Involvement of N-terminally truncated variants of p73, deltaTAp73, in head and neck squamous cell cancer: a comparison with p53 mutations.
p73, a p53-related gene, encodes two classes of isoforms with opposing functions: (1) a full-length transactivation-competent p73 protein (TAp73) with tumour suppressor activity; and (2) a group of NH2-terminally truncated, transactivation-deficient p73 proteins, deltaEx2p73, deltaEx2-3p73, deltaNp73 and deltaN'p73 (collectively named deltaTAp73) with oncogenic activity. In this study, for the first time, we analyse the deregulations of TAp73 and deltaTAp73 in head and neck squamous cell cancer (HNSCC) and compare them to p53 status. We found that all the p73 isoforms in HNSCC tissue were upregulated with respect to those in normal adjacent tissue. Concomitant upregulations of p73 transcripts were often found in cancer tissue but not in normal tissue. p53 mutations and p73 transcript alterations are not mutually exclusive. All the HNSCC specimens studied had at least one p53 mutation and/or one deltaTAp73 transcript alteration. Although both the deltaNp73 and the TAp73 transcripts were found to be upregulated in head and neck cancers, the predominant protein in the cancers analysed was deltaNp73. TAp73, in contrast, was only weakly expressed. This finding is highly relevant and sheds light on the puzzling question of the biological significance of TAp73 upregulation in cancers. deltaNp73 protein levels were significantly overexpressed in HNSCC tissue compared to matched normal tissue (p = 0.003). Furthermore, a trend was found for better overall survival in patients with a low expression of deltaNp73. Our results show that the deregulation of both the p53 and the p73 pathways plays an important role in inducing head and neck cancers.


Tilting Styx and Nix but not Uranus with a Spin-Precession-Mean-motion resonance.
A Hamiltonian model is constructed for the spin axis of a planet perturbed by a nearby planet with both planets in orbit about a star. We expand the planet-planet gravitational potential perturbation to first order in orbital inclinations and eccentricities, finding terms describing spin resonances involving the spin precession rate and the two planetary mean motions. Convergent planetary migration allows the spinning planet to be captured into spin resonance. With initial obliquity near zero, the spin resonance can lift the planet's obliquity to near 90 or 180 degrees depending upon whether the spin resonance is first or zero-th order in inclination. Past capture of Uranus into such a spin resonance could give an alternative non-collisional scenario accounting for Uranus's high obliquity. However we find that the time spent in spin resonance must be so long that this scenario cannot be responsible for Uranus's high obliquity. Our model can be used to study spin resonance in satellite systems. Our Hamiltonian model explains how Styx and Nix can be tilted to high obliquity via outward migration of Charon, a phenomenon previously seen in numerical simulations.


Covariant maturation of nocifensive oral behaviour and c-fos expression in rat superior colliculus.
Injections of formalin into the rodent paw elicit a rapid orientation of the head and mouth to the source of discomfort, followed by licking and biting the injected area. Previous work has shown this response is dependent on the integrity of the midbrain superior colliculus. The present experiments were initiated to examine the ontogeny of this oral nocifensive reaction and to determine whether it is correlated with the functional maturation of collicular responses to noxious stimuli (as indicated by c-fos immunohistochemistry). Rat pups at various postnatal ages received formalin injections in either the hindpaw or perioral regions. Behaviour was videotaped, and after 120 min, animals were killed and the brain and spinal cord processed for Fos-like immunoreactivity. Uninjected controls were treated identically. Formalin-induced oral responses following injections into the hindpaw and the expression of Fos in the superior colliculus were virtually absent until 10 days postnatal, despite the presence of Fos-like immunoreactivity in many other structures (e.g. spinal cord, parabrachial area, periaqueductal grey). In contrast, animals from day 1 were able to use limbs to localise the perioral injection site. From day 10 onward, there was a progressive increase in oral nocifensive behaviours and Fos expression in the superior colliculus. Our observations are consistent with the hypothesis that the normal elaboration of pain-induced oral behaviour is initiated only after a functionally active superior colliculus has developed, and support previous observations that link the colliculus particularly with oral nocifensive behaviours.


Comprehensive assessment of ECM turnover using serum biomarkers establishes PBC as a high-turnover autoimmune liver disease.
Primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are phenotypically distinct autoimmune liver diseases that progress to cirrhosis and liver failure; however, their histological fibrosis distribution differs. We investigated the extracellular matrix (ECM) profiles of patients with PSC, PBC, and AIH to establish whether the diseases display differential patterns of ECM turnover. Serum samples were retrospectively collected from the UK (test cohort; PSC n = 78; PBC n = 74; AIH n = 58) and Norway (validation cohort; PSC n = 138; PBC n = 28; AIH n = 27). Patients with ulcerative colitis without liver disease (n = 194) served as controls. We assessed specific serological biomarkers of ECM turnover: type III and V collagen formation (PRO-C3, PRO-C5), degradation of type III and IV collagen (C3M, C4M), biglycan (BGM) and citrullinated vimentin (VICM). Most of the ECM markers showed elevated serum levels in PBC compared with PSC or AIH (p <0.01). PRO-C3 correlated well with liver stiffness and showed the most striking differences between advanced and non-advanced liver disease; several of the other ECM markers were also associated with stage. PRO-C3 and other ECM markers were inversely associated with ursodeoxycholic acid treatment response in PBC and remission in AIH. All ECM remodelling markers were significantly elevated (p <0.05) in patients with PSC, PBC, or AIH compared with ulcerative colitis. In this first study comparing ECM turnover in autoimmune liver diseases, we found increased ECM turnover in PBC compared with either PSC or AIH. The study indicates that ECM remodelling is different in PSC, PBC, and AIH, suggesting differing opportunities for therapeutic intervention. The level of scarring is linked to prognosis in autoimmune liver diseases such as primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis; hence, the scarring process is a possible target for novel therapy. Investigating the scarring process using highly specific technology, we show that the scarring process is different between the 3 autoimmune liver diseases, and this may have important implications for the development of medical treatment.


Navigating the complexity of chronic HIV-1 associated immune dysregulation.
Despite successful viral suppression with antiretroviral therapy, chronic HIV-1 infection is associated with ongoing immune dysfunction. Investigation of the complex immune response in treated and untreated individuals with chronic HIV-1 infection is warranted. Immune alterations such as monocyte phenotype and Th-17/Treg ratios often persist years after the reduction in viraemia and predispose many individuals to long-term comorbidities such as cardiovascular disease or cancer. Furthermore, while there has been extensive research on the latent reservoir of treated patients with chronic HIV-1, which prevents the discontinuation of treatment, the mechanism behind this remains elusive and needs further investigation. In this review, we assist in navigating the recent research on these groups of individuals and provide a basis for further investigation.


Prediction of the functional refractory period of the atrioventricular node.
Based on the new description of AV-nodal conductivity from our laboratory, we developed an equation which describes AV-nodal conduction time in the dog heart at all coupling intervals. This allows us to predict the functional refractory period (FRP) of the AV-node based on the AV-nodal conduction times of only five extra stimuli having relatively long coupling intervals. The equation predicted the FRP within acceptable limits when compared to values obtained by the classical technique in which the full range of extrasystolic intervals must be tested. Changes in FRP after the administration of antiarrhythmic drugs (lidocaine and quinidine) or due to changes in heart rate were predicted accurately. The ease and accuracy of the present method could allow determination of FRP in a short time.


Phytic acid decreases deoxynivalenol and fumonisin B1-induced changes on swine jejunal explants.
The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters on intestinal explants exposed to deoxynivalenol (DON) and fumonisin B1 (FB1). The jejunal explants were exposed for 4 h to different treatments: control, DON (10 μM), DON plus 2.5 mM or 5 mM IP6, FB1 (70 μM), and FB1 plus 2.5 mM or 5 mM IP6. Both mycotoxins induced significant intestinal lesions and decreased villi height. The presence of 2.5 mM and 5 mM IP6 significantly inhibited the morphological changes caused by the mycotoxins. DON induced a significant increase in caspase-3 (83%) and cyclooxygenase-2 (71.3%) expression compared with the control. The presence of 5 mM IP6 induced a significant decrease in caspase-3 (43.7%) and Cox-2 (48%) expression compared with the DON group. FB1 induced a significant increase in caspase-3 expression (47%) compared to the control, whereas IP6 induced no significant change in this expression. A significant decrease in cell proliferation was observed when explants were exposed to 5 mM of IP6 in comparison with the DON and FB1 groups. The present data provide evidence that phytic acid modulates the toxic effects induced by DON and FB1 on intestinal tissue.


Diagnostic performance and safety of a three-dimensional 14-core systematic biopsy method.
To investigate the diagnostic performance and safety of a three-dimensional 14-core biopsy (3D14PBx) method, which is a combination of the transrectal six-core and transperineal eight-core biopsy methods. Between December 2005 and August 2010, 1103 men underwent 3D14PBx at our institutions and were analysed prospectively. Biopsy criteria included a PSA level of 2.5-20 ng/mL or abnormal digital rectal examination (DRE) findings, or both. The primary endpoint of the study was diagnostic performance and the secondary endpoint was safety. We applied recursive partitioning to the entire study cohort to delineate the unique contribution of each sampling site to overall and clinically significant cancer detection. Prostate cancer was detected in 503 of the 1103 patients (45.6%). Age, family history of prostate cancer, DRE, PSA, percentage of free PSA and prostate volume were associated with the positive biopsy results significantly and independently. Of the 503 cancers detected, 39 (7.8%) were clinically locally advanced (≥cT3a), 348 (69%) had a biopsy Gleason score (GS) of ≥7, and 463 (92%) met the definition of biopsy-based significant cancer. Recursive partitioning analysis showed that each sampling site contributed uniquely to both the overall and the biopsy-based significant cancer detection rate of the 3D14PBx method. The overall cancer-positive rate of each sampling site ranged from 14.5% in the transrectal far lateral base to 22.8% in the transrectal far lateral apex. As of August 2010, 210 patients (42%) had undergone radical prostatectomy, of whom 55 (26%) were found to have pathologically non-organ-confined disease, 174 (83%) had prostatectomy GS ≥7 and 185 (88%) met the definition of prostatectomy-based significant cancer. This is the first prospective analysis of the diagnostic performance of an extended biopsy method, which is a simplified version of the somewhat redundant super-extended three-dimensional 26-core biopsy. As expected, each sampling site uniquely contributed not only to overall cancer detection, but also to significant cancer detection. 3D14PBx is a feasible systematic biopsy method in men with PSA <20 ng/mL.


Short chain fatty acids stimulate insulin secretion and reduce apoptosis in mouse and human islets in vitro: Role of free fatty acid receptor 2.
To evaluate the role of free fatty acid receptor 2 (FFAR2)/G-protein coupled receptor 43 in mediating the effects of the short chain fatty acids (SCFAs) sodium acetate (SA) and sodium propionate (SP) on islet function in vitro, and to identify the intracellular signalling pathways used in SCFA-induced potentiation of glucose-induced insulin secretion. Islets of Langerhans were isolated from wild-type and FFAR2-/- mice and from human donors without diabetes. The effects of SA and SP on dynamic insulin secretion from perifused islets were quantified by radioimmunoassay, signalling downstream of SCFAs was profiled by single-cell calcium microfluorimetry, and measurement of cAMP was performed using a fluorescence assay. Islet apoptosis was induced by exposure to cytokines or sodium palmitate, and the effects of SA and SP in regulating islet apoptosis were assessed by quantification of caspase 3/7 activities. Deletion of FFAR2 did not affect islet morphology or insulin content. SA and SP reversibly potentiated insulin secretion from mouse islets in a FFAR2-dependent manner. SCFA-induced potentiation of insulin secretion was coupled to Gq activation of phospholipase C and protein kinase C, with no evidence of Gi-mediated signalling. SA and SP protected human and mouse islets from apoptosis, and these pro-survival properties were dependent on islet expression of FFAR2. Our results indicate that FFAR2 directly mediates both the stimulatory effects of SA and SP on insulin secretion and their protection against islet apoptosis. We have also shown that SCFA coupling in islets occurs via Gq-coupled intracellular signalling.


Association of number of follow-up providers with outcomes in survivors of hematologic malignancies.
Studies examining follow-up care among cancer survivors have increased in number, and are mostly focused on who best provides care. It is not known whether having single or multiple physicians as follow-up providers has outcome implications. We prospectively studied the association between number of follow-up providers among survivors of hematologic malignancies and serious medical utilization (defined as emergency room visits or hospitalizations) within a 6-month period. Patients completing treatment (n = 314) were included. Patients seeing multiple follow-up providers were more likely to be younger, to reside farther away from the university hospital, to have prescription drug insurance, to have received prior cancer treatment, to have multiple myeloma, and to have undergone hematopoietic cell transplant as a part of cancer treatment. Multivariate analysis showed that the number of follow-up providers was not associated with serious medical utilization (odds ratio 1.29, 95% confidence interval 0.68–2.48, p = 0.44) after adjusting for patient factors. Our study showed that among survivors of hematologic malignancies, outcomes were not different for survivors who were seen by single or multiple follow-up providers.


PPARγ/LXRα axis mediated phenotypic plasticity of lung fibroblasts in silica-induced experimental silicosis.
Silicosis is a disease mainly caused by pulmonary interstitial fibrosis caused by long-term inhalation of dust with excessively high content of free SiO2. Transdifferentiation of lung fibroblasts into myofibroblasts is an important cellular basis for silicosis, but the key transcription factors (TFs) involved in this process are still unclear. In order to explore the biological regulation of transcription factor PPARγ/LXRα in silica-induced pulmonary fibrosis, this study explored the molecular mechanism of PPARγ/LXRα involved in regulating transcription factors related to SiO2-induced lung injury at the cellular level and in animal models. ChIP-qPCR detected that PPARγ directly regulated the transcriptional activity of the LXRα gene promoter, while the PPARγ agonist RSG increased the expression of LXRα. In addition, we demonstrated in the cell model that upregulation of LXRα can inhibit silica-mediated fibroblast transdifferentiation, accompanied by an increase in the expression of SREBF1, PLTP and ABCA1. The results of LXRα silencing experiment matched those of overexpression experiment. These studies explored the role of LXRα in plasticity and phenotypic transformation between lung fibroblasts and myofibroblasts. Therefore, inhibiting or reversing the transdifferentiation of lung fibroblasts to myofibroblasts by intervening PPARγ/LXRα may provide a new therapeutic target for the treatment of silicosis.


Neurophysiological Deficits During Reappraisal of Negative Emotional Stimuli in Opioid Misuse.
Opioid misuse is hypothesized to compromise the ability to regulate negative emotions, as manifested through visceral and peripheral physiological signals. However, neurophysiological impairment of top-down cognitive emotion regulation in opioid misuse has not previously been shown. Patients with chronic pain who had been taking opioids for 90 days or longer (N = 149; female, n = 98) underwent a negative emotion regulation task with electroencephalography. Participants were instructed to view or reappraise negative images presented for 3 seconds. Using a validated cutoff score on the Current Opioid Misuse Measure, participants were classified as exhibiting aberrant drug-related behavior consistent with opioid misuse (MISUSE+) or as being low risk for opioid misuse (MISUSE-). Participants reported their craving in response to negative emotions over the past week. We observed a group × condition interaction (p = .003) such that the MISUSE- group decreased the late positive potential of the electroencephalography during reappraisal, whereas the MISUSE+ group showed increased late positive potential during reappraisal. This deficit in negative emotion regulation remained significant after controlling for an array of potential confounding variables, including opioid dose, pain, and depression. Heightened late positive potential during reappraisal was associated with more severe opioid craving. Opioid misuse may occasion top-down deficits in emotional regulation that begin as early as 400 ms after presentation of negative stimuli. It remains unknown whether emotion dysregulation is the cause, correlate, or consequence of opioid misuse. Nonetheless, targeting emotion dysregulation in opioid misuse with reappraisal-focused interventions may represent an important treatment approach.


Simultaneous measurement of doxorubicin and reduced metabolite doxorubicinol by UHPLC-MS/MS in human plasma of HCC patients treated with TACE.
A sensitive, selective, accurate and precise method for simultaneous quantification of doxorubicin (DOX) and doxorubicinol (DOXol) in human plasma of patients diagnosed as having intermediate stage unresectable hepatocellular carcinoma (HCC) was developed. The method was based on electrospray tandem mass spectrometry in selected reaction monitoring mode. DOX, DOXol and trofosfamide, an internal standard, were extracted from plasma by using a simple solid phase extraction (SPE) procedure after the addition of 0.1 M hydrochloric acid. A 200-μL aliquot of the extracted sample reconstituted in mobile phase was analyzed on a Zorbax SB-C18 UHPLC column (50 mm × 2.1 mm, 1.8 μm particle size) in 8 min. The mobile phase consisted of acetonitrile and 0.1% formic acid pH 4.5 (95:05 v/v). Good accuracy and precision of this method were demonstrated by determination of spiked plasma QC samples in four consecutive days. The SPE extraction recoveries ranged from 72.3 to 77.3% and 75.5 to 98.4% for doxorubicin and doxorubicinol, respectively. The intra-day and inter-day precisions were less than 11.4%. The limit of quantitation was 1.0 ng/mL for both compounds. The calibration curves of DOX and DOXol were analyzed by weighted linear regression with 1/x as a weighting factor. They were linear over the concentration range of 1.0-100.0 ng/mL with R(2) greater than 0.99. This developed method was successfully applied to study plasma pharmacokinetics in patients affected by HCC and treated with transarterial chemoemolization practices (TACEs) using HepaSphere™ pre-loaded with DOX in a standardized procedure.


Effects of kangaroo rat exclusion on vegetation structure and plant species diversity in the Chihuahuan Desert.
Long-term (1977-90) experimental exclusion of three species of kangaroo rats from study plots in the Chihuahuan Desert resulted in significant increases in abundance of a tall annual grass (Aristida adscensionis) and a perennial bunch grass (Eragrostis lehmanniana). This change in the vegetative cover affected use of these plots by several other rodent species and by foraging birds. The mechanism producing this change probably involves a combination of decreased soil disturbance and reduced predation on large-sized seeds when kangaroo rats are absent. Species diversity of summer annual dicots was greater on plots where kangaroo rats were present, as predicted by keystone predator models. However, it is not clear whether this was caused directly by activities of the kangaroo rats or indirectly as a consequence of the increase in grass cover. No experimental effect on species diversity of winter annual dicots was detected. Our study site was located in a natural transition between desert scrub and grassland, where abiotic conditions and the effects of organisms may be particularly influential in determining the structure and composition of vegetation. Under these conditions kangaroo rats have a dramatic effect on plant cover and species composition.


Electrochemical immunosensor based on multi-order Rubik's cube-type platinum nickel nanocubes and Au NPs/cPDA NTs for detection of CEA.
Herein, an innovative sandwich-type electrochemical immunosensor based on multi-order Rubik's cube-type platinum nickel nanocubes and Au NPs/cPDA NTs was used for the ultrasensitive detection of carcinoembryonic antigen (CEA). In this process, an appropriate amount of uniformly dispersed gold nanoparticles (Au NPs) was effectively immobilized on nitrogen riched carbonized polydopamine nanotubes (cPDA NTs) through Au-N bonds, avoiding the stacking and agglomeration of Au NPs, thereby enhancing the conductivity. Subsequently, multi-order Rubik's cube-type platinum nickel nanocubes (PtNi NCs), composed of numerous small interlaced nanocubes, was successfully prepared to immobilize the secondary antibodies (Ab2) effectively. Due to its inherent hierarchical architectures and high density of active sites, PtNi NCs exhibited excellent mass and electron transfer performance towards the reduction of hydrogen peroxide (H2O2) for amplifying the current signal to detect CEA. The rationally designed immunosensor presented a broad linear ranging from 50 fg mL-1 to 100 ng mL-1 and a low limit of detection of 17.78 fg mL-1 (S/N = 3) for CEA determination under optimal conditions. Furthermore, the as-fabricated immunosensor exhibited excellent selectivity, reproducibility and stability, which can be extended to accurate and sensitive detection of other biomarkers.


Lymphocytic mastitis mimicking breast carcinoma, radiology and pathology correlation: review of two cases.
Lymphocytic mastitis, or diabetic mastopathy, is an unusual finding in early-onset and long-standing diabetes. It can presents as a non-tender or tender palpable breast mass. Mammogram and ultrasound frequently demonstrate findings suspicious of malignancy, thus biopsy and histological confirmation is usually required. We reviewed two cases of lymphocytic mastitis with characteristics findings on mammogram, ultrasound, and histopathology. Diagnoses were confirmed with excision biopsy.


Metabolism in Huntington's disease: a major contributor to pathology.
Huntington's disease (HD) is a progressively debilitating neurodegenerative disease exhibiting autosomal-dominant inheritance. It is caused by an unstable expansion in the CAG repeat tract of HD gene, which transforms the disease-specific Huntingtin protein (HTT) to a mutant form (mHTT). The profound neuronal death in cortico-striatal circuits led to its identification and characterisation as a neurodegenerative disease. However, equally disturbing are the concomitant whole-body manifestations affecting nearly every organ of the diseased individuals, at varying extents. Altered central and peripheral metabolism of energy, proteins, nucleic acids, lipids and carbohydrates encompass the gross pathology of the disease. Intense fluctuation of body weight, glucose homeostasis and organ-specific subcellular abnormalities are being increasingly recognised in HD. Many of these metabolic abnormalities exist years before the neuropathological manifestations such as chorea, cognitive decline and behavioural abnormalities develop, and prove to be reliable predictors of the disease progression. In this review, we provide a consolidated overview of the central and peripheral metabolic abnormalities associated with HD, as evidenced from clinical and experimental studies. Additionally, we have discussed the potential of metabolic biomolecules to translate into efficient biomarkers for the disease onset as well as progression. Finally, we provide a brief outlook on the efficacy of existing therapies targeting metabolic remediation. While it is clear that components of altered metabolic pathways can mark many aspects of the disease, it is only conceivable that combinatorial therapies aiming for neuronal protection in consort with metabolic upliftment will prove to be more efficient than the existing symptomatic treatment options.


Secondary malignant giant cell tumor of bone due to malignant transformation 40 years after surgery without radiation therapy, presenting as fever of unknown origin: a case report.
Malignant transformation of giant cell tumors of bones, that is, secondary malignant giant cell tumor of bone, is rare. The most common symptoms are local pain and swelling. There are no prior reports of giant cell tumor of bone with fever of unknown origin at the onset. Here we present a case of a secondary malignant giant cell tumor of bone due to malignant transformation 40 years after surgery without radiation therapy, presenting as fever of unknown origin. A 75-year-old Asian man presented with a 3-week history of continuous pyrexia and left knee pain and swelling. He had been diagnosed at age 35 years with a giant cell tumor of bone of his left distal femur and underwent bone curettage and avascular fibula grafting at that time. Postoperative radiation therapy was not performed. He remained recurrence-free for 40 years after surgery. At age 75, histopathological findings suggested a secondary malignant giant cell tumor of bone. The tumor specimen expressed tumor necrosis factor-α. Neoplastic fever was suspected, and a naproxen test was conducted. His pyrexia showed immediate resolution. Surgery was performed under a diagnosis of a secondary malignant giant cell tumor of bone with neoplastic fever. His pyrexia and inflammatory activities diminished postoperatively. This is the first reported case, to the best of our knowledge, of the detection of a secondary malignant giant cell tumor of bone based on fever of unknown origin after long-term (40 years) follow-up. After curettage and bone grafting, giant cell tumor of bone may transform to malignancies within a few years or even decades after surgery. Therefore, meticulous follow-up is essential. The fever might be attributable to the tumor releasing inflammatory cytokines. Not only pain and swelling but also continuous pyrexia may suggest the diagnosis of a secondary malignant giant cell tumor of bone.


Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis.
High-dose chemotherapy with autologous stem cell rescue has been proposed as an intensive therapy for severe rheumatoid arthritis (RA). In view of previous observations of abnormal haemopoiesis in RA patients, the composition and function of peripheral blood stem cell harvests (PBSCH) was investigated. Compared with PBSCH from healthy allogeneic donors mobilized with the same dose of G-CSF (filgrastim; 10 microg/kg/d, n = 14), RA PBSCH (n = 9) contained significantly fewer mononuclear cells (375 v 569 x 10(6)/kg, P = 0.03) and CD34+ cells (2.7 v 5.8 x 10(6)/kg, P = 0.003). However, there were increased proportions of CD14+ cells (P = 0.006) and CD14+ CD15+ cells (the phenotype of previously described 'abnormal' myeloid cells, P = 0.002) in the RA PBSCH which translated into 3.5- and 7-fold increases respectively on a per CD34+ cell basis. There were no differences in T-cell activation status as judged by proportions of CD4+ and CD8+ expressing CD45RA, CD45RO, HLA-DR and CD28 (RA PBSCH, n = 7, donor PBSCH, n = 5, P = 0.2-0.7). Phytohaemagglutinin responses determined fluorocytometrically with induction of CD69 expression were reduced in CD4+ and CD8+ cells following filgrastim administration in 3/3 RA patients tested. Compared with bone marrow as a potential source of CD34+ cells, PBSCH contained 11-fold more T cells (P < 0.0005), 8-fold more B cells (P < 0.0005) and 4-fold more monocytes (P = 0.02). In short-term methylcellulose culture there were no differences in colony counts (CFU-GM, CFU-GEMM, BFU-E) per CD34+ cell from PBSCH from RA patients (n = 11) and healthy donors (n = 10). Long-term culture initiator cells were cultured successfully from cryopreserved PBSCH from RA patients (n = 9). In conclusion, PBSCH from RA patients differed significantly in composition from normal individuals, but in vitro studies support normal stem and progenitor cell function. Changes in T-cell function occur during mobilization in RA patients. This work provides reassurance for the use of PBSCH as haematological rescue and baseline data for clinical trials of graft manipulation strategies in patients with RA.


Gastrin and EGF synergistically induce cyclooxygenase-2 expression in Swiss 3T3 fibroblasts that express the CCK2 receptor.
Over-expression of cyclooxygenase-2 (COX-2) has been demonstrated to be tumorigenic in transgenic mice. Chronic treatment with NSAIDs is chemoprotective for colorectal cancer. Gastrin is a growth factor for gastric mucosa and has been shown to promote proliferation of colorectal cells. Recent studies suggest that COX-2 expression levels could mediate the growth effects of gastrin. Here, we report that gastrin increased PGE2 secretion in Swiss 3T3 cells expressing the CCK2 receptor. Gastrin dose dependently induced COX-2 protein levels in a time dependent manner. COX-2 mRNA levels were rapidly induced by a dose dependent increase in gastrin. Prior treatment of the cells with the CCK2 receptor specific antagonist, L365,260, inhibited gastrin-induced COX-2 protein and mRNA expression. Pretreatment with L364,714, the CCK1 receptor specific antagonist did not block COX-2 induction by gastrin. Inhibition of de novo protein synthesis by cycloheximide did not block COX-2 mRNA induction by gastrin. Also, gastrin-dependent COX-2 expression did not require PKC activity, activation of ERK, or transactivation of EGFR. However, co-stimulation with EGF and gastrin synergistically induced COX-2 protein and mRNA expression and PGE2 secretion. Measurements of COX-2 mRNA stability and COX-2 gene transcription reveal that EGF significantly increased the half-life of COX-2 mRNA with only a slight increase in the COX-2 transcription rate. Conversely, gastrin significantly increased COX-2 gene transcription rates but did not enhance COX-2 mRNA stability.


An integrated microfluidic platform for magnetic microbeads separation and confinement.
An innovative microfluidic platform for magnetic beads manipulation is introduced, consisting of novel microfabricated 3D magnetic devices positioned in a microfluidic chamber. Each magnetic device comprises of an embedded actuation micro-coil in various design versions, a ferromagnetic pillar, a magnetic backside plate and a sensing micro-coil. The various designs of the micro-coils enable efficient magnetic beads trapping and concentration in different patterns. The finite element analysis (FEA) results show a significant increase of the developed force on suspended magnetic beads when the magnetic pillar and backside plate were integrated into the device structure. These simulation results were confirmed experimentally by measuring the magnetic beads trapping ratios for the different designs and structures of the devices under continuous flow conditions. The trapping ratios and profiles were studied using beads counting, measuring the change of inductance with the sensing micro-coil and by image processing. The devices have efficiently demonstrated a controlled and localized magnetic beads trapping and concentration at small spatial locations for the first time. The new results shown in this study demonstrate the feasibility of efficiently using these original devices as key elements in complex bio-analysis systems.


Negatively charged nano-hydroxyapatite can be used as a phosphorus fertilizer to increase the efficacy of wollastonite for soil cadmium immobilization.
Improper application of phosphorus (P) fertilizer during soil cadmium (Cd) immobilization reduces the efficiency of fertilizer and Cd remediation. In this study, we synthesized three types of nano-hydroxyapatite (NHAP) with different surface charges as slow-release P fertilizers during Cd immobilization. We also evaluated the effects of wollastonite application with or without NHAP addition, in comparison with triple superphosphate (TSP) or bulk hydroxyapatite, on Cd accumulation in Amaranthus tricolor L. The results showed that adding wollastonite significantly reduced P availability (23.5%) in the soil, but it did not inhibit plant P uptake. In wollastonite-amended soil, the application of negatively/positively charged NHAP significantly increased plant biomass by 643-865% and decreased Cd uptake by 74.8-75.1% compared to the unamended soil as well as showed greater efficiency than those with TSP. This was ascribed to the increased soil pH (from 3.94 to 6.52-6.63) and increased abundance of organic acids (including citric acid, malic acid, lactic acid, and acetic acid) secreted by plants. In addition, the P-preferring bacterial class Bacteroidia was specific to soils amended with both wollastonite and NHAP-. These results suggest that NHAP- may be an appropriate P fertilizer for soil Cd immobilization using wollastonite.


Cell surface antigens on avian erythroid cells. Their expression at various stages of cell differentiation.
Chicken erythroblasts transformed by a temperature-sensitive erythroblastosis virus (tsAEV) can terminally differentiate at the non-permissive temperature (42 degrees C). Morphological changes, as well as production of hemoglobin were shown to occur during maturation. The above system, as well as fractions of normal bone marrow cells were used to study the expression of cell surface antigens on erythroid cells. Four distinct reactivities were found with monoclonal antibodies (MAbs) and polyvalent sera: The MAb 4.5A5 was found to react with erythroblasts only. The MAb 4-M-12-26 reacted with tsAEV erythroblasts shifted to the non-permissive temperature (42 degrees C). The MAb 4.6C1 reacted weakly with erythroblasts and strongly with reticulocytes. The anti-Ery sera reacted with reticulocytes and erythrocytes. In addition the reactivity of MAb 4-M-12-26 was found only on virus-producing erythroblasts, though this MAb was found to react with myeloid cells which produce a helper virus of the same class.


Pentosidine effects on human osteoblasts in vitro.
Osteoporosis, a multifactorial and progressive skeletal metabolic disease, is characterized by low-mass density and structural deterioration of bone micro-architecture that leads to enhanced bone fragility and increased susceptibility to fractures. Recently, it has been proposed that age-related bone loss could be correlated with the glycoxidative process. The aim of the present study was to investigate the in vitro effects of pentosidine, a glycoxidative end product, on human osteoblasts (HOb). The mineralization rate, the specific bone markers (alkaline phosphatase [ALP], collagen Ialpha1 [COL Ialpha1], osteocalcin [BGP]), and the human receptor for advanced glycation end products (RAGE) gene expression have been evaluated. Pentosidine incubation of HOb caused a significant decrease in ALP, Col Ialpha1, and RAGE mRNA levels, but only the RAGE gene expression decreased with no dose dependency. Moreover, pentosidine incubation of osteoblasts hampered the formation of bone nodules. No effect was observed on BGP gene expression under all experimental conditions. Our data gives further support to a detrimental effect of AGEs on bone that leads to functional alterations of osteoblasts. This study addresses a crucial role of protein glycoxidation in the bone mineralization process. AGEs formation and accumulation in bone may be one of the first pathogenetic steps of bone remodeling in aging and in age-related diseases, leading to enhanced bone mass loss.


Endovascular treatment of traumatic penile arteriospongious fistula in a patient with erectile dysfunction: a case report and literature review.
An arteriovenous fistula is an abnormal communication between an artery and a vein. Traumatic penile arteriospongious fistula is a rare complication and has been described as a cause of erectile dysfunction. Clinical evaluation of patients with erectile dysfunction after penile trauma includes a thorough history, physical examination, vascular assessment, and other complementary exams. Treatment consists of endovascular embolization, surgical ligation, or a combination of both techniques. A 40-year-old man presented with erectile dysfunction that had persisted since suffering blunt trauma a few months ago. He reported problems with short duration of erection and insufficient penile tumescence. Due to high suspicion of an arteriovenous fistula, he was referred to angiography, which confirmed the diagnosis of an abnormal connection between the pudendal vessels. The patient was treated with the coil embolization technique and the symptoms were successfully resolved after endovascular treatment. The appearance of a post-traumatic arteriospongious fistula is a rare complication with almost non-existent literature reported. Rapid development in endovascular techniques, in which we use embolic agents to block anomalous blood flow, has allowed safe, effective and less invasive alternative to surgery. Our case demonstrates that endovascular approach is a successful treatment for post-traumatic arteriospongious fistula since the symptoms were resolved, and normal erectile function was regained after the intervention.


[Is cancer a transmittable disease?].
A direct, horizontal and natural transmission of neoplasic cells has only recently been accepted by the biomedical community. There are three known examples in mammals: the Tasmanian Devil Tumor Disease, the Canine Transmissible Venereal Tumor and a similar disease in Sirian Hamsters. These diseases are not anecdotic cases only, but provide support for the cancer clonal evolution hypothesis.


Bladder growth and development after complete primary repair of bladder exstrophy in the newborn with comparison to staged approach.
We assessed bladder growth and dynamics following complete primary repair of bladder exstrophy (CPRE) compared to the staged approach. We reviewed the records of 16 boys and 7 girls who underwent CPRE within 3 days of life from 1996 to 2004 and compared them to the records of 8 boys and 6 girls treated with a staged repair from 1979 to 1996. Screening methods included voiding cystourethrogram, radionuclide cystogram and urodynamic study. We estimated growth curves for bladder capacity following repair in each group, and compared percent predicted bladder capacity (PPBC), compliance and detrusor overactivity between the CPRE and staged repair groups following bladder neck reconstruction. Bladder capacity in the staged repair group was 69.8 ml (95% CI 46.7-104.4) immediately after bladder neck reconstruction and increased by 15.0% per year thereafter (95% CI 6.2-24.5, p = 0.002). In the CPRE group bladder capacity was 29.0 ml (95% CI 21.3-39.5) initially and increased by 28.9% per year thereafter (95% CI 17.4-41.5, p <0.001). PPBC started at 45.6% (95% CI 35.7-55.5) and increased 1.2% per year (95% CI -1.1-3.5, p = 0.29) following repair for all genders and surgery groups. Compliance was 124.4% (95% CI 22.6-310.7, p = 0.01) greater in the CPRE group at all times following repair. Detrusor overactivity was present in 0 of 19 patients in the CPRE group and 6 of 13 (46%) in the staged group (exact p = 0.002). Within the CPRE group bladder stability was universal, and sphincter electromyography was normal suggesting no neuromuscular compromise of the pelvic floor. At early followup, our results suggest that PPBC is equivalent irrespective of gender or management. Further objective evaluation is needed in both groups.


Thioredoxin-like 6 protects retinal cell line from photooxidative damage by upregulating NF-kappaB activity.
Apoptosis is the common pathway to photoreceptor cell death in many eye diseases including age-related macular degeneration which affects more than 8 million individuals in the United States alone. RdCVF, a truncated mouse thioredoxin is specifically expressed by rod photoreceptor cells and prevents the apoptosis of cone cells. However the protective mechanism of RdCVF and the implications of its human homologue, thioredoxin-like 6 (TXNL6), on the apoptosis of retinal cells remain unknown. In this study, we examined the function of TXNL6 and investigated its mechanism of protection using a cone photoreceptor cell line, 661W. We found that the photooxidative stress-induced degradation of NF-kappaB proteins is rescued by overexpression of TXNL6, which enabled the NF-kappaB transactivation activity. Furthermore, the overexpression of TXNL6 rescued the photooxidative stress-induced apoptosis of 661W cells. Interestingly, this protective effect was significantly blocked by NF-kappaB specific inhibitors demonstrating that TXNL6 exerts its protective effect against apoptosis via NF-kappaB. Taken together, our study shows that the TXNL6 probably protects retinal cells from photooxidative damage-induced apoptosis via upregulation of NF-kappaB activity. The identification of TXNL6 and the demonstration of its protective mechanism offer new insights into treatment possibilities for photoreceptor cell degradation.


Atypical receptors mediate the response to endothelin-1 and sarafotoxin S6b in the human umbilical artery.
The receptors mediating smooth muscle response to endothelin-1 and sarafotoxin S6b in the human umbilical artery were investigated in vitro. Both agonists induced contractions that were unaffected by the endothelin ET(B) receptor antagonist BQ 788 (10(-9), 10(-8), 10(-7) M). The non-selective endothelin ET(A/B) receptor antagonist PD 142893 (10(-7) M) decreased the contraction induced by endothelin-1. PD 142893 (10(-9) M) enhanced the contraction induced by sarafotoxin S6b whereas higher concentrations had no effect. Removing the endothelium did not affect the antagonising action of PD 142893 on endothelin-1-induced contractions while the enhancement of the sarafotoxin S6b-induced contraction was abolished. Sarafotoxin S6b induced relaxation in segments precontracted by 5-hydroxytryptamine and exposed to the endothelin ET(A) receptor antagonist BQ 123 (10(-7) M) and PD 142893 (10(-9) M) abolished this relaxation. These endothelial receptors seem neither to be classical endothelin ET(A) nor endothelin ET(B) receptors and they are not activated by endothelin-1.


Long-term effects of tear film component deposition on the surface and optical properties of two different orthokeratology lenses.
To understand the effects of long-term deposition of tear film components on the surface and optical properties of orthokeratology (ortho-k) lenses, two different lenses, Brighten 22 and Optimum Extra, were tested here. Ortho-k lenses were immersed in artificial tears and cleaned with a commercial care solution repeatedly for up to 90 days. Both the daily and accumulated lysozyme deposition amounts using an Enzyme-Linked ImmunoSorbent Assay were then analyzed. The base curve, central thickness, power, and transmission of visible light, ultraviolet A, and ultraviolet B were analyzed before and after repeated tear film component deposition procedures. The surface roughness using atomic force microscopy was observed and an energy dispersive spectrometer was used to analyze the composition of the deposits. The highest levels of lysozyme were adsorbed on both lens materials during the first four days of the procedure and became saturated by day 6. For both lens materials, contamination on the lenses was easily observed by day 30, and the degree of surface roughness was higher. The transmission levels of different light spectrums were reduced showing that the optical characteristics of both lenses were also affected. The results provide in vitro evidence that lysozyme could not be completely removed from orthokeratology lenses. Both surface and optical properties were affected by the deposition of tear film components. However, only one commercial multipurpose care solution was used to clean the lens in this study when the main ingredient was a surfactant, and the results might be different when other care regimens with other key ingredients are used. In addition, whether tear film component deposition might result in increased risks of infection or corneal abrasion will require further investigation.


Concentration and purification of plant pathogenic viruses by field step electrophoresis.
Concentration and purification of plant pathogenic viruses by field step electrophoresis comprises a new and rapid preparative method with high throughput and short separation time. With this technique and combinations of field step and zone electrophoresis it is possible to purify plant pathogenic viruses from several contaminants in one separation step. Another application of field step electrophoresis allows the separation of viruses from each other.


Mica Nanoparticle, STB-HO Eliminates the Human Breast Carcinoma Cells by Regulating the Interaction of Tumor with its Immune Microenvironment.
Mica, an aluminosilicate mineral, has been proven to possess anti-tumor and immunostimulatory effects. However, its efficacy and mechanisms in treating various types of tumor are less verified and the mechanistic link between anti-tumor and immunostimulatory effects has not been elucidated. We sought to investigate the therapeutic effect of STB-HO (mica nanoparticles) against one of the most prevalent cancers, the breast cancer. STB-HO was orally administered into MCF-7 xenograft model or directly added to culture media and tumor growth was monitored. STB-HO administration exhibited significant suppressive effects on the growth of MCF-7 cells in vivo, whereas STB-HO did not affect the proliferation and apoptosis of MCF-7 cells in vitro. To address this discrepancy between in vivo and in vitro results, we investigated the effects of STB-HO treatment on the interaction of MCF-7 cells with macrophages, dendritic cells (DCs) and natural killer (NK) cells, which constitute the cellular composition of tumor microenvironment. Importantly, STB-HO not only increased the susceptibility of MCF-7 cells to immune cells, but also stimulated the immunocytes to eliminate cancer cells. In conclusion, our study highlights the possible role of STB-HO in the suppression of MCF-7 cell growth via the regulation of interactions between tumor cells and anti-tumor immune cells.


Distribution of gadomelitol in a human breast tumor model in mice.
The study evaluates the tumor distribution of the rapid clearance blood pool agent (RCBPA) gadomelitol, in a breast tumor model. Different techniques were used : (1) tissue gadolinium concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), (2) whole body quantitative autoradiography using radiolabeled [153Gd] gadomelitol and (3) dynamic contrast-enhanced MRI with compartmental analysis. An accumulation of gadomelitol in tumors compared to muscle was observed 30 min and 3 h post injection (p.i.). Thirty minutes p.i., the gadomelitol tumor distribution evaluated by autoradiography showed a marked difference between the rim and the center, whereas both areas showed comparable concentrations after 3 h. Using dynamic contrast-enhanced MRI, three phases could be observed during the 1 hour observation period: (1) rapid tumor uptake within the first few minutes post-injection (2) a progressive increase in tumor signal enhancement over 10 min and (3) a steady-state phase. Average +/- SD (n=5) transendothelial permeability K(PS) and the fractional blood volume fBV were 12.2+/-1.6 microl/min(-1)/g and 5.4+/-0.2% respectively. Due to its slow extravasation and high tumor residence time, gadomelitol may potentially be useful to improve characterization between benign versus malignant tumors using dynamic MRI.


Testicular seminoma: the M. D. Anderson experience. An analysis of pathological and patient characteristics, and treatment recommendations.
We treated 240 patients with testicular seminoma at our institution between January 1960 and December 1982. The over-all 5-year survival free of disease for these patients regardless of stage was 93.6 per cent. The 165 patients (69 per cent) with stage I disease had a 95.5 per cent 5-year survival free of disease that remained constant at 20 years. Stage II cancer was diagnosed clinically in 62 patients (26 per cent), while 13 (5 per cent) presented with more advanced (stages III and IV) disease. The 5-year survival rate free of disease for all patients with stage II cancer was 85 per cent. There were 14 pathological and patient characteristics analyzed, 4 of which were statistically significant. All but 1 of these factors (spermatic cord invasion) was related to tumor volume (stage, palpable mass and hydronephrosis). Based on the data of this retrospective review, the Canadian experience without prophylactic mediastinal irradiation and the development of effective chemotherapy, we recommend radiation therapy without prophylactic mediastinal irradiation for patients with stage I or IIA disease and chemotherapy for patients with stage IIB, III or IV disease. In an attempt to improve our results in the latter patients we recently instituted adjunctive radiotherapy for those with a persistent radiographic mass. Our current guidelines for the staging evaluation and followup of patients with this neoplasm also are discussed.


Matrix vesicle calcification of ectopically induced osteoid tissue in 1-hydroxethylidene-1,1-bisphosphonate (HEBP)-treated mice.
The effects of 1 hydroxethylidene-1, 1-bisphosphonate (HEBP) on the mineralization of osteoid induced ectopically by a murine, osteosarcoma-derived, bone-inducing substance was examined at the ultrastructural level. Samples of Dunn osteosarcoma were chemically processed, lyophilized into pellets of uniform dimensions and protein content, and implanted into the back muscles of male, 4 week old, ddY mice. In control animals injected intraperitoneally (i.p.) with saline each day for 30 days, the pellets exhibited ectopic cartilage and bone formation in a sequential manner consistent with endochondral ossification. Daily administration of HEBP (30 mg/kg i.p. per day) to animals over the same period produced wide anastomosing strands of osteoid and haematopoietic marrow in the pellets. Electron microscopical examination revealed a tightly packed organization of collagen fibrils with many membrane bounded organelles or matrix vesicles (0.05-0.3 micron diameter) dispersed throughout this nonmineralized matrix. After withdrawal of HEBP, mineralization proceeded initially within matrix vesicles and secondarily by involvement of the surrounding collagen fibrils. In pellets retrieved at 30 days after HEBP withdrawal, most of the matrix had been mineralized and remodeled to reveal thin bony trabeculae and an overall histologic appearance similar to that seen in the control pellets. This model of ectopic bone formation permits clear visualization of the sequence of mineral nucleating events in osteoid in the absence of an established mineralizing front. The results add further support to the hypothesis that matrix vesicles are directly responsible for the initiation of mineralization in bone.


Anaesthesia for caesarean section in patients with uncontrolled hyperthyroidism.
The anaesthetic management of two patients with uncontrolled hyperthyroidism requiring Caesarean section is described. The first patient was diagnosed as hyperthyroid during pregnancy but was resistant to medical management with propylthiouracil (PTU). At 38 weeks' gestation, after optimizing her heart rate with intravenous propranolol, she received an epidural anaesthetic for the Caesarean section. The baby had manifestations of hypothyroidism immediately after birth but later became hyperthyroid. The second patient's hyperthyroidism was well controlled but she stopped her medication one week before delivery. The Caesarean section was performed under general anaesthesia for fetal distress. The baby died in the neonatal period of extreme prematurity. The anaesthetic management of the hyperthyroid parturient is discussed. Preoperative control of hyperthyroidism, bearing in mind pregnancy and time constraints, is essential. The use of PTU, propranolol, iodine, and glucocorticoids is described in the preparation of the parturient. Fetal and neonatal effects of these drugs are discussed.


Interaction of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, with valproate: a pharmacokinetic study.
The mechanism responsible for the valproate (VPA)-induced elevation of serum carbamazepine-10,11-epoxide (CBZ-E) levels was investigated in 6 normal subjects who received single oral doses of CBZ-E (100 mg) in a control session and during concurrent treatment with sodium VPA [500 mg twice daily (b.i.d.)]. VPA caused a significant prolongation of CBZ-E terminal half-life (t1/2 from 6.3 +/- 1.2 to 9.0 +/- 2.0 h, mean values +/- SD) and decreased CBZ-E clearance (from 90.6 +/- 18.8 to 63.2 +/- 16.1 ml h-1 kg-1, mean values +/- SD) without affecting CBZ-E apparent volume of distribution (from 0.82 +/- 0.19 to 0.81 +/- 0.24 l kg-1, mean values +/- SD). These findings indicate that VPA impairs the elimination of CBZ-E, presumably by inhibiting its metabolism.


Histologic evaluation of the bone-ceramic interface of an alumina ceramic cup arthroplasty retrieved after 25 years in vivo.
A 47-year-old man underwent ceramic cup arthroplasty when he was 22 years old. Revision total hip arthroplasty was performed 25 years later because of limited range of motion without implant loosening. Histologic examination revealed that the femoral head and ceramic implant were well fixed through a thin fibrous membrane. The energy-dispersive X-ray analysis indicated that calcium and phosphorus were detected in the same peak pattern as cancellous bone in the bone-ceramic interface.


Serum acid phosphatase elevation associated with transurethral resection syndromes.
In 6 patients undergoing transurethral resection of the prostate for benign prostatic hyperplasia symptoms of post-transurethral prostate resection syndrome developed. Serum acid phosphatase determinations in the recovery room showed that all patients had high acid phosphatase levels although each had normal levels preoperatively. All patients showed a normal acid phosphatase level on the first postoperative day. The acid phosphatase elevations indicate significant intraoperative absorption of prostate tissue substances. The association of clinical symptoms with enzyme elevation suggests that the etiology of the confusing clinical syndromes following transurethral prostate surgery may be due to the intravenous absorption of not only irrigant solution but also tissue substances from the prostate gland.


Rhodotorula rubra peritonitis in patients undergoing continuous ambulatory peritoneal dialysis.
Although still uncommon, fungal peritonitis is being reported with increasing frequency in patients with renal failure who are undergoing long-term peritoneal dialysis. Although most cases have involved Candida albicans, other opportunistic pathogens have been reported as well. Recently, three patients were seen with serious peritoneal infections due to Rhodotorula rubra, a "nonpathogenic" fungus. In two patients, peritoneal fibrosis made further peritoneal dialysis impossible. The third patient died from complications of peritonitis. Environmental cultures revealed a possible common-source outbreak. Literature review reveals that infection due to this organism is most unusual and occurs only in the hospital setting in patients with serious compromise of host defenses.


Are chemical barriers necessary for evolution of butterfly-plant associations?
The association between heliconiine butterflies and Passion flower vines is composed of three or more subassociations, in which each Heliconius species group feeds on a different Passiflora subgenus. The relationships are consistent with the adaptive zone hypothesis of Ehrlich and Raven, which would suggest that (1) species of the subgenus Plectostemma proliferated as a result of chemical barriers to herbivory, which created a herbivore-free adaptive zone in which speciation and diversification took place, and (2) species of the H. erato-charitonia group overcame these barriers and entered a competitor-free adaptive zone, in which they proliferated and speciated with those plants as hosts. The hypothesis that plant secondary chemicals were responsible for creating such barriers to herbivory was tested using heliconiine species as bioassays, in which reduced growth rates indicated presence of chemical barriers to feeding. Contrary to expectation, plants of the subgenus Plectostemma showed little or no chemical defense against any species of heliconiine caterpillar. In contrast many plants of the "primitive" subgenus Granadilla possessed significant chemical barriers against herbivory by heliconiine larvae, excepting those species in the H. numata-melpomene species group. I concluded that chemical barriers to feeding were not responsible for proliferation and diversification in the subgenus Plectostemma, nor did chemicals create a competitor-free "adaptive zone" in which the H. erato-charitonia species-group could proliferate and speciate. Chemical barriers may have been important in the evolution of the subgenus Granadilla-heliconiine association. I suggest that plant allelochemics are only one of many possible barriers to herbivory which can help create "adaptive zones" for plants and their herbivores, and that the patterns of butterfly foodplant specialization discussed by Ehrlich and Raven (1964) are not necessarily the result of biochemical adaptation and counteradaptation.


Immunological consequences of laparoscopic versus open transhiatal resection for malignancies of the distal esophagus and gastroesophageal junction.
Surgery remains the only curative therapy for esophageal cancer. The objective of the current study was to evaluate the impact of laparoscopic transhiatal esophagectomy versus open transhiatal esophagectomy on both inflammatory and immunological responses. Seventeen patients undergoing laparoscopic or open surgery were included in the study. The postoperative inflammatory response was assessed by measuring WBC count and CRP, IL-6, IL-8, soluble TNF I and II receptor, and elastase levels. The postoperative immune function was assessed by measuring the monocyte HLA-DR expression. LPS-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) were measured to evaluate bacterial translocation. The IL-6 level increased significantly more in the patients who received open surgery as compared with the laparoscopic group. Both LBP and BPI increased predominantly in the laparoscopic group as compared with the group who received open surgery. No difference was found in HLA-DR expression between the two groups. Although both laparoscopic and conventional esophageal resections result in an activation of the inflammatory response, this study suggests that this response could be less pronounced after the laparoscopic approach. However, in the laparoscopic group higher LBP and BPI levels were seen, suggesting an increased endotoxemia. We postulate that the persistently elevated abdominal pressure results in a loss of mucosal barrier function, resulting in bacterial translocation. The cellular acidification of the cells of the peritoneum induced by CO(2) insufflation, however, blunts the expected inflammatory response.


Prediction of risk for shoulder dystocia with neonatal injury.
The purpose of this study was to develop a predictive model of risk for shoulder dystocia (ShD) with injury. Medical records in 3 urban university teaching hospitals were reviewed to identify and characterize 498 cases of ShD, including 90 with neonatal injury and a comparison group with of 622 with vaginal delivery (VgD) without ShD. The data were subjected to logistic regression modeling to find the best combination of variables to discriminate between the injury and VgD groups. The best model included birth weight in combination with maternal height and weight as well as gestational age and parity. A score over 0.5 detected 50.7% of the shoulder dystocia cases with brachial plexus injury along with a false positive rate of 2.7%. Using a statistical model it is possible to identify adverse combinations of factors that are associated with ShD and neonatal injury along with a relatively low false positive rate.


Low FODMAP diet reduces gastrointestinal symptoms in irritable bowel syndrome and clinical response could be predicted by symptom severity: A randomized crossover trial.
Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) can provoke symptoms in patients with irritable bowel syndrome (IBS). We aimed to compare the effects of diets with low vs. moderate FODMAP content on gastrointestinal (GI) symptoms and bowel habits, and to identify possible predictors of clinical response to a low FODMAP diet and FODMAP sensitivity in IBS. Adult participants with IBS (Rome IV criteria, n = 29) were included and adhered to two 7-day diet periods, with either low (4 g/day) or moderate (23 g/day) amounts of FODMAPs, in this randomized, double-blind, crossover study. The periods were separated by a wash-out period (≥14 days). IBS-Severity Scoring System (IBS-SSS) and a stool diary (Bristol Stool Form) were completed before and after the diet periods. At baseline, severity of GI symptoms and gut microbial fermentation were assessed (every 15 min, 4 h) during the Lactulose Nutrient Challenge Test (LNCT). Clinical response and FODMAP sensitivity were defined by reduction after low FODMAP period, and increase after moderate FODMAP period in IBS-SSS (≥50 points), respectively. Severity of GI symptoms (P = 0.04), stool consistency (P = 0.01), and stool frequency (P = 0.01) differed between the interventions, with reduced overall GI symptom severity, abdominal pain intensity and frequency, bowel habits dissatisfaction, and daily life interference (P < 0.05 for all), as well as more firm (P = 0.03) and less frequent (P < 0.01) stools after low FODMAP intervention, but not after moderate FODMAP intervention. A third (34%) responded clinically to the low FODMAP diet, and the response could be predicted by higher IBS-SSS at baseline (P = 0.02). Although modest associations between FODMAP sensitivity (22%) and GI symptoms during LNCT were observed, no independent predictors could be identified. A diet low in FODMAPs reduces GI symptoms and affects bowel habits in IBS, compared with a moderate FODMAP diet. Assessment of IBS severity before the intervention may be used to predict clinical response to a low FODMAP diet. Trial registry (http://www. gov): Registered under Clinical Trial number NCT05182593.


[Clear-cell carcinoma of the kidney in a patient with hairy-cell leukemia. Immunologic and epidemiologic considerations].
The paper describes a case of light-cell carcinoma of the kidney in a patient affected by hairy-cell leukemia. The immunological status is assessed revealing a severe deficit of NK phenotype lymphocytes. Therapy with alpha interferon was proposed in order to stimulate killing and recruitment processes of new NK cells.


Health-Risk Behavior Profiles and Reciprocal Relations With Depressive Symptoms From Adolescence to Young Adulthood.
We examined co-occurrences of multiple health-risk behaviors among adolescents in a 5-year longitudinal design as well as their associations with mental health outcomes. Latent transition analyses explored subgroups of adolescents (N = 229; 51% males) who engaged in distinct patterns of health-risk behaviors and transitions over time. Moreover, longitudinal relations between risk behavior profiles and depressive symptoms were also explored. We identified four latent profiles based on risk levels of safety and violence, sexual behavior, alcohol use, and marijuana and other drug use at both 18 years and 23 years: low risk, modest risk, medium risk, and high risk. Some adolescents maintained their latent profile membership over time, but more transitioned between risk profiles. Adolescents with more depressive symptoms had a higher probability of developing into the high-risk versus low-risk and modest risk profiles at 23 years. Adolescents in the high-risk, low-risk, and modest risk profiles at 18 years developed more depressive symptoms in young adulthood compared with medium risk adolescents. This study provides a better understanding of the prevalence, distribution, and change patterns of health-risk profiles across adolescence and young adulthood in a European American sample. Reciprocal relations between high-risk profiles and depressive symptoms suggest the need for integrated but tailored prevention and intervention programs.


Transmethylation in immunity and autoimmunity.
The activation of immune cells is mediated by a network of signaling proteins that can undergo post-translational modifications critical for their activity. Methylation of nucleic acids or proteins can have major effects on gene expression as well as protein repertoire diversity and function. Emerging data indicate that indeed many immunologic functions, particularly those of T cells, including thymic education, differentiation and effector function are highly dependent on methylation events. The critical role of methylation in immunocyte biology is further documented by evidence that autoimmune phenomena may be curtailed by methylation inhibitors. Additionally, epigenetic alterations imprinted by methylation can also exert effects on normal and abnormal immune responses. Further work in defining methylation effects in the immune system is likely to lead to a more detailed understanding of the immune system and may point to the development of novel therapeutic approaches.


Epidemiology and economic burden of bronchiectasis requiring hospitalisation in Singapore.
Little is known about the epidemiology and cost of bronchiectasis in Asia. This study describes the disease burden of bronchiectasis in Singapore. A nationwide administrative dataset was used to identify hospitalisations with bronchiectasis as a diagnosis. Population statistics and medical encounter data were used to estimate the incidence, mortality, prevalence and direct medical costs associated with bronchiectasis requiring hospitalisation. There were 420 incident hospitalised bronchiectasis patients in 2017, giving an incidence rate of 10.6 per 100 000. Age-standardised incidence declined on average by 2.7% per year between 2007 and 2017. Incidence rates increased strongly with age in both men and women. Tuberculosis was a secondary diagnosis in 37.5% of incident hospitalisations in 2007, but has declined sharply since then. Patient survival was considerably lower in both men (5-year relative survival ratios (RSR) 0.63, 95% CI 0.59-0.66) and women (5-year RSR 0.75, 95% CI 0.72-0.78). The point prevalence of bronchiectasis was 147.1 per 100 000 in 2017, and increased sharply with age, with >1% of people aged ≥75 years having bronchiectasis. Total first-year costs among incident bronchiectasis patients in 2016 varied widely, with a mean±sd USD 7331±8863. Approximately 10% of the patients admitted in 2016 had total first-year costs of more than USD 14 380. Bronchiectasis is common and imposes a substantial burden on healthcare costs and survival rates of patients in Singapore.


Neuronal response to high negative affective stimuli in major depressive disorder: An fMRI study.
Disturbed emotion processing underlies depression. We examined the neuronal underpinnings of emotional processing in patients (PAT) with major depressive disorder (MDD) compared to healthy volunteers (HV) using functional magnetic resonance (fMRI) scan. Thirty-six MDD patients and 30 HV underwent T2-weighted fMRI assessments during the presentation of an implicit affective processing task in three conditions. They differed regarding their affective quality (=valence, high negative, low negative and neutral stimuli) and regarding the arousal based on stimuli from the International Affective Picture System. Group contrasts showed lower left-sided activation in dorsolateral prefrontal cortex (DLPFC), anterior PFC, precentral and premotor cortex in PAT compared with HV (Cluster-level threshold, 5000 iterations, p<0.01). We found a significant interaction effect of valence and group, a significant effect of emotional valence and a significant effect of group. All effects were shown in brain regions within the emotional network (Cluster-level threshold, 5000 iterations, p<0.01). Higher arousal (rho=-0.33, p<0.01) and higher valence (rho=-0.33, p<0.01) during high negative stimuli presentation as well as more severe depression (Beck Depression Inventory II [BDI II]; r = 0.39, p = 0.01) were significantly negatively associated with left DLFPC activity in patients. Potential influence of psychopharmacological drugs on functional activation is one of the most discussed source of bias in studies with medicated psychiatric patients. The results highlight the importance of left DLPFC during the processing of negative emotional stimuli in MDD. The integration of a neurophysiological model of emotional processing in MDD may help to clarify and improve therapeutic options.


Investigation of Predictors of Successful Replantation of Distal Digits at the Nail Bed Level: The Contribution of Digital Nerve Repair to Survival Rate.
Replantation of amputated digits at the nail bed level is surgically challenging and differs from replantation at a more proximal amputation level. This study aimed to determine the predictors influencing the success rate of fingertip replantation. Overall, 239 digits of 226 patients who underwent replantation surgery from August of 2009 to March of 2020 were considered. A total of 15 independent variables (i.e., sex; age; injured hand; digit; history of smoking; history of hypertension or diabetes; injury mechanism; amputation level; ischemia duration; surgeon's expertise; numbers of repaired arteries, veins, and nerves; and the need for a vein graft) were investigated for their effects on the survival of the replanted digits. Of all 239 digits, 190 (79.5 percent) survived. Univariate analysis indicated that non-crush-avulsion injury, expertise and experience of the surgeon, vein repair, and nerve repair contributed to increasing the survival rate. Binary logistic regression analysis demonstrated that injury mechanism, vein repair, and nerve repair were significant predictive factors. In addition, in non-vein-repaired, blunt cut, or Ishikawa subzone II cases, digital nerve repair contributed significantly to promote the success rate relative to vein-repaired, crush-avulsion-type injury, and subzone I cases. Vein repair, nerve repair, non-crush-avulsion injury, and surgeon's expertise and experience were the predictors for successful replantation. Intraoperative vein and nerve repair are recommended to improve the survival rate of fingertip replantation at the nail bed level. Risk, III.


Potential role of ovomucin and its peptides in modulation of intestinal health: A review.
Intestinal dysfunction, which may cause a series of metabolic diseases, has become a worldwide health problem. In the past few years, studies have shown that consumption of poultry eggs has the potential to prevent a variety of metabolic diseases, and increasing attention has been directed to the bioactive proteins and their peptides in poultry eggs. This review mainly focused on the biological activities of an important egg-derived protein named ovomucin. Ovomucin and its derivatives have good anti-inflammatory, antioxidant, immunity-regulating and other biological functions. These activities may affect the physical, biological and immune barriers associated with intestinal health. This paper reviewed the structure and the structure-activity relationship of ovomucin,the potential role of ovomucin and its derivatives in modulation of intestinal health are also summarized. Finally, the potential applications of ovomucin and its peptides as functional food components to prevent and assist in the pretreatment of intestinal health problems are prospected.


The effects of intermittent ischemic arrest on the perfusion of myocardium supplied by collateral coronary arteries.
Six weeks after placement of an ameroid constrictor on the circumflex coronary artery, blood flow in a collateral region was compared with flow in myocardium supplied by normal arteries during cardiopulmonary bypass (80 mm Hg). Myocardial blood flow was determined using radionuclide-labeled microspheres (8 to 10 mu) before 10 minutes of ischemic arrest and after 1, 5, and 10 minutes of reperfusion. The retrograde circumflex pressure was monitored continuously and served as an additional index of perfusion of the collateral region. During reperfusion, endocardial flow in the collateral region remained unchanged despite a threefold increase in a similar layer having normal arteries (p less than 0.01). Following ischemic arrest, mean transmural and subendocardial hyperemic responses both persisted for longer than 10 minutes in normal regions. Simultaneously, peripheral circumflex pressures decreased at 1 and 5 minutes of reperfusion (p less than 0.001) but returned to control within 10 minutes. Persistently elevated endocardial flow in the normal arteries and the absence of a hyperemic response in the collateral region during an associated decrement in retrograde circumflex pressure may indicate incomplete flow repayment even after 10 minutes of reperfusion. Marked transmural flow imbalances despite adequate coronary perfusion pressures suggest that intermittent ischemic arrest may cause cumulative ischemia, and this occurrence may be detrimental especially in collateral regions of myocardium.


Damage and protection of the human gastric mucosa. A multiparameter assessment.
Studies in animals and humans have indicated that endogenous prostaglandins as well as synthetic prostaglandin analogues can prevent gastric mucosal damage induced by various agents. Methods were developed to assess induced damage and the effects of potentially protective agents (synthetic prostaglandin analogues and the histamine [H2]-receptor antagonist cimetidine) on the human gastric mucosa by measuring ion fluxes and transmucosal potential difference, as well as by observations with gastrointestinal endoscopy. Commonly ingested agents, such as aspirin, 1,300 mg, and 20 percent ethanol increased hydrogen ion and sodium ion fluxes, decreased potential difference, and caused gross mucosal damage, as observed by endoscopy. Conversely, acetaminophen, 2,600 mg, and 10 percent ethanol did not have any significant effects. Hyperosmolar solutions (1,800 and 3,600 mOsm/kg) also produced acute damage. Sodium taurocholate (10 mmol/liter) when instilled into the stomach, either at pH 1.1 or 7.0, produced both functional and structural damage. When given as a single dose, neither 15(R)15-methyl PGE2 nor the synthetic PGE1 analogue, misoprostol, prevented mucosal damage induced by aspirin and taurocholate (pH 1.1), respectively. Cimetidine, 400 mg orally, however, did reduce aspirin-induced mucosal damage, and this effect was independent of gastric acid inhibition.


Radiology education: a glimpse into the future.
The digital revolution in radiology continues to advance rapidly. There are a number of interesting developments within radiology informatics which may have a significant impact on education and training of radiologists in the near future. These include extended functionality of handheld computers, web-based skill and knowledge assessment, standardization of radiological procedural training using simulated or virtual patients, worldwide videoconferencing via high-quality health networks such as Internet2 and global collaboration of radiological educational resources via comprehensive, multi-national databases such as the medical imaging resource centre initiative of the Radiological Society of North America. This article will explore the role of e-learning in radiology, highlight a number of useful web-based applications in this area, and explain how the current and future technological advances might best be incorporated into radiological training.


Changes in quantitative ultrasound in infants born at less than 32 weeks' gestation over the first 2 years of life: influence of clinical and biochemical changes.
Studies in preterm infants show reduced speed of sound (SOS) as measured by quantitative ultrasound (QUS) during the immediate neonatal period. There is a scarcity of data on SOS changes following hospital discharge. The aim of this study was to assess SOS over the first 2 years in preterm infants. Infants were recruited from a neonatal follow-up clinic. Tibial QUS was performed using the Omnisense 7000P scanner. Thirty-nine infants born at <32 weeks' gestation had a single SOS measurement (median 3,203 m/second, range 2,609-3,495) which correlated with corrected gestational age (CGA) (r = 0.8, P < 0.005). The majority of measurements were within the manufacturer's reference range for term infants. SOS standard deviation score (SDS) in infants aged 0-6 months CGA demonstrated a negative correlation with duration of total parenteral nutrition (r = 0.7, P < 0.05) and a positive correlation with serum phosphate (r = 0.6, P < 0.05.) Two groups of infants had serial measurements: eight had measurements performed at term CGA and early infancy (early) and seven had measurements in later infancy (late). In the early group SOS SDS increased (P < 0.005), and the greatest increase in SOS over time occurred in infants with the lowest SOS at term (r = 0.9). In the late group there was no significant change over time. SOS SDS change did not show any correlation to weight SDS change. Catch-up in SOS occurs postterm in most infants by 6 months and is independent of postnatal growth. Infants with the lowest SOS at term have the fastest rate of catch-up. The opportunity for catch-up may be greatest in early infancy.


The clinical course of non-muscle invasive bladder cancer after transurethral resection of the tumor with or without subsequent intravesical application of bacillus Calmette-Guérin: The influence of patients gender and age.
BACGROUND/AIM: The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) after transurethral resection (TUR) of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC). The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I) and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using χ2 test and the Kolmogorov-Smirnov test. This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years.


Inter versus intra-molecular photoinduced charge separation in solid films of donor-acceptor molecules.
We report on photoinduced charge separation in solid films of two perylene diimides; intramolecular charge separation and recombination is correlated with a reduction in the yield of long-lived, intermolecular charge-separated species.


Referral without access: for psychiatric services, wait for the beep.
We examine access to care for acute depression by insurance status compared to access for acute medical conditions in 9 metropolitan areas in the United States. Using an audit study design, trained research assistants posing as patients referred from a local emergency department (ED) for treatment of depression called each clinic twice, with differing insurance status. The main outcome measure was the ability to schedule a mental health appointment within 2 weeks of the ED visit. In 45% of 322 calls to mental health clinics, the research assistant reached an answering machine compared with 8% of calls to medical clinics. As a result, only 31% of callers with depression vignettes were able to determine whether they could get an appointment versus 78% of callers with medical complaints. When they reached appointment personnel by telephone, 57% of depression callers successfully arranged an appointment (39% within 14 days). Among depression callers who reached appointment personnel, 67% of privately insured and 33% of Medicaid callers were able to make an appointment, for overall appointment rates of 22% and 12%, respectively. Appointment success for the uninsured was comparable to that of Medicaid patients. The high percentage of callers who encountered answering machines prevented us from completing the designed analysis of paired calls to individual clinics. Our findings indicate that the process for obtaining urgent follow-up appointments is systematically different for patients seeking behavioral health care than for those with physical complaints. The use of voicemail, in lieu of having a person answer the telephone, is much more prevalent in behavioral than physical health settings. More work is needed to determine the effect of this practice on depressed individuals and vulnerable populations.


Non-toxigenic Vibrio cholerae in an autologous stem cell and renal transplant recipient.
A patient with a renal transplant after an autologous stem cell transplant for multiple myeloma developed non-toxigenic Vibrio cholerae diarrhea after travel to Mexico. This is a rare cause of diarrhea in transplant recipients, and the patient had not had pre-travel counseling. This case reflects the lack of referral of transplant recipients for travel infectious disease review before overseas travel and the role of the live attenuated cholera vaccine.


Effect of non-invasive ventilation on the measurement of ventilatory and metabolic variables.
The effect of non-invasive ventilation (NIV) on the accuracy of measurements of ventilation, oxygen consumption (V˙O2) and carbon dioxide production (V˙CO2) was examined using a simulator. Known gas volumes of oxygen and carbon dioxide were delivered to a metabolic system that measured tidal volume, respiratory rate, V˙O2 and V˙CO2, both with and without NIV. Bland-Altman analyses were used to compare between conditions. NIV at pressure support (PS) 20cm H2O compared to without NIV showed: VT, mean difference (MD) 0mL (limits of agreement (LOA) -21 to 21) mL; V˙O2 MD -413 (LOA -810 to 16) mL/min; and V˙CO2 MD 32 (LOA -32 to 97) mL/min. For V˙O2 measurements during NIV, a correction was applied to account for increased air density due to PS. After correction, V˙O2 measurement accuracy improved; MD -46 (LOA -108 to 17) mL/min. Tidal volume and metabolic variables can be measured with acceptable accuracy during NIV, providing V˙O2 is corrected for altered gas density.


Molecularly Defined Circuitry Reveals Input-Output Segregation in Deep Layers of the Medial Entorhinal Cortex.
Deep layers of the medial entorhinal cortex are considered to relay signals from the hippocampus to other brain structures, but pathways for routing of signals to and from the deep layers are not well established. Delineating these pathways is important for a circuit level understanding of spatial cognition and memory. We find that neurons in layers 5a and 5b have distinct molecular identities, defined by the transcription factors Etv1 and Ctip2, and divergent targets, with extensive intratelencephalic projections originating in layer 5a, but not 5b. This segregation of outputs is mirrored by the organization of glutamatergic input from stellate cells in layer 2 and from the hippocampus, with both preferentially targeting layer 5b over 5a. Our results suggest a molecular and anatomical organization of input-output computations in deep layers of the MEC, reveal precise translaminar microcircuitry, and identify molecularly defined pathways for spatial signals to influence computation in deep layers.


Developmental changes in functional characteristics of aortic baroreceptor afferents in rats.
To investigate postnatal developmental changes in functional characteristics of the afferent pathway of the aortic baroreceptor reflex, the responses of aortic nerve activity (ANA) to blood pressure (BP) changes elicited by phenylephrine and sodium nitroprusside administration were tested in 3-, 8- and 20-week-old male rats under chloralose (60 mg kg(-1) i.p.) and urethane (600 mg kg(-1) i.p.) anaesthesia. The function curve of ANA in response to BP changes showed a sigmoid shape that shifted to the right from 3 to 8 weeks of age. The maximal activity and maximal gain of the aortic nerve, which were calculated by a logistic function analysis, were significantly higher in 20-week-old rats (maximal activity, 532 +/- 47% of baseline; maximal gain, 7.9 +/- 0.8% of baseline mmHg(-1); n = 9) than in 3-week-old rats (maximal ANA, 268 +/- 25% of baseline, P < 0.001; maximal gain, 4.9 +/- 0.5% of baseline mmHg(-1), P < 0.01, n = 9) and 8-week-old rats (maximal ANA, 309 +/- 18% of baseline, P < 0.001; maximal gain, 4.9 +/- 0.3% of baseline mmHg(-1), P < 0.01, n = 11). These results suggest that the operating point of aortic baroreceptor afferents is reset to the higher pressure level during development from 3 to 8 weeks of age and, thereafter, the afferent gain increases from 8 to 20 weeks of age. This functional change may be an important factor to prevent an excess increase of BP, which would result in pathophysiological problems.


Use of Expedited Partner Therapy for Sexually Transmitted Diseases in College and University Health Centers in the United States, 2011-2012.
We examined expedited partner therapy for chlamydia and gonorrhea in college and university health centers by institutional and policy characteristics. Expedited partner therapy awareness and use was low (44.1% used), did not differ by institutional characteristics, and differed by policy environment. Our findings suggest missed opportunities for sexually transmitted disease prevention in college and university health centers.


New radiopharmaceuticals and new applications in medicine.
All areas of radiology are constantly evolving. At times rapid advances are made because new equipment or pharmaceuticals are introduced. At others the evolution is gradual as established procedures and techniques are refined. The following review of selected areas in nuclear medicine includes both dramatic changes due to new developments and evolutionary changes in established techniques. The first section reviews the development of monoclonal antibodies for use in radioscintigraphy of neoplastic disease. Although many articles have been written about this topic over the years, the clinical applications have suddenly expanded because the Food and Drug Administration (FDA) recently approved one monoclonal antibody for use in the imaging of colorectal and ovarian cancer. It is anticipated that a number of other antibodies will be approved for clinical scintigraphy of both malignant and benign disease and immunotherapy. It is advised that the radiologist performing nuclear medicine procedures become knowledgeable about this expanding area of clinical application. The second section reviews several new radiopharmaceuticals that are being used with increasing frequency for myocardial imaging. The behavior of these tracers is different from that of thallium, and specialized imaging techniques are required. Although the clinical value of these agents is still questioned by some, they are widely used. Familiarity with this topic is recommended. The last section reviews some of the radiopharmaceuticals available for renal imaging and functional evaluation. The relatively new technetium-labeled pharmaceutical that approximates the behavior of hippuran is emphasized. New applications with the renal cortical imaging agent technetium DMSA are also reviewed. A thorough knowledge of the biologic behavior of these tracers and appropriate imaging and measurement techniques is extremely important for their appropriate clinical use.


Predicting Posttraumatic Stress Symptom Prevalence and Local Distribution after an Earthquake with Scarce Data.
After a major earthquake, the assignment of scarce mental health emergency personnel to different geographic areas is crucial to the effective management of the crisis. The scarce information that is available in the aftermath of a disaster may be valuable in helping predict where are the populations that are in most need. The objectives of this study were to derive algorithms to predict posttraumatic stress (PTS) symptom prevalence and local distribution after an earthquake and to test whether there are algorithms that require few input data and are still reasonably predictive. A rich database of PTS symptoms, informed after Chile's 2010 earthquake and tsunami, was used. Several model specifications for the mean and centiles of the distribution of PTS symptoms, together with posttraumatic stress disorder (PTSD) prevalence, were estimated via linear and quantile regressions. The models varied in the set of covariates included. Adjusted R2 for the most liberal specifications (in terms of numbers of covariates included) ranged from 0.62 to 0.74, depending on the outcome. When only including peak ground acceleration (PGA), poverty rate, and household damage in linear and quadratic form, predictive capacity was still good (adjusted R2 from 0.59 to 0.67 were obtained). Information about local poverty, household damage, and PGA can be used as an aid to predict PTS symptom prevalence and local distribution after an earthquake. This can be of help to improve the assignment of mental health personnel to the affected localities. Dussaillant F , Apablaza M . Predicting posttraumatic stress symptom prevalence and local distribution after an earthquake with scarce data. Prehosp Disaster Med. 2017;32(4):357-367.


[Diagnosis and treatment of esophagus perforation caused by esophageal foreign bodies].
Summarize the treatment skills of esophagus perforation caused by esophageal foreign bodies. Retrospectively analyze the seven cases of esophagus foreign body perforation with various complications in our department. Six cases recovered in 3 to 18 days after operation, on average 14.2 day, while one case recovered in 49 days by conservative method. Foreign bodies removing, fistulae repairing, abscess incising, effusion rinsing, effective antibiotics administrating and support treatment are effective to treat esophagus perforation caused by esophageal foreign bodies. It will take a relative long time to be treated only by conservative way.


Tyrosine hydroxylase activity in rat brain regions after chronic treatment with +/--propranolol.
Rats were injected twice daily with +/--propranolol (6 mg kg-1 day-1) for 14 days and killed 16 h after the final injection. Tyrosine hydroxylase activity was measured in both soluble and particle-bound forms in various brain regions. The activity of the soluble enzyme was not significantly altered by propranolol treatment in any of the brain regions studied. The tyrosine hydroxylase activity in the particulate fraction was significantly increased in corpus striatum and unchanged in other brain regions. The propranolol concentrations in the various brain regions in this chronic study were far lower than necessary to produce a significant change in tyrosine hydroxylase activity in acute experiments. It was concluded that chronic propranolol treatment produces a persistent increase in bound tyrosine hydroxylase activity in rat corpus striatum.


Can the follow-up of patients with papillary thyroid carcinoma of low and intermediate risk and excellent response to initial therapy be simplified using second-generation thyroglobulin assays?
In view of the low probability of recurrence, the cost-effective follow-up of patients with papillary thyroid carcinoma (PTC) of low or intermediate risk and excellent response to initial therapy represents a challenge. This study evaluated the cases of structural recurrence among these patients. The sample comprised 578 patients with PTC of low or intermediate risk, who were submitted to total thyroidectomy with or without (131) I therapy and exhibited an excellent response to initial therapy defined based on nonstimulated thyroglobulin (Tg) ≤0·2 ng/ml and negative neck ultrasonography (US). Twelve patients (2%) showed structural recurrence. At the time when recurrence was 'confirmed', Tg elevation had not occurred in only two patients, one with lymph node metastases <1 cm detected by US and the other with pulmonary metastases. Antithyroglobulin antibodies (TgAb) were undetectable in both patients. The first alteration observed in patients with recurrence was Tg elevation in six patients, Tg elevation associated with suspicious US in three, and suspicious US in two. An increase in TgAb was not the first alteration in any of the patients. Among the 560 patients who continued to have Tg ≤ 0·2 ng/ml, US permitted the detection of only one neck recurrence. Measurement of TgAb did not detect any recurrence. Our results confirm that in patients with PTC of low or intermediate risk an excellent response to initial therapy can be defined based on nonstimulated Tg ≤ 0·2 ng/ml. Follow-up consisting only of clinical examination and periodic measurement of Tg with a second-generation assay may be sufficient.


Zero malaria: a mirage or reality for populations of sub-Saharan Africa in health transition.
The global burden of malaria continues to be a significant public health concern. Despite advances made in therapeutics for malaria, there continues to be high morbidity and mortality associated with this infectious disease. Sub-Saharan Africa continues to be the most affected by the disease, but unfortunately the region is burdened with indigent health systems. With the recent increase in lifestyle diseases, the region is currently in a health transition, complicating the situation by posing a double challenge to the already ailing health sector. In answer to the continuous challenge of malaria, the African Union has started a "zero malaria starts with me" campaign that seeks to personalize malaria prevention and bring it down to the grass-root level. This review discusses the contribution of sub-Saharan Africa, whose population is in a health transition, to malaria elimination. In addition, the review explores the challenges that health systems in these countries face, that may hinder the attainment of a zero-malaria goal.


Critical appraisal meets clinical reality: evaluating evidence in the literature using canine hemangiosarcoma as an example.
The many gaps in our understanding of cancer are a great frustration for veterinarians and their clients. Unfortunately, what has been done has not always addressed the questions clinicians need answered. How can clinicians deal more effectively with the literature? Can missing information be identified, coped with clinically, and addressed by researchers?