IgM antibody to hepatitis B core antigen in Korean patients with hepatocellular carcinoma.
Primary hepatocellular carcinoma (PHC) has been linked etiologically to persistent hepatitis B virus (HBV) infections by epidemiologic, serologic and molecular lines of evidence. To evaluate the frequency of IgM antibody to the viral core antigen (IgM anti-HBc) detected by a highly sensitive radioimmunoassay, we compared 110 Korean patients with PHC to a group of 63 age- and sex-matched control patients with other tumors. Results were correlated with those of commercially available HBV assays. IgM anti-HBc was found in 74 of 110 PHC patients (67%), but only 1 of 63 (1.6%) control patients. Although HBsAg was found in a larger percentage of PHC patients (81%), it was also present in more control patients (14%). Thus, IgM anti-HBc was more specifically associated with PHC than was the presence of HBsAg. IgM anti-HBc was found in 91% of PHC patients with detectable HBeAg and 74% of PHC patients with positive anti-HBe tests (p less than 0.04). The frequency of IgM anti-HBc was similar among HBsAg-positive PHC patients with and without anti-HBs, or those with low or high levels of serum alpha-fetoprotein. In 18 patients with PHC, IgM anti-HBc was further characterized by rate-zonal centrifugation of sera, all were found to have 19S IgM anti-HBc although 6 also had greater or equal IgM anti-HBc reactivity in the low molecular weight region. The presence of IgM anti-HBc in adult Korean HBsAg carriers may indicate an especially high risk for the development of PHC, and this should be evaluated in prospective studies.


Tiotropium bromide inhibits TGF-β-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro.
chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and structural alterations (ie, tissue remodeling) throughout the conducting airways, parenchyma, and pulmonary vasculature. Matrix metalloproteinases (MMPs) are extracellular degrading enzymes that play a critical role in inflammatory cell infiltration and tissue remodeling, but the influence of the agents that are used for the treatment of COPD on the production of MMPs is not well understood. the present study aimed to examine the influence of tiotropium bromide hydrate (TBH) on the production of MMPs from lung fibroblasts (LFs) induced by transforming growth factor (TGF)-β in vitro. LFs, at a concentration of 5 × 10(5) cells·mL(-1), were stimulated with TGF-β in the presence of various concentrations of TBH. MMP-1 and MMP-2 levels in culture supernatants were examined by enzyme-linked immunosorbent assay (ELISA), and MMP messenger ribonucleic acid (mRNA) expression was examined by real-time polymerase chain reaction (RT-PCR). The influence of TBH on TGF-β signaling pathways was also analyzed by examining Smad activation and signaling protein phosphorylation by ELISA. TBH at more than 15 pg·mL(-1) inhibited the production of MMP-1 and MMP-2, but not tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2, from LFs, after TGF-β stimulation. TBH also suppressed MMP mRNA expression through the inhibition of Smad activation and signaling protein, extracellular-signal-regulated kinase (ERK) 1 and 2, and c-Jun N-terminal kinase (JNK), phosphorylation. These results may suggest that TBH suppresses MMP production from LFs, through interference of TGF-β-mediated signaling pathways and results in favorable modification of the clinical status of COPD.


3D Apicoectomy Guidance: Optimizing Access for Apicoectomies.
When conventional endodontic treatment resources are depleted, endodontic surgery becomes an alternative treatment for apical periodontitis to remove unreachable infected areas and seal the root canal. Digital workflows have been used more frequently in many dental applications in recent years. In endodontics, virtual 3-dimensional (3D) planning and endodontic guidance are new aspects important for the treatment of complex cases. This report aimed to present 3D Apicoectomy Guidance, a novel method of performing guided ultraconservative endodontic surgery with conventional implant-guided drills, and to describe its application in a case with a complex anatomic scenario and intimate contact with the maxillary sinus. Implantology computer software, as well as cone-beam computed tomography images and a digital scanning 3D impression, enabled virtual planning of the surgical procedure. Subsequently, a 3D template was produced to guide the instruments used in the osteotomy and root resection. The patient was completely asymptomatic at the 1-week follow-up visit. Cone-beam computed tomography scans were performed at 1 and 6 months after surgery and showed that resection of the apex of the root was performed accurately and that a thin dentin slice remained distally, preventing the rupture of the sinus membrane. The patient remained asymptomatic, and the tissue healed normally. The method used was shown to be very straightforward and reliable. This method allowed the patient to be treated expeditiously with very precise tissue removal.


Immunogenicity and Safety of a 3-Dose Regimen of a SARS-CoV-2 Inactivated Vaccine in Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.
Control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic needs effective vaccines. In a phase 2 randomized, double-blind, placebo-controlled trial, 500 adults aged 18-59 years or ≥60 years were randomized in 2:2:1 ratio to receive 3 doses of 5 μg or 10 μg of a SARS-CoV-2 inactivated vaccine, or placebo separated by 28 days. Adverse events (AEs) were recorded through day 28 after each dosing. Live virus or pseudovirus neutralizing antibodies, and receptor binding domain immunoglobulin G (RBD-IgG) antibody were tested after the second and third doses. Two doses of the vaccine elicited geometric mean titers (GMTs) of 102-119, 170-176, and 1449-1617 for the 3 antibodies in younger adults. Pseudovirus neutralizing and RBD-IgG GMTs were similar between older and younger adults. The third dose slightly (<1.5 fold) increased GMTs. Seroconversion percentages were 94% or more after 2 doses, which were generally similar after 3 doses. The predominant AEs were injection-site pain. All the AEs were grade 1 or 2 in intensity. No serious AE was deemed related to study vaccination. Two doses of this vaccine induced robust immune response and had good safety profile. A third dose given 28 days after the second dose elicited limited boosting antibody response.


Under the banyan tree--exclusion and inclusion of people with mental disorders in rural North India.
Social exclusion is both cause and consequence of mental disorders. People with mental disorders (PWMD) are among the most socially excluded in all societies yet little is known about their experiences in North India. This qualitative study aims to describe experiences of exclusion and inclusion of PWMD in two rural communities in Uttar Pradesh, India. In-depth interviews with 20 PWMD and eight caregivers were carried out in May 2013. Interviews probed experiences of help-seeking, stigma, discrimination, exclusion, participation, agency and inclusion in their households and communities. Qualitative content analysis was used to generate codes, categories and finally 12 key themes. A continuum of exclusion was the dominant experience for participants, ranging from nuanced distancing, negative judgements and social isolation, and self-stigma to overt acts of exclusion such as ridicule, disinheritance and physical violence. Mixed in with this however, some participants described a sense of belonging, opportunity for participation and support from both family and community members. These findings underline the urgent need for initiatives that increase mental health literacy, access to services and social inclusion of PWMD in North India, and highlight the possibilities of using human rights frameworks in situations of physical and economic violence. The findings also highlight the urgent need to reduce stigma and take actions in policy and at all levels in society to increase inclusion of people with mental distress and disorders.


Outcomes and complications in superior semicircular canal dehiscence surgery: A systematic review.
Superior semicircular canal dehiscence (SSCD) represents a rare condition that may be associated to some particular symptoms as vertigo, autophony, and Tullio phenomenon. In those patients who present severe symptoms surgical treatment is required. Middle fossa craniotomy and transmastoid approaches are both described. Concerning repairing techniques, plugging and/or resurfacing are typically used to close the defect. Our aim was first to analyze the overall outcomes and complications of this surgery. Our second aim was to make a comparison between the different surgical modalities to investigate the eventual advantages and disadvantages. A search through Ovid MEDLINE was organized in January 2015 to include all eligible articles. A statistical analysis of the obtained data was performed. Twenty studies comprising a total of 150 procedures were included. Four modalities of canal repair were described (plugging, capping, resurfacing, plugging with resurfacing). The overall rate of success resulted in 94% (95% confidence interval: 87%-97%). No statistically significant differences were observed among the different modalities of canal repair concerning both success rate and surgical complications. Differences observed between the middle fossa approach and transmastoid approach in terms of outcome were not statistically significant. This review showed that surgical treatment for SSCD represents a safe option for those patients with severe symptoms of this condition. Differences observed in terms of success rate or complications were analyzed between the different surgical techniques with results that were not statistically significant. NA Laryngoscope, 126:1218-1224, 2016.


Stereotactic Body Radiotherapy and Ablative Therapies for Lung Cancer.
The treatment paradigm for early stage lung cancer and oligometastatic disease to the lung is rapidly changing. Ablative therapies, especially stereotactic body radiation therapy, are challenging the surgical gold standard and have the potential to be the standard for operable patients with early stage lung cancer who are high risk due to co- morbidities. The most commonly used ablative modalities include stereotactic body radiation therapy, microwave ablation, and radiofrequency ablation.


Depletion of cathepsin D by transglutaminase 2 through protein cross-linking promotes cell survival.
Transglutaminase 2 (TGase 2) promotes nuclear factor-κB (NF-κB) activity through depletion of the inhibitory subunit of NF-κB (I-κBα) via protein cross-linking, leading to resolution of inflammation. Increased expression of TGase 2 contributes to inflammatory disease pathogenesis via constitutive NF-κB activation. Conversely, TGase 2 inhibition often reverses inflammation in animal models. The role of TGase 2 in apoptosis remains less clear, as both pro- and anti-apoptotic functions of TGase 2 have been demonstrated under different experimental conditions. Apoptosis is intact in a TGase 2 knock out mouse (TGase2(-/-)), which is phenotypically normal. However, upon exposure to tumor necrosis factor (TNF)-α-induced apoptotic stress, mouse embryonic fibroblasts (MEFs) from TGase2(-/-) mice were more sensitive to cell death than MEFs from wild-type (TGase 2(+/+)) mice. In the current study, to explore the role of TGase 2 in apoptosis, TGase 2-binding proteins were identified by LC/MS. TGase 2 was found to associate with cathepsin D (CTSD). Binding of TGase 2 to CTSD resulted in the depletion of CTSD via cross-linking in vitro as well as in MEFs, leading to decreased levels of apoptosis. Furthermore, cytoplasmic CTSD levels were higher in MEFs from TGase 2(-/-) mice than in those from TGase 2(+/+) mice, as were caspase 3 activation and poly (ADP-ribose) polymerase (PARP) processes. These results suggest that TGase 2, while not previously implicated as a major regulatory factor in apoptosis, may regulate the balance between cell survival and cell death through the modulation of CTSD levels.


Plasma lipidic fingerprint associated with type 2 diabetes in patients with coronary heart disease: CORDIOPREV study.
We aimed to identify a lipidic profile associated with type 2 diabetes mellitus (T2DM) development in coronary heart disease (CHD) patients, to provide a new, highly sensitive model which could be used in clinical practice to identify patients at T2DM risk. This study considered the 462 patients of the CORDIOPREV study (CHD patients) who were not diabetic at the beginning of the intervention. In total, 107 of them developed T2DM after a median follow-up of 60 months. They were diagnosed using the American Diabetes Association criteria. A novel lipidomic methodology employing liquid chromatography (LC) separation followed by HESI, and detection by mass spectrometry (MS) was used to annotate the lipids at the isomer level. The patients were then classified into a Training and a Validation Set (60-40). Next, a Random Survival Forest (RSF) was carried out to detect the lipidic isomers with the lowest prediction error, these lipids were then used to build a Lipidomic Risk (LR) score which was evaluated through a Cox. Finally, a production model combining the clinical variables of interest, and the lipidic species was carried out. LC-tandem MS annotated 440 lipid species. From those, the RSF identified 15 lipid species with the lowest prediction error. These lipids were combined in an LR score which showed association with the development of T2DM. The LR hazard ratio per unit standard deviation was 2.87 and 1.43, in the Training and Validation Set respectively. Likewise, patients with higher LR Score values had lower insulin sensitivity (P = 0.006) and higher liver insulin resistance (P = 0.005). The receiver operating characteristic (ROC) curve obtained by combining clinical variables and the selected lipidic isomers using a generalised lineal model had an area under the curve (AUC) of 81.3%. Our study showed the potential of comprehensive lipidomic analysis in identifying patients at risk of developing T2DM. In addition, the lipid species combined with clinical variables provided a new, highly sensitive model which can be used in clinical practice to identify patients at T2DM risk. Moreover, these results also indicate that we need to look closely at isomers to understand the role of this specific compound in T2DM development. Trials registration NCT00924937.


Conjoined twinning in Sweden.
A small "epidemic" of conjoined twinning is reported occurring at the Skövde Central hospital in 1975-76. Three parts were observed, the annual birth number of 2300. During a ten-year period, 10 cases of conjoined twinning were reported to the Register of Congenital Malformations in Sweden, indicating a probable incidence of 1:75000 births. These 10 cases were distributed all over the country. Interviews with the three women who gave birth to the Skövde conjoined twins revealed no common factor which could be of aetiological significance.


On the fate of LAS, NPEOs and DEHP in municipal sewage sludge during composting.
The fate of hydrophobic xenobiotic pollutants such as linear alkylbenzene sulfonates (LAS), nonylphenol ethoxylates (NPEO) and di-ethyl-hexyl phthalate (DEHP) during sewage sludge composting was addressed in this work. The experiments were conducted in a fully automated in-vessel autothermal composting system which was fed with a mixture of primary and secondary sludge and manure. The mixture composition was determined to achieve satisfactory humidity, C/N ratio and free air space (FAS). The effect of various parameters, such as the initial xenobiotic concentration, the presence of multiple xenobiotic compounds and the temperature of composting material sustained during the process on the xenobiotics biodegradation kinetics was investigated. It was generally established that significant xenobiotic reduction is achievable through composting under all conditions tested. According to the obtained results, the presence of LAS, NPEO and DEHP even at higher concentrations was not inhibitory to the bioprocess. However, the presence of multiple xenobiotic compounds such as NPEO, NP and DEHP in the sludge can influence LAS removal during LAS composting.


The Association Between Seeing People Walk and Neighborhood Social Cohesion.
To examine the association between frequency of seeing people walk within sight of home and neighborhood social cohesion among adults, and whether this association varies by race/ethnicity. We used cross-sectional 2015 National Health Interview Survey data on Latino, non-Latino White, non-Latino Black, and non-Latino Asian adults (N = 33,099). Multinomial logistic regression models were used to estimate the associations. Seeing people walk every day and every 2-3 days were significantly more likely to report medium levels of neighborhood social cohesion, relative to low. The association between seeing people walk and neighborhood social cohesion varied by race/ethnicity. Higher frequency of seeing others walk may contribute to higher levels of neighborhood social cohesion.


Detection and discrimination of low concentration explosives using MOS nanoparticle sensors.
In the present study, four explosives of NH(4)NO(3), mineral explosives (ME), picric acid (PA) and 2,6-dinitrotoluene (2,6-DNT) have been investigated by using ZnO-doped nanoparticle sensors with additives of Sb(2)O(3), TiO(2), V(2)O(5) and WO(3). Firstly, eighteen ZnO-doped nanoparticle sensors were optimized and selected six best sensors to compose a new optimized array. Then, the detection capability of the sensor array was studied by using static sampling method. The results showed that with the increase in concentration of samples, the sensitivities of the sensors also increased, and the lowest detection limit of the four samples were low to 3.34 microg/L. At last, for the sake of approaching closer practical application, these four explosives were also studied with full dynamic sampling method and the results demonstrated that all the samples could be well identified completely at the concentration of 15.4 microg/L when maximum values of slope were extracted as the feature parameters to DFA analysis.


Selective PF4 release in vitro induced by heparin and related glycosaminoglycans (GAGs)--correlation with beta-TG release and platelet aggregation.
We studied human platelet aggregation and beta-TG/PF4 release induced by heparin and related GAGs in vitro both in normal PRP and in PRP after aspirin. In our experimental conditions, heparin and related GAGs always caused PF4 release in vitro from normal platelets, whether or not there was measurable platelet aggregation in the aggregometer. Significant beta-TG release was induced only by the mucosal heparin preparation (which also induced platelet aggregation in some citrated PRP). Therefore, while beta-TG release in vitro seems to correlate with platelet aggregating activity of heparin, the selective PF4 release, caused by heparin and related GAGs also in conditions in which neither platelet aggregation nor beta-TG are measurable, is probably associated with the high affinity of PF4 for heparin. The degree of affinity of GAGs for PF4 (heparin greater than DeS greater than HS) seems to correlate with PF4 release. Moreover, the significant reduction in PF4 release in vitro after aspirin suggests that GAGs-induced PF4 release is related to a cyclooxygenase-dependent activation process.


Carrageenan-induced acute inflammatory response in chicks.
Carrageenan from two commercial sources was used in varying concentrations to evoke an acute inflammatory response in the foot pad of chickens. Oedema formation and increased vascular permeability were less severe using this experimental model than with turpentine-induced injury. Inflammation was monophasic, of short duration and apparently mediated by histamine and serotonin as their respective antagonists diminished the response. Prostaglandins seemed to play only a minor role as indomethacin blocked only the later phase of oedema. Bothrops jararaca venom did not potentiate the inflammatory response, implying that bradykinin was not a significant mediator.


Sex pheromone receptors of the light brown apple moth, Epiphyas postvittana, support a second major pheromone receptor clade within the Lepidoptera.
Sex pheromones facilitate species-specific sex communication within the Lepidoptera. They are detected by specialised pheromone receptors (PRs), most of which to date fall into a single monophyletic receptor lineage (frequently referred to as "the PR clade") within the odorant receptor (OR) family. Here we investigated PRs of the invasive horticultural pest, Epiphyas postvittana, commonly known as the light brown apple moth. Ten candidate PRs were selected, based on their male-biased expression in antennae or their relationship to the PR clade, for functional assessment in both HEK293 cells and Xenopus oocytes. Of these, six ORs responded to compounds that include components of the E. postvittana ('Epos') sex pheromone blend or compounds that antagonise sex pheromone attraction. In phylogenies, four of the characterised receptors (EposOR1, 6, 7 and 45) fall within the PR clade and two other male-biased receptors (EposOR30 and 34) group together well outside the PR clade. This new clade of pheromone receptors includes the receptor for (E)-11-tetradecenyl acetate (EposOR30), which is the main component of the sex pheromone blend for this species. Interestingly, receptors of the two clades do not segregate by preference for compounds associated with behavioural response (agonist or antagonist), isomer type (E or Z) or functional group (alcohol or acetate), with examples of each scattered across both clades. Phylogenetic comparison with PRs from other species supports the existence of a second major clade of lepidopteran ORs including, EposOR30 and 34, that has been co-opted into sex pheromone detection in the Lepidoptera. This second clade of sex pheromone receptors has an origin that likely predates the split between the major lepidopteran families.


Can uncertainty estimation predict segmentation performance in ultrasound bone imaging?
Segmenting bone surfaces in ultrasound (US) is a fundamental step in US-based computer-assisted orthopaedic surgeries. Neural network-based segmentation techniques are a natural choice for this, given promising results in related tasks. However, to gain widespread use, we must be able to know how much to trust segmentation networks during clinical deployment when ground-truth data is unavailable. We investigated alternative ways to measure the uncertainty of trained networks by implementing a baseline U-Net trained on a large dataset, together with three uncertainty estimation modifications: Monte Carlo dropout, test time augmentation, and ensemble learning. We measured the segmentation performance, calibration quality, and the ability to predict segmentation performance on test data. We further investigated the effect of data quality on these measures. Overall, we found that ensemble learning with binary cross-entropy (BCE) loss achieved the best segmentation performance (mean Dice: 0.75-0.78 and RMS distance: 0.62-0.86mm) and the lowest calibration errors (mean: 0.22-0.28%). In contrast to previous studies of area or volumetric segmentation, we found that the resulting uncertainty measures are not reliable proxies for surface segmentation performance. Our experiments indicate that a significant performance and confidence calibration boost can be achieved with ensemble learning and BCE loss, as tested on 13,687 US images containing various anatomies and imaging parameters. However, these techniques do not allow us to reliably predict future segmentation performance. The results of this study can be used to improve the calibration and performance of US segmentation networks.


Blood Impairs Viability of Fat Grafts and Adipose Stem Cells: Importance of Washing in Fat Processing.
Fat processing plays a pivotal role in graft survival. Each component of the blood in lipoaspirate affects fat survival in different ways, but the mechanisms are not clear. The aim of this study was to investigate, by various experimental methods, the effect of blood on the viability of fat grafts and adipose stem cells (ASCs). Blood and fat samples were obtained from 6 female patients undergoing aesthetic liposuction. For the in vivo experiment, we compared fat mixed with normal saline or various ratios of blood in nude mice. The samples were explanted at 2 and 8 weeks to evaluate the gross volume retention and histologic and immunohistochemical characteristics. For in vitro experiments, ASCs were pretreated with hemoglobin at different concentrations and for different times. We then assessed the proliferation, migration, adipogenesis, and reactive oxygen species production of ASCs. Blood in the graft led to a decrease in graft viability, as evaluated by general observation and histologic and immunohistochemical morphology in vivo. In vitro experiments showed inhibited proliferation, migration, and adipogenesis, and increased reactive oxygen species production in ACSs, after hemoglobin treatment, suggesting impaired ASC viability. This study suggests that blood impairs the viability of fat grafts and ASCs and provides evidence that washing to remove blood is important in fat processing.


Suprasternal Doppler ultrasound for assessment of stroke distance.
An assessment of a non-invasive technique for measurement of stroke distance was made using a portable Doppler ultrasound machine. The aim was to determine the measurement error of repeated stroke distance measurements (Within-observer variability) and to assess measurement agreement between two operators (between-observer variability). The measurement error (within-observer variability) for both operators was similar at approximately 2 cm. However, the measurements of the two operators (between-observer variability) did not agree well. Using the mean (SD) of three readings by each operator, the mean difference between the operators was -0.21 cm (1.96) giving a 95% confidence interval for the differences of -4.0 to +3.6 cm. There were significant positive and negative correlations between stroke distance and a variety of variables (age, height, weight, heart rate), but the relations were weak. The results indicate that the Doppler ultrasound technique for measurement of stroke distance would best be used to study trend changes in an individual patient, or subject, by a single operator.


Liver Transplantation for Acute on Chronic Liver Failure.
Acute-on chronic liver failure (ACLF) is defined as acute insult on previous liver disease that causes sudden worsening of liver functions. ACLF is characterized by high incidence of organ failure and prognosis is remarkably worse than patients with cirrhosis. Incidence of organ failures is very high despite best medical care and timely liver transplant before development of multi organ failure is associated with good survival rates. At present, there are no reliable score or ways to correctly identify patients who are going to recover from patients who will need transplantation. Organ failures are important part of prognosis and to define need or futility of early liver transplantation. Asian Pacific Association for the Study of the Liver (APASL) published their recommendations regarding ACLF in 2014. Several important studies regarding course/nature of disease and transplantation for ACLF became available after 2014 APASL recommendations and still there are some unanswered areas. The current review discusses various issues regarding liver transplantation in patients with ACLF.


Multiple genotypes of the merozoite surface proteins 1 and 2 in Plasmodium falciparum infections in a hypoendemic area in Iran.
In Iran, malaria transmission mainly occurs in south-eastern regions through both Plasmodium falciparum and P. vivax. The genetic diversity of P. falciparum isolates was analysed in 108 patients attending the regional hospital in Chabahar District, using the molecular markers msp1 and msp2. Multiple genotypes were detected in 87% of patients and the mean numbers of msp1 and msp2 genotypes were 2.51 (95% CI: 2.29-2.73) and 2.61 (95% CI: 2.39-2.83) respectively. Various allelic types of msp1 and msp2 were found, with msp2 3D7/IC type detected in 94% of infections. Plasmodium falciparum infections in south-east Iran appear to have a higher genetic diversity than expected for an area of low transmission. A situation of higher transmission in this area may be emerging, possibly because of reduced efficacy of first-line treatments.


Epineurectomy for thoracic outlet syndrome.
The authors' approach to patients with TOS starts with a thorough evaluation, including a detailed history, physical examination, electromyography, and radiographs. Once the work-up is complete a treatment plan is formulated with the patient. All diagnoses are prioritized, together with various options for treatment of each. Therapy is initiated when appropriate and a surgical plan addresses the worst nerve entrapments sequentially. The authors' favored procedure for TOS release is an anterior scalenectomy with epineurectomy, with decompression of any structures impinging on the brachial plexus. The authors encourage patients to attend therapy for approximately 3 months after surgery, and to follow a home program of rehabilitation to maximize their gains and decrease the chance of recurrence.


Intranasal insulin therapy: the clinical realities.
To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time.


Assessing dynamic change in muscle during treatment of patients with cancer: Precision testing standards.
Computed tomography images acquired during routine cancer care provide an opportunity to determine body composition with accuracy and precision. Quantification of skeletal muscle is of interest owing to its association with clinical outcomes. However, the standards of precision testing considered mandatory in other areas of radiology are lacking from the literature in this area. We aim to describe the change in skeletal muscle over time at different anatomical levels using the precision error. Thirty-eight male patients with squamous cell carcinoma of the head and neck were evaluated at two time points encompassing their treatment plan. Precision testing consisted of analyzing the cross-sectional area (CSA) of the skeletal muscle and total adipose tissue of 76 CT studies (38 images at baseline repeated twice and 38 follow-up images repeated twice) measured by a skilled observer. The % coefficient of variation (%CV), the root-mean-square standard deviation (RMS SD) and the corresponding 95% least significant change (LSC) were calculated for four anatomical levels: upper arm, thigh, chest and abdomen. The median time between scans was 223.6 (SD 31.2) days. Precision error (% CV) for total skeletal muscle cross sectional area was 0.86% for upper arm, 0.26% for thigh, 0.39% for chest and 0.63% for abdomen. The corresponding LSC values in upper arm, thigh, chest and abdomen were 2.4%, 0.7%, 1.1% and 1.8%, respectively. Based on the LSC for RMS SD, patients were classified in two categories according to muscle cross-sectional area: stable (i.e within LSC value) or gained and loss. To compare the four anatomical levels, the proportion of patients with muscle loss exceeding the LSC value was 74.3% for arm, 86.2% for thigh, 82.9% for chest and 76.3% for abdomen. For these same anatomic regions, the mean muscle loss for those patients classified below the LSC was 14.6% (SD 9.3), 13.4% (SD 7.8), 11.9% (SD 6.5) and 11.6% (SD 5.5), respectively. Only the loss of muscle area was significantly higher in thigh (p = 0.023), using L3 as the reference level. We recommend the uniform use of a standard precision test when reporting muscle change over time. LSC values vary from 0.7 to 2.4% depending on anatomic site; with the lowest precision error to detect change in the thigh. Based on this analysis, muscle wasting appears to be systemic and while present in limbs and trunk is significantly higher in the thigh than in the chest, abdomen or upper arm.


[The importance of antagonistic soil micro-flora for eliminating soil-born fungal pathogens in intensive corn-growing (author's transl)].
In a sandy soil, the antagonistic bacterial and fungal flora was analysed and their effectivity with respect to corn foot and stem rot was investigated. Measures that promoted total micro-flora in soil (organic fertilization) stimulated, in most cases, the antagonists as well. Different organic substances supported various types of antagonists. In soil with inhibited aeration the antagonists were reduced. A full effectivity of the antagonistic biological soil component presupposes the absence of host plants.


Homogenous high enhancement surface-enhanced Raman scattering (SERS) substrates by simple hierarchical tuning of gold nanofoams.
Surface enhanced Raman scattering (SERS) is a powerful tool for vibrational spectroscopy, providing orders of magnitude increase in chemical sensitivity compared to spontaneous Raman scattering. Yet it remains a challenge to synthesize robust, uniform SERS substrates quickly and easily. Lithographic approaches to produce substrates can achieve high, uniform sensitivity but are expensive and complex, thus difficult to scale. Facile solution-phase chemical approaches often result in unreliable SERS substrates due to heterogeneous arrangement of "hot spots" throughout the material. Here we demonstrate the synthesis and characterization of a homogeneous gold nanofoam (AuNF) substrate produced by a rapid, one-pot, four-ingredient synthetic approach. AuNFs are rapidly nucleated with macroscale porosity and then chemically roughened to produce nanoscale features that confer homogeneous and high signal enhancement (~109) across large areas, a comparable performance to lithographically produced substrates.


Adjuvant concurrent chemoradiation followed by chemotherapy for high-risk endometrial cancer.
The adjuvant treatment of high-risk endometrial cancer (HREC) remains controversial. This prospective phase-II clinical trial was conducted to evaluate the adjuvant concurrent chemoradiotherapy followed by chemotherapy in patients with HREC. Altogether 122 patients were enrolled between January 2007 and January 2013, in which 112 were analyzable. The inclusion criteria included endometrioid endometrial cancer of histological grade 3 and with greater than 50% myometrial invasion, cervical stromal invasion, pelvic and/or para-aortic lymph node metastases; non-endometrioid endometrial cancer; no residual disease and distant metastases. Pelvic radiation was administered with cisplatin on days 1 and 28. Para-aortic radiation was administered with confirmed para-aortic lymph node metastases, and vaginal afterloading brachytherapy with cervical stromal invasion after total hysterectomy. Four courses of paclitaxel and carboplatin (PC) or cisplatin, cyclophosphamide and epirubicin (CEP) were administered at three-week interval after radiation. Ninety-six patients (85.7%) completed the planned treatment. Treatment discontinuation was the result of toxicity (5/112, 4.5%), disease progression (8/112, 7.1%), and patients refusal (3/112, 2.7%). There was no life-threatening toxicity. Twenty-five (22.3%) patients recurred, in which 4 cases recurred in the field of radiation, and 13 (11.6%) patients died of endometrial cancer during follow-up. The estimated five-year progression-free survival and overall survival were 73% and 84%, respectively. Adverse effects were less common in patients who received PC than CEP (p=0.001). This regimen demonstrated acceptable toxicity and good survival outcomes despite a preponderance (62.5%) of late stage disease. PC showed less adverse effects than CEP. A well designed randomized trial is under development. https://clinicaltrials.gov/: 070148-7.


Evaluation of the Novel Automated Anti-Tachycardia Pacing Algorithm Successfully Terminating Sustained Monomorphic Ventricular Tachycardia in an Electrophysiology Study.
We report the usefulness of novel automated anti-tachycardia pacing (ATP) for ventricular tachycardia (VT) termination evaluated in an electrophysiology study. This intrinsic, automated ATP with an implanted cardiac resynchronization therapy-defibrillator successfully terminated the sustained VT, which had not been suppressed by repetitive burst pacing from the electrode catheter. The reproduction of programed pacing of the automated ATP by a right ventricular electrode catheter was effective in terminating VT, and this termination was absolute and reproducible. Further detailed assessment in an electrophysiology study could highlight the algorithm of the automated ATP and its possible benefit in terminating the reentrant VT.


Selective amino acids changes in the medial and lateral preoptic area in the formalin test in rats.
A combination of microdialysis in freely moving rats and capillary zone electrophoresis coupled to laser induced fluorescence detection was used to measure extracellular concentrations of amino acid neurotransmitters in different hypothalamic areas during noxious stimulation. Arginine, glutamate and aspartate were monitored every 30 s before and after a s.c. injection of formalin (5%, 50 microl) or saline (0.9%) in the right hind paw. In the medial and lateral preoptic area, calcium and nerve impulse dependent increases of arginine, glutamate and aspartate were observed during the first 2 min after formalin injection. However, amino acid changes were not detected in the lateral hypothalamus or in the ventromedial nucleus when compared with pre-injection levels or with the levels from animals injected with saline in the hind paw. Flinching behavior was also scored during the first 10 min following the formalin or saline injection. Flinching frequency was maximum at minute 2 after formalin injection, whereas saline injection did not elicited any flinching behavior. These results show that nociceptive stimulation induces rapid and differential amino acids changes in discrete areas of the hypothalamus that can be associated with pain-related behavior.


A neonate with respiratory distress and a chest wall deformity.
Infants with respiratory distress commonly present to a pediatric emergency department. There are rare but serious conditions that need to be considered in the differential diagnosis. We report the history of an infant that presented to our institution with respiratory distress ultimately diagnosed with a mesenchymal hamartoma of the chest wall. The presentation, diagnosis, and treatment options for mesenchymal hamartoma are discussed.


Diagnostic mock-ups as an objective tool for predictable outcomes with porcelain laminate veneers in esthetically demanding patients: a clinical report.
This clinical report demonstrates how a clinician can objectively overcome some of the barriers associated with providing patients with predictable esthetics, in a mutually satisfactory manner. Two such barriers are identified and discussed. The first is related to psychology and patient attitude to treatment. The second is related to the actual clinical procedure. A direct mock-up technique is described which serves as an effective communication tool between the dentist, patient, and dental laboratory technician.


Evaluation of twenty-one human adenovirus types and one infectivity-enhanced adenovirus for the treatment of malignant melanoma.
Advanced melanoma is associated with poor prognosis warranting the development of new therapeutics, such as oncolytic adenoviruses for immunovirotherapy. Since this approach critically depends on efficient transduction of targeted tumor cells, we screened a panel of 22 different adenovirus types for their internalization efficiency in melanoma cells. We demonstrated that the virions of Ad35, Ad38, and Ad3 have significantly higher internalization efficiency in melanoma cells than Ad5, so far the only adenovirus type used in clinical trials for melanoma. Therefore, we developed a conditionally replication-competent Ad5-based vector with the Ad35 fiber shaft and knob domains (Ad5/35) and compared its therapeutic efficacy with the homologous vector carrying the native Ad5 fiber. To further enhance virotherapy, we combined the oncolytic adenovirus vectors with intratumoral expression of measles virus fusogenic membrane glycoproteins H and F (MV-H/F) and dacarbazine chemotherapy. In a human melanoma xenograft model, established from a short-term culture of primary melanoma cells, we demonstrated that the Ad5/35-based therapy had a significantly greater anti-neoplastic effect than the homologous Ad5-based therapy. Furthermore, the combination of virotherapy, intratumoral expression of MV-H/F, and chemotherapy was clearly superior to single- or double-agent therapy. In conclusion, Ad35-based vectors are promising for the treatment of melanoma.


Transcriptome analysis of the Mg2+-responsive PhoP regulator in Yersinia pestis.
PhoP was previously shown to be important for Yersinia pestis survival in macrophage and under macrophage-induced stresses. In this work, a phoP disruptant of Y. pestis 201 was generated using the Red cloning procedure. The transcription profile of the wild-type Y. pestis was then compared with that of the phoP mutant under Mg2+-limiting conditions. It was revealed that PhoP/PhoQ governed a wide set of cellular pathways in Y. pestis, especially including the positive regulation of many metabolic processes, Mg2+ transport, peptidoglycan remodeling, lipopolysaccharide (LPS) modification and various stress-protective functions. The Mg2+ transport system regulated by PhoP may make Y. pestis to maintain the magnesium homeostasis under low Mg2+ environments. The PhoP-controlled stress-protective functions likely constitute the molecular basis for the observation that mutation of the phoP gene rendered the bacteria more sensitive to various macrophage-induced stresses. Modification of LPS mediated by PhoP is hypothesized to not only neutralize negative charges as normally done by Mg2+ ions, but also mediate the resistance of Y. pestis to antimicrobial peptides. The microarray results provide a population of candidate genes or pathways, and further biochemical experiments are needed to elucidate the PhoP-dependent mechanisms by which Y. pestis survives the antibacterial strategies employed by host macrophages.


Microbial production of cis,cis-muconic acid from aromatic compounds in engineered Pseudomonas.
Industrial expansion has led to environmental pollution by xenobiotic compounds like polycyclic aromatic hydrocarbons and monoaromatic hydrocarbons. Pseudomonas spp. have broad metabolic potential for degrading aromatic compounds. The objective of this study was to develop a "biological funneling" strategy based on genetic modification to convert complex aromatic compounds into cis,cis-muconate (ccMA) using Pseudomonas putida B6-2 and P. brassicacearum MPDS as biocatalysts. The engineered strains B6-2 (B6-2ΔcatBΔsalC) and MPDS (MPDSΔsalC(pUCP18k-catA)) thrived with biphenyl or naphthalene as the sole carbon source and produced ccMA, attaining molar conversions of 95.3% (ccMA/biphenyl) and 100% (ccMA/naphthalene). Under mixed substrates, B6-2ΔcatBΔsalC grew on biphenyl as a carbon source and transformed ccMA from non-growth substrates benzoate or salicylate to obtain higher product concentration. Inserting exogenous clusters like bedDC1C2AB and xylCMAB allowed B6-2 recombinant strains to convert benzene and toluene to ccMA. In mixed substrates, constructed consortia of engineered strains B6-2 and MPDS specialized in catabolism of biphenyl and naphthalene; the highest molar conversion rate of ccMA from mixed substrates was 85.2% when B6-2ΔcatBΔsalC was added after 24 h of MPDSΔsalC(pUCP18k-catA) incubation with biphenyl and naphthalene. This study provides worthwhile insights into efficient production of ccMA from aromatic hydrocarbons by reusing complex pollutants.


Visualization of risk-area myocardium as a high-intensity, hyperenhanced "hot spot" by myocardial contrast echocardiography following coronary reperfusion: quantitative analysis.
We examined whether delayed post-injection imaging of a new ultrasound contrast agent (BR-14) could produce prolonged opacification and hyperenhancement of myocardium subjected to coronary occlusion/reperfusion. We hypothesized that ultrasound exposure destroyed BR-14 and eliminated visualization of sustained myocardial opacification from retained microbubbles. We studied eight open-chest dogs with 3 h of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Myocardial contrast echocardiography (MCE) was performed before occlusion and 120 min after the onset of both occlusion and reperfusion. Ultrasound imaging was initiated 15 min after injection. Myocardial blood flow (MBF) was assessed by microspheres. Pre-occlusion images revealed uniform opacification of left ventricular myocardium greater than that of the cavity, with a mean intensity of the LAD bed of 8.66 +/- 1.38 dB. During occlusion, MCE resulted in the appearance of a perfusion defect in the LAD risk area (intensity 2.08 +/- 1.10 dB). After 120 min of reperfusion, the LAD risk-area myocardium manifested dense opacification of a higher intensity ("hot spot") than baseline (13.7 vs. 8.7 dB), but with reduced MBF consistent with accumulation of a high concentration of microbubbles. Increased MCE intensity was associated with a greater myeloperoxidase score. These data establish that contrast opacification by BR-14 may be selectively retained within the perfusion bed of a coronary artery subjected to occlusion/reperfusion. Such opacification exhibits defects with occlusion, manifests hyperenhanced intensity (hot spot) with reperfusion, is associated with the level of myeloperoxidase activity, and conforms to the area of myocardium subjected to altered flow.


Gold nanoparticle deposition on Si by destabilising gold colloid with HF.
Gold nanoparticles from commercially available colloids were deposited onto a hydrogen-terminated silicon substrate without the use of a polyelectrolyte linker by the addition of HF acid. The deposition density was shown to be controlled over three orders of magnitude by varying the colloid concentration, and finer control is achieved by varying the deposition time. In order to minimise agglomeration, however, we show that deposition times should be minimised since nanoparticle agglomeration increases rapidly over the first 2 min after the addition of HF. To increase nanoparticle density without increasing agglomeration, we show that successive depositions of short times linearly increase the deposition density without increasing the agglomeration of nanoparticles.


Perceptions About Health, Nutrition Knowledge, and MyPlate Food Categorization Among US Adolescents: A Qualitative Study.
To understand how adolescents define related nutrition terms and use food groups to classify commonly consumed foods into the MyPlate food groups. Qualitative study with telephone interviews. Houston metropolitan area in Texas. A convenience sample of 21 adolescents from a volunteer database of the research center. Sociodemographic questions were asked before semiquantitative structured interviews. The interview focused on understanding how adolescents defined health, other nutrition terms, and food groups, and how to use the MyPlate icon in categorizing commonly consumed foods into groups. Hybrid thematic approach with inductive and deductive analyses. Adolescents defined being healthy in terms of wellness-type behaviors (eg, diet, physical activity, and sleep). They perceived clear differences between terms such as healthy vs unhealthy food but struggled to define others (eg, energy-dense foods and processed foods). Mixed dishes, hard candies, chocolate chip cookies, and potato chips were the most difficult foods for the adolescents to classify into the MyPlate food groups, whereas apple, lettuce, and milk were easily classified. Food guidance systems, public health policies, and behavioral nutrition programs targeting adolescents might use health and nutrition terms and prescriptive food categories more clearly understood by adolescents.


ORIENT-31 as the Sakigake "Charging Samurai" Born of IMpower150 but Will MARIPOSA-2 IMPRESS in the "Meiji Modernization" of Post-3G EGFR TKI Progression?
Tyrosine kinase inhibitors (TKIs) have become the preferred first line therapy for those patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Given superior progression free survival (PFS) and overall survival (OS) when compared to earlier generations, third generation EGFR TKIs have become the first choice therapy in many parts of the world. Even though multiple strategies are in development to target both "on-target" and "off-target" resistance, the continuation of EGFR TKIs at the time of progression remains a controversial topic. This commentary focuses on both the "classic" clinical trials of IMpower150 and IMPRESS and compares them to the recently reported ORIENT-31 and ongoing MARIPOSA-2 to discuss the future therapeutic strategies in the setting of progression post-third generation EGFR TKIs.


Effect of face mask on skin characteristics changes during the COVID-19 pandemic.
Previous studies have demonstrated the possibility of adverse effects of prolonged wearing of personal protective equipment in healthcare workers. However, there are a few studies about the effects on skin characteristics after wearing a mask for non-healthcare workers. In this study, we evaluated the dermatologic effects of wearing a mask on the skin over time. Twenty-one healthy men and women participated in the study. All participants wore masks for 6 hours consecutively. Three measurements were taken (a) before wearing the mask, (b) after wearing the mask for 1 hour, and (c) after wearing the mask for 6 hours. Skin temperature, skin redness, sebum secretion, skin hydration, trans-epidermal water loss, and skin elasticity were measured. The skin temperature, redness, hydration, and sebum secretion were changed significantly after 1 and 6 hours of wearing a mask. Skin temperature, redness, and hydration showed significant differences between the mask-wearing area and the non-mask-wearing area. Mask-wearing conditions and time can change several skin characteristics. In particular, it is revealed that the perioral area could be most affected.


Measurement of left atrial systolic time intervals in hypertensive patients using Doppler echocardiography: relation to fourth heart sound and left ventricular wall thickness.
The concept of left atrial systolic time intervals and Doppler echocardiography were used in a quantitative assessment of left atrial function in relation to the presence or absence of a fourth heart sound and to left ventricular hypertrophy in 47 patients with hypertension. Left atrial systolic time interval indexes included atrial pre-ejection period (the time between the onset of an electrocardiographic P wave and the onset of left ventricular inflow during atrial systole [A wave]), corrected atrial pre-ejection period (the atrial pre-ejection period divided by the duration of the P wave), and atrial ejection time (the time between the onset and cessation of the A wave). Twenty-one patients with a fourth heart sound on the phonocardiogram had a shorter atrial pre-ejection period (81 +/- 10 versus 89 +/- 14 ms p less than 0.05) and a corrected atrial pre-ejection period (66 +/- 17 versus 83 +/- 18 ms, p less than 0.01), as well as a longer atrial ejection time (147 +/- 15 versus 126 +/- 13 ms, p less than 0.001) than did 26 patients without a fourth heart sound. The ratio of atrial pre-ejection period to atrial ejection time and that of corrected atrial pre-ejection period to atrial ejection time was smaller in patients with than in patients without a fourth heart sound (0.56 +/- 0.08 versus 0.71 +/- 0.11, p less than 0.001; 0.46 +/- 0.16 ms-1 versus 0.67 +/- 0.17 ms-1, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Care delivery options for infusion therapy services.
Patients have various options to consider when determining the optimal location for receiving outpatient infusion therapy and specialty treatments. Understanding the benefits and challenges of each site of care will enable nurses to help patients make informed decisions.


Serotonin in the control of the sleep-like states in frogs.
It has been established that brain serotonin (5-HT) is involved in the control of behavioral phenomena in amphibians. The transition of frogs from active wakefulness to sleep-like states was accompanied by alteration of brain 5-HT metabolism, i.e., in sleep-like state with plastic muscle tone 5-hydroxyindoleacetic acid (5-HIAA) level was reduced and in sleep-like state with rigid muscle tone both brain 5-HIAA and 5-HT were decreased. An experimental decrease of brain 5-HT level by inhibition of its biosynthesis by p-chlorophenylalanine (200 mg/kg) induced the sleep-like state of catatonic type, i.e., the state which was characterized by lowered brain 5-HT.


Studies on the regulation of the biosynthesis of glucose-containing oligosaccharide-lipids. Effect of energy deprivation.
Energy deprivation, induced in thyroid slices by incubation with an uncoupler of oxidative phosphorylation (carbonyl cyanide m-chlorophenylhydrazone) or inhibitors of respiration (N2 or antimycin A), led to a disturbance in oligosaccharide-lipid metabolism which was characterized by a pronounced depletion of the glucosylated (Glc3Man9GlcNAc2) dolichyl pyrophosphoryl saccharide with an attendant accumulation of the Man9GlcNAc2 and, to a lesser extent, the Man8GlcNAc2 lipid-linked species. A concomitant decrease in the N-glycosylation of proteins was furthermore observed. The distribution of lipid-derived oligosaccharides observed by thin layer chromatographic separation was similar whether radiolabeling was achieved by a metabolic ([14C]glucose or [2-3H]mannose incubation) or chemical ([3H]NaBH4) procedure. The latter method proved useful for measuring the levels of individual oligosaccharide-lipids in unincubated tissue, and in this way it was found that unless thyroid was rapidly frozen or immediately immersed in oxygenated medium a marked decrease of glucose-containing oligosaccharide-lipids occurred which could, however, be reversed by a short incubation. The addition of glucose to the slice incubations did not prevent the Man8-9GlcNAc2 accumulation brought about by the inhibitors of energy production, nor did it alter the oligosaccharide-lipid pattern of uninhibited slices. The effect of the inhibitors on metabolically labeled liver slices was similar to that observed in thyroid. The size of the total chloroform/methanol/water (10:10:3)-extractable oligosaccharide-lipid pool (Glc3-Man9GlcNAc2 to Man5GlcNAc2) of thyroid remained quite constant (about 2 nmol/g) regardless of the energy state, and no substantial change in the level of smaller oligosaccharide-lipids, primarily represented by Man2GlcNAc2 (0.5 nmol/g) was evident. Moreover, no change in the total pool sizes was observed in puromycin-treated slices. The possible mechanisms by which energy deprivation leads to an accumulation of the glucose-free oligosaccharide-lipids are evaluated. While it is likely that a selective impairment of glucosylation of newly formed molecules occurs, it is also possible that an imbalance occurs in a postulated glucosyltransferase-glucosidase shuttle with a trapping of the oligosaccharide-lipid in its unglucosylated form.


Role of L-type Ca2+ channels in attenuated morphine antinociception in streptozotocin-diabetic rats.
The role of L-type Ca2+ channels in morphine antinociception was studied in streptozotocin-induced diabetic and control rats, using [3H]PN200-110 [isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-2,6-dimethyl-5-methoxycabonylpyridine-3-caboxylate] binding (0.005-1.0 nmol/l) and rat whole brain membranes, to determine if the attenuation of morphine antinociception was related to alterations in dihydropyridine-sensitive Ca2+ channel binding characteristics. The tail-flick antinociceptive effect of morphine (4 mg/kg, i.p.) was significantly reduced in diabetic rats in comparison to that in controls. Nimodipine (0.1-3 mg/kg, i.p.) did not produce antinociception but significantly potentiated the morphine response in control rats. Nimodipine (0.3-3 mg/kg, i.p.) reversed the attenuation of morphine antinociception in a dose-dependent manner in diabetic rats. Moreover, insulin (2 U/kg, s.c.) [correction of mu/kg] reversed the attenuated morphine antinociception in streptozotocin-diabetic rats. A significant increase in the Bmax (+41%) of [3H]PN200-110 binding was observed in diabetic rat brain membranes compared to that in control rats. However, there was no change in affinity (Kd) value of [3H]PN200-110. The reduced morphine response in diabetic rats, in accordance with up-regulation of dihydropyridine sites, may be due to an increased Ca2+ influx through L-type channels. These results suggest a functional role of L-type Ca2+ channels in morphine antinociception and the diabetic state may lead to alterations in their density.


Physical compatibility of binary and ternary mixtures of morphine and methadone with other drugs for parenteral administration in palliative care.
The parenteral administration of combinations of drugs is often necessary in palliative medicine, particularly in the terminal stage of life, when patients are no longer able to take medication orally. The use of infusers to administer continuous subcutaneous infusions is a well-established practice in the palliative care setting and enables several drugs to be given simultaneously, avoiding the need for repeated administrations and the effects of peaks and troughs in the doses of medication. The method is also appreciated by patients and caregivers in the home care setting because the devices and infusion sites are easy to manage. Despite their frequent use, however, the mixtures of drugs adopted in clinical practice are sometimes not supported by reliable data concerning their chemical and physical compatibility. The present study investigates the chemical compatibility of binary mixtures (morphine with ketorolac) and the physical compatibility of binary (morphine or methadone with ketorolac) or ternary mixtures (morphine with ketorolac and/or haloperidol, and/or dexamethasone, and/or metoclopramide, and/or hyoscine butylbromide) with a view to reducing the aleatory nature of the empirical use of such combinations, thereby increasing their safety and clinical appropriateness.


Gadolinium-loaded liposomes allow for real-time magnetic resonance imaging of convection-enhanced delivery in the primate brain.
Drug delivery to brain tumors has long posed a major challenge. Convection-enhanced delivery (CED) has been developed as a drug delivery strategy to overcome this difficulty. Ideally, direct visualization of the tissue distribution of drugs infused by CED would assure successful delivery of therapeutic agents to the brain tumor while minimizing exposure of the normal brain. We previously developed a magnetic resonance imaging (MRI)-based method to visualize the distribution of liposomal agents after CED in rodent brains. In the present study, CED of liposomes was further examined in the non-human primate brain (n = 6). Liposomes containing Gadoteridol, DiI-DS, and rhodamine were infused in corona radiata, putamen nucleus, and brain stem. Volume of distribution was analyzed for all delivery locations by histology and MR imaging. Real-time MRI monitoring of liposomes containing gadolinium allowed direct visualization of a robust distribution. MRI of liposomal gadolinium was highly accurate at determining tissue distribution, as confirmed by comparison with histological results from concomitant administration of fluorescent liposomes. Linear correlation for liposomal infusions between infusion volume and distribution volume was established in all targeted locations. We conclude that an integrated strategy combining liposome/nanoparticle technology, CED, and MRI may provide new opportunities for the treatment of brain tumors. Our ability to directly monitor and to control local delivery of liposomal drugs will most likely result in greater clinical efficacy when using CED in management of patients.


Correction: Trypanosoma cruzi-specific IFN-γ-producing cells in chronic Chagas disease associate with a functional IL-7/IL-7R axis.
[This corrects the article DOI: 10.1371/journal.pntd.0006998.].


Comparison of balloon valvuloplasty with operative treatment for mitral stenosis.
To determine the optimal role for percutaneous balloon mitral valvuloplasty or open mitral commissurotomy, the outcome of 164 consecutive patients undergoing either percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, or mitral valve replacement for mitral stenosis was reviewed. No preoperative differences existed between percutaneous balloon mitral valvuloplasty and open mitral commissurotomy in age, symptoms, or mitral valve characteristics. Symptoms improved similarly in all groups, and median hospital stays after procedures were 2, 9, and 10 days for percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, and mitral valve replacement (p < 0.005). Actuarial survivals at 36 months did not differ significantly (83% +/- 6%, 94% +/- 4%, and 90% +/- 4%). Actuarial freedoms from subsequent mitral valve procedures at 36 months were 66% +/- 7%, 87% +/- 6%, and 100% +/- 13% (p < 0.005), with the linearized rate of subsequent mitral valve procedures being 12% +/- 3%, 4% +/- 2%, and 1.2% +/- 0.8%/patient-year for percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, and mitral valve replacement (p < 0.01). Prior mitral commissurotomy increased the likelihood of subsequent mitral procedures after percutaneous balloon mitral valvuloplasty from 10% +/- 3% to 20% +/- 7%/patient-year.


Differential features of muscle fiber atrophy in osteoporosis and osteoarthritis.
We demonstrated that osteoporosis is associated with a preferential type II muscle fiber atrophy, which correlates with bone mineral density and reduced levels of Akt, a major regulator of muscle mass. In osteoarthritis, muscle atrophy is of lower extent and related to disease duration and severity. Osteoarthritis (OA) and osteoporosis (OP) are associated with loss of muscle bulk and power. In these diseases, morphological studies on muscle tissue are lacking, and the underlying mechanisms of muscle atrophy are not known. The aim of our study was to evaluate the OP- or OA-related muscle atrophy and its correlation with severity of disease. Muscle levels of Akt protein, a component of IGF-1/PI3K/Akt pathway, the main regulator of muscle mass, have been determined. We performed muscle biopsy in 15 women with OP and in 15 women with OA (age range, 60-85 years). Muscle fibers were counted, measured, and classified by ATPase reaction. By statistical analysis, fiber-type atrophy was correlated with bone mineral density (BMD) in the OP group and with Harris Hip Score (HHS) and disease duration in the OA group. Akt protein levels were evaluated by Western blot analysis. Our findings revealed in OP a preferential type II fiber atrophy that inversely correlated with patients' BMD. In OA, muscle atrophy was of lower extent, homogeneous among fiber types and related to disease duration and HHS. Moreover, in OP muscle, the Akt level was significantly reduced as compared to OA muscles. This study shows that in OP, there is a preferential and diffuse type II fiber atrophy, proportional to the degree of bone loss, whereas in OA, muscle atrophy is connected to the functional impairment caused by the disease. A reduction of Akt seems to be one of the mechanisms involved in OP-related muscle atrophy.


Wind Tunnel Measurement Systems for Unsteady Aerodynamic Forces on Bluff Bodies: Review and New Perspective.
Wind tunnel tests have become one of the most effective ways to evaluate aerodynamics and aeroelasticity in bluff bodies. This paper has firstly overviewed the development of conventional wind tunnel test techniques, including high frequency base balance technique, static synchronous multi-pressure sensing system test technique and aeroelastic test, and summarized their advantages and shortcomings. Subsequently, two advanced test approaches, a forced vibration test technique and hybrid aeroelastic- force balance wind tunnel test technique have been comprehensively reviewed. Then the characteristics and calculation procedure of the conventional and advanced wind tunnel test techniques were discussed and summarized. The results indicated that the conventional wind tunnel test techniques ignored the effect of structural oscillation on the measured aerodynamics as the test model is rigid. A forced vibration test can include that effect. Unfortunately, a test model in a forced vibration test cannot respond like a structure in the real world; it only includes the effect of structural oscillation on the surrounding flow and cannot consider the feedback from the surrounding flow to the oscillation test model. A hybrid aeroelastic-pressure/force balance test technique that can observe unsteady aerodynamics of a test model during its aeroelastic oscillation completely takes the effect of structural oscillation into consideration and is, therefore, effective in evaluation of aerodynamics and aeroelasticity in bluff bodies. This paper has not only advanced our understanding for aerodynamics and aeroelasticity in bluff bodies, but also provided a new perspective for advanced wind tunnel test techniques that can be used for fundamental studies and engineering applications.


The relationship between ovine lymphocyte antigens and parasitological and production parameters in Romney sheep.
The occurrence of ovine lymphocyte antigen (OLA) types in two flocks of New Zealand Romney sheep was examined in relation to resistance to nematode parasites [as judged by faecal egg counts (FEC)], plasma pepsinogen levels, liveweight and weight gains. A panel of OLA-typing antisera (SY 1-16) which determine class 1 MHC antigens of the sheep was used. The OLA combination SY 1a + 1b was found exclusively in Romney sheep of both flocks having below average FEC, but was present in low frequency (5%). In one flock, sheep possessing this antigen combination had consistently lower FEC from weaning to 1 year of age than sheep without this combination. SY 6 occurred significantly more frequently in above average FEC sheep and was associated with significantly higher FEC during secondary challenge infection. Plasma pepsinogen levels were significantly lower in those sheep possessing SY 2 or SY 3 but these OLA types were not associated with lower than average FEC. No OLA type was associated with above average weight gain but in one flock sheep with SY 1b and SY 1a + 1b had significantly lower weight gains between weaning and 6 months of age than sheep without these OLA types. A similar association was not found in the other flock. Sheep in one flock with SY 16 were significantly heavier than those without this antigen. No other associations between OLA types and liveweight were found.


Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV.
Dipeptidyl-peptidase IV/CD26 (DPP IV) is a cell-surface protease belonging to the prolyloligopeptidase family. It selectively removes the N-terminal dipeptide from peptides with proline or alanine in the second position. Apart from its catalytic activity, it interacts with several proteins, for instance, adenosine deaminase, the HIV gp120 protein, fibronectin, collagen, the chemokine receptor CXCR4, and the tyrosine phosphatase CD45. DPP IV is expressed on a specific set of T lymphocytes, where it is up-regulated after activation. It is also expressed in a variety of tissues, primarily on endothelial and epithelial cells. A soluble form is present in plasma and other body fluids. DPP IV has been proposed as a diagnostic or prognostic marker for various tumors, hematological malignancies, immunological, inflammatory, psychoneuroendocrine disorders, and viral infections. DPP IV truncates many bioactive peptides of medical importance. It plays a role in glucose homeostasis through proteolytic inactivation of the incretins. DPP IV inhibitors improve glucose tolerance and pancreatic islet cell function in animal models of type 2 diabetes and in diabetic patients. The role of DPP IV/ CD26 within the immune system is a combination of its exopeptidase activity and its interactions with different molecules. This enables DPP IV/CD26 to serve as a co-stimulatory molecule to influence T cell activity and to modulate chemotaxis. DPP IV is also implicated in HIV-1 entry, malignant transformation, and tumor invasion.


Functional role of the interaction between polysialic acid and myristoylated alanine-rich C kinase substrate at the plasma membrane.
Polysialic acid (PSA) is a homopolymeric glycan that plays crucial roles in the developing and adult nervous system. So far only a few PSA-binding proteins have been identified. Here, we identify myristoylated alanine-rich C kinase substrate (MARCKS) as novel PSA binding partner. Binding assays showed a direct interaction between PSA and a peptide comprising the effector domain of MARCKS (MARCKS-ED). Co-immunoprecipitation of PSA-carrying neural cell adhesion molecule (PSA-NCAM) with MARCKS and co-immunostaining of MARCKS and PSA at the cell membrane of hippocampal neurons confirm the interaction between PSA and MARCKS. Co-localization and an intimate interaction of PSA and MARCKS at the cell surface was seen by confocal microscopy and fluorescence resonance energy transfer (FRET) analysis after the addition of fluorescently labeled PSA or PSA-NCAM to live CHO cells or hippocampal neurons expressing MARCKS as a fusion protein with green fluorescent protein (GFP). Cross-linking experiments showed that extracellularly applied PSA or PSA-NCAM and intracellularly expressed MARCKS-GFP are in close contact, suggesting that PSA and MARCKS interact with each other at the plasma membrane from opposite sides. Insertion of PSA and MARCKS-ED peptide into lipid bilayers from opposite sides alters the electric properties of the bilayer confirming the notion that PSA and the effector domain of MARCKS interact at and/or within the plane of the membrane. The MARCKS-ED peptide abolished PSA-induced enhancement of neurite outgrowth from cultured hippocampal neurons indicating an important functional role for the interaction between MARCKS and PSA in the developing and adult nervous system.


Evaluation of the pyroantimonate method for detecting intracellular calcium localization in smooth muscle fibers by the X-ray microanalysis of cryosections.
The validity of the pyroantimonate method, which has been used for detecting intracellular Ca localization and translocation in smooth muscles, was examined by making cryosections of the relaxed anterior byssal retractor muscle (ABRM) of Mytilus edulis at various stages of procedures for preparing ordinary Epon-embedded sections and determining the elemental concentration ratios of the pyroantimonate precipitate, localized along the inner surface of the plasma membrane, with an energy dispersive X-ray microanalyzer. The concentration of Ca (relative to that of Sb) in the precipitate stayed constant after the procedures of fixation, dehydration and Epon-embedding, while the concentrations of K, Mg, Na and Os showed their respective characteristic changes after the above procedures, being lower than that of Ca in the Epon-embedded sections. The presence of Ca in the precipitate was also demonstrated with an electron energy-loss spectrometer. The localization of Ca underneath the plasma membrane was also observed in the cryosections of the ABRM fibers prepared after mild fixation with acrolein vapor without using pyroantimonate. These results indicate that the pyroantimonate precipitate serves as a valid measure of intracellular Ca localization.


MiR-671-5p sponging activity of circMMP1 promotes esophageal squamous cancer progression.
The aim of this study was to explore the function and mechanism of circular RNA (circRNA) matrix metallopeptidase 1 (circMMP1) in the progression of esophageal squamous cell carcinoma (ESCC). CircMMP1 expression was detected by quantitative real-time PCR (qRT-PCR), and its relationship with the prognosis of ESCC patients was evaluated by Kaplan-Meier analysis. Cells were transfected using corresponding plasmids, and the cell proliferation activity, migration and invasion capabilities in vitro were assessed. The protein level in tissues and cells was analyzed using western blotting. RNA pulldown, dual-luciferase reporter assay and RNA immunoprecipitation assay were performed in ESCC cells to detect the interaction between circMMP1 and miR-671-5p, or the correlation between miR-671-5p and ANO1. Xenograft tumor experiment was carried out to uncover the function of circMMP1 in vivo. The high level of circMMP1 in tumor tissues was associated with poor prognoses of ESCC patients. Knockdown of circMMP1 suppressed ESCC cell proliferation, migration and invasion in vitro. MiR-671-5p was the target of circMMP1 and mediated the inhibition effect of circMMP1 on ESCC cells. CircMMP1 targeted miR-671-5p to regulate ANO1 expression, which was downstream of miR-671-5p. Overexpression of ANO1 weakened tumor-repressive function of circMMP1 knockdown in ESCC cells. Moreover, silencing of circMMP1 impeded ESCC tumor growth in vivo. Our study provided novel evidence that circMMP1 accelerated ESCC progression by acting as a miR-671-5p sponge to enhance ANO1 expression.


Pseudo-affinity chromatographic approach to probe heterogeneity in buffalo pituitary luteinizing hormone: probable pseudolectin-like behavior of immobilized Cibacron Blue 3GA.
The alpha (α) and beta (β) subunits of buffalo pituitary luteinizing hormone (LH) were chromatographed on Cibacron Blue 3GA agarose and their immunoreactivity was quantitated using anti-α and anti-β anti sera. Subsequent analyses showed α subunits were relatively more hydrophilic than β subunits. Further, the naturally occurring free α and β subunits were more hydrophobic than their native counterparts which were dissociated and isolated from heterodimeric LH. The lesser sugar content in freely occurring α and beta subunits may be attributed for increased hydrophobicity and consequent upon the existence of their uncombined free forms. In order to ascertain putative sugar-dye interaction, crude LH carrying free subunits, pure LH, and non-glycosylated recombinant β subunit of LH were loaded separately on Cibacron Blue. Methyl mannoside was able to elute 33% of the bound protein in case of crude and pure LH, whereas there was little (3%) elution in case of recombinant LH β subunit. This study suggests a compositional heterogeneity in free and native subunits of LH from the buffalo pituitary. In addition, our findings reveal the pseudolectin-like behavior of Cibacron Blue.


Recommendation of Aspirin-Guide App and Physicians Clinical Decision of Aspirin Use to Prevent CVD Among Diabetic Patients, Is there any Differences?
This study aims to identify the prevalence of aspirin use among type 2 diabetic (T2DM) patients and assess the concordance in aspirin use among these patients as prescribed by physicians and as recommended by the Aspirin-Guide app. A total of 301 T2DM patients from King Khalid University Hospital in Riyadh, Saudi Arabia participated in this cross-sectional study. Patient's electronic medical records through eSihi system were reviewed and all data included in the free online and mobile app called Aspirin-Guide were collected in a specially designed data checklist. The prevalence of aspirin use was more common in patients who were in the age group of 51 to 59 and male participants' with T2DM. Males were nearly twice more likely to use aspirin compared to females (P = 0.001). Based on recommendations from the Aspirin-Guide app, 26% of the patients who were on aspirin (N = 51) were not eligible for aspirin therapy, while 37.7% (N = 40) of the patients eligible for aspirin therapy had not been put on aspirin by their physicians (P = 0.039). Male sex (P = 0.003), use of statins (P = 0.001), and being advised to use aspirin (P = 0.041), were significantly associated with aspirin use in T2DM patients. There was a significant difference in the proportion of patients currently on aspirin as prescribed by their physicians and those eligible for aspirin therapy as per the Aspirin-Guide app. The use of an app to uniformized aspirin use among eligible patients should be based on up-to-date guidelines and account for patient acceptability and willingness to commence treatment.


Evaluation of a collaborative chronic care approach to improve outcomes in kidney transplant recipients.
Several studies found that renal transplant recipients with chronic kidney disease have untreated complications and do not attain recommended clinical targets. Using a before/after design with propensity score-matched controls, we evaluated whether an advanced practice nurse-led interprofessional collaborative chronic care approach could improve clinical outcomes for CKD transplant patients compared with a traditional physician-led model. The intervention included strategies for disease self-management, shared decision making, and healthcare system reorganization. The primary outcome was the proportion of patients attaining at least seven of nine targets as per published guidelines. A greater proportion of intervention patients achieved the outcome (68% vs. 10%; p = 0.0001) and had discussions about end-stage treatment options (88% vs. 13%; p = 0.0001) compared with controls. The intervention patients had significantly fewer emergency room visits (incidence rate ratio [IRR] 0.53; 95% CI 0.29-0.91; p = 0.02) and hospital admissions (IRR 0.34; 95% CI 0.16-0.68; p = 0.001) compared with the control patients. There were no significant differences found between the groups in systolic/diastolic blood pressure, carbon dioxide, hemoglobin, or phosphate parameters. An advanced practice nurse-led approach, based on the chronic care model, has the potential to improve clinical outcomes for renal transplant recipients and needs to be tested in a multicenter randomized controlled trial.


Human-computer interaction reflected in the design of user interfaces for general practitioners.
To address the problem of properly built health information systems in general practice as an important issue for their approval and use in clinical practice. We present how a national general practitioner (GP) network was built, put in practice and several results of its activity seen from the clinician's and the software application team's points of view. We used a multi-level incremental development appropriate for the conditions of the required information system. After the development of the first version of the software components (based on rapid prototyping) of the sentinel network, a questionnaire addressed the needs and improvements required by the health professionals. Based on the answers, the functionality of the system and the interface were improved regarding the real needs expressed by the end-users. The network is functional and the collected data from the network are being processed using statistical methods. The academic software team developed a GP application that is well received by the GPs in the network, as resulted from the survey and discussions during the training period. As an added confirmation, several GPs outside the network enrolled after seeing the software at work. Another confirmation that we did a good job was that after the final presentation of the results of the project a representative from the Romanian Society for Cardiology expressed the wish of this society to access the data yielded by the network.


The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in patients with type 2 diabetes mellitus.
To determine the efficacy and tolerability of PHX1149, a novel dipeptidyl peptidase-4 (DPP4) inhibitor, in patients with type 2 diabetes. This is a multicentre, randomized, double-blind, placebo-controlled, 4-week study in patients with type 2 diabetes with suboptimal metabolic control. Patients with a baseline haemoglobin A(1c) (HbA(1c)) of 7.3 to 11.0% were randomized 1 : 1 : 1 : 1 to receive once-daily oral therapy with either PHX1149 (100, 200 or 400 mg) or placebo; patients were on a constant background therapy of either metformin alone or metformin plus a glitazone. Treatment with 100, 200 or 400 mg of PHX1149 significantly decreased postprandial glucose area under the curve AUC(0-2 h) by approximately 20% (+0.11 +/- 0.50, -2.08 +/- 0.51, -1.73 +/- 0.49 and -1.88 +/- 0.48 mmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p = 0.002, 0.008 and 0.004 vs. placebo). Postprandial AUC(0-2 h) of intact glucagon-like peptide-1, the principal mediator of the biological effects of DPP4 inhibitors, was increased by 3.90 +/- 2.83, 11.63 +/- 2.86, 16.42 +/- 2.72 and 15.75 +/- 2.71 pmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p = 0.053, 0.001 and 0.002 vs. placebo). Mean HbA(1c) was lower in all dose groups; the placebo-corrected change in the groups receiving 400 mg PHX1149 was -0.28% (p = 0.02). DPP4 inhibition on day 28 was 53, 73 and 78% at 24 h postdose in the groups receiving 100, 200 and 400 mg PHX1149, respectively. There were no differences in adverse events between PHX1149-treated and placebo subjects. Addition of the DPP4 inhibitor PHX1149 to a stable regimen of metformin or metformin plus a glitazone in patients with type 2 diabetes was well tolerated and improved blood glucose control.


Photodynamic Inactivation Mediated by Erythrosine and its Derivatives on Foodborne Pathogens and Spoilage Bacteria.
The purpose of the present study was to evaluate the efficacy of photodynamic inactivation (PDI) mediated by erythrosine (ERY) and its ester derivatives erythrosine methyl ester (ERYMET) and erythrosine butyl ester (ERYBUT) on foodborne pathogens and spoilage bacteria. We evaluated Staphylococcus aureus ATCC 25923, Aeromonas hydrophila ATCC 7966, Salmonella enterica serotype Typhimurium ATCC 14028, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853. The toxicity of all of the compounds was assessed in VERO cells. PDI mediated by ERY and its derivatives combined with a light-emitting diode was performed at different concentrations and exposure times. S. aureus was more photosensitive than Gram-negative bacteria to ERY, ERYMET, and ERYBUT. The ERY-mediated PDI of S. aureus induced a significant reduction of 4.0 log CFU/ml at a light dose of 40 J/cm(2). ERYMET and ERYBUT at lower light doses than ERY completely eradicated S. aureus. When photoirradiated with ERY at light doses of 156 and 234 J/cm(2), A. hydrophila was completely eradicated. ERYBUT was more efficient in the PDI of A. hydrophila than ERYMET, even at 1 x 10(-5) M and lower light doses. Salmonella Typhimurium, E. coli, and P. aeruginosa required higher concentrations of photosensitizers to reduce cell survival. ERYBUT and ERY may be promising photosensitizing agents against A. hydrophila and S. aureus. They were effective at reducing bacterial counts at nontoxic concentrations. The photoinactivation rate of the evaluated bacteria decreased in the following order: S. aureus > A. hydrophila > E. coli > S. Typhimurium > P. aeruginosa.


Interleukin-12p40 mediates transient protection against Mycobacterium avium infection in the absence of interleukin-12.
Produced by macrophages and dendritic cells, interleukin (IL)-12 is composed of a p35 and a p40 subunit and promotes protection against intracellular pathogens through the development of interferon-gamma (IFNgamma) -producing T cells. The p40 subunit is also shared by the dimeric cytokines IL-12p40 homodimer and IL-23. In man, genetic defects in IL-12p40-mediated mechanisms are responsible for the familial occurrence of nontuberculous mycobacterial infections, the most common of which is infection with Mycobacterium avium. To experimentally differentiate the contribution of IL-12p40-containing cytokines in the outcome of M. avium infection, we studied wild-type, p35- and p35/p40 doubly deficient mice in an intravenous infection model which reflects many parameters of the disseminated infection in humans. Our study shows that in contrast to p35/p40 doubly deficient mice, p35-deficient mice mount a transient antibacterially protective response against M. avium although such animals were unable to produce detectable levels of IFNgamma or generate efficient granulomas. In conclusion, our results identify an antibacterial effector mechanism preserved in p35-deficient mice that is absent in mice devoid of p35 and p40. This phenotype probably reflects an IL-12p40-dependent effect on macrophage activation at the level of innate immunity.


Management of multiple stones in a single session using minimally invasive methods in infants with renal failure: renal salvage.
The goal in the treatment of stone disease causing infantile obstructive uropathy is to obtain a quick resolution of the obstruction using the least invasive treatment modality available and rendering the patient stone-free, if possible. Two infants with bilateral kidney stones, the first of whom also had ureteral stone, were referred to our clinic with acute renal failure and were treated successfully in a single session using minimally invasive methods. In this report, we discuss the management of these two cases, aged 9 and 26 months, which resulted in favorable outcomes.


Nonlinear transfer of elements from soil to plants: impact on radioecological modeling.
In radioecology, transfer of radionuclides from soil to plants is typically described by a concentration ratio (CR), which assumes linearity of transfer with soil concentration. Nonlinear uptake is evidenced in many studies, but it is unclear how it should be taken into account in radioecological modeling. In this study, a conventional CR-based linear model, a nonlinear model derived from observed uptake into plants, and a new simple model based on the observation that nonlinear uptake leads to a practically constant concentration in plant tissues are compared. The three models were used to predict transfer of (234)U, (59)Ni and (210)Pb into spruce needles. The predictions of the nonlinear and the new model were essentially similar. In contrast, plant radionuclide concentration was underestimated by the linear model when the total element concentration in soil was relatively low, but within the range commonly observed in nature. It is concluded that the linear modeling could easily be replaced by a new approach that more realistically reflects the true processes involved in the uptake of elements into plants. The new modeling approach does not increase the complexity of modeling in comparison with CR-based linear models, and data needed for model parameters (element concentrations) are widely available.


[Cavernous hemangioma of the larynx in the adult. Apropos of a case].
We present a case of cavernous hemangioma located in the supraglottic area in an adult, whose clinical debut was airway obstruction. We remark on the singularity of this case, because the great majority are present during the first year of life, located in subglottis. A review of the literature and current modes of treatment of hemangiomas is also presented.


Bioactivity under laboratory conditions of Brevibacillus laterosporus towards larvae and adults of Chrysomya putoria (Diptera: Calliphoridae).
Brevibacillus laterosporus was tested for entomopathogenic activity towards larvae and adults of Chrysomya putoria (Diptera: Calliphoridae) under laboratory conditions. Sublethal effects related to feeding activity or development were observed, including reduction in larval weight gain, probably by inhibition of feeding, and variation in the duration of the developmental stages of the insect. Larval mortality was dose dependent following ingestion. The experiments were performed with newly emerged adults exposed to a sugar based diet containing spore suspensions. Concentrations of 1.13 × 109 CFU/ml caused 70.5% of mortality. The present study highlights the potential of B. laterosporus to control populations of C. putoria, a dipteran of medical-veterinary and sanitary importance, both in larval and adult stages.


Eisenmenger ventricular septal defect in a Humboldt penguin (Spheniscus humboldti).
The Eisenmenger ventricular septal defect is an uncommon type of ventricular septal defect characterised in humans by a traditionally perimembranous ventricular septal defect, anterior deviation (cranioventral deviation in small animal patients) of the muscular outlet septum causing malalignment relative to the remainder of the muscular septum, and overriding of the aortic valve. This anomaly is reported infrequently in human patients and was identified in a 45-day-old Humboldt Penguin, Spheniscus humboldti, with signs of poor growth and a cardiac murmur. This case report describes the findings in this penguin and summarises the anatomy and classification of this cardiac anomaly. To the authors' knowledge this is the first report of an Eisenmenger ventricular septal defect in a veterinary patient.


Evidence-based change of practice in the management of unilateral inguinal hernia.
Contralateral inguinal exploration in children with unilateral inguinal hernia is still controversial. Only 20% of patients with patent processus vaginalis would develop a clinically apparent hernia [Miltenburg DM, Nutctern JG, Jaksic Tkozinetz CA. Meta-analysis of the risk of metachronous hernia in infants and children. Am J Surg 1997;174:741-4]. In 1999, our unit changed the practice of performing routine contralateral inguinal exploration of male children younger than 2 years and female children younger than 5 years to inguinal herniotomy of the symptomatic side only based on a meta-analysis published by Miltenburg et al [Meta-analysis of the risk of metachronous hernia in infants and children. Am J Surg 1997;174:741-4]. We explored the contralateral inguinal area only in babies with a history of prematurity. A prospective study of patients subjected to unilateral inguinal herniotomy from 1999 to 2001 was performed. Age, sex, side of the hernia, and incarceration at presentation were recorded. The incidence of metachronous inguinal hernia (MIH) and its risk factors were analyzed. The follow-up ranged from 36 to 72 months. Of the 409 patients who presented with inguinal hernia, 264 underwent unilateral inguinal herniotomy. The rest were either children with bilateral inguinal hernia or premature babies who were offered bilateral inguinal herniotomy. Of these 264 patients, 180 (68%) had right-sided inguinal hernia and 84 (32%) had left-sided inguinal hernia. Fourteen (5%) patients subsequently presented with MIH. Of these 14 patients, 8 were younger than 2 years at the initial presentation and 11 originally presented with left-sided inguinal hernia. No female child presented with MIH. Twelve (85%) re-presentations with MIH occurred within 1 year of the original operation. The treatment of only the symptomatic inguinal hernia has not significantly increased the incidence of MIH. This evidence-based change of practice has avoided 152 operations in 264 patients. Presentation with incarceration and age at presentation have no significant impact on the incidence of MIH. Left-sided presentation has a statistically significant high incidence of MIH.


'Whiplash injuries' of the neck: a retrospective study.
This is a retrospective study of 102 patients with whiplash injuries of the neck followed up at approximately 2 years. The results show that 67 patients were asymptomatic by this time and the remaining 35 patients still exhibited symptoms. Prognostic indicators were found to be age, occipital headaches, referred symptoms, interscapular pain, abnormal neurological signs, positive radiological findings and osteoarthritic changes of the cervical spine. Symptoms that persisted for more than 2 months indicated prolonged disability.


A high degree of aneuploidy, loss of p53 gene, and low soluble p53 protein serum levels are detected in ulcerative colitis patients.
The causes for the increased risk of colorectal cancer associated with ulcerative colitis have not been fully defined. Colonic tissue of ulcerative colitis patients was examined for changes in chromosome-17-centromere copy number, loss of the p53 gene, and alterations in serum levels of the 53-kDa protein. This study was performed under the assumption that these molecular events correlate with ulcerative colitis status and duration. Ulcerative colitis patients (n = 42) and healthy controls (n = 37) participated in the study. All participants were histopathologically and medically diagnosed. The stage of ulcerative colitis patients was stratified according to increasing risk factors for the development of colorectal cancer: left-sided colitis, pancolitis, sclerosing cholangitis, and dysplasia-associated lesions or masses. Changes in centromere number of chromosome 17 alone or in association with changes in copy number of the p53 gene were analyzed in colon tissue biopsies by fluorescence in situ hybridization. Serum p53 level was determined in blood samples by immunoprecipitation followed by separation using high-pressure liquid chromatography. Changes in chromosome 17 and p53 copy number and lower levels of serum p53 protein in ulcerative colitis patients directly correlated with colorectal cancer risk factors. All values significantly differed from controls. Significant direct correlations were obtained for ulcerative colitis disease duration, levels of p53 in the serum, and extent of aneuploidy. We demonstrate that in the colonic mucosa of ulcerative colitis patients, high levels of genomic instability, changes in p53 gene copy number, and lower levels of p53 in the serum directly correlate with the extent of disease duration and increased risk factors for colorectal cancer. Any of the measurements described herein can provide an acceptable prognostic tool in the assessment of colorectal cancer risk in ulcerative colitis patients.


Lidoflazine does not improve neurologic outcome when administered after complete cerebral ischemia in primates.
In order to investigate the effects of the calcium entry blocker lidoflazine on neurologic outcome in primates following an episode of global brain ischemia, 12 pigtail monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia, followed by 48 h of intensive care treatment and daily neurologic evaluations for 96 h. The monkeys were randomly assigned to receive, in a blind fashion, either lidoflazine 1.0 mg/kg (n = 6) or inactive lidoflazine solvent (n = 6) at 5 min, 8 h, and 16 h postischemia. One monkey in the lidoflazine group did not meet preestablished protocol criteria and was excluded from data analysis. The remaining monkeys were well matched for age, sex, and other physiologic variables. Neurologic outcome was not significantly different between the lidoflazine- and placebo-treated groups (p greater than 0.5). No monkey in either group achieved a normal neurologic exam by 96 h postischemia. Three lidoflazine-treated monkeys and two placebo-treated monkeys died prior to the 96-h neurologic evaluation. These deaths were judged to be neurologic in origin. The authors concluded that lidoflazine does not improve neurologic outcome in primates when administered after 17 min of complete cerebral ischemia.


Fine structure of the myotendinous junction of lathyritic rat muscle with special reference to connectin, a muscle elastic protein.
The fine structure of the myotendinous junction of the skeletal muscle of lathyritic rats caused by beta-aminopropionitrile was investigated. In the junction there are finger-like processes of muscle fibers, in which thin filaments were extended from the last Z lines of myofibrils and attached to the sarcolemma of the processes. By the heavy meromyosin decoration technique, these thin filaments were identified as actin filaments. In the lathyritic muscle, the thin filaments were markedly fewer in number and distributed sparsely in the sarcoplasm. The content of connectin, an elastic protein, which is localized in myofibrils and also in sarcolemma was significantly decreased in the lathyritic muscle. A possible relationship between the changes in the fine structure of the myotendinous junction and in the connectin contents is discussed.