck bifurcation aneurysms remains challenging despite the introduction of new techniques (Y stenting, waffle cone technique, or flow diverter stents). The Woven EndoBridge (WEB) device is an innovative solution for this type of cerebral aneurysm. A new WEB 17 is now available and has been designed to offer smaller sized devices to optimize navigability and delivery. Between February 2017 and April 2018 all patients treated with the WEB 17 device in our center were retrospectively reviewed. 25 patients with 28 non-ruptured aneurysms were identified and analyzed. Three patients with two aneurysms both treated with the WEB device were identified. The device was successfully deployed in all cases. Procedure related morbidity was 4% and mortality was 0%. In one case, a delayed postprocedural thromboembolic event occurred owing to device protrusion. Technical success, complications, angiographic outcomes, procedural data, and follow-ups are reported. The modified Rankin Scale score at discharge was 0 for 24 patients (96%). At the 3, 6, or 9 month follow-up, angiograms were taken of 21 of the 25 patients (84%) (24 of 28 aneurysms had been controlled); 3 patients (3 aneurysms) did not receive angiographic follow-up at the time of submission of this work. Complete occlusion was achieved in 22 of 24 aneurysms (91.66%), and 2 of 24 aneurysm (8.33%) showed a neck remnant. The WEB 17 is safe and technically feasible, according to this retrospective single center analysis. For very small bifurcation aneurysms, the WEB 17 seems to have lower complication rates than stent assisted techniques. However, further studies are needed to evaluate the complication rate and long term efficiency.


Reject water: treating of process water in large wastewater treatment plants in Germany--a case study.
The increase of the hydraulic loading of a municipal wastewater treatment plant caused by the sludge dewatering process is of minor importance. However, the rejected nitrogen load accounts for up to 25% of the nitrogen load in the raw sewage. As a result, the process water significantly influences the stage volume of the biological treatment steps. Rejection management can prevent critical nitrogen concentrations in the effluent of the plant. In some cases, the treating capacity must be increased. Separate treatment of the process water can be an alternative to the enlargement of the main wastewater treatment stages. This article describes the compositions of the process waters from different sludge treatment steps, the influence on the main wastewater treatment steps, possible strategies to handle the rejection problem, and processes for separate treatment of the sludge liquor. Some results of a German case study on large wastewater treatment plants illustrate the situation concerning separate process water treatment in Germany. These results suggest that side stream treatment can be a practical alternative to a classic increase in the length of the main stream stages. Moreover, they prove that many different processes are useful for the separate treatment of sludge liquor.


Results of treatment of acute myeloid leukemia and myelodysplastic syndrome with etoposide, thioguanine, cytarabine (ETC) in elderly patients.
Treatment in elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains controversial, and results have been poor with most regimens. In order to study the efficacy of a new regimen in the treatment of these diseases in elderly patients assessed as not tolerating full-scale anthracycline-containing intensive chemotherapy, 14 patients over 60 years were enrolled in our study. The median age was 69 years, range 60-85 years. Eight patients had MDS (one transformed to AML) and six had AML. Anthracycline-lacking therapy (ETC) consisted of etoposide 120 mg/m² and thioguanine 100 mg/m² p.o. twice daily on days 1-5 and cytarabine (araC) 40 mg/m² s.c. on day 1. The preliminary results were as follows: 7 of the 14 patients (50%) achieved complete remission. The median survival was 10 months. Days spent at hospital were 28. Neutropenia was observed for 11 days and thrombocytopenia for 15 days. No severe infection was detected. Early death was observed in 2 (14%) of the patients. In conclusion, this novel treatment with a complete response of 50% appears to be a simple, safe, cost-effective form of therapy for elderly patients.


Late haematological complications in severe aplastic anaemia.
137 patients with severe aplastic anaemia (SAA) were treated in Basel from 1976 to 1986. 34 underwent bone marrow transplantation (BMT) and 103 received antilymphocyte globulin (ALG) therapy. We have analysed the incidence of late haematological complications in both groups of patients. 20 patients treated with ALG developed a late haematological complication. A myelodysplastic syndrome or frank leukaemia occurred in eight and paroxysmal nocturnal haemoglobinuria (PNH) in 13 patients. Nine of the 13 patients with PNH had clinical signs of haemolysis, four only had positive laboratory tests. One patient had PNH and acute leukaemia. The risk of developing a haematological complication increased continuously and reached 57% at 8 years. Neither PNH nor leukaemia occurred in patients treated with BMT. The increased survival rate and the long observation time after ALG therapy have revealed a new perspective of the prognosis of aplastic anaemia. Patients treated with BMT appear to be cured whereas those treated with ALG remain at risk for late complications.


Spatial variability of urban forest topsoil properties: towards representative and robust sampling design.
Background: Soil spatial variability is a major concern when deciding how to collect a representative topsoil sample for laboratory analysis. Sampling design to capture site-specific variability is documented in the agricultural literature, but poorly understood for urban forest soils where soils may be characterized by strong horizontal and vertical variability and large temporal anthropogenic disturbances. Methods: This paper evaluates the spatial variability of selected topsoil properties under urban trees to define a statistically robust sampling design that optimizes the number of samples to reliably characterize basal soil respiration (BSR), a property associated with soil health. To provide a reference on variability, two additional soil properties were measured, unrelated to BSR: electrical conductivity (EC) and bulk density (BD). Thirteen sampling sites comprising both park and street trees ( Acer rubrum) were selected in Cambridge, MA, USA. Results: Results indicate street tree topsoil had approximately twice as much variation, requiring more intensive sampling, as did park tree topsoil, even though street trees had smaller soil sampling zones, constricted by tree pits. The variability of BSR was nearly identical to that of EC, and BD results varied least. A large number of samples would be required for acceptable levels of statistical reliability (90% CI - 10% ER) of 44.4, 41.7, and 6.4 for BSR, EC, and BD, respectively, whereas by accepting a lower level of certainty (80% CI - 20% ER) the number of required soil samples was calculated as 6.8, 6.4, and 0.4 for BSR, EC, and BD, respectively. Conclusions: The use of EC testing as a baseline measure to determine spatial variation in the topsoil is proposed, to alleviate the financial implications of more expensive BSR testing. Factors of topsoil disturbance and soil access restrictions at sites with severe root-sidewalk conflicts and the overall generalizability of the results are also discussed.


The escalating number of uninsured in the United States.
Data from the Census Bureau's Annual Report on Poverty show that 37.4 million Americans--two million more than the previous year--had no health insurance during 1992. The proportion of people with no health insurance also increased from 14.1 percent in 1991 to 14.7 percent in 1992. This is the largest annual increase--both in the number of people and the proportion of the population lacking health care coverage--since 1987, the first year for which comparable data are available. In 1987, the Census data show, 31 million people--12.9 percent of the population--were not covered by health insurance. Both the number of people and the proportion of the population without health insurance have increased each year since 1987. Not all of the changes from one year to the next were statistically significant. Between 1991 and 1992, however, the increases both in the number of people without insurance and the proportion of the population lacking insurance were statistically significant. The Bureau reported that 36.9 million Americans were poor in 1992, which represented the largest number of poor people in 30 years. Among the poor, 28.5 percent had no health insurance in 1992. Lack of insurance was not limited to the poor, however. Of those without insurance in 1992, more than 70 percent were above the poverty line.


The adaptive significance of adult neurogenesis: an integrative approach.
Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts.


Robust Stabilization of Linear Time-Delay Systems under Denial-of-Service Attacks.
This research examines new methods for stabilizing linear time-delay systems that are subject to denial-of-service (DoS) attacks. The study takes into account the different effects that a DoS attack can have on the system, specifically delay-independent and -dependent behaviour. The traditional proportional-integral-derivative (PID) acts on the error signal, which is the difference between the reference input and the measured output. The approach in this paper uses what we call the PID state feedback strategy, where the controller acts on the state signal. Our proposed strategy uses the Lyapunov-Krasovskii functional (LKF) to develop new linear matrix inequalities (LMIs). The study considers two scenarios where the time delay is either a continuous bounded function or a differentiable and time-varying function that falls within certain bounds. In both cases, new LMIs are derived to find the PID-like state feedback gains that will ensure robust stabilization. The findings are illustrated with numerical examples.


Peripartum Anesthesia Considerations for Placenta Accreta.
Placenta accreta spectrum is becoming more common and is the most frequent indication for peripartum hysterectomy. Management of cesarean delivery in the setting of a morbidly adherent placenta has potential for massive hemorrhage, coagulopathies, and other morbidities. Anesthetic management of placenta accreta spectrum presents many challenges including optimizing surgical conditions, providing a safe and satisfying maternal delivery experience, preparing for massive hemorrhage and transfusion, preventing coagulopathies, and optimizing postoperative pain control. Balancing these challenging goals requires meticulous preparation with a thorough preoperative evaluation of the parturient and a well-coordinated multidisciplinary approach in order to optimize outcomes for the mother and fetus.


[Toxicity evaluation of purified terephthalic acid wastewater by using model Caenorhabditis elegans].
By using model Caenorhabditis elegans, the toxicity of purified terephthalic acid (PTA) wastewater was evaluated through a battery of biotest, including life span, days of 50% lethal, generation time, brood size, head thrashes, and body bends. The results revealed that compared with control, the life span and generation time of C. elegans exposed to 660 mg PTA x L(-1) were delayed to some degree, and its head thrashes and body bends were inhibited. The procreation function of C. elegans exposed to PTA wastewater was greatly affected, with the brood size being as low as 25% of the normal one. The most sensitive indicator, brood size of C. elegans, might be a potential indicator in evaluating PTA wastewater toxicity.


Staining characteristics of colonies of Anaplasma marginale Theiler in Dermacentor andersoni Stiles.
Colonies of Anaplasma marginale Theiler were studied in midgut epithelial cells of adult Dermacentor andersoni Stiles that were infected as nymphs. The colonies were demonstrated in plastic sections (1 micrometer) and frozen sections (6 micrometer) with Mallory's stain. Colonies were also demonstrated in frozen sections, using direct fluorescent antibody technique. Colonies were not observed in plastic or frozen sections stained by the Giménez method. In all preparations, the colonies were usually found near the basement membrane of the midgut tissue.


Neutral alleles at hybrid sterility loci of Oryza glaberrima from AA genome relatives in Genus Oryza.
Hybrid sterility between Oryza sativa and O. glaberrima is a main reproduction barrier when transferring the favorable alleles from O. glaberrima to O. sativa and it happens due to allelic interaction at sterility loci. Neutral alleles at each locus have the potential to overcome the sterility between the two cultivated rice species. In this study, an O. sativa cultivar Dianjingyou 1 (DJY1) and its near-isogenic lines (NILs) harboring the single sterility allele S1-glab, S19-glab, S20-glab, S37-glab, S38-glab and S39-glab as the tested lines were crossed with O. glaberrima, O. rufipogon, O. nivara, O. glumaepatula, O. barthii, O. meridionalis and O. sativa so as to detect the neutral alleles of these loci. Pollen fertility was investigated in the paired F1s based on two seasons' result and genotypic segregation was also analyzed in some F2 populations to confirm the results of pollen fertility investigation. The neutral alleles of S38-n and S39-n were identified based upon the pollen fertility and genotypic segregation analysis for the first time. The neutral alleles of sterility loci detected from present report have the potential to know of the nature of interspecific hybrid sterility, and to overcome the interspecific hybrid sterility between O. sativa and O. glaberrima.


Equilibrium studies on the formaldehyde reaction with native DNA.
Equilibrium analysis of the reaction of formaldehyde with native calf thymus DNA was carried out at temperatures below the thermal transition zone by the spectrophotometric method. The apparent equilibrium constant, Kconf., for the conformational opening and closing reaction of base pairs along the double-helical chain, was measured in various concentrations of formaldehyde, and these values were extrapolated to the zero concentration. The value of KOconf. thus obtained in the absence of the chemical probe was 0.12 in 5 mM 2-(N-morpholino)ethane sulfonic acid buffer (Mes), and 0.003 in 0.15 M NaCl plus 5 mM Mes, pH 7.0, at 50 degrees C. These results make it possible to calculate roughly that 230 base pairs and 7 base pairs are open respectively, at 50 degrees C in the native DNA molecule composed of 2300 base pairs, using Mr = 1.5 x 10(6) for the sample used. This conformational reaction was also characterized by the following thermodynamic parameters: deltaGOconf. = 1.36 kcal - mol-1 (5.68 kJ - mol-1), deltaHOconf. = 36.8 kcal - mol-1 (154 kJ - mol-1), and deltaSOconf. = 110 cal - mol-1 - K-1 (460 J - mol-1 - K-1) in 5 mM Mes, pH 7.0, at 50 degrees C, and the nature of the 'breathing' of base pairs was discussed.


Periodontal health predicts self-rated general health: A time-lagged cohort study.
There is limited evidence of a temporal relationship between periodontal diseases and self-perceived general health. To plug this knowledge gap, we aimed to assess how periodontal health affects future self-rated health (SRH). We collected data from five waves of an annual nationwide Japanese survey of dental patients from 2015 to 2019. The analysis of repeated measurements included 9306 observations from 4242 patients aged 20 years or older. The clinical periodontitis measurements were bleeding on probing, deepest periodontal pocket depth and most severe clinical attachment loss (CAL). We used a self-administered questionnaire to collect data on sociodemographic characteristics, diabetes history, health behaviour, SRH and self-reported periodontitis. We applied 2-level ordered logistic regression models for repeated measurements to examine the relationships between SRH (time t) and 1-year-lagged periodontal health (time t-1) after adjusting for covariates. The percentage of SRH responses recorded at time t as 'good', 'moderate' and 'poor' were 36.9%, 52.4% and 10.7%, respectively. Multivariate analyses showed that the risk of poorer SRH at time t increased in patients with CAL ≥7 mm (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.02-1.30), those who reported bleeding gums (OR = 1.33, 95% CI = 1.21-1.46) and those who perceived swollen gums (OR = 1.40, 95% CI = 1.26-1.56) at time t-1. Sensitivity analyses using the 4-year follow-up model and 3-year-lagged cohort model also showed consistent results. Periodontitis shows a gradual contribution to future SRH in dental patients, even after adjusting for sociodemographic characteristics, general health and health-related behaviours.


LAI estimation based on physical model combining airborne LiDAR waveform and Sentinel-2 imagery.
Leaf area index (LAI) is an important biophysical parameter of vegetation and serves as a significant indicator for assessing forest ecosystems. Multi-source remote sensing data enables large-scale and dynamic surface observations, providing effective data for quantifying various indices in forest and evaluating ecosystem changes. However, employing single-source remote sensing spectral or LiDAR waveform data poses limitations for LAI inversion, making the integration of multi-source remote sensing data a trend. Currently, the fusion of active and passive remote sensing data for LAI inversion primarily relies on empirical models, which are mainly constructed based on field measurements and do not provide a good explanation of the fusion mechanism. In this study, we aimed to estimate LAI based on physical model using both spectral imagery and LiDAR waveform, exploring whether data fusion improved the accuracy of LAI inversion. Specifically, based on the physical model geometric-optical and radiative transfer (GORT), a fusion strategy was designed for LAI inversion. To ensure inversion accuracy, we enhanced the data processing by introducing a constraint-based EM waveform decomposition method. Considering the spatial heterogeneity of canopy/ground reflectivity ratio in regional forests, calculation strategy was proposed to improve this parameter in inversion model. The results showed that the constraint-based EM waveform decomposition method improved the decomposition accuracy with an average 12% reduction in RMSE, yielding more accurate waveform energy parameters. The proposed calculation strategy for the canopy/ground reflectivity ratio, considering dynamic variation of parameter, effectively enhanced previous research that relied on a fixed value, thereby improving the inversion accuracy that increasing on the correlation by 5% to 10% and on R2 by 62.5% to 132.1%. Based on the inversion strategy we proposed, data fusion could effectively be used for LAI inversion. The inversion accuracy achieved using both spectral and LiDAR data (correlation=0.81, R2 = 0.65, RMSE=1.01) surpassed that of using spectral data or LiDAR alone. This study provides a new inversion strategy for large-scale and high-precision LAI inversion, supporting the field of LAI research.


Molecular Recognition in Mitochondrial Cytochromes P450 That Catalyze the Terminal Steps of Corticosteroid Biosynthesis.
The mitochondrial cytochromes P450 11B1 and P450 11B2 are responsible for the final stages of cortisol and aldosterone synthesis, respectively. Dysregulation of both enzymes has been implicated in secondary forms of hypertension. Molecular recognition of the cytochromes P450 with their corresponding redox partner is a key step in the catalytic cycle, yet the precise nature of the interaction of P450 11B1 or P450 11B2 with their proximal partner, adrenodoxin (Adx), is still unknown. Here, we obtained P450 11B1·Adx2 and P450 11B2·Adx2 complexes using the zero-length cross-linker ethyl-3-[3-(dimethylamino)propyl]carbodiimide, which formed best under low-ionic strength conditions. R-to-K mutations were introduced into the P450s at residues predicted to form salt bridges with Adx and allow cross-linking with the carbodiimide reagent. Mass spectrometric analysis of the chymotrypsin-digested ternary complexes identified seven cross-linked peptide pairs. Consistent with the electrostatic interaction of K370 in P450 11B1-WT and K366 in P450 11B2-R366K with D79 of Adx, Adx mutation L80K abolished complex formation. Using these sites of interaction as constraints, protein docking calculations based on the crystal structures of the two proteins yielded a structural model of the P450 11B1·Adx2 complex. The appositional surfaces include R/K366, K370, and K357 of P450 11B1, which interact with D79, D76, and D113 (second molecule) of Adx, respectively. Similar to P450 11B1, P450 11B2 also forms a complex with the Adx dimer via three lysine residues. We describe similarities and differences in our models of the P450 11B1·Adx2 and P450 11B2·Adx2 complexes with the structure of the P450 11A1-Adx fusion protein.


Regeneration of mandibular osteoradionecrosis defect with platelet rich plasma gel.
Osteoradionecrosis (ORN) of the mandible is a major complication of radiation therapy of head and neck cancer with a potential of occurrence ranging from 5 to 15% of the irradiated patients. Due to the gradual necrotic process, the mandibular bone becomes necrotic and looses its spontaneous regeneration ability. Containing an elevated content of mitogenic and osteogenic growth factors, the use of platelet rich plasma (PRP) from autologous source has been suggested to re-activate the healing process of osteogenesis. Autologous PRP gel was introduced into the ORN necrotic defect of a 44-year old patient previously treated for squamous cell carcinoma of the tongue, subsequent to proper surgical debridement. We report post-operative two-year follow-up demonstrated by panoramic X-ray which showed regain of the mandibular bone continuity with a complete repair of the necrotic defects. We conclude that this case illustrates an incident of successful regeneration of ORN critical-sized defect of the mandible by autologous PRP gel.


Asthma, glucocorticoids and growth.
Most asthmatic children grow normally. However, the disease itself and the treatments used, e.g. glucocorticoids (GCs) may affect growth, especially delaying puberty. Presently, the extensive use of early anti-inflammatory therapy is changing asthma to a milder disease and the effects on growth will probably further decline. Also, the use of inhaled instead of oral GCs has minimized the risk of systemic side-effects. High doses of inhaled GCs have systemic effects, and because there are individual differences in sensitivity to GCs, growth should be monitored in every child treated with GCs. The preparations with the lowest systemic bioavailability and the lowest dose to control asthma should be used.


Bacterial Periplasmic Oxidoreductases Control the Activity of Oxidized Human Antimicrobial β-Defensin 1.
The antimicrobial peptide human β-defensin 1 (hBD1) is continuously produced by epithelial cells in many tissues. Compared to other defensins, hBD1 has only minor antibiotic activity in its native state. After reduction of its disulfide bridges, however, it becomes a potent antimicrobial agent against bacteria, while the oxidized native form (hBD1ox) shows specific activity against Gram-negative bacteria. We show that the killing mechanism of hBD1ox depends on aerobic growth conditions and bacterial enzymes. We analyzed the different activities of hBD1 using mutants of Escherichia coli lacking one or more specific proteins of their outer membrane, cytosol, or redox systems. We discovered that DsbA and DsbB are essential for the antimicrobial activity of hBD1ox but not for that of reduced hBD1 (hBD1red). Furthermore, our results strongly suggest that hBD1ox uses outer membrane protein FepA to penetrate the bacterial periplasm space. In contrast, other bacterial proteins in the outer membrane and cytosol did not modify the antimicrobial activity. Using immunogold labeling, we identified the localization of hBD1ox in the periplasmic space and partly in the outer membrane of E. coli However, in resistant mutants lacking DsbA and DsbB, hBD1ox was detected mainly in the bacterial cytosol. In summary, we discovered that hBD1ox could use FepA to enter the periplasmic space, where its activity depends on presence of DsbA and DsbB. HBD1ox concentrates in the periplasm in Gram-negative bacteria, which finally leads to bleb formation and death of the bacteria. Thus, the bacterial redox system plays an essential role in mechanisms of resistance against host-derived peptides such as hBD1.


N6-methyladenosine modification participates in neoplastic immunoregulation and tumorigenesis.
This review aims to provide insight into the role of N6-methyladenosine (m6A) modification in neoplastic immunity and subsequent tumorigenesis. m6A modification, which is catalyzed by methyltransferases, demethylases and reader proteins, has emerged as a widespread regulatory mechanism that controls immune-related gene expression and immune reactions during tumorigenesis. Aberrant m6A modification changes the neoplastic immune response in multiple cancers by regulating immune cell infiltration, tumor-promoting inflammation, immunosuppression, immune surveillance, and antitumor immune responses. m6A modification affects immune cell recruitment and cancer-promoting inflammation in hepatocellular carcinoma (HCC) to alter the progression of HCC. m6A modification has been implicated in the infiltration of immune cells and the activation of immune pathways, changing the proliferation and metastasis of gastric cancer. Immune surveillance and the antitumor immune response in breast cancer were enhanced via m6A modification, which inhibited tumor proliferation. m6A modification participates in neoplastic immunoregulation to influence tumor progression.


Influence of bifentrin, a pyrethriod pesticide, on human colorectal HCT-116 cells attributed to alterations in oxidative stress involving mitochondrial apoptotic processes.
The widespread use of pesticides is beneficial for food production; however, there are numerous adverse consequences reported in the ecosystem and humans associated with exposure to these contaminants. The pyrethriod bifenthrin (BIF) is utilized for (1) maintenance, growth, and storage of agricultural products; (2) control of internal and external parasites of farm animals; and (3) eradication of insects threatening public health. Numerous data are available regarding environmental and ecological impact of pyrethriods on the central and peripheral nervous systems; however few studies focused on non-target tissues especially in humans. Therefore, the aim of this investigation was to determine the potential cytotoxic effects of BIF on a non-target tissue using human colorectal HCT-116 cells as a model. Data demonstrated that BIF reduced cell viability and disrupted mitochondrial functions which were accompanied by increased reactive oxygen species (ROS) levels indicating the presence of oxidative stress. BIF produced a significant elevation in levels of malondialdehyde (MDA) supporting the role of oxidative stress in pesticide-mediated toxicity. Concomitantly, a fall of mitochondrial transmembrane potential (Δψ), consequently producing perturbation of fluidity as well as excitability of cellular membranes was noted. Our results also indicated that BIF induced a rise in DNA damage as evidenced by the comet assay. An increase in mitogen-activated protein kinases (MAPKs), JNK (N-terminal Kinase), p38, and ERK (extracellular-signal-regulated kinase) suggested an apoptotic effect. Data thus indicated that BIF-induced cytotoxicity in human colorectal HCT-116 cells was associated with oxidative stress, mitochondrial dysfunction, and apoptosis.