Characterization of mouse natural killer cell activating factor (NKAF) induced by OK-432: evidence for interferon- and interleukin 2-independent NK cell activation.
The bacterial immunopotentiator OK-432 induced natural killer cell activating factor (NKAF) from mouse spleen cells. OK-432-induced NKAF showed a single peak with an apparent mol. wt of 70 Kd by Sephadex G-100 chromatography and OK-432-induced interleukin 2 (IL-2) had the same mol. wt as NKAF. However, OK-432-induced interferon (IFN) showed molecular heterogeneity with two peaks at 90 Kd and 45 Kd. Further purification was achieved by Blue Sepharose affinity chromatography which copurified NKAF and IFN. The affinity-purified NKAF, however, was stable to heat (56 degrees C) and acid (pH 2) treatments. Moreover, anti-IFN failed to abolish NKAF activity and this activity was not absorbed by IL-2 dependent T cells. From isoelectric focusing analysis, a dissociation of NKAF and IFN was observed over the range of pI 6.5 to 8.0. Based on these results, KNAF appears to be a new kind of cytokine distinguishable from IFN and IL-2.


Non-Hodgkin's lymphoma in four children infected with the human immunodeficiency virus. Association with Epstein-Barr Virus and treatment.
Reports on lymphoid malignancy and its treatment in children infected with human immunodeficiency virus (HIV) are limited. Antibodies to Epstein-Barr virus (EBV) were detected by indirect immunofluorescence. DNA was extracted from peripheral blood lymphocytes or biopsy specimens. Polymerase chain reaction was run using primers for EBV. Reaction products underwent Southern blot analysis to confirm EBV specificity. Tumor clonality was assessed by immunohistochemistry and by Southern blot analysis of immunoglobulin heavy-chain and T-cell receptor beta-gene rearrangement. Within 1 year, non-Hodgkin's lymphoma (NHL) was diagnosed in four children infected with HIV. All four were EBV-seropositive and had detectable EBV DNA in peripheral blood lymphocytes. The EBV-linked disorders lymphoid interstitial pneumonia and recurrent parotid enlargement preceded NHL in three and two of the children, respectively. In all four patients, NHL involved at one time the central nervous system (CNS). All three tested NHL tissues were positive for EBV DNA: A 12-week course of chemotherapy given to two children resulted in rapid tumor regression. One of these children experienced meningeal relapse and died 16 months after diagnosis. The other child, who in addition received local irradiation of the affected eye and who underwent surgical removal of the involved ovaries, has been in continuous remission for 20 months. EBV-associated NHL may be seen more frequently in pediatric patients with HIV. Treatment protocols taking into account NHL propensity for the CNS in this age group need to be developed.


A small GTP-binding protein (G protein) recognized by smg p25A GDP dissociation inhibitor (GDI) in human platelet membranes and GDI for this small G protein in human platelet cytosol.
We have recently purified from bovine brain cytosol a novel type of regulatory protein for smg p25A, named smg p25A GDP dissociation inhibitor (GDI), that regulates the GDP/GTP exchange reaction of smg p25A by inhibiting the dissociation of GDP from and thereby the subsequent binding of GTP to it. This smg p25A GDI is inactive for other ras p21/ras p21-like small GTP-binding proteins (G proteins) including c-Ha-ras p21, smg p21, rhoA p21 and rhoB p20. In human platelet membranes, smg p25A was not detected but a G protein with an apparent Mr value of 24,000 (24KG) was recognized by smg p25A GDI and the dissociation of GDP from and the binding of GTP to 24KG were inhibited by smg p25A GDI. The doses of smg p25A GDI necessary for these activities for both 24KG and smg p25A were the same. This 24KG was not recognized by an anti-smg p25A monoclonal antibody. The GDI activity for human platelet 24KG and smg p25A was detected in human platelet cytosol. This human platelet GDI was recognized by an anti-smg p25A GDI polyclonal antibody. These results indicate that there is a 24KG-24KG GDI system similar to a smg p25A-smg p25A GDI system in human platelets.


Control of an Outbreak of Middle East Respiratory Syndrome in a Tertiary Hospital in Korea.
In 2015, a large outbreak of Middle East respiratory syndrome (MERS) occurred in the Republic of Korea. Half of the cases were associated with a tertiary care university hospital. To document the outbreak and successful control measures. Descriptive study. A 1950-bed tertiary care university hospital. 92 patients with laboratory-confirmed MERS and 9793 exposed persons. Description of the outbreak, including a timeline, and evaluation of the effectiveness of the control measures. During the outbreak, 92 laboratory-confirmed MERS cases were associated with a large tertiary care hospital, 82 of which originated from unprotected exposure to 1 secondary patient. Contact tracing and monitoring exposed patients and assigned health care workers were at the core of the control measures in the outbreak. Nontargeted screening measures, including body temperature screening among employees and visitors at hospital gates, monitoring patients for MERS-related symptoms, chest radiographic screening, and employee symptom monitoring, did not detect additional patients with MERS without existing transmission links. All in-hospital transmissions originated from 3 patients with MERS who also had pneumonia and productive cough. This was a retrospective single-center study. Statistical analysis could not be done. Because this MERS outbreak originated from a superspreader, effective control measures could differ in endemic areas or in other settings. Control strategies for MERS outbreaks should focus on tracing contacts of persons with epidemiologic links. Adjusting levels of quarantine and personal protective equipment according to the assumed infectivity of each patient with MERS may be appropriate. Samsung Biomedical Research Institute.


Biosynthesis of salivary proteins in the parotid gland of the subhuman primate, Macaca fascicularis. Cell-free translation of the mRNA for a proline-rich glycoprotein and partial amino acid sequence and processing of its signal peptide.
The major anionic proline-rich proteins in the parotid and submandibular secretions of subhuman primates and man perform the important biological function of inhibiting crystal growth of calcium phosphate salts from saliva, which is supersaturated with calcium phosphate salts, thereby preventing excess deposition of hydroxylapatite on tooth surfaces. The present work was initiated as a first step towards investigating proline-rich protein biosynthesis in parotid glands using the subhuman primate, Macaca fascicularis, as a model system. RNA was isolated from macaque parotid glands and separated into poly(A)-enriched and poly(A)-deficient fractions by chromatography on oligo(dT)-cellulose. The mRNAs in both fractions promoted incorporation of radiolabeled amino acids into polypeptides in an mRNA-dependent reticulocyte lysate translation system. Five major proline-rich polypeptides were detected and one of these was shown to be the in vitro precursor of the major anionic macaque proline-rich protein (MPRP), which is the structural and functional counterpart of the major anionic proline-rich proteins in the parotid and submandibular secretions of man (Oppenheim, F.G., Offner, G.D., and Troxler, R.F. (1982) J. Biol. Chem. 257, 9271-9282). Radiosequencing of the material in anti-MPRP immune precipitates showed that the in vitro precursor of MPRP contained an 18-residue signal peptide. The in vitro precursor of MPRP was processed in dog pancreas vesicles to a form with a lower apparent Mr and with an NH2-terminal amino acid sequence identical to that of native MPRP. The phenylthiohydantoin derivatives of Ala and Ile were detected at residue 9 and those of Val and Met were detected at residue 16 of the signal peptide. This indicated that the in vitro precursor of MPRP, which migrated electrophoretically as a single band in anti-MPRP immune precipitates, contained two different in vitro polypeptides derived from two different mRNAs. These results are discussed in the context of the genetic polymorphism among the major anionic proline-rich proteins in the parotid and submandibular secretions of man.


Prevalence of smokers among air-conditioned coaches, Pakistan.
To estimate the proportion of smokers among passengers of air-conditioned (A/C) coaches running between Karachi and Hyderabad. Pakistan. A cross-sectional survey was done on passengers and staff members of 20 air-conditioned coaches. Of 847 passengers interviewed, 17.3% were smokers and 11.7% passengers smoked during travel while rest of them remained passive smokers. Out of 147 smokers 91.2% were literate persons. Among staff members 59.3% were smokers. Approximately 56% of smokers among passengers were in the age range of 14-40 years. In 95% of A/C coaches there were no anti-smoking warning signs or written words present. In this study majority of smokers were literate, so inter-personal communication and counseling may change the smoking behavior. Ministry of Health should disseminate educational messages regarding hazards of passive smoking among commuters of AC coaches and above all proper implementation of legislation for smoking at public places especially in transport.


Skin-flap coverage of polytetrafluoroethylene vascular access graft exposed by previous infection.
In selected patients with localized infection of polytetrafluoroethylene graft arteriovenous fistulas, the access route can be preserved by treatment with antibiotics and surgical drainage. However, such treatment may result in exposure of the graft, which in itself is a threat to continued survival of the graft. This article describes a simple method that has been successfully used to achieve skin coverage of such grafts.


Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model.
Effect of noopept (N-phenylacetyl-prolylglycine ethyl ester) on viability of neurons exposed to neurotoxic action of glutamic acid (5 mM) was studied in vitro in immortalized mouse hippocampal HT-22 neurons. Noopept added to the medium before or after glutamic acid improved neuronal survival in a concentration range of 10-11-10-5 M. Comparison of the effective noopept concentrations determined in previous studies on cultured cortical and cerebellar neurons showed that hippocampal neurons are more sensitive to the protective effect of noopept.


Effects of intranigral administration of dopamine agonists and antagonists and baclofen on concentrations of dopac and dopamine in the striatum and substantia nigra of the rat.
Systemic administration of haloperidol to rats failed to alter the concentration of dopamine but increased the concentration of 3,4-dihydroxy-phenylacetic acid (DOPAC), the major metabolite of dopamine, in both the striatum and substantia nigra. These haloperidol-induced changes in DOPAC were prevented by an intranigral microinjection of baclofen, a drug which reduces nigrostriatal dopaminergic neuronal activity. It has been proposed that nigrostriatal neurons are regulated, in part, by the activation of autoreceptors in substantia nigra. However, intranigral microinjections of high concentrations of several dopaminergic antagonists failed to mimic the biochemical effects resulting from systemic administration of these drugs; instead, they slightly increased the concentrations of both dopamine and DOPAC in the striatum and decreased dopamine in substantia nigra. Intranigral microinjections of the dopamine agonist, apomorphine, failed to alter the concentration of DOPAC in the striatum, but reduced both dopamine and DOPAC in the nigra. If DOPAC concentrations reflect nigrostriatal dopaminergic neuronal activity, the present results suggest that dopaminergic agonists and antagonists acting in substantia nigra do not exert a major influence on the activity of these neurons.


Women in the UK academic medicine workforce.
This study aimed to compare data on the employment profiles (such as grade, place of work, etc.) of male and female clinical academics. We carried out a comparative review of workforce data within academic medicine for 2004 and 2005, pertaining to the workforce in all specialties in UK medical schools. We identified 3255 and 3365 lecturers, senior lecturers, readers and professors in 2004 and 2005, respectively, of whom 21% were women. In 2004 and 2005, 12% and 11%, respectively, of 1157 and 1364 UK medical professors were women. The number of women filling such positions in individual schools ranged from 0% to 33% across schools. The total numbers of women post-holders and their full-time equivalents were similar, indicating that the majority of posts were full-time. In England only 1 in 10 medical clinical professors are women. At the onset of the study period, 6 medical schools employed no female professors, with a consequent lack of female role models at these institutions. Large variations between schools suggest that some workforce practices may be detrimental to women's academic careers.


Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly.
The oxidative stress hypothesis of aging predicts that a reduction in the generation of mitochondrial reactive oxygen species (ROS) will decrease oxidative damage and extend life span. Increasing mitochondrial proton leak-dependent state 4 respiration by increasing mitochondrial uncoupling is an intervention postulated to decrease mitochondrial ROS production. When human UCP2 (hUCP2) is targeted to the mitochondria of adult fly neurons, we find an increase in state 4 respiration, a decrease in ROS production, a decrease in oxidative damage, heightened resistance to the free radical generator paraquat, and an extension in life span without compromising fertility or physical activity. Our results demonstrate that neuronal-specific expression of hUCP2 in adult flies decreases cellular oxidative damage and is sufficient to extend life span.


Variability of gait is dependent on direction of progression: implications for active control.
Typical healthy walking displays greater variability in the mediolateral direction compared to the anteroposterior direction. This greater variability is thought to represent increased uncertainty in movement. As a result, it has been postulated that the mediolateral direction of gait requires more active control by the central nervous system while the anteroposterior direction is controlled through passive actions. However, this theory has only been tested on gait where progression occurs in the anteroposterior direction. Therefore, the purpose of this study was to investigate how the amount of variability is affected if progression occurs in the mediolateral direction using a lateral stepping gait. Results showed the anteroposterior direction had a significantly greater amount of variability than the mediolateral direction (p<0.001). The results do not support current models of a partition of active control to different anatomical planes. Rather, it seems that other physical entities involved in motion, such as momentum and inertia, are able to decrease the dependence on active control from the central nervous system. In a lateral stepping gait, such physical entities were no longer assisting in the anteroposterior direction but had a larger impact in the mediolateral direction as it was the direction of progression. As a result variability in the anteroposterior direction increased. Thus, it is possible to infer increased reliance on active control from the central nervous system in the direction orthogonal to progression.


Antihypertensive drugs may not delay the symptom progression of Parkinson's disease: A 2-year follow-up study.
Parkinson's disease (PD) is one of the most common neurodegenerative disease, and half of PD patients have hypertension as well. The effect of antihypertensive drugs on the progression of PD has been less studied. The focus of this study was on the changes in dopamine transporter (DAT) levels to assess the effect of antihypertensive drugs on the progression of PD. Data from 321 drug-naïve patients from the Parkinson's Disease Progression Marker Initiative (PPMI) were collected over a 2-year period. Patients were divided into the PD with arterial hypertension (AH) group (102 cases) with antihypertensive drugs, the PD with other cardiovascular risk factors (CVRFs) group (60 cases) with antidiabetic and/or lipid-lowering drugs, and the pure PD group (159 cases) without CVRFs. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Hoehn-Yahr (H&Y) stage were used to assess progression. DAT semiquantitative values were used to evaluate damage to dopaminergic neurons in the substantia nigra, including the contralateral and ipsilateral count density ratio and asymmetry index. There were no significant differences among the three groups in MDS-UPDRS score and H&Y stage. Changes in DAT levels among the three groups were without distinct differences in the first year and second year. In each group, DAT decreased more in the first year than in the second year. There was no decrease in DAT uptake in the PD with AH group compared with the other groups during the follow-up period. There is no evidence that antihypertensive drugs can delay PD progression within 2 years.


Treatment of closed subtalar joint dislocation: A case report and literature review.
Subtalar dislocation is defined as a separation of the talocalcaneal and talonavicular articulations, commonly caused by high-energy mechanisms, which include falls from height, motor vehicle crashes, and twisting leg injuries. The dislocations are divided into medial, lateral, anterior, and posterior types on the basis of the direction in which the distal part of the foot has shifted in relation to the talus. The most common type is medial dislocation resulted from inversion injury. Subtalar dislocation may accompany with other fractures. Physical examination must be performed carefully to assess for neurovascular compromise. Most of the subtalar dislocations can be treated with closed reduction under sedation. If this is not possible, open reduction without further delay should be conducted. After primary treatment, X-ray and computed tomography scan should be performed to evaluate the alignment and the fractures. We report a 37-year-old male patient sustained a subtalar dislocation without any bony injury when he was playing football. The patient was successfully treated by closed reduction, and a good alignment was observed at the last follow-up. The pathogenesis and treatment method of this case were analyzed, and the related literature were reviewed, which provided a reference for future clinical treatment.


Spherical coordinates transformation pre-processing in Deep Convolution Neural Networks for brain tumor segmentation in MRI.
Magnetic Resonance Imaging (MRI) is used in everyday clinical practice to assess brain tumors. Deep Convolutional Neural Networks (DCNN) have recently shown very promising results in brain tumor segmentation tasks; however, DCNN models fail the task when applied to volumes that are different from the training dataset. One of the reasons is due to the lack of data standardization to adjust for different models and MR machines. In this work, a 3D spherical coordinates transform during the pre-processing phase has been hypothesized to improve DCNN models' accuracy and to allow more generalizable results even when the model is trained on small and heterogeneous datasets and translated into different domains. Indeed, the spherical coordinate system avoids several standardization issues since it works independently of resolution and imaging settings. The model trained on spherical transform pre-processed inputs resulted in superior performance over the Cartesian-input trained model on predicting gliomas' segmentation on Tumor Core and Enhancing Tumor classes, achieving a further improvement in accuracy by merging the two models together. The proposed model is not resolution-dependent, thus improving segmentation accuracy and theoretically solving some transfer learning problems related to the domain shifting, at least in terms of image resolution in the datasets.


In vitro efficacy of two terpenes against ancyrocephalid monogeneans from Nile tilapia.
Terpenes are naturally produced compounds with a broad range of biological activities. Currently, there is limited information regarding the anthelminthic effect of terpenes against monogenean parasites of fish. The aim of this work was to evaluate the in vitro efficacy of two terpenes [α-terpinene and (+)-limonene oxide] against ancyrocephalid monogeneans found on farmed Nile tilapia (Oreochromis niloticus). (+)-Limonene oxide was more effective in killing these parasites than α-terpinene, with 86 and 90% mortality at concentrations of 36 and 55.4 mg/L, respectively, with a 5-h treatment. The estimated 5-h EC50 of (+)-limonene oxide was 4.8 mg/L. Even though this compound has the potential to be used as an anthelmintic compound in finfish aquaculture, before in vivo experiments are performed, additional studies are needed to find a more effective concentration, as well as to evaluate other terpenic compounds.


The perceived value of local knowledge tourism: dimension identification and scale development.
Local knowledge tourism encompasses the rich cultural heritage, historical narratives, and traditional practices of a specific destination. Despite its significance in enhancing the tourist experience, there is a dearth of research examining the subjective perceptions and values of visitors engaging in local knowledge tourism. Consequently, there is a pressing need to explore the composition of perceived tourist values in this unique context. Due to the exploratory nature of this research, a constructivist grounded theory and content analysis are applied to analyze the data. This study identifies and conceptualizes five distinct dimensions of perceived values in local knowledge tourism: functional value, emotional value, social value, cognitive value, and self-actualization value. Furthermore, an 18-item scale is developed to measure these dimensions quantitatively. This research makes several significant contributions: (1) it expands the scope of perceived value research within the tourism domain and enhances our understanding of the tourist experience in local knowledge tourism; (2) it provides a reliable instrument for future quantitative investigations into the behavior and mindset of local knowledge tourists; and (3) it offers theoretical foundations and practical insights for destination managers seeking to develop tourism products tailored to the preferences and expectations of local knowledge tourists.


Effects of noradrenaline and carbachol on temperature regulation of cold-stressed and cold-acclimated rats.
1 Noradrenaline (20 micrograms) and carbachol (1 microgram) injected into the anterior hypothalamus of rats at an ambient temperature of 23 degrees C evoked significant falls in core temperature and increases in tail temperature. 2 When rats were cold-stressed (4 degrees C for 90 min) or cold-acclimated (4 degrees C for 4 weeks) and the above amine injections repeated, only carbachol evoked significant falls in core temperature and neither amine increased tail temperature. 3 Central injections of noradrenaline and carbachol also evoked increases in plasma glucose concentrations but not plasma non-esterified fatty acid (NEFA) concentrations in control, acutely cold-stressed and cold-acclimated rats. 4 Although concentrations of plasma glucose and blood lactate of rats were unaffected by cold exposure to 4 degrees C for 1 to 28 days, glucose oxidation rate of both cold-stressed and cold-acclimated rats was significantly greater than in rats at 23 degrees C. Concentrations of plasma NEFA were increased after 1 to 28 days of cold exposure.


In situ harvesting of adhered target cells using thermoresponsive substrate under a microscope: principle and instrumentation.
A novel technique and instrumented device were developed to harvest target cells from multicellular mixture of different cell types under a microscope. The principle of the technique is that cells cultured on a thermoresponsive-substance-coated dish were detached by a region-specific cooling device and simultaneously harvested using a micropipette, both of which were assembled in an inverted microscope. Thermoresponsive coating consists of the mixture of poly(N-isopropylacrylamide) (PNIPAAm) and PNIPAAm-grafted gelatin. The former non-cell-adhesive polymer dissolves below at 32.1 degrees C in water and precipitates over that temperature (called lower critical solution temperature, LCST), and the latter cell-adhesive polymer has LCST of 34.1 degrees C. The appropriate mixing ratio of these thermoresponsive polymers exhibited high cell adhesion at physiological temperature and complete cell detachment at room temperature. A device developed as to cool at only a tiny area of the bottom of the dish, beneath which a cell that was targeted under a microscope, was assembled in a microscope. It was demonstrated that single cell or two cells that adhered to each other was detached from the surface and harvested by a micropipette within approximately 30s.


Inter omental-cerebral vascularization induced by omental graft to the rat brain.
The omentum of 13 rats were removed from the abdomen and placed directly on the brain. 5-14 days later the omentum and the underlying brain were joined by numerous vascular anastomoses in 9 rats. The purpose of this work was to study the use of omentum to establish extracranial vascularization of the brain.


Number, shape, and topography of leakage points in acute type I central serous retinopathy.
The evaluation of 430 consecutive eyes (87.5% from male, 12.5% from female patients) showed a leakage point with uniform dye spread in 93%. In 7%, a smoke-stack phenomenon was observed. The number of leakage points reached from 1 (71.6%) to 7 (0.2%). Most leakage points were found in a 1-mm-wide ring-shaped zone starting 0.5 mm from the center of the fovea. Beyond this zone the incidence dropped rapidly with the exception of the upper nasal quadrant. Of the leakage points, 33.2% were located in the upper nasal, 21.2% in the lower nasal, 19.0% in the upper temporal, and 14.8% in the lower temporal quadrant. Leakage points occurred more than 3 mm away from the center of the fovea in 11.8%. The papillomacular bundle contained 25.4% of the leakage points. Leakage points in recurrences were located within 1 mm of the primary leakage point in 80% of the cases.


Multiresistant Shigella species isolated from pediatric patients with acute diarrheal disease.
A total of 57 strains of Shigella (36 S sonnei, 21 S flexneri), isolated from children with acute diarrheal disease who presented for treatment at the Andes University Hospital, Merida, Venezuela, from June 1993 to June 1995, were tested for their susceptibility to trimethoprim, sulfamethoxazole, ampicillin, cefamandole, ceftriaxone, streptomycin, fleroxacin, and nalidixic acid, by the agar dilution method. Twenty-seven strains (75%) of S sonnei and eight strains of S flexneri (38.1%) isolates showed high-level resistance to trimethoprim (MIC90 > 1024 microg/mL), which was also associated with other resistance patterns. The most common resistant phenotype associated with trimethoprim-resistance among S sonnei isolates was sulfamethoxazole-streptomycin (63%); among S flexneri isolates, it was sulfamethoxazole-ampicillin-streptomycin (87.5%). Individual resistance was only observed for ampicillin, mainly in four isolates of S flexneri, and in one isolate of S sonnei. Most Shigella strains were resistant to three or more antimicrobial agents. These results confirmed that multiresistant strains of Shigella are present in Merida, and emphasize the importance to maintain these under surveillance in order to assess local susceptibility patterns and empiric therapy.


The application of gemcitabine and pirarubicin in patients with non-muscle invasive bladder cancer.
To investigate the value of gemcitabine and pirarubicin in patients with non-muscle-invasive bladder cancer (NMIBC). 405 patients with non-muscle invasive bladder cancer admitted to our hospital from January 2012 to December 2020 who underwent transurethral bladder tumor electronic resection were studied. 177 patients were treated with gemcitabine (Gemcitabine group) and 228 patients were treated with pirarubicin (Pirarubicin group) after surgery. The efficacy and adverse effects of the two groups were observed and the patients were followed up. No differences were found when comparing age, gender, smoking, bladder mass, number of masses, hypertension, diabetes, coronary artery disease, hematuria and tumor diameter between the 2 groups (P > 0.05). In the Gemcitabine group, bladder irritation signs, meatus hematuria, fever, nausea and vomiting were lower than those in the Pirarubicin group (P < 0.05). The recurrence rates were 6.21% and 12.28% at 1 year, 11.86% and 23.68% at 2 years, 15.82% and 25.88% at 3 years in the Gemcitabine and Pirarubicin groups respectively, with the Gemcitabine group having a significantly lower recurrence rate than the Pirarubicin group (P < 0.05). The tumor recurrence-free survival rate for 5 years of gemcitabine was significantly higher than that of the Pirarubicin group (P < 0.05). Gemcitabine and pirarubicin are both effective in treating patients with non-muscle invasive bladder cancer, with gemcitabine having a lower incidence of adverse reactions, a higher safety rating, a lower recurrence rate and an improved survival outcome.


A CO(2)-responsive pillar[5]arene: synthesis and self-assembly in water.
The aggregate morphology of a CO2-responsive pillar[5]arene was reversibly controlled between toroid-like assemblies and irregular aggregates by bubbling CO2 and N2 repeatedly.


Differential control of H-reflex amplitude in different weight-bearing conditions in young and elderly subjects.
This study measured the modulation of conditioned (femoral nerve, paired-stimuli) and unconditioned soleus H-reflexes in young and elderly subjects when changing weight-bearing (WB) requirements and body position. Conditioned and unconditioned H-reflexes were examined in 14 elderly subjects and 11 young subjects during six different WB conditions: (1) lying supine with no WB, (2) supine position inclined by 30° with 50% WB, (3) standing with 50%, (4) 75%, (5) 100% and (6) 125% WB. The elderly subjects had consistently higher background soleus EMG activity across the WB conditions compared to the young. Femoral nerve conditioning caused facilitation of the H-reflex that changed across WB conditions in the young subjects, but not in the elderly subjects. Finally, elderly subjects had less depression with paired-stimulation (PRD) across WB conditions, which was not observed in the young subjects. The elderly may have more direct activation of motoneurons from descending pathways, coupled with less segmental spinal control of inhibitory interneurons, as evidenced by the increased background soleus activity, H/M-max ratios and the lack of modulatory control observed when conditioning the H-reflex. There was an age-specific response from descending and segmental pathways during conditions that involved either different WB requirements or changes in body position.


Atypical echocardiographic and angiographic presentation of a postoperative pseudoaneurysm of the left ventricle after repair of a true aneurysm.
Subsequent to the repair of a true aneurysm from the posteromedial-basal aspect of the left ventricle, a 58 year old man developed a draining wound at the site of the sternotomy. Two-dimensional echocardiography revealed recurrence of the aneurysm at the site of the previous aneurysm repair. This aneurysm had a wide neck and looked similar in appearance to the previous true aneurysm. However, at surgery the patient was found to have a ventricular pseudoaneurysm with a cardiocutaneous fistula.


The final frontier: nursing in the emerging health-care environment.
The final frontier heralds a new era in which nursing finally assumes its rightful place as the leader in the health-care delivery industry through a systematized body of knowledge, new nursing technologies, and the final assumption of power through modern management techniques. Nursing is the agent of change for moving health care from a cottage industry to a full-fledged business enterprise--a business with compassion, empathy, and quality.


Short-term effect of coronary artery bypass grafting on the signal-averaged electrocardiogram.
Ventricular late potentials at the end of the QRS can be detected on the body surface during sinus rhythm by recording a signal-averaged electrocardiogram (SAECG). In patients with coronary artery disease, these late potentials have been shown to be markers for spontaneous or inducible ventricular tachycardia, or both. The short-term (before and 10 +/- 4 days after coronary revascularization) influence of coronary artery bypass grafting (CABG) on the quantitative SAECG variables was studied in 40 patients with chronic coronary artery disease. Twenty-five of these patients had a previous myocardial infarction. In the 15 patients without previous myocardial infarction, no abnormal SAECG indexes were recorded before CABG and no change in the quantitative SAECG variables was observed after surgery. In the patients with a previous myocardial infarction, 7 (28%) had a late potential before CABG. After CABG, 5 (71%) patients remained late potential-positive, whereas the other 2 (29%) lost their late potential. The mean values of their SAECG variables improved after coronary revascularization. In the entire group of postmyocardial infarction patients, the high-frequency QRS duration had shortened (p less than 0.01) after CABG (the other SAECG indexes did not change). The postoperative arrhythmic complications (transient atrial fibrillation, new onset of ventricular couplets) tended to be more frequent in the postmyocardial infarction group and in patients with late potentials. Our findings suggest that the reported increase in ventricular arrhythmias after CABG is probably not related to a change in the arrhythmogenic substrate for ventricular reentry but is associated with changes in the arrhythmogenic milieu.


Inhibition of integrins αv/α5-dependent functions in melanoma cells by an ECD-disintegrin acurhagin-C.
Acurhagin-C, a Glu-Cys-Asp (ECD)-disintegrin from Agkistrodon acutus venom, has been reported as an endothelial apoptosis inducer, previously. Here we further evaluate its potential applications in cancer therapy. In vitro assays indicated that acurhagin-C not only may influence the cell viability at higher concentration, but also can potently and dose-dependently decrease cell proliferation in murine B16-F10 melanoma. Otherwise, it also had a dose-dependent inhibition on B16-F10 cell adhesion to extracellular matrices, collagen VI, gelatin B and fibronectin, as well as disturbed transendothelial migration of B16-F10 cell. Morphological study found that acurhagin-C dramatically affected B16-F10 cell adhesion to immobilized fibronectin, leading to the formation of multicellular aggregates with rounded shape. Detected by flow cytometry, acurhagin-C was able to induce B16-F10 cell apoptosis and alter cell cycle distribution through its interactions with integrins αv/α5, and thereafter initiation the apoptotic pathways of caspase-8/-9. Furthermore, acurhagin-C could synergistically enhance the anti-proliferative activity of methotrexate in B16-F10 cells and human melanoma SK-MEL-1 cells, without diminishing the growth of human epidermal melanocytes. Taken together, acurhagin-C proved to be a potent inhibitor of integrin-based functions in melanoma cells by activating the complex apoptotic pathways.


Estimated molecular structure of a carbon nanotube molecular heater based on binding properties to a target protein.
Carbon nanotubes exhibit strong absorbance in the near-infrared (NIR) region and are considered as potent candidates for hyperthermic therapy because they generate significant amounts of heat upon excitation with NIR light. We prepared a single-walled carbon nanotube (SWNT)/IgG complex to use as a "smart molecular heater" for hyperthermic therapy. The aim of the present study was to assess the binding efficiency of DNA-functionalized SWNT/IgG complexes to a target protein. 3 types of complexes with different lengths of spacer arm chain (13.5, 29, and 56 Å) linked to biotinylated IgG were prepared, and we evaluated the effect of the spacer arm length on the specificity, affinity, and capacity of binding to a target protein. Complexes with longer spacer lengths showed increased binding affinity to a target protein. This could be due to a reduction in steric hindrance by increasing the segmental flexibility of the spacer arm. The results of this study suggested that DNA-functionalized SWNT/IgG complexes could act as a heating nano-device for hyperthermic cancer therapy, and the complexes can bind various types of tumor by modifiying the specific antibody.


Synthesis and antimicrobial evaluation of 4-phenyl-3-isoquinolinoyl-hydrazones.
2-Methyl-1-oxo-1,2-dihydro-3-carbazoyl-4-phenylisoquinoline 2, 1-methoxy-7 and 1-chloro-3-carbazoyl-4-phenylisoquinoline 12 as well as a series of their 2-hydrazono-derivatives 3 a-i, 8 a-i and 14 a-i were synthesized and evaluated for their antibacterial and antifungal activities, in vitro. Compound 3 h was fairly active against Staphylococcus aureus, Staphylococcus epidermidis and streptococci group B.


Optimal management for patients not meeting the inclusion criteria after endoscopic submucosal dissection for gastric cancer.
The necessity of additional gastrectomy for patients not meeting the inclusion criteria after endoscopic submu cosal dissection (ESD) is controversial. The aim of this study was to elucidate the risk factors for lymph node metastasis (LNM) and residual cancer (RC) in patients not meeting the inclusion criteria after ESD and to determine additional treatment strategies. Of 1443 gastric cancer patients who underwent ESD between 2004 and 2013, 167 patients diagnosed as having a lesion not meeting the inclusion criteria after ESD were retrospectively analyzed. Of the 167 cases, 100 cases underwent additional gastrectomy, and 67 cases were observed without surgery. Overall, 9.0 % (9/100) and 9.0 % (9/100) of patients not meeting the inclusion criteria after ESD presented with LNM and RC, respectively, but neither was observed in 83 patients (83.0 %). Multivariate analysis revealed that lymphovascular involvement (LVI) (OR 38.38; 95 % CI 1.94-761.43, p = 0.017) and undifferentiated type (OR 45.58; 95 % CI 2.88-720.94, p = 0.007) were independent risk factors for LNM, and positive horizontal margin was an independent risk factor for RC (OR 9.48; 95 % CI 1.72-52.13, p = 0.010). In differentiated types without LVI, no cases had LNM (0/38) in the additional gastrectomy group, and there was no lymph node or distant recurrence (0/39) in the observation group. Additional treatment is necessary for patients with LVI, undifferentiated type, and positive horizontal margin. Careful follow-up may be acceptable for patients with the differentiated type without LVI, especially for the elderly or patients with severe comorbidities.


Dendrimer-based magneto-plasmonic nanosorbents for water quality monitoring using surface-enhanced Raman spectroscopy.
In this work, we report the synthesis of magneto-plasmonic dendrimer-based nanosorbents containing Au nanostars and we demonstrate that they can be used as versatile optical sensors for the detection of pesticides in spiked water samples. The magnetic hybrid nanoparticles were obtained by conjugating silica-functionalized G5-NH2 PAMAM dendrimers to silica-coated magnetite cores. The resulting magnetic-PAMAM conjugates were then used to reduce and sequester Au seeds for the subsequent in situ growth of Au nanostars. The dendrimer-based magneto-plasmonic substrates containing the Au anisotropic nanophases were then investigated regarding their ability to monitor water quality through surface-enhanced Raman scattering (SERS) spectroscopy. As a proof-of-concept, the ensuing multifunctional materials were investigated as SERS probing systems to detect dithiocarbamate pesticides (ziram and thiram) dissolved in water samples. It was observed that the magneto-plasmonic hybrid materials enhance the Raman signal of these pesticides under variable operational conditions, suggesting the versatility of these systems for water quality monitoring. Moreover, a detailed analysis of the SERS data was accomplished to predict the adsorption profile of the dithiocarbamate pesticides to the Au surface.


Comparison of outcomes between variceal and non-variceal gastrointestinal bleeding in patients with cirrhosis: Insights from a Nationwide Inpatient Sample.
Variceal upper gastrointestinal bleeding (VUGIB) occurs in patients with decompensated cirrhosis, but non-VUGIB (NVUGIB) is not uncommon. We compared the outcomes of VUGIB and NVUGIB in cirrhotic patients. This retrospective study used Nationwide Inpatient Sample employing International Classification of Diseases codes for adult NVUGIB and VUGIB patients. Mortality, morbidity, and resource utilization were compared. Analyses were performed using STATA; proportions and continuous variables were compared using Fisher's exact and Student's t-test, respectively. Confounding variables were adjusted using propensity matching, multivariate logistic and linear regression analyses. Of 2,166,194 cirrhotics, 92,439 had a diagnosis of NVUGIB and 17,620 VUGIB. VUGIB patients had higher rates of mortality [adjusted odds ratio (aOR) 1.42, 95% confidence interval (CI) 1.19-1.69], hemorrhagic shock (aOR 1.84, 95%CI 1.54-2.17) and intensive care unit admission (aOR 2.47, 95%CI 2.18-2.81), greater hospitalization costs ($16,251 vs. $12,295, P<0.001), more need for packed red blood cell transfusion (aOR 1.12, 95%CI 1.03-1.22) or endoscopic therapy (aOR 2.71, 95%CI 2.47-2.93), and a longer hospital stay compared to NVUGIB. However, NVUGIB had higher aOR of undergoing diagnostic endoscopy and radiography-guided vessel embolization. There were no differences in the rates of acute kidney injury between the 2 groups. Ascites and spontaneous bacterial peritonitis were independently associated with increased VUGIB mortality. VUGIB in patients with cirrhosis is associated with greater hospital costs, mortality, and morbidity burden than NVUGIB. This study provides updated and current knowledge of patient characteristics and differences in outcomes between VUGIB and NVUGIB, required to successfully address the healthcare delivery gaps.


A versatile supramolecular nanoagent for three-pronged boosting chemodynamic therapy.
Chemodynamic therapy (CDT) utilizing toxic hydroxyl radicals (·OH) to kill cancer cells exhibits huge potentiality in antitumor treatment. However, inadequate acidity, insufficient hydrogen peroxide (H2O2) amount, and overexpressed reduced glutathione (GSH) inside cancer cells severely restrict the efficacy of CDT. Although numerous efforts have been made, fabricating a versatile CDT material for surmounting these obstacles simultaneously is still a great challenge, especially for supramolecular materials owing to lacking an active metal unit for the Fenton reaction. Here, we intriguingly proposed a powerful supramolecular nanoagent (GOx@GANPs) based on the host-guest interaction between pillar[6]arene and ferrocene for all-sided boosting CDT efficacy via in situ cascade reactions. GOx@GANPs could stimulate intracellular glucose conversion into H+ and H2O2 to optimize the in situ Fenton reaction conditions and continuously produce sufficient •OH. Meanwhile, consumption of the original intracellular GSH pool and inhibition of GSH regeneration were synchronously achieved through the GSH-responsive gambogic acid prodrug and cutting off adenosine triphosphate (ATP) supply for GSH resynthesis, respectively. This complete GSH exhausting characteristic of GOx@GANPs effectively suppressed •OH elimination, ultimately resulting in a superior CDT effect. Furthermore, GOx@GANPs also produced synergistic effects of starvation therapy, chemotherapy, and CDT, exhibiting low toxicity toward normal tissues. Thus, this work introduces a valuable way for optimizing and elevating CDT efficiency and synergistic treatment of tumors.


Discriminative control of the vaginal vasomotor response.
With use of a discriminative control procedure and operant techniques, women significantly increased their vaginal pulse amplitude (produced vaginal vasodilation) but did not significantly decrease vaginal pulse amplitude (produce vaginal vasoconstriction). Acquisition of vaginal pulse amplitude control was rapid with no significant improvement over trials or the 5 experimental days. Specificity of vaginal pulse amplitude control occurred in relation to the other vasomotor responses, including vaginal blood volume and digital pulse amplitude. Vagnial pulse amplitude changes were not related to somatic-muscular, respiratory, or heart-rate changes. Women who used oral contraceptives were better able to control vaginal pulse amplitude than women who used other forms of birth control. Although the sexual behavior of these two groups and did not differ, women in the latter group tended to be more clitorally oriented.


Reorganization of hair follicles in human skin organ culture induced by cultured human follicle-derived cells.
Studies of human hair follicle (HF) induction by follicle-derived cells have been limited due to a lack of suitable test systems. In this study, we established a skin organ culture system which supports HF formation by follicle-derived cells. Long-term skin organ cultures were set up from human retroauricular skin specimens and maintained in culture for up to 8 weeks. In vitro expanded human HF-derived cells from the dermal papilla (DP) and the outer root sheath (ORS) were injected together into the skin specimens and evaluated for their ability to induce reorganization of HFs. Macroscopic analysis of the cultured skin specimens demonstrated the growth of velus-like hair after 4 weeks in culture. Histologic evaluation of the cultured skin specimens after 8 weeks of culture revealed multiple miniaturized HFs with sebaceous glands. In addition, cell clusters of various differentiation stages could be demonstrated in serial sections of the cultured skin specimens. Labeling of HF-derived cells with the fluorescence dye CFDA-1 prior to injection suggested a de novo reorganization of HFs out of the injected cells. In conclusion, the study demonstrated HF formation by HF-derived cells in an in vitro skin organ culture model.


Acute cystitis in women: experience with a telephone-based algorithm.
This paper evaluates short-term (60-day) outcomes for women with symptoms of acute cystitis evaluated and treated with a telephone-based protocol. We used a retrospective analysis of medical records of patients evaluated and treated according to a guideline-based algorithm for symptoms of acute cystitis. The algorithm was utilized in the care of 273 women reporting symptoms of urinary tract infection (UTI), with 75.4% being treated without urinalysis or cultures. Over the next 60 days, 46 (16.8%) were seen or made phone contact for recurrent or persistent urinary tract symptoms, with 6 patients (2.2%) diagnosed with pyelonephritis. No other adverse events were identified in the 60 days after use of the protocol. A telephone-based nurse evaluation and treatment algorithm can allow for successful management of the majority of women identifying symptoms of uncomplicated lower UTIs.


Inactivation of oncoprotein binding by a single Cys706-to-Tyr substitution in the retinoblastoma protein.
We previously found a new single amino acid substitution at codon 706 (Cys-to-Tyr) of the retinoblastoma (RB) gene in a sporadic retinoblastoma patient. The glutathione S-transferase-RB fused protein containing this mutation was here tested for binding to SV40 large T antigen and adenovirus E1A protein, and was shown to have lost its binding affinity. Thus, Tyr, as well as Phe, residues substituted for Cys706 were found to abolish the RB protein activity.


Investigation of flow dynamics of wastewater in a pilot-scale constructed wetland using radiotracer technique.
Constructed wetlands (CWs) are used for the treatment of wastewater by natural processes. Knowledge of the flow dynamics of wastewater through the CWs is required to evaluate their performance, operation and design. The residence time distribution (RTD) approach was used to evaluate the above-mentioned parameters in a CW. The RTD of wastewater flowing through a pilot-scale CW was measured using Technetium-99 m (99mTc) as a radiotracer. The measured data were analyzed, and mean residence time and stagnant volumes were quantified under different operating conditions. A plug flow component in series along with a tank-in-series model with an exchange between the active and dead zones was used to simulate the measured RTD curves and investigate the flow dynamics of the flowing wastewater. The results of the study showed that the optimum flow rate and wastewater level in the CW was 2.3 m3/s and 0.6 m, respectively. Moreover, the results of the study will help in the operation and design of the existing wetland and design of new wetlands.


Ultrastructural histochemical study on glycoconjugates of the submandibular gland of rabbits.
An ultrastructural histochemical study was carried out on submandibular glands of rabbits. Stainings were performed with dialysed iron (DI), high iron diamine (HID), tannic acid uranyl acetate (TA-U), tannic acid-ferric chloride (TA-F) sequence, and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method. It was demonstrated that neutral glycoproteins are present in the cells with dark granules of the preterminal tracts, and that neutral and acid glycoproteins are present in the cells with light granules of the terminal tracts. Result are discussed and compared to other previously obtained histochemical and biochemical data.


Mass spectrometric identification of Cu, Zn, Fe, Co, Mn, Mg, and Pb in mammalian brain.
Combining the techniques of thin-layer chromatography (TLC) and mass spectrometry, we unambiguously identified the trace metals Cu, Zn, Fe, Pb, Mn, Co, and Mg in the brain of a female human who had no evidence of any pathologic disease in the central nervous system, and in brains from mouse, rat, guinea pig, and rabbit. These trace metals were also found in anatomic regions of human brain: cortex (gray), cortex (white), caudate nucleus, putamen, hippocampus, and thalamus, and in anatomic regions of rat brain: hypothalamus, cerebellum, stem striatum, and "the rest." The metals were characterized from the color and Rf values of their tetraphenylporphyrin chelates on TLC and from the mass and pattern of molecule ion cluster of the mass spectrum. The unexpected presence of lead in the brain is discussed.


Evidence that the C-terminal PB2-binding region of the influenza A virus PB1 protein is a discrete alpha-helical domain.
The influenza A virus RNA-dependent RNA polymerase is a heterotrimer composed of PB1, PB2 and PA subunits and essential for viral replication. However, little detailed structural information is available for this important enzyme. We show by circular dichroism spectroscopy that polypeptides from the C-terminus of PB1 that are capable of binding efficiently to PB2 fold into stable alpha-helical structures. Structure prediction analysis of this region of PB1 indicates that it likely consists of a three-helical bundle. Deletion of any of the helices abrogated transcriptional function. Thus, PB1 contains a C-terminal alpha-helical PB2-binding domain that is essential for nucleotide polymerization activity.


Effects of age and knee osteoarthritis on the modular control of walking: A pilot study.
Older adults and individuals with knee osteoarthritis (KOA) often exhibit reduced locomotor function and altered muscle activity. Identifying age- and KOA-related changes to the modular control of gait may provide insight into the neurological mechanisms underlying reduced walking performance in these populations. The purpose of this pilot study was to determine if the modular control of walking differs between younger and older adults without KOA and adults with end-stage KOA. Kinematic, kinetic, and electromyography data were collected from ten younger (23.5 ± 3.1 years) and ten older (63.5 ± 3.4 years) adults without KOA and ten adults with KOA (64.0 ± 4.0 years) walking at their self-selected speed. Separate non-negative matrix factorizations of 500 bootstrapped samples determined the number of modules required to reconstruct each participant's electromyography. One-way Analysis of Variance tests assessed the effect of group on walking speed and the number of modules. Kendall rank correlations (τb) assessed the association between the number of modules and self-selected walking speed. The number of modules required in the younger adults (3.2 ± 0.4) was greater than in the individuals with KOA (2.3 ± 0.7; p = 0.002), though neither cohorts' required number of modules differed significantly from the unimpaired older adults (2.7 ± 0.5; p ≥ 0.113). A significant association between module number and walking speed was observed (τb = 0.350, p = 0.021) and individuals with KOA walked significantly slower (0.095 ± 0.21 m/s) than younger adults (1.24 ± 0.15 m/s; p = 0.005). Individuals with KOA also exhibited altered module activation patterns and composition (which muscles are associated with each module) compared to unimpaired adults. These findings suggest aging alone may not significantly alter modular control; however, the combined effects of knee osteoarthritis and aging may together impair the modular control of gait.


Detection of high-risk Avian Pathogenic Escherichia coli (APEC) isolated from broilers in São Paulo, Brazil.
Some high-risk Avian Pathogenic Escherichia coli (APEC) clones have been associated with increased economic losses caused by avian colibacillosis. They may represent an additional food consumption concern due to the potential zoonotic role causing urinary tract infections mainly related to E. coli ST73 and ST95 lineages. This study aimed to characterize APEC isolated from slaughterhouse carcasses presenting lesions compatible with avian colibacillosis. We analyzed about 6500 broilers carcasses, and 48 showed lesions consistent with colibacillosis. Forty-four strains of E. coli were isolated, with 77.27% (n = 34/44) classified as APEC. The isolates belonged to the phylogenetic groups B2 (41.17%, n = 14/34), G (20.59%, n = 7/34), A (17.65%, n = 6/34), B1 (8.82%, n = 3/34), and E (5.88%, n = 2/34). Determining the phylogenetic group of 5.88% (n = 2/34) of the strains was impossible. Moreover, 20.59% (n = 7/34) were positive to the clonal groups ST117, 8.82% (n = 3/34) to ST95, and 8.82% (n = 3/34) were classified as belonging to serogroup O78 by PCR screening. Strains of APEC from O78 serogroup and ST117 are considered high-risk clones for poultry, and our data reinforced the need for surveillance of these pathogens in poultry farms and slaughterhouses.


Regioselective synthesis of heteroaryl triflones by LDA (lithium diisopropylamide)-mediated anionic thia-Fries rearrangement.
Novel heteroaryl triflones including oxindole, pyrazolone, pyridine, and quinoline derivatives have been regioselectively synthesized by LDA-mediated thia-Fries rearrangement for the first time. These reactions are also the first examples of the application of anionic thia-Fries rearrangement in heteroaromatic compounds.


Assessment of phagosome formation and maturation by fluorescence microscopy.
Phagocytosis of invading microorganisms by neutrophils is an important early response to infection. Here, we describe protocols designed for the quantitative study of particle internalization and of the subsequent maturation of the newly formed phagosomes using sheep red blood cells as a model target particle and neutrophils as phagocytes. Techniques to label the particles with fluorescent pH-sensitive dyes are presented, along with complement and immunoglobulin opsonization procedures. These labeling techniques, in combination with high-resolution digital imaging, allow for the quantitative assessment of phagocytosis at the single-cell level by bright field and fluorescence microscopy. Lastly, qualitative and quantitative methods of investigating the intraphagosomal pH are presented. We describe the use of a fluorescent weak base that accumulates in acidic cellular compartments and functions as a marker of phagosome acidification, as well as more quantitative phagosomal pH measurements by fluorescence ratio imaging. A brief description of the hardware and software components necessary for digital imaging is also provided.


Fingerprints of Teaching Interactions: Capturing and Quantifying How Supervisor Regulate Autonomy of Residents in the Operating Room.
Supervisors and residents agree that entrusted autonomy is central to learning in the Operating Room (OR), but supervisors and residents hold different opinions about entrustment: residents regularly experience that they receive insufficient autonomy while supervisors feel their guiding is not appreciated as teaching. These opinions are commonly grounded on general experiences and perceptions, instead of real-time supervisors' regulatory behaviors as procedures unfold. To close that gap, we captured and analyzed when and to what level supervisors award or restrain autonomy during procedures. Furthermore, we constructed fingerprints, an instrument to visualize entrustment of autonomy by supervisors in the OR that allows us to reflect on regulation of autonomy and discuss teaching interactions. All interactions between supervisors and residents were captured by video and transcribed. Subsequently a multistage analysis was performed: (1) the procedure was broken down into 10 steps, (2) for each step, type and frequency of strategies by supervisors to regulate autonomy were scored, (3) the scores for each step were plotted into fingerprints, and (4) fingerprints were analyzed and compared. University Medical Centre Groningen (the Netherlands). Six different supervisor-resident dyads. No fingerprint was alike: timing, frequency, and type of strategy that supervisors used to regulate autonomy varied within and between procedures. Comparing fingerprints revealed that supervisors B and D displayed more overall control over their program-year 5 residents than supervisors C and E over their program-year 4 residents. Furthermore, each supervisor restrained autonomy during steps 4 to 6 but with different intensities. Fingerprints show a high definition view on the unique dynamics of real-time autonomy regulation in the OR. One fingerprint functions as a snapshot and serves a purpose in one-off teaching and learning. Multiple snapshots of one resident quantify autonomy development over time, while multiple snapshots of supervisors may capture best teaching practices to feed train-the-trainer programs.


Tetrahydronorharmane modulates the depolarisation-induced efflux of 5-hydroxytryptamine and dopamine and is released by high potassium concentration from rat brain slices.
Tetrahydronorharmane (THN), a compound which occurs in man and in rats is supposed to act as a modulator of 5-hydroxytryptaminergic neurones. It is reported here that THN stimulated the potassium-induced release of the neurotransmitter from brain slices. This suggests enhancement of the efflux as a mechanism for the 5-hydroxytryptamine-like action of THN in pharmacological experiments. Furthermore, THN decreased the potassium-evoked efflux of (3H)-dopamine. This is consistent with the inhibition of dopaminergic neurones by THN as seen previously in various in vivo experiments. Finally it is demonstrated that a high concentration of potassium evokes the efflux of (14C)-THN from brain slices. This finding suggests that THN is taken up into neurones and exerts its modulating action on serotonergic neurones either inside or outside the cell.


The single-copy actin gene of Phytophthora megasperma encodes a protein considerably diverged from any other known actin.
This paper reports the cloning and sequencing of a Phytophthora megasperma actin gene. Sequence analysis revealed that the gene does not contain introns and encodes a putative actin protein remarkably diverged from any other known actins. Genomic Southern analysis indicates that there is a single actin gene per haploid genome, which is actively transcribed in vivo, as revealed by S1 mapping of the transcripts. The transcripts are heterogeneous in size because they have different 3' termini, none of which contains the conventional AATAAA polyadenylation signal.


Endoscopic submucosal dissection with reinforcement using a laparoscopic approach for a duodenal cavernous hemangioma.
Video 1Endoscopic submucosal dissection with reinforcement using a laparoscopic approach (duodenal-laparoscopic and endoscopic coordinated surgery with endoscopic submucosal dissection) for a duodenal cavernous hemangioma. The mucosal defect was reinforced with laparoscopic seromuscular sutures after duodenal endoscopic submucosal dissection was performed.


Morphometrically-distinct sperm subpopulations defined by a multistep statistical procedure in ram ejaculates: intra- and interindividual variation.
The existence of sperm subpopulations within the mammalian ejaculate has now been widely recognized. However, to the best of our knowledge, no data exist regarding the existence of sperm morphometric subpopulations within the ovine ejaculate. Computer assisted sperm morphometry analysis (ASMA) data and clustering methods were used in this study to identify sperm-head subpopulations in ram semen. Two experiments were carried out. In Experiment 1, ejaculates from 226 mature rams of the Manchega breed belonging to 36 different herds were used. A minimum of 100 sperm heads were analyzed from each male and eight morphometric characteristics for each individual sperm were recorded. Subpopulation analysis was performed in sequential steps: variable group analysis and correlation analysis to select which morphometric characteristics to use in cluster analyses; nonhierarchical clustering analysis using sperm head length and p2a (also known as roundness) shape factor as initial classificatory variables; and hierarchical clustering analysis to obtain the final number of clusters. The clustering analyses, based on 26,306 individual cells, revealed the existence of four sperm subpopulations (SP1, SP2, SP3 and SP4) with different morphometric characteristics. Significant differences in the proportion of spermatozoa in the SP1 and SP3 were found between rams belonging to different herds. In Experiment 2, the intra- and intermale variability on the distribution of sperm subpopulations was assessed. Three ejaculates from each of 21 rams were collected and the same multistep clustering analysis was performed. For all subpopulations defined, the intermale variability resulted in high values, being the intramale variability much lower. This fact would allow the use of sperm head morphometry to characterize a male and might provide valuable information to asses its fertility. In conclusion, our results show that using computer assisted sperm morphometry analysis and multivariate cluster analyses, four sperm subpopulations with different head phenotype were identified in ram ejaculates.


Incorporation of radiolabelled alphafetoprotein in the brain and other tissues of the developing rat.
The time course of uptake and autoradiographic localization of alphafetoprotein (AFP) were studied in the brain and other organs of fetuses, neonates and young rats injected with homologous radiolabelled AFP. Comparative data of radioactivity accumulation in the brain relative to that of several tissues (blood, liver, tongue, small intestine) showed bimodal patterns reflecting two periods of more active incorporation, with a maximum before the 16th day of fetal development. In brain autoradiographs, the strongest labelling was observed in 17-day-old fetuses 24 h after injection into the mother of [125I]AFP. The labelling included all regions of the brain. The results presented here give experimental support to the hypothesis that the presence of AFP in the developing nervous system of mammals and birds is primarily due to protein uptake rather than in situ synthesis.


A study of renal outcomes in obese living kidney donors.
Little is known about the long-term outcomes of obese living kidney donors (OLKDs). We undertook this study to describe renal outcomes of OLKDs several years after donation. We invited 101 OLKDs for follow-up health evaluation. Thirty-six subjects (35.6%) completed evaluation at 6.8±1.5 years postdonation. The mean estimated glomerular filtration rate (eGFR) using the abbreviated modification of diet in renal disease (MDRD) equation (MDRD-eGFR) at follow-up was 72.1±16.3 (range: 42-106) mL/min per 1.73 m, and 47.2% of subjects had an MDRD-eGFR of 30 to 59. The absolute decrease in MDRD-eGFR from the time of donation to follow-up was 27.2 ± 13.1 mL/min per 1.73 m (P<0.001 on paired t test), which represents a 29.2% drop in the serial MDRD-eGFRs. Seven subjects (19.4%) had microalbuminuria (30-300 μg/mg creatinine). Subjects with microabuminuria were more likely to have MDRD-eGFR of less than 60 mL/min per 1.73 m (P=0.021). Subjects whose body mass index was greater than or equal to 35 kg/m (n=14) were found to have an absolute decrement in MDRD-eGFR similar to those with body mass index less than 35 kg/m (31.5 ± 15.6 and 24.7 ± 11.0 mL/min/1.73 m, respectively; P=not significant). Fifteen (41.6%) were hypertensive at follow-up. On medium-term follow-up, a large proportion of OLKDs will have a MDRD-eGFR of less than 60 mL/min per 1.73 m, and the likelihood increases markedly among those who develop microalbuninuria. This raises concern for hyperfiltration injury. Furthermore, OLKDs experience a substantial incidence of hypertension. Caution is advised in selecting OLKDs pending further data on long-term outcomes.


A conformational study of the dehydroalanine: dipeptide and homopolypeptide.
A molecular mechanics study of polydehydroalanine [poly-(delta Ala)] is presented. For this purpose the AMBER 3a program has been used to perform the calculations. With exception of the point charges, the parameters for the terminal groups were taken from AMBER 3a libraries, whereas those for the delta Ala residue from Alagona et al. [J. Comp. Chem. (1991) Vol. 12, pp. 934-942]. Charges for the residue and terminal groups have been fitted from the MNDO electrostatic potential and scaled to achieve an ab initio 6-31G* quality. Calculations have been carried out using the continuous solvent approximation with three different dielectrics epsilon = 1, 1r, and 4r. The results show that, despite the preferred structure for the isolated residue is an extended conformation, a 310-helix is the preferred conformation in the solid state (epsilon = 1 and 1r), whereas a peculiar structure with psi = 0 degree is preferred with epsilon = 4r.


Detecting IoT User Behavior and Sensitive Information in Encrypted IoT-App Traffic.
Many people use smart-home devices, also known as the Internet of Things (IoT), in their daily lives. Most IoT devices come with a companion mobile application that users need to install on their smartphone or tablet to control, configure, and interface with the IoT device. IoT devices send information about their users from their app directly to the IoT manufacturer's cloud; we call this the "app-to-cloud way". In this research, we invent a tool called IoT-app privacy inspector that can automatically infer the following from the IoT network traffic: the packet that reveals user interaction type with the IoT device via its app (e.g., login), the packets that carry sensitive Personal Identifiable Information (PII), the content type of such sensitive information (e.g., user's location). We use Random Forest classifier as a supervised machine learning algorithm to extract features from network traffic. To train and test the three different multi-class classifiers, we collect and label network traffic from different IoT devices via their apps. We obtain the following classification accuracy values for the three aforementioned types of information: 99.4%, 99.8%, and 99.8%. This tool can help IoT users take an active role in protecting their privacy.


Sound Transmission Validation and Sensitivity Studies in Numerical Models.
In 1974, Norris and Harvey published an experimental study of sound transmission into the head of the bottlenose dolphin. We used this rare source of data to validate our Vibroacoustic Toolkit, an array of numerical modeling simulation tools. Norris and Harvey provided measurements of received sound pressure in various locations within the dolphin's head from a sound source that was moved around the outside of the head. Our toolkit was used to predict the curves of pressure with the best-guess input data (material properties, transducer and hydrophone locations, and geometry of the animal's head). In addition, we performed a series of sensitivity analyses (SAs). SA is concerned with understanding how input changes to the model influence the outputs. SA can enhance understanding of a complex model by finding and analyzing unexpected model behavior, discriminating which inputs have a dominant effect on particular outputs, exploring how inputs combine to affect outputs, and gaining insight as to what additional information improves the model's ability to predict. Even when a computational model does not adequately reproduce the behavior of a physical system, its sensitivities may be useful for developing inferences about key features of the physical system. Our findings may become a valuable source of information for modeling the interactions between sound and anatomy.


Prevention and recovery in early psychosis (PREP(®)): building a public-academic partnership program in Massachusetts, United States.
Recently, there has been increasing emphasis on early intervention (EI) for psychotic disorders. EI programs in public mental health settings have been established in countries such as Australia, the United Kingdom, and Canada. However, there are relatively few EI programs in the United States (U.S.). Here we describe the conceptual origins and practical development of the PREP program, i.e., Prevention and Recovery in Early Psychosis, as it evolved in a public academic psychiatry setting in Boston, Massachusetts, U.S. PREP developed over a decade through a partnership between the Massachusetts Department of Mental Health and academic institutions within the Harvard Department of Psychiatry. We discuss the evolution, programmatic features, funding mechanisms, staffing, and the role of clinical training in PREP. The key principles in developing the PREP Program include the focus on early, evidence based, person-centered and phase-specific, integrated and continuous, comprehensive care. This program has served as a foundation for the emergence of related services at our institution, including a research clinic treating those at clinical high risk or within the putative "prodromal" period preceding frank psychosis. This account offers one possible blueprint for the development of EI programs despite the lack in the U.S. of a national mandate for EI or prevention-based mental health programs.


Tellurite-exposed Escherichia coli exhibits increased intracellular α-ketoglutarate.
The tellurium oxyanion tellurite is toxic to most organisms because of its ability to generate oxidative stress. However, the detailed mechanism(s) how this toxicant interferes with cellular processes have yet to be fully understood. As part of our effort to decipher the molecular interactions of tellurite with living systems, we have evaluated the global metabolism of α-ketoglutarate a known antioxidant in Escherichia coli. Tellurite-exposed cells displayed reduced activity of the KG dehydrogenase complex (KGDHc), resulting in increased intracellular KG content. This complex's reduced activity seems to be due to decreased transcription in the stressed cells of sucA, a gene that encodes the E1 component of KGDHc. Furthermore, it was demonstrated that the increase in total reactive oxygen species and superoxide observed upon tellurite exposure was more evident in wild type cells than in E. coli with impaired KGDHc activity. These results indicate that KG may be playing a pivotal role in combating tellurite-mediated oxidative damage.


Incremental benefits of a daily report card intervention over time for youth with disruptive behavior.
This study examined the percentage of children who respond positively to a daily report card (DRC) intervention and the extent to which students achieve incremental benefits with each month of intervention in a general education classroom. Participants were 66 children (87% male) with attention-deficit hyperactivity disorder or disruptive behavior problems who were enrolled in a school-based intervention program in rural, low-income school districts in a Midwest state. The DRC was implemented by each child's teacher, who received consultation from a graduate student clinician, school district counselor, or school district social worker. A latent class analysis using growth-mixture modeling identified two classes of response patterns (i.e., significant improvement and significant decline). Results indicated that 72% of the sample had all of their target behaviors classified as improved, 8% had all of their targets classified as declining, and 20% had one target behavior in each class. To examine the monthly incremental benefit of the DRC, individual effect sizes were calculated. Results for the overall sample indicated that most children experience a benefit of large magnitude (.78) within the first month, with continued incremental benefits through Month 4. The differential pattern of effect sizes for the group of improvers and the group of decliners offer data to determine when and if the DRC should be discontinued and an alternative strategy attempted. Evidence-based guidelines for practical implementation of the DRC are discussed.


Cytoprotection by omega-3 fatty acids as a therapeutic drug vehicle when combined with nephrotoxic drugs in an intravenous emulsion: Effects on intraglomerular mesangial cells.
During therapeutic interventions, blood concentrations of intravenously applied drugs are higher, and their onset of pharmacological action is faster than with other routes of drug administration. However, acute drug therapy often produces nephrotoxic side effects, as commonly seen after treatment with Ketorolac or Gentamicin leading to questions about their use, especially for patients at risk for acute renal failure. Omega-6(n-6) and omega-3(n-3) polyunsaturated fatty acids (PUFA) affect eicosanoid metabolism, which plays a role in the regulation of inflammation. Eicosanoids derived from n-6 FA have proinflammatory and immunoactive functions, whereas eicosanoids derived from n-3 PUFA have anti-inflammatory and cytoprotective properties. We hypothesized that providing such injectable drugs with nephrotoxic potential in combination with n3-PUFAs from the outset, might afford rapid cytoprotection of renal cells, given the recent evidence that intravenously administered n3-PUFAs are rapidly incorporated into cell membranes. We used intraglomerular mesangial cells (MES13) that are sensitive to treatment with Ketorolac or Gentamicin instead of proximal tubular cells which do not respond to Ketorolac. We found a significant inhibition of Ketorolac (0.25, 0.5, 1 mM) or Gentamicin (2.5, 5 mM) induced cytotoxicity after pretreatment of MES13 cells with 0.01% of 20%w/v LipOmega-3 Emulsion 9/1, containing 90:10 wt/wt mixture of fish oil derived triglycerides to medium chain triglycerides.


Using zebrafish to unravel the genetics of complex brain disorders.
The zebrafish has been prominently utilized in developmental biology for the past three decades and numerous genetic tools have been developed for it. Due to the accumulated genetic knowledge the zebrafish has now been considered an excellent research tool in other disciplines of biology too, including behavioral neuroscience and behavior genetics. Given the complexity of the vertebrate brain in general and the large number of human brain disorders whose mechanisms remain mainly unmapped in particular, there is a substantial need for appropriate laboratory research organisms that may be utilized to model such diseases and facilitate the analysis of their mechanisms. The zebrafish may have a bright future in this research field. It offers a compromise between system complexity (it is a vertebrate similar in many ways to our own species) and practical simplicity (it is small, easy to keep, and it is prolific). These features have made zebrafish an excellent choice, for example, for large scale mutation and drug screening. Such approaches may have a chance to tackle the potentially large number of molecular targets and mechanisms involved in complex brain disorders. However, although promising, the zebrafish is admittedly a novel research tool and only few empirical examples exist to support this claim. In this chapter, first I briefly review some of the rapidly evolving genetic methods available for zebrafish. Second, I discuss some promising examples for how zebrafish have been used to model and analyze molecular mechanisms of complex brain disorders. Last, I present some recently developed zebrafish behavioral paradigms that may have relevance for a spectrum of complex human brain disorders including those associated with abnormalities of learning and memory, fear and anxiety, and social behavior. Although at this point co-application of the genetics and behavioral approaches is rare with zebrafish, I argue that the rapid accumulation of knowledge in both of these disciplines will make zebrafish a prominent research tool for the genetic analysis of complex brain disorders.


Le choix thérapeutique : médicaments du psoriasis et grossesse avant, pendant et après la grossesse.
Psoriasis typically affects young adults and therefore many women with a desire to become pregnant or already pregnant. In this particular situation, treatment can be a real challenge for some patients, especially in the case of severe forms. In addition to local treatments, which are generally well tolerated, UVB phototherapy and cyclosporin remain the first-line systemic treatments. Acitretin and methotrexate are contraindicated. Safety data regarding the administration of biologic agents during pregnancy, are reassuring, the main adverse event being immunosuppression of the newborn if treatment is not discontinued. Biologic agents should ideally be discontinued before pregnancy, but in case of absolute necessity, they can be maintained or even initiated during pregnancy. Overall, it is recommended that biologic agents should not be continued beyond the second trimester because of the risk of maternal-fetal infection. If a biologic agent should be initiated during pregnancy, tanercept or certolizumab will be preferred, because of their low transplacental passage and more extensive safety data.


TAVR: nemesis of NOACs?
Data on non-vitamin K antagonist oral anticoagulants (NOACs) in transcatheter aortic valve replacement (TAVR) patients are controversial. In patients without atrial fibrillation (AF), rivaroxaban showed enhanced ischemia and bleeding as compared to standard of care. ENVISAGE showed enhanced bleeding in AF patients as compared to vitamin K antagonist (VKA). Only apixaban was non-inferior but failed superiority regarding bleeding in AF patients after TAVR. One could hypothesize that this might be due to pharmacokinetics of NOACs. Therefore, we compared outcome in rivaroxaban/edoxaban (once-daily) and apixaban (twice-daily) treated patients. 568 patients with indication for permanent oral anticoagulation due to AF undergoing TAVR were analyzed via inverse probability of treatment weighting. Valve academic research consortium complications during 30-day follow-up were assessed. Bleeding complications were similar in once-daily and twice-daily NOACs (major: 22 (7.5%) vs. 14 (5.3%), p = 0.285; minor: 66 (22.4%) vs. 46 (17.4%), p = 0.133). Complications did not change when splitting the cohort in the different agents apixaban, rivaroxaban and edoxaban. These findings remained robust after multivariate analysis. In summary, twice-daily and once-daily NOACs did not differ regarding bleeding complications in a hypothesis generating real-world cohort of TAVR patients with AF.


In vitro enhancement of the mutagenicity of 4-nitro-o-phenylenediamine by plant S-9.
The direct-acting mutagen 4-nitro-o-phenylenediamine (NOP) was activated in vitro by pea or tobacco S-9 into a more potent mutagen in Salmonella typhimurium strain TA98. NOP mutagenicity was not altered by Aroclor 1254-induced rat liver S-9. The plant S-9 activation of NOP was heat-sensitive but was not NADPH-dependent, did not involve superoxide radicals, and was not inhibited by CO. A direct relationship between plant peroxidase and NOP activation was established. Several purified peroxidases including horseradish peroxidase, chloroperoxidase, and lactoperoxidase also activated NOP. The perodoxidative process was not H2O2-dependent but was partially inhibited by a peroxidase inhibitor.


An In Vitro Study of Factors Influencing the Performance of Digital Intraoral Impressions Operating on Active Wavefront Sampling Technology with Multiple Implants in the Edentulous Maxilla.
To evaluate the performance (accuracy and repeatability) and the factors affecting the clinical performance of a recently released intraoral scanner based on active wavefront sampling technology. A single resin model of an edentulous maxilla fitted with six implants inserted at various depths and angulations was measured with a coordinated measuring machine (CMM) at 3 to 5 μm, and this acted as the "true," or reference, values of the study. Six corresponding cylindrical PEEK scanbodies were then mounted onto the implants, and four calibrated observers independently repeated the digital intraoral scan five times with a True Definition (TrueDef) scanner. Using implant position #15 as a reference, five linear and angular measurements were compared with the reference values (CMM), and the data were analyzed via one-way ANOVA and two-sample t-test. Mean linear and angular deviations for the TrueDef from CMM measurements were from 5.38 ± 12.61 μm to -26.97 ± 50.56 μm and from 0.16º ± 0.04º to -0.43º ± 0.1º, respectively. Experienced observers performed significantly better than inexperienced ones (p = 0.006), and scan distance (quadrant) significantly affected scanning accuracy (p = 0.003). Visible length of the scanbody affected measurement accuracy (p = 0.0001), while implant angulation did not (p = 0.757). The TrueDef scanner provides measurements within clinically accepted limits. Yet scanbody visibility, observer experience, and scan length remain relevant factors affecting accuracy.


[The study on freezing intercostal nerves for the relief of postoperative chest pain].
To explore the best freezing time and the optimum analgesia modality. In dogs, intercostal nerves were froze at -70 degrees C at different time including 30, 60, 90, 120, 180 s. Samples were got at the operative day, in 10 days and 60 days respectively, then carried on the pathology exam. In clinical study, 150 patients undergoing thoracotomy were randomly designated into 5 groups, all patients were recorded the heart rate, blood pressure, SO2, VAS, the dosage of dolantin, and observed the complications and side effects. At operative day, the freezing nerves appeared brown print macroscopically, and presented degeneration, necrosis of the nerve fiber microscopically with more than 90 s. After 10 days, nerves with more than 90 s became thinner than normal. After 60 days, all nerves had no obvious differentiation than normal. In clinical study, both 90 s group and 90 s with PCIA group were significantly better than 60 s group or PCIA group; The VAS of 90 s with PCIA group was significantly lower than 90 s group but had more side effects such as vomiting, nausea. At -70 degrees C, the freezing time should be no less than 90 s. The freezing intercostal nerves can safely and effectively relieve postoperative chest pain. The effect of analgesia of 90 s with PCIA group is the best, but has many side effects.


Longitudinal Cognitive and Biomarker Measurements Support a Unidirectional Pathway in Alzheimer's Disease Pathophysiology.
Amyloid-β (Aβ) likely plays a primary role in Alzheimer's disease pathogenesis, but longitudinal Aβ, tau, and neurodegeneration (A/T/N) measurements in the same individuals have rarely been examined to verify the temporal dynamics of these biomarkers. In this study, we investigated the temporal ordering of Aβ, tau, and neurodegeneration using longitudinal biomarkers in nondemented elderly individuals. A total of 395 cognitively unimpaired individuals and 204 individuals with mild cognitive impairment (320 [53%] were female) were classified into 8 A±/T±/N± categories according to the abnormal (+)/normal (-) status of Aβ (18F-florbetapir or 18F-florbetaben) positron emission tomography (PET), 18F-flortaucipir PET, and adjusted hippocampal volume (aHCV). Follow-up Aβ PET, tau PET, and aHCV measurements at 0.6 to 4.1 years were available for 35% to 63% of the sample. Baseline Aβ, tau, and aHCV were compared between different A/T/N profiles. We investigated the associations of baseline and longitudinal Aβ, tau, and neurodegeneration in relation to one another continuously. Among T- participants, tau was higher for A+/T-/N- individuals compared with the A-/T-/N- group (p = .02). Among N- participants, neurodegeneration was worse among A+/T+/N- individuals compared with the A-/T-/N- group (p = .001). High baseline Aβ was associated (p < .001) with subsequent tau increase and high baseline tau was associated (p = .002) with subsequent aHCV decrease, whereas high tau and low aHCV at baseline were not associated with subsequent Aβ increase. These findings define a sequence of pathological events in Alzheimer's disease that support a current model of Alzheimer's disease pathogenesis in which Aβ appears early, followed by deposition of abnormal tau aggregates and subsequent neurodegeneration.


Glatiramer acetate in multiple sclerosis.
Glatiramer acetate (Copaxone) is a disease-modifying agent approved by several health authorities worldwide for the treatment of relapsing-remitting multiple sclerosis. Although its primary target is the inflammatory component of the disease, there are emerging pieces of evidence suggesting that glatiramer acetate might also have a neuroprotective effect. In this review, the results of glatiramer acetate clinical trials and other relevant studies as well as the place of glatiramer acetate among other approved disease-modifying treatments for relapsing-remitting multiple sclerosis are discussed critically.


Double-membraned vesicles and their possible role in the ontogeny of microbodies of Basidiobolus haptosporus.
A concomitant but transient occurrence of large numbers of double-membraned vesicles with immature, culturally induced microbodies was demonstrated in thin sections of Basidiobolus haptosporus soon after transfer of the fungus to a defined medium containing xanthine or its catabolites as the sole source of nitrogen. Double-membraned vesicles were rapidly formed as derivatives of endoplasmic cisternae later to occur free in the cytoplasm, often as the most predominant cytoplasmic inclusion. Densitometric measurements revealed that heavy metal-binding cytoplasmic constituents were concentrated within the vesicular lumen. Most of the double-membraned vesicles appeared to undergo degeneration; they were rare to absent in thin sections of older cells. At times, double-membraned vesicles were seen connected to newly formed microbodies in a manner suggesting ontogenic relationships. The outer vesicular membrane was continuous with the single limiting membrane of the microbody via a short tubule. We interpret these observations as empirical ultrastructural evidence to suggest that some double-membraned vesicles become specialized and function as precursor inclusions in the biogenesis of new microbody populations committed to purine salvage.


Gingival Crevicular Fluid Turnover Markers in Premenopausal vs Postmenopausal Women receiving Orthodontic Treatment.
Orthodontic treatment is one of the commonly used dental treatments. Orthodontic forces act on the bone by modulating the biomolecules, chiefly the osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor kappa-B (RANK), and RANK ligand (RANKL) (OPG ligand). Hormonal changes are known to cause marked alteration in the levels of these biomolecules. Hence, we planned this study to evaluate the response of bone biomarkers in the gingival crevicular fluid (GCF) in postmenopausal women undergoing fixed orthodontic therapy. This study included assessment of 50 subjects who underwent orthodontic treatment from June 2012 to July 2016. All the patients were divided into two study groups with 25 patients in each group: premenopausal group and postmenopausal group. Similar orthodontic wires were used for controlling the forces applied in subjects of both the study groups and their GCF levels of RANKL, and OPN was assessed at baseline and 24 hours after the activation of orthodontic forces. All the results were compiled, assessed, and analyzed by Statistical Package for the Social Sciences software version 16.0. Chi-square test, Student's t-test, and Mann-Whitney U test were used for the assessment of the level of significance. The mean values of RANKL and OPN in the premenopausal and postmenopausal groups were found to be 241.52 and 317.15 pg/μL respectively. The mean values of RANKL at baseline in the premenopausal and postmenopausal groups were found to be 7.15 and 3.84 pg/μL respectively. Nonsignificant results were obtained while comparing mean OPN and RANKL level alteration in between the two study groups. The mean alterations in the GCF levels of bone biomarkers are similar for both premenopausal and postmeno-pausal women. For women with either premenopausal or postmenopausal status, orthodontic treatment appears to be equally safer.


Current trends in pulp therapy: a survey analyzing pulpotomy techniques taught in pediatric dental residency programs.
The study's purpose was to survey directors of pediatric dental residency programs in order to evaluate the materials currently being taught and used for pulpotomy procedures for primary teeth in educational and clinical settings. A web-based survey was emailed to all graduate pediatric dental residency program directors in the United States. Seventy one emails were sent to program directors, 47 responded but only 39 respondents (55%) were included in the study. Results suggested a slight decrease in utilization of formocresol 1:5 dilution (P<.01) and an increase in both ferric sulfate (P<.05) and mineral trioxide aggregate (MTA; P<.02) utilization for primary tooth pulpotomy procedures. The most common reasons for elimination of formocresol (18% of respondents) were systemic health concerns and carcinogenicity, in addition to evidence-based literature. Even though 25% of respondents have begun to use MTA for primary pulpotomy procedures, the most common reason for utilization of other medicaments over MTA was its higher cost. With 82% of graduate pediatric dental residency programs still utilizing formocresol 1:5 dilution for pulpotomy procedures in primary teeth, there has been no major shift away from its clinical use, in spite of increased usage of newer medicaments over the last 5 years.


Donor lung procurement: assessment and operative technique.
Given the relative scarcity of suitable donors and the widespread application of cardiac and pulmonary transplantation, it is imperative that a heart and two lungs be extracted from each donor. From increasing clinical experience and laboratory investigation in lung preservation, more flexible criteria for the assessment of potential lung donors are emerging. In this communication, we present our current criteria of donor lung suitability, and a simple and reliable technique of combined cardiopulmonary extraction that has provided suitable heart and lung grafts with excellent preservation, used in our last 150 donor organ procurements.


Bradykinin preconditions postischemic arterial endothelial function in humans.
Arterial endothelial dysfunction is an important mechanism of tissue injury caused by ischemia-reperfusion (I/R). Earlier studies of I/R have shown that intracoronary preinfusion with 2.5-5 microg/mL bradykinin (BK) could alleviate the postischemic myocardial damage. Using an experimental human model of I/R, we investigated whether preceding infusion with BK could prevent the I/R-induced arterial endothelial dysfunction. The left radial artery (LRA) from 16 healthy male adults, 18 to 30 years old, was submitted to I/R by completely occluding the left brachial artery with a pressure tourniquet for 20 minutes (ischemia), followed by its release (reperfusion). Prior to I/R, half of the subjects were randomly assigned to receive either BK (5 microg/mL) or saline, both being infused into the left brachial artery (0.5 mL/min, 10 min). The infusion was followed by a 10-minute drug-free period. The endothelial function of the LRA was studied by measuring the flow-mediated dilation (FMD) at baseline (prior to drug infusion), and at 15 minutes of reperfusion. In addition, baseline radial artery diameter, plasma nitrate, and von Willebrand factor were measured at these time points, and immediately before I/R (pre-I/R). BK had no effect on the pre-I/R plasma nitrate (p > 0.5 vs. saline) and diameter of LRA (p > 0.5 vs. baseline). At 15 minutes of reperfusion, FMD was significantly decreased in the saline group as compared to baseline (absolute dilation: 0.08 +/- 0.03 vs. 3.02 +/- 0.8 mm, respectively, p < 0.01; percentage dilation: 3 +/- 0.6 vs. 8 +/- 0.6%, respectively, p < 0.001), but it remained unaffected in the BK group (absolute dilation: 3.06 +/- 0.9 vs. 3.27 +/- 0.8 mm, respectively, p > 0.5; percentage dilation: 7 +/- 0.7 vs. 8 +/- 0.8%, respectively, p > 0.5). A similar trend was observed with regard to plasma nitrate, which remained unchanged in the BK group (37.01 +/- 4.14 vs. 39.14 +/- 4.49 micromol/L, p > 0.5) but decreased in the saline group (35.91 +/- 3.03 vs. 28.91 +/- 2.81 micromol/L, p < 0.1). Infusion of BK could protect the arterial endothelial function against I/R injury in humans, possibly in part by preserving the endothelial NO availability. The findings support the use of BK in the prevention of tissue injury due to I/R and might reveal an additional mechanism whereby ACE inhibitors exert their preconditioning effects on myocardium.


Change of glucagon reacting to 30 K antibody in totally depancreatized dogs.
Total pancreatectomy was performed in dogs; and arginine test was conducted at the first, second and third weeks after surgery, and measurement was made of blood glucose, glucagon and insulin on a time-course basis for a comparative study with normal dogs. 1) After total pancreatectomy, glucagon reacting to 30 K antibody decreased once but increased with the lapse of time when no insulin was administered. 2) In the arginine test, glucagon showed a biphasic reaction in normal dogs, but a monophasic reaction in totally depancreatized dogs. This reaction declined three weeks after surgery. 3) When blood samples were taken from the pancreaticoduodenal vein, the left-gastroepiploic and mesenteric veins, during and after arginine was infused for 30 minutes. Glucagon in the pancreaticoduodenal vein increased markedly, but there were no such prominent changes in the left-gastroepiploic or mesenteric veins, Meanwhile, the level of glucagon in the left-gastroepiploic vein increased remarkably in dogs one week after total pancreatectomy.


Inflammation and post-operative recovery in patients undergoing total knee arthroplasty-secondary analysis of a randomized controlled trial.
Reduced function persists for many patients after total knee arthroplasty (TKA). Inflammation is part of osteoarthritis' pathophysiology, and surgery induces a marked inflammatory response. We therefore wanted to explore the role of inflammation in long-term recovery after TKA, and thus conducted this secondary analysis of our randomized controlled trial (RCT) of physical rehabilitation ± progressive strength training (PST). We aimed to investigate whether (1) inflammation is associated with functional performance, knee-extension strength, and knee pain before TKA; (2) PST affects inflammation, and the inflammatory state over time; (3) baseline or surgery-induced inflammation modifies the effect of rehabilitation ± PST on change in 6-min walk test (Δ6MWT); and (4) baseline or surgery-induced inflammation is associated with Δ6MWT following TKA. In the primary trial report's per-protocol analysis, 72/82 patients were included. Sixty had ≥1 blood sample before and after TKA, and were included in this secondary analysis. Inflammation was measured by interferon γ-inducible protein (IP)-10, soluble urokinase plasminogen activator receptor (suPAR), interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α at baseline; day 1, week 4, 8, and 26 after TKA. At baseline, suPAR (P = 006) was negatively associated with 6MWT. Neither baseline nor surgery-induced inflammation modified the response to rehabilitation ± PST. Only surgery-induced IL-10 was associated with Δ6MWT26 weeks-baseline (P = 0.001), also adjusted for 6MWTbaseline, age, sex and body mass index (BMI). In this secondary analysis, only increased surgery-induced IL-10 response was associated with decreased long-term functional performance after TKA. The importance of controlling the surgery-induced immune response remains to be investigated further. NCT01351831.