Tongue peak pressure: a tool to aid in the identification of obstruction sites in patients with obstructive sleep apnea/hypopnea syndrome.
Purpose of this study was to evaluate whether tongue peak pressure measured using the Iowa Oral Performance Instrument is correlated with the topographic site of obstruction in patients with obstructive sleep apnea/hypopnea syndrome observed during drug-induced sleep endoscopy. Thirty-five consecutive adult patients (29 men, 6 women) were prospectively enrolled after having been diagnosed with severe obstructive sleep apnea/hypopnea syndrome by polysomnography. An apnea-hypopnea index > 30 was confirmed, and age, gender, and body mass index were recorded by Epworth Sleepiness Scale questionnaire, and a thorough evaluation of the upper airway by video-flexible endoscopy. Twenty healthy controls according to age and sex were chosen for IOPI measurements. After drug-induced sleep endoscopy, a topographic diagnosis was done using the VOTE classification. Tongue and lip peak pressures were both measured using the Iowa Oral Performance Instrument in all patients and in 20 healthy controls. Main outcomes and measures: the correlations between office findings, Iowa Oral Performance Instrument measures, and the VOTE tongue classification during drug-induced sleep endoscopy (T0, T1, T2) were then investigated. RESULTS: The average Iowa Oral Performance Instrument tongue and lip pressure were 44.02 ± 12.29 and 15.03 ± 3.71 kPa, respectively. The Iowa Oral Performance Instrument scores were both significantly lower than values in healthy controls (P < 0.001). The VOTE classification referring to the tongue position was T0 in 13 cases (37.1%), T1 in 12 cases (34.3%), and T2 in 10 cases (28.6%). A significant correlation was found between the Iowa Oral Performance Instrument tongue pressure and the T size during drug-induced sleep endoscopy (Kruskal-Wallis χ2 25.82; P ≤ 0.001). CONCLUSIONS: In our experience, the Iowa Oral Performance Instrument is a useful tool for evaluating tongue collapse for the topographic diagnosis of patients with obstructive sleep apnea/hypopnea syndrome.


HIV genotype resistance testing in antiretroviral (ART) exposed Indian children--a need of the hour.
Development of drug resistance in HIV infected children with treatment failure is a major impediment to selection of appropriate therapy. HIV genotype resistance assays predict drug resistance on the basis of mutations in the viral genome. However, their clinical utility, especially in a resource limited setting is still a subject of debate. The authors report two cases in which both the children suffered from treatment failure of various antiretroviral therapy regimes. In both the cases, Genotype Resistance Testing (GRT) prompted a radical change from proposed failure therapy as per existing guidelines. GRT was specifically important for the selection of a new dual Nucleoside reverse transcriptase inhibitors (NRTI) component of failure regimen by identifying TAMS and M184V mutations in the HIV genome. These case reports highlight the importance of GRT in children failing multiple antiretroviral regimes; and emphasizes the need to recognize situations where GRT is absolutely essential to guide appropriate therapy, even in a resource limited setting.


Morphogenesis of the Hirano body in neurons of the squirrel monkey dorsal horn.
Electron microscopic investigation of laminae I-III in the lumbosacral region of the squirrel monkey spinal cord has disclosed possible stages in the morphogenesis of the Hirano body. These bodies occur occasionally in nerve cell bodies and dendrites. They are round to oval in shape, measure up to 2.2 micrometer in diameter and are composed of circular layers of 10 nm filaments. In several instances in the present study, Hirano bodies were observed in close association with the Golgi apparatus. Here Golgi-related vesicles were attached to the external surface of the Hirano bodies. In one instance a cluster of developing Hirano bodies of various sizes was observed. The smaller bodies were located nearest the Golgi apparatus while the larger were further away. In this case several short filaments, which may be precursors of the longer filaments which make up the layers of the inclusion, were observed in the cytoplasm between the Golgi cisternae and the smaller Hirano bodies. These observations suggest that the Golgi apparatus plays a major role in the production of the Hirano body. The significance of the occurrence of these inclusions is discussed.


Function and heterogeneity of fish lectins.
Lectins are primordial molecules with multiple known functions. They have been known to exist in fish and other animals for decades and were initially identified as (hem)agglutinins. Demonstration of the importance of vertebrate lectins in innate immunity is a recent effort and is still largely unrealised for fish. This mini-review will tabulate those fish lectins identified since the last major review. In addition, particular lectins for which either functional relevance or functional or structural heterogeneity has been demonstrated are discussed in greater detail.


New developments in fluorescein angiography.
New developments in fluorescein angiography concern the apparatus employed, technique and the photographic laboratory. A wide-angle retinograph has been developed which enables us to photograph the periphery of the fundus. Television, with a very sensitive camera, permits us to obtain very well defined dynamic views with pictures at the rate of 25 per second. This technique enables us to resolve some new problems. The use of television produces stronger fluorescence than that achieved by ordinary photography and allows us to choose the best pictures relating to a clinical problem.


Central and juxta-endplate vertebral body screw placement: a biomechanical analysis in a human cadaveric model.
In vitro biomechanical testing of transvertebral body screws in different positions in both axial pull-out and toggle. To determine the relative strength of unicortical versus bicortical screw fixation within the vertebral body and to determine comparative strength of juxta-endplate and central screw positions with and without staples in both axial pull-out and toggle modes. Loss of fixation is common in centrally placed screws at the rostral end of a construct. To preserve segmental vessels, juxta-endplate screw positions are often used. The biomechanical strength of such screw placement methods has not been measured. Eighty-three human cadaveric vertebral bodies were tested for axial pull-out and toggle with and without staples. Screw positions included central, juxta superior, and inferior endplate. Juxta-endplate screws were toggled in both the rostral and caudal directions perpendicular to the screw axes. Unicortical fixation resulted in a 93% decrease in axial pull-out strength compared with bicortical fixation. Centrally placed screws and juxta-endplate screws were equivalent in axial pull-out if no staples were used. The juxta-endplate screw with a staple that was toggled away from the endplate had the highest yield strength, followed by the central screw with a staple, and then the juxta-endplate screw without a staple toggled away from the endplate. Bicortical fixation is much stronger than unicortical fixation. Centrally placed screws are significantly stronger when used with a staple. When preservation of segmental vessels is desirable, juxta-endplate screws should be placed in such a manner that compressive forces are directed away from the endplate.


Differential effects of phenobarbitone and 3-methylcholanthrene induction on the hepatic microsomal metabolism and cytochrome P-450-binding of phenoxazone and a homologous series of its n-alkyl ethers (alkoxyresorufins).
The metabolism and cytochrome P-450-binding of phenoxazone and a homologous series of its n-alkyl ethers (1-8C) was studied in hepatic microsomes of control, phenobarbitone-pretreated (PB) and 3-methylcholanthrene-pretreated (3MC) C57/BL10 mice. Phenoxazone and its ethers were hydroxylated and O-dealkylated respectively to a common metabolite, resorufin. The three categories of microsomes differed greatly in activity for the metabolism and binding of the various substrate homologues. The most rapidly metabolised substrates for control microsomes were phenoxazone and its shortest-chain ethers, for PB microsomes phenoxazone and the pentyl ether, and for 3MC microsomes the ethyl and propyl ethers. The variations in activity occurred in Vmax rather than in the apparent Km-value. All the ethers gave Type I cytochrome P-450-binding spectra. The substrates giving the largest Type I spectra were the same for all microsomes--the ethyl, propyl and butyl ethers--but the magnitudes of the spectra differed in the order 3MC- greater than PB- greater than control microsomes. Phenoxazone and resorufin gave Modified Type II cytochrome P-450-binding spectra. PB-induction was most marked for the depentylation reaction (increased 101-fold), whereas 3MC-induction was most marked for depropylation and debutylation (88- and 96-fold). The intermicrosomal differences were interpreted as reflecting the different metabolic specificities of variant forms of cytochrome P-450. Substrate lipophilicity increased with increasing ether chain length and was not a major influence on specificity. The main substrate influence on specificity was steric, due to the presence and length of the ether side chain. The preeminent effect of ether chain length was considered to be on the rate of substrate transformation rather than on substrate interaction with cytochrome P-450.


Complement and autoimmunity.
The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.


Sensitivity of cultured rat hepatocytes to aflatoxin B1 and benzo(a)pyrene.
We have tested the sensitivity of a cloned rat hepatocyte line, RL-PR-C, to aflatoxin B1 and benzo(a)pyrene as a function of population-doubling level. The cells were much more sensitive to the cytotoxic action of these agents subsequent to 230 population doublings. This sensitivity corresponded to the enhanced inducibility of aryl hydrocarbon hydroxylase activity by 3-methylcholanthrene.


Phytoaccumulation of antimicrobials from biosolids: impacts on environmental fate and relevance to human exposure.
Triclocarban and triclosan, two antimicrobials widely used in consumer products, can adversely affect ecosystems and potentially impact human health. The application of biosolids to agricultural fields introduces triclocarban and triclosan to soil and water resources. This research examined the phytoaccumulation of antimicrobials, effects of plant growth on migration of antimicrobials to water resources, and relevance of phytoaccumulation in human exposure to antimicrobials. Pumpkin, zucchini, and switch grass were grown in soil columns to which biosolids were applied. Leachate from soil columns was assessed every other week for triclocarban and triclosan. At the end of the trial, concentrations of triclocarban and triclosan were determined for soil, roots, stems, and leaves. Results indicated that plants can reduce leaching of antimicrobials to water resources. Pumpkin and zucchini growth significantly reduced soil concentrations of triclosan to less than 0.001 mg/kg, while zucchini significantly reduced soil concentrations of triclocarban to 0.04 mg/kg. Pumpkin, zucchini, and switch grass accumulated triclocarban and triclosan in mg per kg (dry) concentrations. Potential human exposure to triclocarban from consumption of pumpkin or zucchini was substantially less than exposure from product use, but was greater than exposure from drinking water consumption. Consequently, research indicated that pumpkin and zucchini may beneficially impact the fate of antimicrobials in agricultural fields, while presenting minimal acute risk to human health.


Correlation between clinical symptoms and peripheral immune response in HAM/TSP.
HTLV-1 infects principally CD4+ T cells that are the main reservoirs of the virus in vivo, which play an important role in the immunological response. Most of the infected patients are asymptomatic. However, 2-3% of patients will develop HAM/TSP or Adult T lymphoma. HAM/TSP is a chronic inflammatory disease of the central nervous system, which is characterized by unremitting myelopathic symptoms. Studies have shown that cytokines levels alterations (IFN-γ and TNF-α) were associated with tissue injury in HAM/TSP. The aims of this study were to compare the gene expression of IFN-γ, IL-4 and IL-10 of asymptomatic and HAM/TSP HTLV-1 infected patients, and to correlate the gene expression with those of clinical symptoms. 28 subjects were included, 20 asymptomatic HTLV-1 and 8 with HAM/TSP. Spasticity was evaluated using the Modified Ashworth Scale and the degree of walking aid was classified on a progressive scale. The relative gene expression of IFN-γ, IL-4, and IL-10 was measured by Real-Time PCR. Results showed high gene expression of IFN-γ for all patients, but it was higher among HAM/TSP. A significant correlation was observed between IFN-γ gene expression and the degree of walking aid, and IFN-γ gene expression was higher among wheelchair users compared to non-wheelchair users. No association was found with IL-4 and IL-10. These findings indicate that HAM/TSP patients express higher amounts of IFN-γ than asymptomatic patients, and more importantly, the expression of this cytokine was strongly correlated with the need of walking aid.


Beaks promote rapid morphological diversification along distinct evolutionary trajectories in labrid fishes (Eupercaria: Labridae).
The upper and lower jaws of some wrasses (Eupercaria: Labridae) possess teeth that have been coalesced into a strong durable beak that they use to graze on hard coral skeletons, hard-shelled prey, and algae, allowing many of these species to function as important ecosystem engineers in their respective marine habitats. While the ecological impact of the beak is well understood, questions remain about its evolutionary history and the effects of this innovation on the downstream patterns of morphological evolution. Here we analyze 3D cranial shape data in a phylogenetic comparative framework and use paleoclimate modeling to reconstruct the evolution of the labrid beak across 205 species. We find that wrasses evolved beaks three times independently, once within odacines and twice within parrotfishes in the Pacific and Atlantic Oceans. We find an increase in the rate of shape evolution in the Scarus+Chlorurus+Hipposcarus (SCH) clade of parrotfishes likely driven by the evolution of the intramandibular joint. Paleoclimate modeling shows that the SCH clade of parrotfishes rapidly morphologically diversified during the middle Miocene. We hypothesize that possession of a beak in the SCH clade coupled with favorable environmental conditions allowed these species to rapidly morphologically diversify.


Prevalence and clonal analysis of Porphyromonas gingivalis in primary endodontic infections.
This study investigated the prevalence of Porphyromonas gingivalis in 62 teeth with primary endodontic infections by using a species-specific 16S rRNA gene-based nested polymerase chain reaction assay. P. gingivalis isolates recovered from 2 infected root canals were also analyzed for clonal diversity by using arbitrarily primed PCR. Overall, P. gingivalis was found in 48% of the samples. This species was specifically detected in 36% of canals of teeth with chronic apical periodontitis, in 46% of the cases of acute apical periodontitis, and in 67% of acute apical abscesses. P. gingivalis was significantly more frequent in abscess aspirates than in canals of teeth with chronic apical periodontitis (P < .05). Typing of colonies retrieved from 2 infected canals revealed 2 clones per individual. These findings confirmed that P. gingivalis can be an important endodontic pathogen, mostly associated with acute abscesses, and demonstrated that different clonal types of this species can colonize the root canal in the same individual.


Subunits in zonulae adhaerentes and striations in the associated circumferential microfilament bundles in chicken retinal pigment epithelial cells in situ.
This study shows that the zonula adhaerens in chicken retinal pigment epithelial (RPE) cells in situ consists of independent subunits which are composed of extracellular intermembrane discs sandwiched between cytoplasmic plaques. These zonula adhaerens complexes (ZACs) are hexagonally arranged within the junction. Previous immunocytochemical studies suggest that the zonula adhaerens region, composed of ZACs, contains the actin associated proteins vinculin and alpha-actinin. The intermembrane discs of ZACs likely mediate cell-to-cell adhesion whereas the cytoplasmic plaques are probably involved in binding the microfilaments of the relatively large circumferential microfilament bundles (CMBs), associated with the zonula adhaerens, to the cell membrane. The CMBs of chicken RPE cells in situ show striations similar to those found in stress fibers of other cell types and in CMBs of cultured epithelial cells. The observation that in the striated regions of CMBs the adjacent junctional membranes tend to follow an undulating path suggests that the CMBs are attached intermittently to the cell membrane and are contractile. The structural similarities between CMBs and stress fibers and the fact that they share similar actin associated proteins support the view that CMBs and stress fibers are related structures.


Japanese patients with Fabry disease predominantly showing cardiac and neurological manifestation with novel missense mutation: R220P.
Fabry disease, an X-linked lysosomal sphingolipid storage disorder caused by mutation of the α-galactosidase A (GLA) gene, results in systemic organ damage. However, the age of onset of clinical manifestations and course of the disease are variable even within the same family. In this study, we evaluated the clinical phenotype and the molecular lesions associated with the GLA gene in a Japanese family with Fabry disease that predominantly showed cardiac and neurological manifestations. A genetic analysis of the GLA gene using conventional genomic sequencing was performed in all seven members of this family, including four hemizygous males and three heterozygous females. Endomyocardial biopsy was performed in two patients with severe left ventricular (LV) hypertrophy. A novel missense mutation was identified at codon 220 in exon 5, thus resulting in an arginine to proline substitution (R220P) in all seven family members. The three adult hemizygous males had LV hypertrophy and developed neurological manifestations in their 50s. One of the adult hemizygotes developed complete atrioventricular block. On the other hand, we could not find any organ damage in a young hemizygous male or the three heterozygous females. We identified a novel missense mutation in a Japanese family with Fabry disease showing cardiac and neurological manifestations. In patients with Fabry disease, advanced organ damage in the heart and brain can be life-threatening, even if renal failure is lacking.


Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome.
To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.


'Over the counter' (OTC) opiate abuse treatment.
Over the counter (OTC) medication abuse is an increasing public health concern. We studied the clinical profiles, treatment and prevalence of patients admitted with OTC opiate abuse. Using a specially designed demographic form, the records of patients admitted to St. Patrick's Hospital, a 280 bed inpatient mental health and addiction treatment facility in Dublin, with a diagnosis of harmful OTC opiate abuse or opiate dependency as defined in ICD-10 were reviewed retrospectively. All patients diagnosed with OTC opiate abuse (ICD F11.1) or dependency (ICD F11.2) on admission to our centre were included in the study. Patients with a diagnosis of primary illicit opiate misuse were excluded. Approximately 1% (n=20) of inpatients admitted in a year were diagnosed with OTC opiate abuse. The average daily codeine intake was 261.0 mg per person. Some 75% percent (n=15) of the inpatients experienced OTC opiate withdrawal and were treated with protocol driven withdrawal regimes for an average of 16.10 days. The female: male ratio was nearly 2:1 with an average age of 49.2 years. Patients tended to have co-morbid psychiatric (n=19, 95%), physical (n=17,85%) and polysubstance (n=13,65%) illness. OTC opiate abuse is a significant problem which is largely covert in nature with serious co-morbidity and frequent complications including withdrawal symptoms which require treatment. Results of this study suggest that further research is warranted in this area.


Recurrence of cerebrovascular thromboembolic event in a woman with accessory mitral valve during puerperium period.
Accessory mitral valve tissue is an extremely rare congenital cardiac anomaly. Most of the cases reported in the literature were associated with left ventricular outflow tract obstruction. In this report, a second cerebrovascular event is presented in the same patient two years after an operation in which septal myectomy was performed but accessory mitral valve tissue was not excised.


Molecular mechanisms of skin wound healing in non-diabetic and diabetic mice in excision and pressure experimental wounds.
Experimental models for chronic skin lesions are excision and pressure ulcer, defined as "open" and "closed" lesions, respectively, only the latter characterized by tissue hypoxia. Moreover, systemic diseases, such as diabetes mellitus, affect wound repair. Thus, models for testing new therapies should be carefully selected according to the expected targets. In this study, we present an extensive and comparative histological, immunohistochemical, and molecular characterization of these two lesions in diabetic (db/db) and non-diabetic (C57BL/6 J) mice. In db/db mice, we found significant reduction in PGP9.5-IR innervation, reduction of capillary network, and reduced expression of NGF receptors. We found an increase in VEGF receptor Kdr expression, and the PI3K-Akt signaling pathway at the core of the altered molecular network. Db/db mice with pressure ulcers showed an impairment in the molecular regulation of hypoxia-related genes (Hif1a, Flt1, and Kdr), while extracellular matrix encoding genes (Itgb3, Timp1, Fn1, Col4a1) were upregulated by hyperglycemia and lesions. Overall, the molecular analysis suggests that db/db mice have a longer inflammatory phase of the wound repair process, delaying the progression toward the proliferation and remodeling phases.


Comparison of the excitatory actions of substance P, carbachol, histamine and prostaglandin F2 alpha on the smooth muscle of the taenia of the guinea-pig caecum.
A comparison was made of the actions of substance P, prostaglandin F2 alpha (PGF2 alpha), histamine and carbachol on the membrane potential and conductance of the longitudinal smooth muscle of the taenia of the guinea-pig caecum using the double sucrose gap apparatus. The increases in conductance produced by the four drugs during matched depolarizations in the sucrose gap were not significantly different and they were substantially larger than the increase in conductance brought about during the same depolarization produced by passing outward current. In sucrose-substituted, Na- and Cl-deficient solution the increases in conductance and depolarization due to carbachol, substance P, and PGF2 alpha were attenuated to a similar extent. The depolarization due to histamine under these conditions was reduced to a significantly greater extent than that due to carbachol. In Tris-benzene-sulphonate substituted Na- and Cl-deficient solution the responses due to carbachol and histamine were attenuated to a similar extent. This suggests that sucrose addition may have a specific effect on the histamine response. In Tris-substituted Na-deficient solution the increases in conductance and depolarization produced by substance P, histamine and carbachol were attenuated to a similar extent. The depolarization due to PGF2 alpha was reduced by a significantly greater amount which may be due to unmasking an inhibitory effect that was sometimes apparent in normal solution. In benzenesulphonate-substituted, Cl-deficient solution the increases in conductance and depolarizations produced by moderate concentrations of PGF2 alpha, histamine and carbachol were attenuated to a similar extent. The response to substance P was little affected. In glucuronate-substituted, Cl-deficient solution the increases in conductance and depolarizations due to substance P and carbachol were attenuated to a similar extent. This result, and the observation that the depolarization to large concentrations of carbachol was not reduced in benzenesulphonate-substituted, Cl-deficient solution, suggest that benzenesulphonate interferes with the reactions of the non-peptide stimulants with their respective receptors. The similarities in the effects of activating the four types of receptor under some conditions could be explained if they all acted on the same population of receptor-operated channels. In addition it seems that PGF2 alpha acts also on a population of inhibitory receptors, sucrose interferes with histamine's action, and benzenesulphonate interferes with the reactions of non-peptide stimulants with their respective receptors.


Resistance to 9-beta-D-arabinofuranosyl-2-fluoroadenine due to reduced incorporation into DNA from competition by excess deoxyadenosine triphosphate: implications for different sensitivities to nucleoside analogues.
The cytotoxic action of the deoxyadenosine analogue 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) depends on the incorporation into DNA after being phosphorylated to F-ara-A triphosphate (F-ara-ATP) by deoxycytidine kinase (dCK). The mechanisms of resistance to F-ara-A were investigated in a newly established variant of L1210 mouse leukemia cells (L1210/F). L1210/F was more than 41-fold more resistant to F-ara-A than the parental cell line and had a 55% lower dCK activity. Interestingly, L1210/F showed a modest level of cross-resistance to deoxycytidine analogues phosphorylated by dCK, for instance, 1-beta-D-arabinofuranosylcytosine (ara-C). The comparative study of F-ara-A and ara-C demonstrated that the difference in the accumulation of their respective triphosphates was minor. In contrast, the incorporation of F-ara-A into DNA was strikingly suppressed compared with that of ara-C. In general, the high natural triphosphate levels interfere with corresponding analogue incorporation into DNA. The deoxyadenosine triphosphate (dATP) and deoxycytidine triphosphate pool sizes in L1210/F cells were increased by 4.9-fold and 1.9-fold, respectively, compared with the parental cells. Treatment with hydroxyurea increased the ratio of F-ara-ATP to dATP 2.1-fold and enhanced the action of F-ara-A in L1210/F. This is the first cell line to show that the profoundly defective incorporation of F-ara-A into DNA during competition with excess dATP confers a high degree of resistance to F-ara-A.


Perceiving Collision Impacts in Alzheimer's Disease: The Effect of Retinal Eccentricity on Optic Flow Deficits.
The present study explored whether the optic flow deficit in Alzheimer's disease (AD) reported in the literature transfers to different types of optic flow, in particular, one that specifies collision impacts with upcoming surfaces, with a special focus on the effect of retinal eccentricity. Displays simulated observer movement over a ground plane toward obstacles lying in the observer's path. Optical expansion was modulated by varying [Formula: see text]. The visual field was masked either centrally (peripheral vision) or peripherally (central vision) using masks ranging from 10° to 30° in diameter in steps of 10°. Participants were asked to indicate whether their approach would result in "collision" or "no collision" with the obstacles. Results showed that AD patients' sensitivity to [Formula: see text] was severely compromised, not only for central vision but also for peripheral vision, compared to age- and education-matched elderly controls. The results demonstrated that AD patients' optic flow deficit is not limited to radial optic flow but includes also the optical pattern engendered by [Formula: see text]. Further deterioration in the capacity to extract [Formula: see text] to determine potential collisions in conjunction with the inability to extract heading information from radial optic flow would exacerbate AD patients' difficulties in navigation and visuospatial orientation.


Effects of online relationship programs for low-income couples during the perinatal period.
Low-income couples experience increased stress and declines in relationship quality during the perinatal period. They also encounter many barriers to accessing relationship services. Using a subsample of low-income perinatal couples (n = 180) from two randomized controlled trials, the current study examined the impact of online relationship interventions, OurRelationship (OR) and ePREP, in a Bayesian framework. From pre to post, relative to waitlist control couples, couples in OR and ePREP experienced improvements in relationship quality (Mean d = 0.51) and psychological distress (Mean d = 0.28); OR couples, relative to waitlist control couples, also experienced improvements in perceived stress (Mean d = 0.33). These improvements were maintained through four-month follow-up and did not differ across gender. These findings suggest brief online relationship interventions may be an important resource for low-income perinatal couples.


[Variability of chromosome 1 with HSR insertions in natural and synanthropous populations of house mouse Mus musculus L. 1758].
House mice carrying aberrant chromosome 1 with an insertion of homogeneously stained regions (HSR) have been studied. The mice were collected in the North Caucasus, Chita and Amur oblasts, Spitzbergen and Kunashir Islands, Altai krai, Khabarovsk krai, Primorye, Sakhalin, Kamchatka, Turkmenistan, and Kazakhstan. In these mice, the aberrant chromosomes were assigned to the "Asian" type, i.e. they carried two HSR insertions. The aberrant chromosome 1 in house mice from different geographic regions was shown to differ in size of HSR, staining intensity, and some other features of Q-H, C, and G-banding, which suggests independent origin of this aberration in house mouse populations from different taxa and regions. A novel variant of chromosome 1 in mice of the subspecies M. m. wagneri was found.


A thermally robust amine-imine nickel catalyst precursor for living polymerization of ethylene above room temperature.
A bulky amine-imine nickel complex containing two 2,6-diisopropyl substituents after activation with MMAO or Et(2)AlCl can polymerize ethylene in a living fashion over a period of 120 minutes at room temperature or above.


Building by Syntax: The Neural Basis of Minimal Linguistic Structures.
Language comes in utterances in which words are bound together according to a simple rule-based syntactic computation (merge), which creates linguistic hierarchies of potentially infinite length-phrases and sentences. In the current functional magnetic resonance imaging study, we compared prepositional phrases and sentences-both involving merge-to word lists-not involving merge-to explore how this process is implemented in the brain. We found that merge activates the pars opercularis of the left inferior frontal gyrus (IFG; Brodmann Area [BA] 44) and a smaller region in the posterior superior temporal sulcus (pSTS). Within the IFG, sentences engaged a more anterior portion of the area (pars triangularis, BA 45)-compared with phrases-which showed activity peak in BA 44. As prepositional phrases, in contrast to sentences, do not contain verbs, activity in BA 44 may reflect structure-building syntactic processing, while the involvement of BA 45 may reflect the encoding of propositional meaning initiated by the verb. The pSTS appears to work together with the IFG during thematic role assignment not only at the sentential level, but also at the phrasal level. The present results suggest that merge, the process of binding words together into syntactic hierarchies, is primarily supported by BA 44 in the IFG.


The 19q13 KRAB Zinc-finger protein ZFP82 suppresses the growth and invasion of esophageal carcinoma cells through inhibiting NF-κB transcription and inducing apoptosis.
To study the epigenetic alternations and biological functions of ZFP82 in esophageal squamous cell carcinoma. Analysis of ZFP82 expression was carried out by quantitative real-time PCR. Cell function was tested by MTS cell proliferation assay, transwell assay and flow cytometry. Gene mechanisms were studied by reverse transcription-PCR (RT-PCR), quantitative real-time PCR, luciferase reporter assay and Western blot. ZFP82 promoter methylation was downregulated in esophageal squamous cell carcinoma. ZFP82 ectopic expression suppressed cell function and regulated NF-κB phosphorylation and genes involved in cell cycle arrest and apoptosis. Moreover, ZFP82 methylation was correlated with age, tumor stage and outcome. ZFP82 is a tumor suppressor and is disrupted by promoter CpG methylation during esophageal carcinogenesis.


Extramedullary plasmacytoma (EMP): Report of a case manifested as a mediastinal mass and multiple pulmonary nodules and review of literature.
Extramedullary plasmacytoma (EMP) is a rare plasma cell neoplasm of soft tissue without bone marrow involvement or other systemic characteristics of multiple myeloma A 42 year-old woman presented with intermittent dry cough of 10 months duration. Her breathing sound was slightly coarse without rales or rhonchi on auscultation. CT scan revealed a right anterior mediastinal shadow with multiple pulmonary nodular lesions. A video-assisted thoracoscopic surgery (VATS) was performed. Histopathology showed it to be a myeloma. This is the first presentation of EMP with a mediastinal mass with multiple pulmonary nodules.


Isolation efficiency of collagenase and EDTA for the culture of corneal endothelial cells.
Tissue engineering of the corneal endothelium, as well as cell therapy, has been proposed as an alternative approach for the treatment of corneal endotheliopathies. These approaches require in vitro amplification of functional corneal endothelial cells (CECs). The goal of this study was to compare two common isolation methods, collagenase A and EDTA (EDTA), and determine whether they influence cell viability, morphology, and barrier function. Human eye bank research-grade corneas were used to isolate and cultivate CECs. All donors were more than 40 years old. Two Descemet membranes from the same donor were used separately to compare the collagenase A and EDTA cell isolation methods. The number of isolated cells, cell viability, morphology, and barrier functionality were compared. A higher isolation efficiency of viable CECs and a higher circularity index (endothelial morphology) were obtained using collagenase A. Passage 3 cells presented similar barrier functionalities regardless of the isolation method. This study showed that isolation of CECs using collagenase A yields higher isolation efficiency than EDTA, delaying the loss of endothelial morphology for early passage cells.


Maternal exposure to Di-n-butyl phthalate (DBP) aggravate gestational diabetes mellitus via FoxM1 suppression by pSTAT1 signalling.
The study focused on the toxicological effect of Di-n-butyl phthalate (DBP) on the expression of Phosphorylated signal transducer and activator of transcription 1 (pSTAT1) -regulated Forkhead box protein M1 (FoxM1), which might provide a new understanding of gestational diabetes mellitus (GDM) development and a potential target for treatment. Streptozotocin (STZ) (40 mg/kg) was introduced in maternal rats by intraperitoneal injection on gestation day 0 (GD 0) in the STZ and STZ + DBP groups. DBP was introduced in maternal rats by oral feeding in the STZ + DBP group over the following 3 days (750 mg/kg/day). The changes in fasting blood glucose level in rats were detected on GD 1 and GD 5. The insulin levels in maternal rats and PIBCs were measured on GD 18. The Oral Glucose Tolerance Test (OGTT) test was performed on GD 18 to check the stability of the GDM model. The primary islet β cells (PIBCs) were established for in vitro experiments. We examined the FoxM1 and pSTAT1 expression in pancreas by immunohistochemistry. Real-time PCR and Western blot were used to detect the pSTAR1 and FoxM1 protein and mRNA gene expression levels in PIBCs. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis was used to test the viability and apoptosis of cells. The results showed that the STZ + DBP group had higher glucose and lower insulin secretion levels than the other groups by both fasting test and OGTT. FoxM1 was significantly suppressed while pSTAT1 was highly expressed after DBP exposure. FoxM1 could be regulated by pSTAT1. DBP can influence the progression of GDM through its toxicological effect, which significantly increases the expression of pSTAT1 and suppresses FoxM1, causing a decline in β cell viability.


Robust PPG motion artifact detection using a 1-D convolution neural network.
Continuous monitoring of physiological parameters such as photoplethysmography (PPG) has attracted increased interest due to advances in wearable sensors. However, PPG recordings are susceptible to various artifacts, and thus reducing the reliability of PPG-driven parameters, such as oxygen saturation, heart rate, blood pressure and respiration. This paper proposes a one-dimensional convolution neural network (1-D-CNN) to classify five-second PPG segments into clean or artifact-affected segments, avoiding data-dependent pulse segmentation techniques and heavy manual feature engineering. Continuous raw PPG waveforms were blindly allocated into segments with an equal length (5s) without leveraging any pulse location information and were normalized with Z-score normalization methods. A 1-D-CNN was designed to automatically learn the intrinsic features of the PPG waveform, and perform the required classification. Several training hyperparameters (initial learning rate and gradient threshold) were varied to investigate the effect of these parameters on the performance of the network. Subsequently, this proposed network was trained and validated with 30 subjects, and then tested with eight subjects, with our local dataset. Moreover, two independent datasets downloaded from the PhysioNet MIMIC II database were used to evaluate the robustness of the proposed network. A 13 layer 1-D-CNN model was designed. Within our local study dataset evaluation, the proposed network achieved a testing accuracy of 94.9%. The classification accuracy of two independent datasets also achieved satisfactory accuracy of 93.8% and 86.7% respectively. Our model achieved a comparable performance with most reported works, with the potential to show good generalization as the proposed network was evaluated with multiple cohorts (overall accuracy of 94.5%). This paper demonstrated the feasibility and effectiveness of applying blind signal processing and deep learning techniques to PPG motion artifact detection, whereby manual feature thresholding was avoided and yet a high generalization ability was achieved.


Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.
To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and <1.0 ng/mL would have modest sensitivity and specificity in predicting the extremes of response. Circulating AMH has the ability to predict excessive and poor response to stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.


Vasectomy and prostate cancer risk: a meta-analysis of cohort studies.
Some studies have suggested that vasectomy is associated with the increased risk of prostate cancer, however, this conclusion is not supported by all the published studies. In order to examine the relationship between vasectomy and prostate cancer risk, we conducted a meta-analysis of cohort studies to clarify this controversial association. PubMed and Medline were used to identify the cohort studies that reported the association of vasectomy with prostate cancer risk from 1980 to January 2015. Based on a random effects model, the RR and 95% CI were used to assess the combined risk. In total, 10 cohort studies involving more than 7027 cases and 429914 participants were included. There was no significant relationship between vasectomy and prostate cancer risk, the pooled RR (95%CI) was 1.11[0.98, 1.27] (P = 0.109). In subgroup-analysis, the relationship between vasectomy and prostate cancer risk was not significantly modified by the length of follow-up and population distribution except Americans. Omission of any single study had little effect on the pooled risk estimate. Little evidence of publication bias was found. In conclusion, our meta-analysis suggests that vasectomy is not associated with the increased risk of prostate cancer. More studies based on other populations including the Chinese are needed.


Difficult weaning from mechanical ventilation.
Difficult weaning is fortunately a rare occurrence in mechanically ventilated patients in ICU. When faced with this problem, a vast number of factors must be carefully considered simultaneously: physiological adjustment, technical problems (tubing, circuit resistances, . . .) [13]. The most promising approach to difficult weaning to date centers on the respiratory muscle function which represents the most common factor allowing weaning success or failure.


Clinical spectrum of non-alcoholic fatty liver disease in patients with diabetes mellitus.
Non-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully. We explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients. This is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software. Among 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03-1.14; p = 0.004), obesity (BMI ≥ 27.5 kg/m2, OR = 2.64; 95% CI: 1.28-5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40-13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02-1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00-1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98-1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18-17.62; p = 0.028) were independent factors associated with increased liver stiffness. Our study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.


Selective inactivation of MAO-B by benzyl-dimethyl-silyl-methanamines in vitro.
The alpha-silyl amines benzyl-dimethyl-silyl-methanamine and the p-fluoro and p-chloro derivatives are potent time-dependent inhibitors of rat brain MAO-B. The inhibition exhibits saturation kinetics, takes place in the enzyme active-site and is irreversible. The most potent inhibitor in the series is 4-fluorobenzyl-dimethyl-silyl-methanamine (KI = 11 microM, tau 1/2 = 2.3 min). Its selectivity for the B-form relative to the A-form of rat brain MAO is higher than 10(4). Benzyl-dimethyl-silyl-methanamines may represent a new family of anti-Parkinsonian agents.


Exercise Therapy and Radiation Therapy for Cancer: A Systematic Review.
Exercise therapy (ET) is shown to improve toxicity and surrogates of survival for patients receiving chemotherapy. Current National Comprehensive Cancer Network (NCCN) guidelines lack recommendations for concurrent radiation therapy (RT) and ET. The main objective was to determine the impact of concurrent ET + RT with respect to (1) acceptability, feasibility, safety; and (2) to demonstrate how incorporating ET in cancer treatment can enhance patient-reported outcomes (PROs) and physical function-defined as strength or exercise capacity. A PICOS/PRISMA selection protocol was used to search PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Review for prospective randomized controlled trials evaluating concurrent ET + RT, including >10 patients and with 1 or more study arms. Acceptability, feasibility, and safety rates were calculated. PROs were assessed with study-specific metrics. Physical function was defined as improvements in strength or range of motion. Statistically significant improvement was defined by P <.05. Twenty-six of 693 screened studies including 1563 patients (831 receiving exercise, 732 controls) with localized breast cancer (67.1% of patients), prostate cancer (27.4%), head and neck cancers (2.8%), and spinal metastases (2.8%) were assessed. Objective 1: Among 3385 patients approached for ET, 1864 (55.1%) accepted the treatment; of those, 1563 patients (83.9%) completed the trials. Objective 2: Statistical improvements were noted in these PROs: quality of life (14 of 15 studies), fatigue (12 of 16 studies), mood/depression (9 of 13), and anxiety (6 of 7). Physical function improved statically in 16 of 16 studies. Combination ET + RT is safe and well-tolerated with improvements in PROs and physical function. Additional studies are needed in patients with metastatic cancers to assess survival and to compare effectiveness of different exercise regimens.


Ethnic identity, perceptions of disadvantage, and psychosis: findings from the ÆSOP study.
Many studies have shown that rates of psychosis are elevated in the Black and minority ethnic (BME) population in the UK. One important, but relatively less researched explanation of these high rates may be social adversity associated with acculturation processes. Strong identification with an ethnic minority group subjected to social disadvantage may exert adverse effects on individuals from BME groups. Using data from a large epidemiological case-control study of first-episode psychosis, we aimed to investigate whether strong ethnic identification is a factor contributing to the excess of psychosis in BME groups compared with the White British, after adjustment for perceptions of disadvantage. All cases with a first episode of psychosis presenting to specialist mental health services within tightly defined catchment areas in London and Nottingham, UK, and geographically matched community controls were included in the study. Data were collected on socio-demographic and clinical characteristics, perceptions of disadvantage, and identification with one's own ethnic group. Analysis was performed on data from 139 cases and 234 controls. There was evidence that, as levels of ethnic identification increased, the odds of psychosis increased in the BME but not in the White British group, independent of potential confounders. However, the association between strong ethnic identity and psychosis in BME individuals was attenuated and non-significant when controlled for perceived disadvantage. Strong identification with an ethnic minority group may be a potential contributory factor of the high rates of psychosis in the BME population, the effects of which may be explained by perceptions of disadvantage.


Cu-BTC metal-organic framework as a biocompatible nanoporous carrier for chlorhexidine antibacterial agent.
Antibacterial materials are an essential part of modern life and many efforts have been made to find a new and effective type of them. In this study, chlorhexidine (CHX) was loaded on Cu-BTC metal-organic framework (MOF), that both of them are known to have antibacterial properties. The antibacterial properties of Cu-BTC, CHX and CHX@Cu-BTC were investigated against Gram-positive and Gram-negative bacteria. Agar well-diffusion method and MIC test showed that CHX@Cu-BTC has high antibacterial activity. Characterization methods, such as FT-IR, XRD, N2 adsorption-desorption isotherm, TGA, SEM, EDX, TEM and zeta potential, were employed to characterize their structures. Cu-BTC MOF nanoparticles were synthesized and used as nanoporous carriers for chlorhexidine. The loading was about 10%, which was absorbed into the pores. Antibacterial activity was investigated against Gram-negative and Gram-positive bacteria by Agar well diffusion method and MIC (minimal inhibitory concentration) assay. The CHX@Cu-BTC had synergistic antibacterial activity of Cu-BTC and chlorhexidine.


Incidental Detection of Dual Spinal Meningiomas on 68 Ga-DOTATATE PET/CT Masquerading as Metastatic Disease in a Patient With Pulmonary Carcinoid Tumor.
Simultaneous occurrence of multiple meningiomas of the spine appearing at different neuroaxial levels is extremely rare event. We present the scintigraphic findings of incidentally detected multiple meningiomas of the spine on 68 Ga-DOTATATE PET/CT during the evaluation of a patient with pulmonary carcinoid tumor. These scintigraphic findings could result in a "false-positive" interpretation by exhibiting highly increased uptake similar to that of metastases of neuroendocrine neoplasm. Nuclear medicine physicians should be aware of this potential pitfall in somatostatin receptor imaging to prevent misinterpretation.


LncRNA SELL/L-selectin promotes HPV-positive HNSCC progression and drives fucoidan-mediated therapeutic strategies.
Positive human papillomavirus (HPV+) head and neck squamous cell carcinoma (HNSCC) presents a higher risk of lymph node metastasis and poor prognosis. Here, advanced microarray analysis of clinically collected HNSCC tissues revealed significant upregulation of the lncRNA SELL in HPV+ HNSCC, and its overexpression was obviously associated with lymph node metastasis. The lncRNA SELL could function as a promigratory and proinvasive mediator as well as an inducer of M1-like tumour-associated macrophages (TAM) by increasing the level of L-selectin. Furthermore, fucoidan, as an L-selectin inhibitor, obviously weakened the formation of tongue lesions induced by 4-Nitroquinoline N-oxide (4-NQO) in HPV16 E6/E7 transgenic mice. This result drove us to synchronously develop a nanodelivery platform to verify fucoidan-mediated anti-growth and anti-metastasis effects. This work highlighted the important influence of the lncRNA SELL/L-selectin on promoting HPV+ HNSCC progression and proposed a potential fucoidan-mediated therapeutic strategy. STATEMENT OF SIGNIFICANCE: Head and neck squamous cell carcinoma (HNSCC) patients with human papillomavirus (HPV) involvement present a greater risk of lymph node metastasis than HPV negative HNSCC patients. However, treatment protocols, including surgery and platinum-based chemo- and radiotherapy, have not improved the 5-year overall survival due to the high tendency of lymphatic metastasis. Here, microarray of clinical HNSCC samples confirms the oncogenic significance of lncRNA SELL, which acts as an M1-like TAM inducer and promotes tumorigenesis by upregulating L-selectin. Fucoidan, as an L-selectin inhibitor, suppresses tongue lesions in transgenic mice, and a fucoidan-mediated nanodelivery platform inhibits HPV+ HNSCC growth. The present study highlights lncRNA SELL/L-selectin on promoting HPV+ HNSCC progression and proposes a potential fucoidan-mediated therapeutic.


When stereopsis does not improve with increasing contrast.
It is well known that stereoacuity for conventional (1st-order) stimuli improves with increasing contrast with an approximate slope of -0.5 on log-log axes (Halpern DL, Blake RR. Perception 1988;17:483-495; Legge GE, Gu Y. Vis Res 1989;29:989-1004). In the experiments reported here a variety of stimuli were used (Gabor patches, amplitude modulated stimuli and 1D noise patches) and tasks (stereoacuity and Dmax) to determine if 2nd-order stereopsis shows a similar square root dependence. The results consistently demonstrate that the effect of contrast on stereopsis is quite different for the 2nd-order stimuli. Increases in stimulus contrast have little effect on performance; the resulting slopes are very shallow. The pattern of results is similar when the interocular contrast ratio is varied, demonstrating that 2nd-order processing is more resilient to stimulus differences in the two eyes than 1st-order.


Effect of porcine placenta steroid extract on myogenic satellite cell proliferation, transdifferentiation, and lipid accumulation.
Intramuscular long-chain fatty acids (LCFAs) play an important role in energy production and initiation of mitochondrial oxidation of lipids. Herein, we report a natural porcine placenta steroid extract (PPSE) that stimulates transdifferentiation and lipid accumulation in bovine myogenic satellite cells (MSCs). The steroids hormones in PPSE were analyzed using enzyme-linked immunosorbant assay and presence of LCFA was established using gas chromatography. At 70% confluent growth, cells were treated with PPSE, LCFAs, transdifferentiation cocktail and commercially available steroid hormones. The working concentrations of all chemicals were manipulated similar to PPSE. The cells were observed for morphological changes and subjected to quantitative analysis of lipid deposition on Days 2, 4, and 6 of treatment. PPSE-treated MSCs exclusively transformed into lipid-accumulated adipose-like cells (ALCs). However, myotubes or adipocytes were formed in cells treated with other chemicals. Expression of different genes was studied to ascertain the molecular mechanism involved in ALC formation. CD36, fatty acid binding protein 4, and peroxisome proliferator-activated receptor-gamma were up-regulated. The expression of CD36 was established through immunocyto-chemical analysis. A viability assay was used to confirm the effect of PPSE on proliferation of MSCs. Hence, a natural steroid extract from porcine was found as a nontoxic mixture, which induces lipid accumulation and transdifferentiation of MSCs to ALCs. From the gene expression studies, it was established that the extract works almost in homogenous manner with other lipid inducers.


The influence of p53 and associated factors on the outcome of patients with oral squamous cell carcinoma.
In several tumour entities the immunohistochemical detection of p53 has proved to be a predictive factor for the survival of the patients. In this study the effector waf1 and the regulator mdm2 responsible for the inactivation of p53 were also determined in 156 tissue samples of primary squamous cell carcinomas in the oral cavity and oropharynx, their lymph node metastases, and the epithelium outside the invasively growing tumour from 107 patients. In this latter epithelium there was a significant correlation between grade of dysplasia and staining for p53 (P<0.01). In the dysplastic epithelium a significant correlation between p53, waf1, and mdm2 was shown (P<0.05). Differences in the immunohistochemical staining between different blocks of the tumour tissue and also between primary tumours and their lymph node metastases were revealed in 11-44% of cases, but there was no correlation with other variables, such as formation of lymph node metastases. In contrast to the conventional tumour grading and staging, no influence of any of the variables determined on survival or recurrence-free survival could be detected. It seems that p53 and associated factors are important in the early stages of cancerogenesis but not in further tumour progression and metastatic spread.


Comparative study of the haemodynamic effects of oral molsidomine and isosorbide dinitrate in man.
The haemodynamic effects of oral molsidomine 4 mg and sustained-release isosorbide dinitrate (ISDN) 40 mg have been compared in 10 patients recovering from acute myocardial infarction. After both drugs pulmonary arterial, pulmonary capillary wedge and systemic arterial blood pressure were reduced to about the same extent. The maximum effect was reached 1.5 to 2 h after ingestion of both drugs, but the effect of molsidomine declined during the following 2 h and control values were almost reached after 4 h. After ISDN there was no rebound during the observation period of 6 h. Unlike molsidomine, ISDN reduced total peripheral resistance, so cardiac output and stroke volume index remained constant despite the reduction in cardiac preload. It is concluded that sustained release ISDN 40 mg and molsidomine 4 mg are about equieffective doses in terms of reduction of cardiac preload, but that the effect of molsidomine is of shorter duration. Since molsidomine alone causes venous pooling, cardiac output and stroke volume index are reduced, which may be an untoward side effect in patients with severe heart failure.


3-D characterization of ganglion cells of the terminal nerve plexus of rat atrioventricular junction.
Three-dimensional (3-D) morphology of neurons of the terminal nerve plexus of the atrioventricular junction was examined in a scanning electron microscope. Distributions of different cell types encountered as well as their relations to different structures of the atrioventricular specialized tissue were also studied. Most neurons were found disseminated in a thin connective tissue layer separating different segments of the atrioventricular conductive tissue from the interventricular septum. Sometimes, they formed small pluricellular ganglia (up to 5 neurons) but, frequently, they occurred isolated in the terminal ramifications of the intramural nerve plexus of specialized tissue. Some intranodal neurons could also be identified. According to their 3-D morphology, nerve cells of the perinodal ganglionated plexus could be divided into three categories: (1) Large unipolar neurons were scattered throughout the atrioventricular junction. Their long and thin axonal projections were often directed towards the interventricular septum. (2) Large pseudounipolar or bipolar neurons were located at a few specific loci, namely all along the bundle of His and its bifurcation into the right and left bundle branches. Frequently, they occurred solitary and immersed amongst strands of surrounding muscle cells. Only occasional synaptic impacts could be identified on the surface of neuronal bodies of these bipolar neurons. On the other hand, their dendritic varicosities were richly innervated. Due to their irregular shape, intimate association with muscular elements and their topographical superposition with occasional spindle-like structures, these nerve cells recall prospective sensory neurons involved in integration of mechanical and neural stimuli to the heart. (3) Small multipolar interneurons could be identified in the retronodal ganglion and within right and left bundle branches. The present description of morphological heterogeneity of intramural nerve cells agrees with recent morphological and functional classifications of autonomic neurons and supports the idea that, at the level of the atrioventricular junction, a self-governed neuronal network may be operating.


Intolerance of uncertainty and maladaptive perfectionism as maintenance factors for eating disorders and obsessive-compulsive disorder symptoms.
Eating disorders (EDs) are highly comorbid with obsessive-compulsive disorder (OCD). In order to develop treatments which better address commonly comorbid ED and OCD symptoms, it is important to identify potential shared mechanisms. Two potential shared mechanisms are maladaptive perfectionism and intolerance of uncertainty (IU). We aimed to assess how maladaptive perfectionism and IU may contribute to the maintenance of ED and OCD symptoms in individuals with EDs. In the current study (N = 168 individuals with an ED), we analysed cross-sectional and prospective path models of maladaptive perfectionism and IU as maintenance factors of ED and OCD symptoms. We found that IU was associated with both ED and OCD symptoms, and maladaptive perfectionism was associated with ED symptoms. We also found that maladaptive perfectionism and IU prospectively predicted OCD symptoms, but not ED symptoms. Overall, these findings suggest that it may be beneficial to target both maladaptive perfectionism and IU in individuals with a current ED diagnosis in order to prevent the development of OCD symptoms.


[Changes in the functional activity of the liver cells in rabbits during a bacterial infection].
In the process of the development of bacterial infections, the activity of marker enzymes in the membrane structure of liver cells has been studied in rabbits by biochemical and electron-histochemical methods. The results of these studies have shown that, simultaneously with the progressing course of cell pathology and inhibition of the function of mitochondria, microsomes and peroxisomes, the lysosomes activate for the realization of the protective function formed in the course of evolution. At the same time the excessive labilization of lysosomal membranes facilitates the development of cell pathology, which is confirmed by the accumulation of residual bodies in the cytoplasm.


Effect of ganglioside-GM1 on the order of phosphatidylcholine-cholesterol multilamellar liposomes. A fluorescence polarization study.
The effect(s) of bovine brain ganglioside-GM1 on the order of phosphatidylcholine-cholesterol membranes were studied using steady-state fluorescence polarization (FPZ) techniques with 1,6-diphenyl-1,3,5-hexatriene (DPH) as the membrane probe. In the absence of cholesterol, GM1 (30 mol%) increases both membrane order and the phase transition temperature of dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) membranes. However, in the presence of cholesterol (0.3 or 0.5, cholesterol/phospholipid molar ratio), GM1 significantly decreases steady-state anisotropy (rs) at temperatures above the Tm for the particular phospholipid. This effect may, in part relate to a dilution of membrane cholesterol and is shared by bovine brain sphingomyelin (SM). GM1 (30 mol%) increases the order of 1-palmityl-2-oleyl-PC (POPC) membranes. However, in the presence of cholesterol (0.3 molar ratio) GM1 neither increases or decreases order. Thus, in cholesterol containing artificial membranes, the effect of GM1 depends on the phosphatidylcholine (PC) fatty acid composition and may not be evident from the effect of GM1 on pure PC membranes.


Enoral laser microsurgery for squamous cell carcinoma of the oral cavity.
The purpose of this study was to investigate oncological and functional results of enoral laser microsurgery in treatment for cancer of the oral cavity. A retrospective chart analysis was carried out. Two hundred thirty-two patients with cancer of the oral cavity were treated by enoral laser microsurgery ± selective neck dissection ± postoperative (chemo)radiotherapy. Seventy-three percent of the patients (n = 170) received a unilateral or bilateral selective or modified radical neck dissection, 32% (n = 75) received adjuvant (chemo)radiotherapy. The median follow-up period was 71.89 months. The 5-year overall survival (OS) was 54.6%, recurrence-free survival (RFS) was 60.2%, and disease-specific survival (DSS) was 70.3%. Nasogastric feeding tubes were needed in 96 patients, only 2 patients required a temporary gastrostomy tube. Enoral laser microsurgery is an efficient therapeutic option in the treatment of oral cavity cancer. Oncological and functional results are comparable to any other treatment regimen, whereas morbidity and complications tend to be lower.


High-dose therapy and autologous stem cell transplantation for relapsed or high-risk diffuse large B-cell lymphoma: a nationwide survey.
To investigate the use of high-dose therapy and autologous stem cell transplantation (ASCT) for relapsed or high-risk diffuse large B-cell lymphoma (DLBCL) between 1990 and 2007, we conducted a nationwide survey using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Of the 1222 patients in the database, 576 (47%) received ASCT in first complete remission (CR1), 140 (12%) in first partial remission, 281 (23%) in sensitive relapse, 150 (12%) in resistant or sensitivity-unknown relapse, and 75 (6%) in primary refractory status. With a median follow-up of 22 months, the 2-year overall survival (OS) and progression-free survival rates were 71% and 68%, respectively. The cumulative incidences of 2-year non-relapse mortality and relapse/progression were 6% and 26%, respectively. Relapse/progression after ASCT in the rituximab era (2002-2007) was significantly lower than that in the pre-rituximab era (1990-2001; P < 0.001). Older age, male gender, poor performance status at ASCT, non-CR1 at ASCT, ASCT performed in 1990-2001, and LEED or MCEC regimen were adverse predictors of OS. Because ASCT for newly diagnosed high-risk DLBCL has not been performed recently, a registry database study to assess the impact of ASCT for relapsed or refractory DLBCL in the rituximab era is warranted.


Evidence for the involvement of histidine at the active site of glutathione S-transferase psi from human liver.
The inhibition of catalytic activity of glutathione S-transferase psi (pI 5.5) of human liver by diethylpyrocarbonate (DEPC) has been studied. It is demonstrated that DEPC causes a concentration dependent inactivation of GST psi with a concomitant modification of 1-1.3 histidyl residues/subunit of the enzyme. This inactivation of GST psi could be reversed by treatment with hydroxylamine. Glutathione afforded complete protection to the enzyme from inactivation by DEPC. It is suggested that a functional histidyl residue is essential for the catalytic activity of the enzyme and that this residue is most likely to be present at or near the glutathione binding site (G-site).


Location of death and hospice use in children with cancer varies by type of health insurance.
Disparities in end-of-life (EOL) care for children with cancer remain understudied. We addressed this gap by examining patterns of EOL care, with a focus on location of death and hospice utilization. We used MarketScan - a nationally representative dataset with Medicaid and commercial claims to conduct a retrospective observational study of children with cancer who died between 2011 and 2017 at age ≤21 years. We examined rates of (a) home death, (b) hospice utilization, (c) and medically intense interventions in the last 30 days (e.g., intubation). Of the 1492 children in the cohort, 44% had Medicaid and 56% commercial insurance; 71% carried a solid tumor diagnosis, and 37% were between the ages of 15 and 21 years at the time of death. Forty percent died at home; children with Medicaid were less likely to die at home (relative risk [RR] = 0.82, 95% confidence interval [CI]: 0.73-0.92; reference: commercial). Forty-five percent enrolled in hospice, for a median of 2 days. Hospice enrollment rates did not vary with insurance. However, children with Medicaid spent less time enrolled (incidence rate ratio [IRR] = 0.22, 95% CI: 0.17-0.27). Among children with Medicaid, Black children were less likely to die at home (RR = 0.69, 95% CI: 0.52-0.92) and enroll on hospice (RR = 0.71, 95% CI: 0.55-0.91) than non-Hispanic White children. Medically intense interventions did not vary with insurance or race. Only 40% of children with cancer die at home, and the duration of hospice enrollment is short. EOL care varies significantly with insurance. It is imperative that we determine if these patterns and disparities represent EOL preferences, provider biases, or differences in quality or availability of hospice.


Evaluation of a psychophysiologically controlled adaptive automation system, using performance on a tracking task.
Three experiments were conducted to evaluate the performance of a psychophysiologically controlled adaptive automation system. Subjects were asked to perform a compensatory tracking task while their electroencephalogram (EEG) was recorded and an engagement index was derived from the EEG, using the alpha, beta, and theta bandwidths: beta/(alpha + theta) and beta/theta. In Experiment I, EEG was recorded from three different sites: frontal, parietal, and temporal. Although tracking performance did not differ as a function of site, the number of task mode allocations was greater under a negative feedback contingency than under a positive feedback contingency. This effect was seen primarily from frontal sites. Experiments II and III evaluated the adaptive automation system, using extended runs under positive and negative feedback with either a slope (Experiment II) or absolute (Experiment III) criterion used to drive the system. Using either criterion, performance was found to be significantly better under negative feedback. Future evaluation and use of psychophysiologically controlled adaptive automation systems are discussed.


Low humidity effects on photosynthesis in single leaves of C4 plants.
It was hypothesized that since sub-stomatal carbon dioxide concentrations are often saturating to photosynthesis at ambient external concentrations in C4 plants at high light, photosynthesis might be insensitive to partial stomatal closure caused by large leaf-air water vapor pressure difference. The response of stomatal conductance and photosynthesis at high irradiance to vapor pressure difference was determined under uniform conditions in C4 plants grown under controlled conditions, and outdoors. In several cases, photosynthesis was less sensitive to stomatal closure than it would have been if photosynthesis had a linear response to sub-stomatal carbon dioxide concentration. No change in photosynthesis at up to 25 mbar vapor pressure difference was demonstrated in the C4 species Portulaca oleracea and Amaranthus hypochondriacus, despite reductions in stomatal conductance of 32 and 17%, respectively. Sensitivity of photosynthesis to leaf-air vapor pressure difference was found to depend on the species and on the growth conditions.


Speciation analysis of selenium in natural water using square-wave voltammetry after preconcentration on activated carbon.
A simple, accurate, sensitive and selective method was described for rapid determination of ultra-trace quantities of selenium. Selenium(IV) was collected on activated carbon (AC) after reduction to elemental Se by l-ascorbic acid. The collected selenium was then dissolved by oxidation reaction with bromate in acidic media and was indirectly determined through the bromide formation using square-wave voltammetry (OSWV). The total amount of Se(IV) and Se(VI) was collected on AC after its reduction by hydrazine. Selenium in the range 0.01-20 microg L(-1) could be determined by this method. The method was used to the determination of Se(IV) and Se(VI) in natural water with satisfactory results.


Factors affecting meniscal extrusion: correlation with MRI, clinical, and arthroscopic findings.
The existence of meniscal extrusion is well known in the natural history of the osteoarthritic knee. However, extruded menisci are also seen in non-pathologic knees. To ascertain the prevalence of meniscal extrusion in non-arthritic patients, the MRIs of 100 knees were prospectively studied. The data were correlated both with clinical and operative arthroscopic findings. The results showed 68.5% of the medial menisci to have some degree of extrusion, averaging at 28% of the meniscal size. While the lateral meniscus were extruded in 18.8% of cases at an average of 15% of the meniscal size. Furthermore, a relationship between the anterior insertion variant of the anterior medial meniscus and meniscal extrusion was found (P=0.001) in this series. The results suggest meniscal extrusion to be much more common in non-arthritic knees than previously estimated. The results also suggest that when the anterior horn of the medial meniscus inserts anteriorly in the tibial plateau, the meniscus tends to be extruded. It must be kept in mind that one of the limitations of this work is that the MRIs are taken in a non-weightbearing position.


Neuroprotection in vitro and in vivo by cell membrane-permeant Ca2+ chelators.
1. A method of attenuating excitotoxic and hypoxic/ischaemic neurodegeneration in vitro and in vivo using cell-permeant Ca(2+)-chelating agents is described. 2. The mechanism of neuroprotection may depend on both pre- and post-synaptic effects on intracellular Ca2+ dynamics. 3. This method is unique, because it targets Ca2+ ions, the presumed triggers of neurodegeneration, rather than a specific cellular receptor.


Clinical features of the spinal form of multiple sclerosis.
Out of a data pool of 1271 patients with Multiple Sclerosis (MS) a total of 109 cases are selected having a sole spinal symptomatology throughout the course of the disease. This group differs in three particular features from the non-spinal forms of MS: In this group there is a higher percentage of females, the age at onset of the disease is higher, and the course of the disease is more often chronic progressive from the beginning. After the mean duration of 11 years, the spinal and the non-spinal cases show the same grade of disability. The ability to work is slightly better for spinal cases; office workers are able to keep their jobs longer after the onset to the disease than patients with any other occupation. The spinal form of MS is discussed in respect to its relationship to the classical form of MS and as a differential diagnosis to other spinal processes.


High electrolyte uptake of MXene integrated membrane separators for Zn-ion batteries.
The recent development of separators with high flexibility, high electrolyte uptake, and ionic conductivity for batteries have gained considerable attention. However, studies on composite separators with the aforementioned properties for aqueous electrolytes in Zn-ion batteries are limited. In this research, a polyacrylonitrile (PAN)/bio-based polyurethane (PU)/Ti3C2Tx MXene composite membrane was fabricated using an electrospinning technique. Ti3C2 MXene was embedded in fibers and formed a spindle-like structure. With Ti3C2Tx MXene, the electrolyte uptake and ionic conductivity reached the superior values of 2214% and 3.35 × 10-3 S cm-1, respectively. The composite membrane presented an excellent charge-discharge stability when assembled in a Zn//Zn symmetrical battery. Moreover, the developed separator exhibited a high flexibility and no dimensional and structural changes after heat treatment, which resulted in the high-performance separator for the Zn-ion battery. Overall, the PAN/bio-based PU/Ti3C2Tx MXene composite membrane can be potentially used as a high-performance separator for Zn-ion batteries.


Methodology to evaluate stress corrosion cracking in ethanol environments, applied to circumferential welds on API 5 L steel pipelines.
This work presents an experimental methodology developed to perform fatigue crack growth (FCG) and slow strain rate (SSR) tests in ethanol environments aiming to evaluate stress corrosion cracking (SCC) susceptibility of circumferential welds on steel pipelines. FCG and SSR specimens were machined from a welded pipe and the notches were properly designed to promote crack propagation in the different regions of the weld. Tests were carried out keeping the crack-tip region fully immersed in an ethanol solution, which was fueled by a circulation system to ensure replenishment and aeration throughout the test. When applied to a welded API X70 steel pipe, this experimental methodology proved to be an efficient and simple method to achieve relevant and important informations on environmentally assisted crack growth and SCC susceptibility. The method developed here is inserted in the aspects as follows:•Perform tests in slow strain rate and cyclic bend loading in circulating ethanol, to promote the fracture in the different regions of a circumferential weld joint of a steel pipe.•Investigate sensitivity to stress corrosion cracking (SCC) of these different weld regions in ethanolic environment.•This method presents constructive details of a suitable apparatus which the experiments can be easily replicated.


Pyourachus in spina bifida: case report and review.
Failure of the urachus to close results in a multitude of clinical anomalies. Such anomalies have been documented as occurring in association with mechanical bladder outlet obstruction. However, no urachal anomalies have been linked specifically to spina bifida. Two cases of urachal abscesses were identified in adolescent male patients with spina bifida at our institution, both with neuropathic bladders and using self-catheterization. The clinical presentations differed, with classic involvement of the umbilicus in 1 case. Because of its varied presentations, the diagnosis of a urachal anomaly is potentially difficult. Urachal anomalies should be considered in the evaluation of pelvic masses in this demographic.


[Determination of cardenolides in Digitalis lanata by a solid-phase immunoenzyme method].
A competitive solid-phase EIA technique using high-affinity digoxin-specific monoclonal antibodies has been developed to determine cardenolides in Digitalis lanata. The test-system can detect digoxin and closely related compounds in concentration of 0.1 nmol/ml. The content of cardenolides, tested by ELISA, correlated well with the total content of digoxin, deslanoside C and lanatoside C as analysed by HPLC. The test-system is useful in estimating the productivity of large series and samples of tissue clones of Digitalis lanata.


Masticadienonic acid from Chios mastic gum mitigates colitis in mice via modulating inflammatory response, gut barrier integrity and microbiota.
Chios mastic gum (CMG) is a traditional Greek medicine used to treat a variety of gastrointestinal disorders, including inflammatory bowel disease (IBD). However, the bioactive compounds of CMG and the mechanisms of action for controlling of IBD remain unknown. Masticadienonic acid (MDA) is one of the most abundant constituents isolated from CMG. This study aims to investigate the potential effects and underlying mechanisms of MDA in the pathogenesis of colitis. The effects of MDA were evaluated using a dextran sulphate sodium (DSS)-induced acute colitis mouse model. The body and spleen weight and colon length and weight were measured and the clinical symptoms were analysed. Blood samples were collected to analyse the level of serum inflammatory markers. Colon tissues were processed for histopathological examination, evaluation of the epithelial barrier function, and investigation of the probable mechanisms of action. The gut microbiota composition was also studied to determine the mechanism for the beneficial effects of MDA on IBD. MDA could ameliorate the severity of IBD by increasing the body weight and colon length, reducing spleen weight, disease activity index, and histological score. MDA treatments reduce the release of serum inflammatory cytokines tumour necrosis factor-alpha (TNFα), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) via inhibiting the MAPK and NF-κB signalling pathways. MDA supplementation could also improve the intestinal barrier function by activating the NF-E2-related factor-2 (Nrf2) signalling pathway and restoring the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. In addition, MDA administration modulates the gut microbiota composition in DSS-induced colitis mice. The results indicate that MDA attenuated experimental colitis by restoring intestinal barrier integrity, reducing inflammation, and modulating the gut microbiota. The present study provides novel insights into CMG-mediated remission of IBD and may facilitate the development of preventive and therapeutic strategies for IBD.


Developmental Trajectories of Internalizing and Externalizing Symptoms in Youth and Associated Gender Differences: A Directed Network Perspective.
Psychopathology in youth is highly prevalent and associated with psychopathology in adulthood. However, the developmental trajectories of psychopathology symptoms, including potential gender differences, are markedly underspecified. The present study employed a directed network approach to investigate longitudinal relationships and gender differences among eight transdiagnostic symptom domains across three years, in a homogenous age sample of youth participants (n = 6,414; mean baseline age = 10.0 years; 78.6% White; Adolescent Brain Cognitive Development study). Anxious/depressed problems and aggressive behaviors were central symptoms and most predictive of increases in other symptom clusters at later timepoints. Rule-breaking behaviors, aggressive behaviors, and withdrawn/depressed problems emerged as bridge symptoms between externalizing and internalizing problems. Results supported cascade models in which externalizing problems predicted future internalizing problems, but internalizing problems also significantly predicted future externalizing problems, which is contrary to cascade models. Network structure, symptom centrality, and patterns of bridge symptoms differed between female and male participants, suggesting gender differences in the developmental trajectories of youth psychopathology. Results provide new insights into symptom trajectories and associated gender differences that may provide promising pathways for understanding disorder (dis)continuity and co-occurrence. The central and bridge symptoms identified here may have important implications for screening and early intervention for youth psychopathology.


Sexual dimorphism in an animal model of Sjögren's syndrome: a potential role for Th17 cells.
Sjögren's syndrome is a complex autoimmune disease with an array of diverse immunological, genetic and environmental etiologies, making identification of the precise autoimmune mechanism difficult to define. One of the most distinctive aspects of Sjögren's syndrome is the high sexual dimorphism with women affected 10-20 times more than men. It is nearly impossible to study the sexual dimorphic development of Sjögren's syndrome in human patients; therefore it is pertinent to develop an appropriate animal model which resembles human disease. The data indicated that female C57BL/6.NOD-Aec1Aec2 mice developed an earlier onset of sialadenitis with a higher composition of CD3(+) T cells and a 10-fold increase in glandular infiltration of Th17 cells at the onset of clinical disease compared to male mice. Inflammatory Th17 cells of female mice exhibited a stronger proliferation in response to disease-specific antigen than their male counterpart. At the clinical disease stage, altered autoantibody patterns can be detected in females whereas they are seldom observed in male C57BL/6.NOD-Aec1Aec2 mice. Interestingly, male C57BL/6.NOD-Aec1Aec2 mice developed an earlier loss of secretory function, despite the fact that female C57BL/6.NOD-Aec1Aec2 mice exhibited a more rapid secretory loss. This data indicates the strong sexual dimorphism in the SjS-susceptible C57BL/6.NOD-Aec1Aec2 animal model, making it an appropriate animal model to examine human disease.


Treatment of colon cancer in rats with rMuTNF and the interferon-inducer bropirimine.
It is well documented that the antitumor activity of tumor necrosis factor (TNF) is improved by interferons (IFN's). Bropirimine (BP) is an immune response modifier which induces IFN. Both TNF and BP have the capacity to inhibit the growth of a transplantable colon tumor (CC531) in inbred WAG rats. In the present study their combined use was investigated in a one-week assay, with the tumor implanted under the renal capsule. The results indicate that BP, given on days 0 and 1, and 1 microgram TNF on days 0, 2 and 4 act additively, leading to an almost complete inhibition of tumor growth.


Gastrin and cancer: a review.
In 1905, a Cambridge physiologist, John Sydney Edkins, initially identified a hormone responsible of gastric acid secretion, which he called gastric secretin, or gastrin. While gastrin's role in acid secretion is now well defined, more recent studies have implicated the various isoforms of gastrin in cancer. Important advances in the last decade have included the recognition of biological activity for processing intermediates such as progastrin and the glycine-extended gastrin. Here, we give an overview of the roles of these peptides in cancer, highlighted by molecular, cellular and integrated studies on animal models for progastrin-derived peptides and their receptors.


Mechanism of neurotensin depolarization of rabbit colonic smooth muscle.
The aims of this study were (1) to measure the effect of neurotensin on the membrane potential of circular muscle of the distal colon of the rabbit and (2) to determine the mechanism by which neurotensin affects the membrane potential of this tissue. The membrane potential was measured with microelectrodes placed intracellularly and the double sucrose gap. Neurotensin (10(-11) M to 10(-7) M) dose-dependently decreased the membrane potential. The maximum decrease in membrane potential occurred with 10(-9) M neurotensin. The ED50 of neurotensin depolarization of the membrane potential was 0.87 +/- 0.33 X 10(-10) M. The frequency of the slow waves was unchanged after neurotensin. The voltage response to a constant current pulse decreased as the concentration of neurotensin increased. The amplitude of the voltage response after a 0.6 microA current pulse decreased by 6 +/- 0.5 mV after neurotensin (10(-7) M) compared to the Krebs control (P less than 0.05). Decreasing the [Na+]o to 0-23 mM did not affect the decrease in membrane potential after neurotensin. However, perfusion with a test solution containing no added Ca2+ or verapamil (10(-5) M) inhibited neurotensin depolarization of the tissue. Evidence was found that neurotensin depolarizes colonic circular smooth muscle, and the decrease in membrane potential is associated with an increase in conductance which is dependent on influx of Ca2+.


A bioceramic endoprosthesis for the replacement of the proximal humerus.
In patients with malignant tumors in the region of the shoulder, radical resection can avoid amputation in most instances. To improve the function of the arm, endoprosthetic replacement of the defect is desirable. A three-component endoprosthesis made of a bioceramic material (aluminium oxide) was designed, implanted without bone cement. Fast anchorage to bone is achieved by using a conical sleeve, fixed upon the previously conically reamed humerus shaft. A stable primary fit is always feasible. Subsequent bone in growth into grooves inside the conical sleeve provides a permanent anchorage of the endoprosthesis. The authors experiences are based on implantations of 38 endoprostheses. The original diseases were primary malignant bone tumors in 19 patients, one case of "solitary" plasmocytoma and metastases into the proximal humerus in 16 patients. In two women, resection was made because of posttraumatic subcapital humeral pseudarthrosis. The follow-up study includes only those 27 cases operated on at least one year ago. 12 of the 14 patients with primary tumors have been surviving for 12-55 months (range 27.4) without signs of metastases or recurrent disease. Seven patients with metastases died of their original diseases after 7.7 months on the average. Owing to extensive resection of the shoulder musculature the mobility in the shoulder joint is considerably reduced. All the patients have good movement of the elbow joint and free function of the hand.


Draft Genome Sequences of Three Type Strains, Acetobacter farinalis KACC 21251, Acetobacter suratthaniensis KACC 21252, and Acetobacter thailandicus KACC 21253.
As part of a genome database construction of type strains, we report the draft genome sequences of three strains of acetic acid bacteria, i.e., Acetobacter farinalis KACC 21251T, Acetobacter suratthaniensis KACC 21252T, and Acetobacter thailandicus KACC 21253T.


Subjective hearing handicap is associated with processing speed and visuospatial performance in older adults without severe hearing handicap.
Age-related hearing loss is a common disorder with significant consequences for quality of life. This study assessed the Hearing Handicap Inventory for the Elderly (HHIE) and cognition (Mini Mental State Exam; MMSE, Logical Memory; LM, Symbol Search; SS, Stroop Test; ST, and Mental Rotation; MR) to investigate which cognitive domains are most strongly involved with hearing self-assessment in older adults. The HHIE and cognitive measures were administered to 196 older adults (average age = 67.7 ± 4.3 years, male 56, female 140) without cognitive impairment and without severe hearing handicap. We conducted permutation tests of multiple regression analysis of the standardized scores on the HHIE and cognitive tests. HHIE showed a significant negative correlation between processing speed performance on the SS (standardized β = -0.095, adjusted p = 0.04) and visuospatial performance on the MR (standardized β = -0.145, adjusted p = 0.04), and no correlation between the scores of the HHIE and either episodic memory performance on the LM (standardized β = 0.060, adjusted p = 0.22) or executive function performance on the ST (standardized β = 0.053, adjusted p = 0.32). People reporting higher hearing handicaps should watch for poor cognitive function in processing speed and visuospatial abilities. These results imply that higher HHIE can have adverse effects on age-related cognitive decline.


Effect of temperature and sample preparation on performance of ion-moderated partition chromatography of organic acids in biological fluids.
A thorough investigation of the behavior of organic acids on the Bio-Rad Aminex cation exchange resin was prompted by both the limitations of, and a number of inexplicable inconsistencies found in, previously published papers using an identical system. In order to stabilise the elution order of various acids it was necessary to analyse samples at a higher temperature than previously recommended. This temperature (50 degrees C) decreased the retention times of all acids permitting the analysis of both aromatic and aliphatic acids within the same 45-min run. Preparation of an acidic fraction of biological fluids improved specificity, allowed direct comparison of urine and plasma profiles and by control of the conditions interference by urate could be substantially reduced. Retention data are given for more than 90 acidic metabolites including nearly 40 of clinical significance and a number derived from diet and drug therapy.