The use of melatonin as a vaccine agent.
Molecules with immunomodulatory properties determine the magnitude and quality of immune responses specific for the coadministered antigen. Melatonin is considered a biological-response modifier of the immune system with broad application in veterinary medicine. In seasonally-breeding animals, the indolamine is able to improve reproductive performance. With the purpose of expanding new advantageous roles for melatonin, we investigated the effect of subcutaneous slow-release melatonin implants in the humoral response after a vaccination. We reported here a new feature of melatonin as an adjuvant-like system towards Dichelobacter nodosus (A1 and C serotypes)--the bacterium which cause ovine footrot--the most important cause of lameness in sheep. Antibody titres determined by both agglutination and ELISA techniques were substantially higher and were sustained for a longer duration than non-implanted animals. Remarkably, the effect of melatonin was completely dependent on the presence of aluminium hydroxide. The finding that melatonin enhances a defined immune response in vivo opens new perspectives for the improvement of Th2-biased immune responses by alum adjuvants.


A novel covalent modification of antibodies at their amino groups with retention of antigen-binding activity.
A novel method of covalent modification of antibodies at their amino groups with retention of antigen-binding activity is described. The procedure is as follows: (a) blockade of those amino groups of antibodies whose integrity is essential to their antigen-binding activity with 2,3-dimethylmaleic anhydride, a reversible amino group-blocking reagent; (b) modification of residual amino groups with reagents reactive with the amino groups; and (c) removal of dimethylmaleyl groups by hydrolysis. This procedure was used for covalent conjugation of methotrexate (MTX) with two monoclonal antibodies against human melanoma-associated antigens using MTX N-succinimidyl ester. MTX attached to the antibodies at sites other than the amino groups via less stable bond(s) was removed by treatment with hydroxylamine.


Neglected PTM in animal adipogenesis: E3-mediated ubiquitination.
Ubiquitination is a widespread post-transcriptional modification (PTM) that occurs during protein degradation in eukaryotes and participates in almost all physiological and pathological processes, including animal adipogenesis. Ubiquitination is a cascade reaction regulated by the activating enzyme E1, conjugating enzyme E2, and ligase E3. Several recent studies have reported that E3 ligases play important regulatory roles in adipogenesis. However, as a key influencing factor for the recognition and connection between the substrate and ubiquitin during ubiquitination, its regulatory role in adipogenesis has not received adequate attention. In this review, we summarize the E3s' regulation and modification targets in animal adipogenesis, explain the regulatory mechanisms in lipogenic-related pathways, and further analyze the existing positive results to provide research directions of guiding significance for further studies on the regulatory mechanisms of E3s in animal adipogenesis.


Blood nickel and chromium levels in association with smoking and occupational exposure among head and neck cancer patients in Tunisia.
Chronic exposure to chromium (Cr) and nickel (Ni) has long been recognized as being capable to increase head and neck cancer (HNC) incidence among exposed human populations. This study represents the first biomonitoring of Cr and Ni exposure in Tunisia and focuses on a possible association with HNC risk. The aim of the present study was to evaluate the concentrations of Cr and Ni in the blood of HNC patients and controls. Metals blood levels of 169 HNC patients and 351 controls were determined using a Perkin-Elmer Analyst 800 Atomic Absorption Spectrometer. Mean blood levels of Cr and Ni in HNC cases (52.15 and 111.60 μg/L, respectively) were significantly higher than those of controls (37.04 and 30.50 μg/L, respectively). Cases' blood levels of Cr and Ni were significantly higher than those of controls after controlling for the other risk factors of HNC, including smoking, shisha consumption, occupational exposure, and nearby environment (P<0.05). Among these risk factors, smoking and occupational exposure presented the most significant association with HNC (odds ratio (OR)=6.54 and 7.66, respectively, P<0.001). Cr and Ni levels in blood sample of cases and controls that are smoker/occupationally exposed were higher than that of non-smoker/non-occupationally exposed (P<0.05). Smokers who are occupationally exposed present the most significant association with HNC (OR=25.08, P<0.0001). High levels of blood Cr (OR=2.09) and high levels of blood Ni (OR=8.87) were strongly associated with HNC after other potential confounders were controlled (P=0.004 and P<0.0001, respectively). This study suggested a potential role of Cr and Ni in the mechanism of HNC development.


The relationship between autism spectrum and sleep-wake traits.
Autistic children and adults often have sleep disturbances, which may affect their and their family's quality of life. Yet, the relationship between sleep-wake patterns and autism spectrum traits is understudied. Identifying such relationships could lead to future research elucidating common mechanistic underpinnings. Thus, we aimed to determine whether sleep-wake patterns, specifically related to sleep, physical activity, and the daily sleep-wake rhythm (i.e., circadian rhythm), are associated with autism spectrum-related traits. Accelerometer-derived sleep-wake parameters were estimated in individuals with autistic spectrum traits and their family members (N = 267). We evaluated autism spectrum traits using the Social Responsiveness Scale (SRS) to assess the presence and severity of social impairment and the Behavior Rating Inventory of Executive Function (BRIEF) to assess executive function. The linear multivariate regression analysis (using SOLAR-Eclipse) showed that in adults, increased core autism spectrum traits and executive dysfunction were associated with disruption of several sleep-wake parameters, particularly related to the daily sleep-wake rhythm, and that executive dysfunction was associated with disrupted sleep quality and level of physical activity. We highlight the interplay between daytime function and disrupted sleep-wake patterns, specifically related to the daily sleep-wake rhythm, that could guide future research into common mechanisms. LAY SUMMARY: Autistic children and adults often report sleep disturbances. To dissect the relationship between a range of autism spectrum traits and sleep-wake patterns, we assessed social interaction and executive function in participants who also wore actimetry watches on their wrists to assess their sleep-wake patterns. We found that increased impairments in social and executive function occurred with increased sleep-wake disturbances, particularly those related to the circadian rhythm, suggesting that these perturbations/disruptions in the sleep-wake cycle could be connected to autism spectrum traits.


Absorption and dissociation mediate the relationship between direct verbal suggestibility and impulsivity/compulsivity.
Direct verbal suggestibility refers to the capacity for an individual to experience perceptual, motor, affective and cognitive changes in response to verbal suggestions. Suggestibility is characterized by pronounced, yet reliable, inter-individual differences. Previous research and theoretical considerations suggest that greater impulsivity and compulsivity is associated to higher suggestibility, but the characteristics and mediating factors of this association are poorly understood. Using established psychometric measures in an online sample, we found positive correlations between the domain comprising impulsivity, compulsivity and behavioural activation, and the domain of suggestibility, dissociation and absorption. We also observed that dissociation and absorption mediated the link between suggestibility and impulsivity, and between suggestibility and behavioural activation, respectively. These results confirm the positive link between suggestibility and the impulsivity/compulsivity domain and shed new light on the characterisation of traits associated with suggestibility.


Maternal age as a factor in determining the reproductive and behavioral outcome of rats prenatally exposed to ethanol.
Nulliparous Long-Evans rats were bred at one of four different ages and assigned to one of three treatment groups within each age condition. Maternal ages were 9, 18, 32, and 36 weeks. Treatment groups were ethanol (E), administered by gavage as 8 g/kg in two divided doses on days 10-14 of gestation, pair-fed (PF) controls, administered as an isocaloric sucrose solution by gavage on days 10-14 of gestation, and ad lib fed controls (C). All offspring were surrogate fostered shortly after delivery to untreated recently parturient dams. Litter sizes were standardized to 8 on the day of birth. Offspring were assessed longitudinally for growth, mortality, and behavior (olfaction, locomotor activity, maze learning, avoidance acquisition and startle). Approximately 85% of the 36 week old dams did not produce viable litters. In the remaining maternal age conditions, ethanol delayed offspring olfactory orientation and increased locomotor activity, the latter dissipating after 50-60 days of age. These ethanol-related effects occurred independent of maternal age condition. Maternal age, independent of ethanol, was a factor which reduced litter size and offspring weight up to 50 days, but produced few effects on behavior. The combination of maternal age and prenatal ethanol interacted to increase pregnancy loss (oldest maternal age), reduce offspring weight up to day 99 (oldest and middle maternal age), alter olfactory orientation performance (oldest and middle maternal age), reverse the typical ethanol-induced increase in activity for males in the figure-8 test (oldest maternal age group), shift the pattern of open-field activity, and change errors in a complex water maze. Not all of these interactions turned out to be specific to the ethanol X old maternal age condition. Several of the interactions occurred in both the old and middle maternal age conditions. The only effect of old maternal age that interacted strongly with ethanol was in their combined effects on reproduction. Here the combination of the two factors increased maternal mortality, the number of early pregnancy losses, and the number of litters where all members were dead or resorbed. It was concluded that short-term prenatal ethanol combined with advanced maternal age produces additive interactions on pregnancy success without affecting longer-term outcomes, while young maternal age showed no clear detrimental effects compared to the middle maternal age reference group.


Microenvironment Matters: Unique Conditions Within Gut-Draining Lymph Nodes Favor Efficient De Novo Induction of Regulatory T Cells.
The gastrointestinal tract constitutes the largest surface of the body and thus has developed multitude mechanisms to either prevent pathogen entry or to efficiently eliminate invading pathogens. At the same time, the gastrointestinal system has to avoid unwanted immune responses against self and harmless nonself antigens, such as nutrients and commensal microbiota. Therefore, it is somewhat not unexpected that the gastrointestinal mucosa serves as the largest repository of immune cells throughout the body, harboring both potent pro- as well as anti-inflammatory properties. One additional key element of this regulatory machinery is created by trillions of symbiotic commensal bacteria in the gut. The microbiota not only simply contribute to the breakdown of nutrients, but are essential in limiting the expansion of pathogens, directing the development of the intestinal immune system, and establishing mucosal tolerance by fostering the induction of regulatory T cells (Tregs). In this review, we will discuss our current understanding about the microenvironmental factors fostering the de novo generation of Tregs within the gastrointestinal immune system, focusing on unique properties of antigen-presenting cells, tolerogenic cytokines, commensal-derived metabolites and the contribution of lymph node stromal cells.


Phylogeny of the avian genus Pitohui and the evolution of toxicity in birds.
Bird species in the avian genus Pitohui contain potent neurotoxic alkaloids that may be used for defense. The genus comprises multiple species that are endemic to New Guinea and were presumed to belong to the family Pachycephalidae or Colluricinclidae, within the core corvoidea, an ancient Australasian radiation of crow-like birds. In order to understand the evolution of toxicity within the genus Pitohui, we sequenced three mitochondrial and two nuclear gene segments and reconstructed a phylogeny of the genus Pitohui and its putative relatives. We show that the genus Pitohui is polyphyletic, and consists of five different lineages. Using Bayesian ancestral state reconstruction, we estimate that toxicity likely evolved multiple times within this group. Furthermore, because the morphological and behavioral similarity among these poisonous birds appears to have evolved convergently, we hypothesize that this may be a possible example of Müllerian mimicry in birds. The Morningbird of Palau, Micronesia, that has often been included in the genus Pitohui, actually belongs in the genus Pachycephala and offers an intriguing case of pronounced evolution on a remote oceanic island.


Unusual metastases from esophageal carcinoma: computed tomography demonstration.
The computed tomography findings of large subcutaneous metastatic implants in the pelvic and inguinal regions from an epidermoid carcinoma of the esophagus are presented. To the best of the authors' knowledge, this appearance has not previously been reported.


Soil organic matter is essential for colony growth in subterranean termites.
Intrinsic dinitrogen (N2) fixation by diazotrophic bacteria in termite hindguts has been considered an important pathway for nitrogen acquisition in termites. However, studies that supported this claim focused on measuring instant N2 fixation rates and failed to address their relationship with termite colony growth and reproduction over time. We here argue that not all wood-feeding termites rely on symbiotic diazotrophic bacteria for colony growth. The present study looks at dietary nitrogen acquisition in a subterranean termite (Rhinotermitidae, Coptotermes). Young termite colonies reared with wood and nitrogen-rich organic soil developed faster, compared to those reared on wood and inorganic sand. More critically, further colony development was arrested if access to organic soil was removed. In addition, no difference of relative nitrogenase expression rates was found when comparing the hindguts of termites reared between the two conditions. We therefore propose that subterranean termite (Rhinotermitidae) colony growth is no longer restricted to metabolically expensive intrinsic N2 fixation, as the relationship between diazotrophic bacteria and subterranean termites may primarily be trophic rather than symbiotic. Such reliance of Rhinotermitidae on soil microbial decomposition activity for optimal colony growth may also have had a critical mechanistic role in the initial emergence of Termitidae.


The comparative virulence of thermotolerant Mucorales species in mice.
The comparative virulence of thermotolerant Mucorales was determined for cortisone-treated and untreated Swiss mice by intravenous administration of spores. The measure of virulence was based on an LD50 value, calculated after the 30-day observation period. Of the known etiological agents of mucormycosis, Mucor meihei, M. pusillus, Rhizopus arrhizus, R. chinensis, R. cohnii, R. microsporus, R. oryzae, R. rhizopodiformis and Cunninghamella elegans were able to produce fatal infections in mice; whereas, Mucor alternans, M. ramosissimus and Syncephalastrum racemosum were avirulent at dosages of up to 10(5) spores. Of those thermotolerant species which have not been reported to cause mucormycosis in human beings, Radiomyces embreei, R. spectabilis, Rhizopus oligosporus and Thermomucor indicae-seudaticae were found to produce fatal infections in mice; whereas, an isolate of Mycotypha africana was avirulent. Cortisone treatment of mice was found to lower their resistance to infection at a given spore dosage as measured by ET50 values.


Lymphatic metastasis-associated circRNA‒miRNA‒mRNA network for exploring the pathogenesis and therapeutic target of triple negative breast cancer based on whole-transcriptome sequencing analysis: an experimental verification study.
The metastatic mechanisms of axillary lymph nodes (ALNs) in triple-negative breast cancer (TNBC) remain unclear. We aimed to identify the potential circRNA regulatory network in ALN metastasis. We performed whole transcriptome sequencing (WTS) to determine the expression profiles of RNAs and screen out differentially expressed messenger RNAs (DEMs), microRNAs (DEMis), and circRNAs (DECs) between ALN-positive and ALN-negative TNBC patients. Functional enrichment analysis and Kaplan-Meier survival analysis were utilized to unearth the potential regulatory mechanisms of the DEMs. A competing endogenous RNA (ceRNA) network was constructed using computational biology. The expression levels of DECs in cell lines were confirmed by real-time polymerase chain reaction (RT‒PCR). Following WTS and differential expression analysis, 739 DEMs, 110 DEMis, and 206 DECs were identified between ALN-positive and ALN-negative TNBC patients. Functional analysis indicated that the DEMs mainly functioned in carcinogenesis and tumor progression-related pathways. ceRNA networks containing eight circRNAs, six miRNAs, and eighteen mRNAs were developed. In the ceRNA network, two mRNAs (RAB3D and EDARADD) that were significantly associated with better overall survival and one mRNA (GSR) that predicted favorable recurrence-free survival in TNBC patients were chosen for further analysis. Then, a survival-related ceRNA network containing two DECs (hsa_circ_0061260 and hsa_circ_0060876), two DEMis (hsa-miR-5000-3p and hsa-miR-4792), and three mRNAs (GSR, RAB3D, and EDARADD) was identified. Then, two candidate DECs were validated by real-time PCR. Our research constructed a ceRNA network that provides novel insights into the molecular mechanism of ALN metastasis and potential therapeutic targets in TNBC.


Vitamin B1 Supports the Differentiation of T Cells through TGF-β Superfamily Production in Thymic Stromal Cells.
Homeostatic generation of T cells, which occurs in the thymus, is controlled at least in part by endogenous cytokines and ligands. In addition, nutritional factors are other key regulators for the homeostasis of host immunity, but whether and how nutrition affects the homeostatic generation of thymocytes remains to be established. Here, we showed that vitamin B1 deficiency resulted in a bias toward the maturation of γδ thymocytes accompanied by decreased differentiation into double-positive thymocytes during thymic involution. These events were mediated through the increased production of TGF-β superfamily members due to the accumulation of branched-chain α-keto acids in thymic stromal cells. These findings revealed essential roles of vitamin B1 in the appropriate differentiation of T cells through the metabolism of thymic stromal cells.


Neural circuits for a top-down control of fear and extinction.
Fear learning and extinction are controlled by the activity of three interconnected regions: the amygdala, hippocampus, and prefrontal cortex. Of these, the medial prefrontal cortex modulates specific aspects in fear and extinction via a top-down regulation. In recent years, extensive progress has been made in our understanding of the neural circuits that mediate fear-related behaviors and their modulation by ascending systems. The development of new experimental techniques is now revealing the details of the intrinsic circuits within these structures as well as the connections between them. Here, we highlight recent advances in our understanding of how the prefrontal cortex may mediate such a top-down regulation.


Rapid hyaluronan uptake is associated with enhanced motility: implications for an intracellular mode of action.
Texas red-labeled hyaluronan (TR-HA) is rapidly taken up in a CD44 independent manner into ras-transformed 10T1/2 fibroblasts, where it accumulates in both cell ruffles/lamellae, the perinuclear area, and the nucleus. HA does not accumulate in the cell ruffles/lamellae of parental 10T1/2 cells. Addition of HA to ras-transformed cells promotes their random motility but has no effect on 10T1/2 cell motility. 10T1/2 cells can be modified to take up HA into cell ruffles by exposure to phorbol ester or direct microinjection of HA into cells. Both treatments significantly stimulate 10T1/2 cell motility.


Gene-based multiple trait analysis for exome sequencing data.
The common genetic variants identified through genome-wide association studies explain only a small proportion of the genetic risk for complex diseases. The advancement of next-generation sequencing technologies has enabled the detection of rare variants that are expected to contribute significantly to the missing heritability. Some genetic association studies provide multiple correlated traits for analysis. Multiple trait analysis has the potential to improve the power to detect pleiotropic genetic variants that influence multiple traits. We propose a gene-level association test for multiple traits that accounts for correlation among the traits. Gene- or region-level testing for association involves both common and rare variants. Statistical tests for common variants may have limited power for individual rare variants because of their low frequency and multiple testing issues. To address these concerns, we use the weighted-sum pooling method to test the joint association of multiple rare and common variants within a gene. The proposed method is applied to the Genetic Association Workshop 17 (GAW17) simulated mini-exome data to analyze multiple traits. Because of the nature of the GAW17 simulation model, increased power was not observed for multiple-trait analysis compared to single-trait analysis. However, multiple-trait analysis did not result in a substantial loss of power because of the testing of multiple traits. We conclude that this method would be useful for identifying pleiotropic genes.


An outbreak of Pasteurella multocida pneumonia in lambs during a field trial of a vaccine against Pasteurella haemolytica.
A vaccine against pneumonic pasteurellosis was evaluated for efficacy at two dilutions in lambs transported by sea from New Zealand to Saudi Arabia. The experimental vaccine was a killed Pasteurella haemolytica serotype A1 and A2 preparation. There was no evidence of either dilution of the vaccine leading to a lower pneumonia death or lesion rate than for the control group. However, bacteriological examinations to establish the causality of the pneumonia cases showed Pasteurella multocida to be the dominant organism, while P. haemolytica types A1 and/or A2 occurred at only a very low incidence.


Activation of the protein kinase B pathway by the HPV-16 E7 oncoprotein occurs through a mechanism involving interaction with PP2A.
Protein kinase B (PKB) or Akt is one of several second messenger kinases that are activated by cell attachment and growth factor signaling, and that transmit signals to the cell nucleus to inhibit apoptosis and thereby increase cell survival during proliferation. Other viral proteins target this pathway by increasing PKB/Akt phosphorylation, and this pathway has been implicated in the transformation of human keratinocytes by HPV E6 and E7, together with activated notch 1. Here, we examine how HPV E7 expression affects the phosphorylation of PKB. We show that HPV-16 E7 increases the level of phosphorylation of PKB in response to serum stimulation, by a mechanism independent of downregulation of PTEN phosphatase, a known inhibitor of the PI3K (PI3 kinase) pathway. The use of specific antibodies shows that some proportion of PKB/Akt that is phosphorylated both on threonine 308 and serine 473 is maintained in the presence of E7 in a PI3 kinase-independent manner, and is activated for phosphorylation of BAD, a known downstream target of PKB/Akt. Use of E7 mutants has ruled out both an inhibition of IGFBP-3, a known E7 target and PKB/Akt modulator, and the interaction of E7 with cellular pocket proteins, as being the mechanism for the PKB/Akt stimulation. PKB binds PP2A and is a known substrate of PP2A. Here, we show that HPV E7 also binds to both the 35 kDa catalytic and 65 kDa structural subunits of PP2A, an interaction that sequesters these subunits and inhibits their interaction with PKB, thereby maintaining PKB/Akt signaling by inhibiting its dephosphorylation.


Neuroendocrine system of the digestive tract in Rhamdia quelen juvenile: an immunohistochemical study.
In this work, an immunohistochemical study was performed to determine the distribution and relative frequencies of some neuromodulators of the digestive tract of silver catfish (Rhamdia quelen). The digestive tract of silver catfish was divided into six portions; the oesophagus, stomach, intestine (ascendant, descendant and convoluted segments), and rectum. Immunohistochemical method using a pool of specific antisera against-gastrin, -cholecystokinin-8, -leu-enkephalin, -neuropeptide Y, -calcitonin gene-related peptide (CGRP), and -vasoactive intestinal peptide (VIP) was employed. Immunoreactivity to all antisera was identified in neuroendocrine cells (NECs) localized in the gut epithelium, although no reaction was observed in the oesophagus or stomach. The morphology of NECs immunopositive to each antibody was similar. They were slender in shape, with basally located nucleus, and their main axis perpendicular to the basement membrane. The number of NECs immunoreactive to all antisera was higher in the ascendant and descendant intestine, exhibiting a decreasing trend toward distal segments of the gut. In addition, immunoreactivity to CGRP and VIP was observed in the myenteric plexus and nerve fibers distributed in the mucosal, submucosal and muscular layers. The higher number of immunopositive NECs in the ascendant and descendant intestine may indicate the primary role of these segments in the control of food intake by means of orexigenic and anorexigenic peripheral signals.


Role of Ca2+/phospholipid-dependent protein kinase in catecholamine secretion from bovine adrenal medullary chromaffin cells.
The role of Ca2+/phospholipid-dependent protein kinase (protein kinase C) in catecholamine secretion from bovine adrenal medullary chromaffin cells was examined using four protein kinase C inhibitors: polymyxin B, sphingosine, staurosporine, and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). For this purpose, digitonin-permeabilized chromaffin cells were used. Secretion of catecholamines from these cells was stimulated by the addition of micromolar amounts of exogenous free Ca2+. 12-O-Tetradecanoylphorbol-13-acetate (TPA) and arachidonic acid, activators of protein kinase C, enhanced the catecholamine secretion evoked by Ca2+. But phorbol-12, 13-diacetate, a phorbol ester analog that does not activate protein kinase C, had no effect on Ca2(+)-evoked secretion. Polymyxin B at a low concentration (1 microM) abolished the enhancement of secretion by TPA or arachidonic acid without affecting the secretion evoked by Ca2+. However, polymyxin B at higher concentrations (10-100 microM) greatly reduced Ca2+-evoked catecholamine secretion. Sphingosine 10 microM-1 mM), Staurosporine (100 nM-1 microM, and H-7 (100-500 microM) inhibited TPA- or arachidonic acid-enhanced secretion but not Ca2(+)-evoked secretion. In cells in which protein kinase C was down-regulated by TPA, specific binding of [3H]phorbol-12,13-dibutyrate to the cells almost disappeared and the enhancement of secretion by TPA was no longer observed, whereas Ca2(+)-evoked secretion was maintained. These results strongly suggest that protein kinase C is not essential for the Ca2(+)-dependent catecholamine secretion from bovine adrenal chromaffin cells, but acts instead as a modulator.


Histopathological alterations in gills of white shrimp, Litopenaeus vannamei (Boone) after acute exposure to cadmium and zinc.
White shrimp, Litopenaeus vannamei, a globally important cultured prawn species, is an ideal animal for studying the impairment caused by the effects of heavy metals that are often detected in coastal areas. In this present study, we detected the acute toxicity of cadmium (Cd) and zinc (Zn) to L. vannamei. Medium lethal time (LT50) values of Cd and Zn on L. vannamei were estimated. Furthermore, we also demonstrated that acute exposure to high concentrations of Cd and Zn resulted in morphological alterations in gills of L. vannamei in this present study.


Correction: Ryss, A.Y.; Subbotin, S.A. New Records of Wood- and Bark-Inhabiting Nematodes from Woody Plants with a Description of Bursaphelenchus zvyagintsevi sp. n. (Aphelenchoididae: Parasitaphelenchinae) from Russia. Plants 2023, 12, 382.
In the original publication [...].


Doppler study and evidences of perfusion changes in the ophthalmic artery of pregnant smokers.
To compare the ophthalmic artery (OA) perfusion of pregnant smokers and nonsmokers by Doppler indexes. Correlate these with the interval of last cigarette, cigarettes per day, years smoking and carbon monoxide expired (COex). Transversal study involving 70 pregnant smokers divided into 33 pregnant who smoked until 2 h: A group (AG) and B group (BG): 37, who smoked between 2 and 24 h before test. Control group (CG) was composed of 51 pregnant nonsmokers. Doppler indexes were assessed: PSV (Peak Systolic Velocity), EDV (End Diastolic Velocity), PI (Pulsatility Index), RI (Resistance Index) and PR (Peak Ratio). Groups were compared using ANOVA, Kruskal-Wallis test, Student's t test, Mann-Whitney and Pearson's correlation coefficient, whereas p < 0.05. RI and PI were higher (p < 0.01) and PSV and EDV were lower (p < 0.05) in B group compared to other groups. A group presented higher PR (p < 0.01) compared to control. AG presented years of smoking, cigarettes per day, COex greater than BG and lower interval of last cigarette than BG. The OA in pregnant smokers shows a biphasic pattern of perfusion correlated with the time of consumption of the last cigarette. There are signs of vasoconstriction and hypoperfusion to tobacco exposure between 2 and 24 and hyperperfusion in A Group compared to B Group.


Rheological properties and antitumor activity of schizophyllan produced with solid-state fermentation.
Schizophyllan (SPG) was produced by the fungus Schizophyllum commune under solid-state fermentation conditions in this study. SPG was physically characterized and its rheological properties and antitumor effects on S180 tumors in vivo were evaluated. SPG is a neutral polysaccharide with three main fractions, and the major fraction comprises 55.5%, with an average molecular weight 4.65 × 10(7) Da. Steady shear rheological measurements showed the typical pseudoplastic flow behavior of SPG at the experimental concentrations. The power law model was used to fit the shear curves of SPG and both its viscosity and consistency indices changed regularly as the concentration increased. SPG solution showed different viscoelastic behaviors at different concentrations: typical viscoelastic behavior was observed at lower concentrations, whereas solid-like behavior was observed at higher concentrations. Experimental doses of SPG exerted extreme antitumor effects in vivo, and the maximum inhibition rate was almost 70%.


Upregulation of lncRNA BANCR associated with the lymph node metastasis and poor prognosis in colorectal cancer.
Growing evidence has supported that long non-coding RNAs (lncRNAs) could play vital roles in the development, progression, and prognosis of colorectal cancer (CRC). However, little is known about the clinical significance of BRAF-activated non-coding RNA (BANCR) in CRC. The aim of this study is to explore the clinical value of lncRNA BANCR in CRC patients. The expression of lncRNA BANCR was measured in 106 CRC tissues and 65 adjacent normal tissues using the quantitative real-time PCR. The study showed that lncRNA BANCR was highly expressed in CRC tissues compared with adjacent normal tissues (P < 0.001). In addition, high expression of lncRNA BANCR was positively correlated with the lymph node metastasis (P < 0.001). Kaplan-Meier analysis showed that patients with high lncRNA BANCR expression had a shorter overall survival (OS) compared with the low lncRNA BANCR expression group (P = 0.001). Interestingly, for the group of patients with the lymph node metastasis, we found the similar result that high lncRNA BANCR expression was related to poor OS (P = 0.004). Furthermore, the multivariate Cox regression model analysis indicated that high expression of lncRNA BANCR was an independent poor prognostic factor in CRC patients (HR 2.24, 95% CI 1.22-4.16, P = 0.009). Upregulation of lncRNA BANCR may be associated with the lymph node metastasis and poor survival of CRC. LncRNA BANCR could be served as a novel and useful biomarker for CRC lymph node metastasis and prognosis.


Mediastinal Fibrosis of the Pulmonary Artery Secondary to Tuberculosis.
Mediastinal fibrosis is an uncommon disease involving the esophagus, respiratory tract, and great vessels. We report a man who presented with dyspnea on exertion. Computed tomography of the chest demonstrated granulomatous disease with dense calcifications leading to severe stenosis of the main pulmonary artery (PA) and narrowing of the superior vena cava. The results of tuberculosis (TB) interferon-γ release assay and TB-polymerase chain reaction were positive for Mycobacterium tuberculosis. The patient received 2 weeks of treatment for latent TB before undergoing resection of fibrotic tissue and replacement of the main and branch PAs using a homograft.


A specific group of patients with diagnostic conversion from depression to bipolar disorder and finally to dementia as a mental GSK-3 disease: A hypothesis.
To focus on a specific group of patients whose diagnoses were changed from unipolar depression to bipolar disorder, and finally to dementia. Qualitative review of the relevant articles. A substantial portion of patients with unipolar depression manifest manic and/or hypomanic episodes, resulting in a change of diagnoses to bipolar disorder. Further, a substantial portion of bipolar patients develop dementia. Previous research suggests that genetic variants in the glycogen synthase kinase 3β (GSK-3β) gene are associated with early onset of unipolar depression, a subset of which may be bipolar depression, with three SNPs (rs334555, rs119258668, and rs11927974) identified. Notably, another promotor SNP (rs334558) of the GSK-3β gene is reportedly associated with unipolar depression, bipolar disorders, and dementia. Additionally, lithium, which is reported to inhibit GSK-3, is generally accepted to be effective for bipolar disorder and recently reported to be effective for dementia. There is a specific group of patients whose diagnoses longitudinally change from depression to bipolar disorder and finally to dementia, and GSK-3 may be a common etiological factor in these diseases and in diagnostic conversions.


iTTCA-RF: a random forest predictor for tumor T cell antigens.
Cancer is one of the most serious diseases threatening human health. Cancer immunotherapy represents the most promising treatment strategy due to its high efficacy and selectivity and lower side effects compared with traditional treatment. The identification of tumor T cell antigens is one of the most important tasks for antitumor vaccines development and molecular function investigation. Although several machine learning predictors have been developed to identify tumor T cell antigen, more accurate tumor T cell antigen identification by existing methodology is still challenging. In this study, we used a non-redundant dataset of 592 tumor T cell antigens (positive samples) and 393 tumor T cell antigens (negative samples). Four types feature encoding methods have been studied to build an efficient predictor, including amino acid composition, global protein sequence descriptors and grouped amino acid and peptide composition. To improve the feature representation ability of the hybrid features, we further employed a two-step feature selection technique to search for the optimal feature subset. The final prediction model was constructed using random forest algorithm. Finally, the top 263 informative features were selected to train the random forest classifier for detecting tumor T cell antigen peptides. iTTCA-RF provides satisfactory performance, with balanced accuracy, specificity and sensitivity values of 83.71%, 78.73% and 88.69% over tenfold cross-validation as well as 73.14%, 62.67% and 83.61% over independent tests, respectively. The online prediction server was freely accessible at http://lab.malab.cn/~acy/iTTCA . We have proven that the proposed predictor iTTCA-RF is superior to the other latest models, and will hopefully become an effective and useful tool for identifying tumor T cell antigens presented in the context of major histocompatibility complex class I.


The burgeoning epidemic of morbid obesity in patients undergoing percutaneous coronary intervention: insight from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium.
This study sought to examine the prevalence and clinical implications of morbid obesity among patients undergoing percutaneous coronary intervention (PCI). The prevalence of obesity, and morbid obesity in particular, continues to rise rapidly in the United States. Obese patients are at increased risk for cardiac disease and are more likely to need invasive cardiac procedures. There is a paucity of contemporary data on the prevalence and clinical implications of morbid obesity among patients undergoing PCI. We examined the prevalence of morbid obesity (body mass index [BMI] ≥ 40 kg/m²) among 227,044 patients undergoing PCI and enrolled in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry from 1998 to 2009. The proportion of morbidly obese patients undergoing PCI increased from 4.38% in 1998 to 8.36% in 2009. Compared with overweight patients (BMI 25 to 30 kg/m²), these patients had significantly increased vascular complications (adjusted odds ratio [OR]: 1.31; 95% CI: 1.17 to 1.47; p < 0.0001), contrast-induced nephropathy (adjusted OR: 1.89; 95% CI: 1.70 to 2.11; p < 0.0001), nephropathy requiring dialysis (adjusted OR: 4.08; 95% CI: 2.98 to 5.59; p < 0.0001), and mortality (adjusted OR: 1.63; 95% CI: 1.33 to 2.00; p < 0.0001). Morbid obesity is increasing in prevalence among patients undergoing PCI and is associated with a higher risk of mortality and morbidity. These epidemiological changes have important implications for technical considerations of cardiac catheterization, design of the catheterization lab to accommodate these patients, and most importantly, for societal effort toward prevention of obesity.


Perturbations in simian virus 40 DNA synthesis by ultraviolet light.
Perturbations of Simian Virus 40 (SV40) DNA replication by ultraviolet (UV) light during the lytic cycle in permissive monkey CV-1 cells resemble those seen in host cell DNA replication. Formation of Form I DNA molecules (i.e. completion of SV40 DNA synthesis) was more sensitive to UV irradiation than synthesis of replicative intermediates or Form II molecules, consistent with inhibition of DNA chain elongation. The observed amounts of [3H]thymidine incorporated in UV-irradiated molecules could be predicted on the assumption that pyrimidine dimers are responsible for blocking nascent DNA strand growth. The relative proportion of labeled Form I molecules in UV-irradiated cultures rapidly increased to near-control values with incubation after 20 or 40 J/m2 of light (0.9--1.0 or 1.8--2.0 dimers per SV40 genome, respectively). This rapid increase and the failure of Form II molecules to accumulate suggest that SV40 growing forks can rapidly bypass many dimers. Form II molecules formed after UV irradiation were not converted to linear (Form III) molecules by the dimer-specific T4 endonuclease V, suggesting either that there are no gaps opposite dimers in these molecules or that T4 endonuclease V cannot use Form II molecules as substrates.


Informing research in primary dental care: setting priorities.
This paper suggests that priorities for research in primary dental care should follow the examples set in other areas of primary healthcare. It reviews the history of research in primary dental care, since 1990, and goes on to explain how the Delphi exercise, initiated by the Faculty of General Dental Practice (UK), has identified five priority areas for research in primary dental care. These areas are:1. Research into the application of evidence-based dentistry into practice.2. The effects of different systems of remuneration on treatment patterns in practice.3. The oral health assessment on determining recall intervals and its effect on oral health.4. Factors that influence and affect dentists' treatment modalities.5. The evaluation of the cost benefits of whole team training.


Therapeutic response to single intravenous bolus administration of formate dehydrogenase in methanol-intoxicated rats.
Methanol remains to be a major public and environmental health hazard. Formic acid is the toxic metabolite responsible for the metabolic acidosis observed in methanol poisoning in humans, in non-human primates and in folate-depleted rodents. Cytochrome oxidase inhibition by formate leads to lactic acid accumulation, which contributes significantly to metabolic acidosis. Toxic effects in human beings are characterized by formic acidemia, metabolic acidosis, ocular toxicity, nervous system depression, blindness, coma and death. Elimination of formate is one of the principles of management in methanol poisoning. Hemodialysis facility is not readily available in all the places, in developing countries like India. Formate dehydrogenase (EC 126.96.36.199) acts directly over formate and converts formate into CO(2) in the presence of NAD. Effect of single intravenous bolus infusion of formate dehydrogenase, obtained from Candida boidinii; in methanol-intoxicated folate deficient rat model was evaluated. Folate depletion induced by methotrexate (MTX) treatment. Carbicarb (Carb) (equimolar solution of sodium carbonate and sodium bicarbonate) was used to treat metabolic acidosis. Experimental design consists of seven groups, namely Saline control, methanol control, MTX control, Enzyme control, MTX-methanol control, MTX-methanol-Carb and MTX-methanol-Carb-Enz group. Male wistar rats treated with MTX (0.3mg/kg) for a week, were injected (i.p.) with methanol (4 gm/kg), 12h latter, Carbicarb solution was infused, following this enzyme was infused (i.v.) in bolus. Blood samples were collected every 15 min for an hour from the cannulated left jugular vein and blood methanol, formate were estimated, respectively, with HPLC and fluorimetric assay. Blood pH, blood gases pO(2), pCO(2) and bicarbonate were monitored with blood gas analyzer in order to evaluate acid base status of the animal. Results obtained show that there is significant elimination of formate within 15 min. It may be concluded that single bolus infusion of formate dehydrogenase facilitates fast removal of formate, a highly toxic metabolite in methanol poisoning.


Complete clinical response of metastatic hepatocellular carcinoma to sorafenib in a patient with hemochromatosis: a case report.
Hepatocellular carcinoma is rare, but increasing in prevalence in the United States. Recent studies have shown that sorafenib, a multikinase inhibitor, can reduce tumor progression in patients with this cancer. However, complete remission has not been observed. We report a case of a 78-year old patient with unresectable metastatic hepatocellular carcinoma who had a rapid and complete clinical response following therapy with sorafenib for six months. No evidence of disease recurrence has been noted for 6 months after discontinuation of therapy.


Can vitamin C supplementation reverse the effects of exercise training in polluted air on oxidative stress markers? A randomized controlled trial.
Air pollution and long-term aerobic exercise are diversely associated with cardiovascular disease (CVD) and mortality. However, the simultaneous effect of exercise in polluted air and vitamin C on oxidative stress markers is less clear. In this study, the effect of these variables on oxidative stress markers was investigated in rats. The study was conducted on 50 male rats. The rats were divided into 5 groups consisting of exercise, exercise with vitamin C, exercise in polluted air, exercise in polluted air with vitamin C, and control group. Animals in the exercise groups exercised on a treadmill for 12 weeks, 5 days/week, 30 minutes/day, at 50-70% of the maximum speed. Animals in the vitamin C groups received 20 mg/kg/day vitamin C orally. After 12 weeks of intervention, 2.5 ml of blood was taken from the rats' apex. Malondialdehyde (MDA) and oxidized low-density lipoprotein (OxLDL) levels were measured using NavandSalamat's Nalondi and Eastbiopharm's OxLDL ELISA kits, respectively. Two-way analysis of variance (ANOVA) was used for data analysis in SPSS software. There were significant differences in MDA and OxLDL levels between all groups after 12 weeks of intervention (P < 0.050). The levels of MDA and OxLDL were significantly higher in the ExPo group compared to the Ex+VitC groups (P < 0.050). However, no significant difference was observed in MDA and OxLDL levels between the vitamin C groups (P > 0.050). These findings demonstrate the oxidative stress effects of air pollution, systemically and in the respiratory tract. Moreover, polluted air significantly increased OxLDL levels in both exercise in polluted air groups. Although, vitamin C slightly decreased MDA and OxLDL levels in the ExPo groups, the difference was not significant. Different vitamin C doses could have diverse and maybe significant results.


Improvement in Pulmonary Function with Short-term Rehabilitation Treatment in Spinal Cord Injury Patients.
Cervical and upper thoracic spinal cord injury causes impairments in respiratory muscle performance, leading to variable degrees of pulmonary dysfunction and rendering deep breathing difficult for affected individuals. In this retrospective study, we investigated the effects of self-directed respiratory muscle training in this context by assessing pulmonary function relative to spinal cord injury characteristics. A total of 104 spinal cord injury patients (tetraplegia/paraplegia; 65/39, acute/subacute/chronic; 14/42/48) were admitted for short-term (4-8 weeks) in-patient clinical rehabilitation. Initial evaluation revealed a compromised pulmonary function with a percentage of predicted value of 62.0 and 57.5 in forced vital capacity in supine and forced vital capacity in sitting positions, respectively. Tetraplegic patients had more compromised pulmonary function compared with paraplegic patients. At follow-up evaluation, the percentage of predicted value of forced vital capacity in supine and sitting position improved overall on average by 11.7% and 12.7%, respectively. The peak cough flow improved by 22.7%. All assessed pulmonary function parameters improved significantly in all subgroups, with the greatest improvements found in patients with tetraplegia and subacute spinal cord injury. Therefore, short-term self-directed respiratory muscle training should be incorporated into all spinal cord injury rehabilitation regimens, especially for patients with tetraplegia and subacute spinal cord injury, as well as those with chronic spinal cord injury.


Chicken DT40 cells stably transfected with the rat P2X7 receptor ion channel: a system suitable for the study of purine receptor-mediated cell death.
We have generated and characterised a clone of chicken DT40 lymphocytes stably transfected with the rat P2X(7) receptor (rP2X(7)). Successful transfection was confirmed by Western blotting. Under voltage clamp, P2X(7)-expressing cells responded to ATP and dibenzoyl-ATP (Bz-ATP) (a more potent P2X(7) receptor agonist) with a rapidly activating and sustained inward current. The EC(50) values for these agonists were 305 and 15 microM, respectively. Bz-ATP evoked Ca(2+) and Mn(2+) influx into transfected cells as determined by Fura-2 spectrofluorimetry. Responses to Bz-ATP were inhibited by pre-treatment of cells with oxidised ATP. Treatment of cells with Bz-ATP for up to 24hr produced time- and concentration-dependent cell death. This was associated with an increase in caspase-3-like activity, exposure of phosphatidylserine on the outside of cell membrane and DNA cleavage, indicating death by apoptosis. Pre-treatment with Z-VAD-fmk, a pan-caspase inhibitor, reduced the DNA fragmentation and phosphatidylserine externalisation, but did not affect overall rates of cell death at 24hr, implicating caspase-independent mechanisms. The properties of rP2X(7) receptors expressed in DT40 cells are similar to those described for other expression systems. Because DT40 cells lack functionally detectable endogenous P2 receptors and are highly amenable to genetic manipulation, stably transfected DT40 cells provide a novel and potentially useful model system in which to investigate the intracellular signal transduction pathways associated with P2X(7) receptor stimulation, in particular those involved in induction of cell death.


Brain, physiological and behavioral modulation induced by immune stimulation in honeybees (Apis mellifera): a potential mediator of social immunity?
Social removal is often an adaptive response for preventing the entry and spread of parasitic infection between kin members of a group. Social isolation via removal or the switching of social tasks has also been observed in insect societies; however, the underlying mechanisms are unclear. We tested in honeybees the role of the immune system in physiological and behavioral modulation. Forager bees are often located in the outer area of the colony, and thus have reduced contacts with individuals of high importance, who are located in the inner area of the colony (e.g. queen and brood). We thus expected that an immune challenge would induce a forager profile. This was confirmed by measuring brain (foraging and malvolio gene expression), physiological (hypopharyngeal glands size) and behavioral (queen attendance) parameters of nurse/forager profiles after a treatment with an immune-activator (lipopolysaccharides). Our results support the idea that the interplay between the brain and immune system may be an important regulatory factor of social immunity in insects.


Effect of different shapes of Nano-Cu2O and humic acid on two-generations of Daphnia Magna.
Nanomaterials (NMs) have significant technological advantages due to their unique properties but their release into the environment also carry potential eco-toxicological risks. Cu2O NMs have numerous industrial and commercial applications, however less is known about the risks to human health and ecosystems. This study investigated different shapes of nano-Cu2O (cubic and octahedron) with humic acid (HA: 2 mg/L and 10 mg/L) on the reproduction, growth, survival rate and Cu accumulation in the two-generations of Daphnia Magna species. Nano-Cu2O cubic and octahedron shapes were analyzed by SEM, demonstrating {111} and {100} facets. The results indicated that octahedron has the more evident toxic effect than cubic shape for both generations. Continuous exposure to nano-Cu2O exhibited negative effects on body length, cumulative neonates and Cu accumulation in filial generation F (1). Survival rate of Cu2O octahedron was the least 66%, while Cu2O cubic was 73% for parental generation F (0). In addition, HA showed a significant reduction in the toxicity of nano-Cu2O for both generations, leading to an enhanced survival rate, body length and reproduction. This study provides insights of the long-term effect of different shapes of nano-Cu2O in the existence of humic acid to the multi-generations ecosystem.


A prospective study of occupational physical activity and breast cancer risk.
Physical activity has been associated with reduced breast cancer risk, but studies of occupational activity have produced inconsistent results. The purpose of this study was to evaluate the relationship between occupational physical activity and breast cancer in a prospective study of women with a family history of breast cancer. We studied breast cancer risk in 47,649 Sister Study participants with an occupational history. Information on occupational activity and breast cancer risk factors was collected during baseline interviews (2004-2009). Physical activity at each job was self-reported and categorized as mostly sitting, sitting and standing equally, mostly standing, and active. Multivariable Cox proportional hazards regression was used to evaluate associations between lifetime occupational activity and incident breast cancer, after adjusting for established risk factors and recreational activity. During follow-up, a total of 1,798 breast cancer diagnoses were reported. Compared with women who did not spend any time in active jobs, women who spent a high proportion (≥75%) of their working years in active jobs had a reduced risk of breast cancer (HR 0.72; 95% CI 0.52-0.98). Associations were strongest among overweight (HR 0.64; 95% CI 0.42-0.98) and postmenopausal (HR 0.67; 95% CI 0.45-0.98) women. Occupational activity was associated with a reduced risk of breast cancer. Occupational activity is a domain of physical activity that should be further examined in studies of postmenopausal breast cancer risk. Additional research is necessary to better understand the mechanisms underlying the relationships between occupational activity, body size, and breast cancer.


Recurrent headache in pediatric outpatients at a public hospital in Delhi.
This observational, descriptive study was conducted to study the clinical profile of children presenting with recurrent headaches to the general pediatric services of a tertiary-care, public hospital in northern India. 43 children, 3-18 year old (23 females, median age 10 years), were enrolled between April, 2011 to January, 2012. History, clinical examination (including fundus evaluation and detailed ophthalmological evaluation) and follow-up were done using a structured proforma. Headache diagnosis was made on the basis of International Classification of Headache Disorders, 2nd edition (ICHD-II). Headache disability and severity were assessed by pedMIDAS, and Visual analog scale and Faces scale, respectively. 26 patients (60.5%) had headache with migraine features (20, migraine without aura), 11 (25.6%) had Tension type headache (TTH), and 4 (9.3%) children had non-specific headache. Stress was the commonest (42.3%) trigger identified by children with migraine. No patient in the study had an ophthalmological problem as cause of headache. 69.2% of migraine patients and 36% of TTH patients had been suffering from it for 1-2 years before reporting to the hospital. Majority of children with recurrent headache present late for medical attention. Ophthalmological problems are an infrequent cause of recurrent headache in these children.


Nanomaterial characterization: Understanding nano-bio interactions.
Nanomaterials are marvelously small, yet they may be harnessed to great effect. Much has been learned with respect to the biological interactions and effects of nanomaterials during the past decade. However, characterization of nanomaterials is typically performed on as-synthesized materials. We posit that nanomaterials are dynamic entities and should be studied and regulated as such. Hence, characterization of nanomaterials should take into account their biotransformation. However, in situ characterization of nanomaterials as they undergo dynamic changes (coronation, dissolution, degradation) in a living system remains a formidable challenge in nanosafety. Material scientists and toxicologists need to join forces to address this issue.


ALK F1174V mutation confers sensitivity while ALK I1171 mutation confers resistance to alectinib. The importance of serial biopsy post progression.
Many acquired resistant mutations to the anaplastic lymphoma kinase (ALK) gene have been identified during treatment of ALK-rearranged non-small cell lung cancer (NSCLC) patients with crizotinib, ceritinib, and alectinib. These various acquired resistant ALK mutations confer differential sensitivities to various ALK inhibitors and may provide guidance on how to sequence the use of many of the second generation ALK inhibitors. We described a patient who developed an acquired ALK F1174V resistant mutation on progression from crizotinib that responded to alectinib for 18 months but then developed an acquired ALK I1171S mutation to alectinib. Both tumor samples had essentially the same genomic profile by comprehensive genomic profiling otherwise. This is the first patient report that demonstrates ALK F1174V mutation is sensitive to alectinib and further confirms missense acquired ALK I1171 mutation is resistant to alectinib. Sequential tumor re-biopsy for comprehensive genomic profiling (CGP) is important to appreciate the selective pressure during treatment with various ALK inhibitors underpinning the evolution of the disease course of ALK+NSCLC patients while on treatment with the various ALK inhibitors. This approach will likely help inform the optimal sequencing strategy as more ALK inhibitors become available. This case report also validates the importance of developing structurally distinct ALK inhibitors for clinical use to overcome non-cross resistant ALK mutations.


Fabrication of chitosan single-component microcapsules with a micrometer-thick and layered wall structure by stepwise core-mediated precipitation.
Incubation of CaCO(3) microparticles in chitosan (CS) solution at pH 5.2 and following with ethylenediaminetetraacetic acid disodium salt (EDTA) treatment resulted in CS single-component microcapsules with an ultra-thick wall structure. Repeating the incubation caused stepwise increase of wall thickness and finally resulted in CS microcapsules with a layered structure. This unique method is mediated by precipitation of CS on the CaCO(3) particles as a result of pH increase caused by the partial dissolution of CaCO(3) . The obtained CS capsules are stable at neutral pH.


Canted seating of the Stryker Modular Dual Mobility liner within a Trident hemispherical acetabular shell.
A 75-year-old woman who suffered a left femoral neck fracture underwent a left total hip arthroplasty using a Stryker Trident (Kalamazoo, MI) hemispherical acetabular shell and Modular Dual Mobility (MDM) metal liner. Post-operative radiographs demonstrated canted seating of the liner. The patient was taken immediately back to the operating room where the acetabular liner appeared well seated superiorly but was in a canted position inferiorly. Removal and replacement was performed and post-operative radiographs demonstrated complete seating. Subsequent follow up at 6 months demonstrated good clinical function with no adverse radiographic findings. Canted seating is a potential complication of the MDM metal liner. Providers should be aware of potential incomplete seating inferiorly despite the superior portion of the liner being well seated.


Features of minor depressive disorder subtypes in conditions of COVID-19 pandemic.
The continuous research on minor depressive disorder is one of the pressing issues in the context of the COVID-19 pandemic. We studied the features of minor depressive disorder subtypes in conditions of the COVID-19 pandemic. Sixty-two patients were observed with the administration of clinical follow-up research method. The following major subtypes of minor depressive disorder were identified: Asthenic, hysterical, hypochondriacal, apathetic, and minor depressive disorder with obsessive-compulsive symptoms. The COVID-19 pandemic lead to an increase in the development of the minor depressive disorder with a predominance of asthenic and obsessive-phobic symptoms. Therapy of minor depressive disorder requires the involvement of a wide range of specialists, preferably with the inclusion of community-based treatment.


Triterpenoids as reversal agents for anticancer drug resistance treatment.
Overexpression of ATP-binding cassette (ABC) transporters in cancer cells results in multidrug resistance (MDR), which is one of the major obstacles in the treatment of cancer patients. None of the strategies to overcome MDR has been successfully applied in the clinic until now. Plenty of evidence shows that some triterpenoids function as reversal agents of MDR for anticancer drug resistance treatment. Here, we review the latest findings of reversing cancer MDR with triterpenoids. Findings are summarized showing that triterpenoids are MDR modulators and potential chemosensitizers. Finally, we contemplate future prospects of modulating MDR in the clinic.


Treatment of umbilical hernia and recti muscles diastasis without a periumbilical incision.
Postpartum rectus diastasis eventually combined with umbilical hernia is a condition that is frequently treated by plastic surgeons and general surgeons. Standard treatment of this condition is abdominoplasty with a periumbilical incision, which often results in an umbilical incision or an inverted-T scar. Limited incision abdominoplasty differs from traditional abdominoplasty by disconnecting the umbilical stalk from the abdominal wall during flap dissection, thus allowing the resection of excess skin above and under the umbilicus without causing periumbilical scarring. We conducted a retrospective cohort study of women undergoing a limited scar abdominoplasty without a periumbilical incision for the treatment of a separation of the recti muscles and/or an umbilical hernia. We recorded the postoperative complications and patient satisfaction with the results of the treatment. We operated on 50 patients from 2002 to 2010. We followed the patients for 2-8 years. The most common complication, as with other abdominoplasty procedures, was minor dehiscention in the middle part of the wound, which occurred in 16 % (n = 8) of the patients. All of these complications were treated conservatively. No recurrence of diastasis or umbilical hernia was observed. Extended miniabdominoplasty with a low suprapubic incision and umbilical caudalization for treating the diastasis of the abdominal rectus muscles and/or an umbilical hernia is an excellent method that results in a small, hidden scar. This method is especially beneficial for young, slim women with an abdominal wall deformity after pregnancy.


Targeting DNA methylation for epigenetic therapy.
Patterns of DNA methylation are established during embryonic development and faithfully copied through somatic cell divisions. Based on current understanding of DNA methylation and other interrelated epigenetic modifications, a comprehensive view of the 'epigenetic landscape' and cancer epigenome is evolving. The cancer methylome is highly disrupted, making DNA methylation an excellent target for anticancer therapies. During the last few decades, an increasing number of drugs targeting DNA methylation have been developed to increase efficacy and stability and to decrease toxicity. The earliest and the most successful epigenetic drug to date, 5-Azacytidine, is currently recommended as the first-line treatment of high-risk myelodysplastic syndromes (MDS). Encouraging results from clinical trials have prompted further efforts to elucidate epigenetic alterations in cancer, and to subsequently develop new epigenetic therapies. This review delineates the latest cancer epigenetic models, the recent discovery of hypomethylation agents as well as their application in the clinic.


Systematic review: the impact of gastro-oesophageal reflux disease on work productivity.
Gastro-oesophageal reflux disease has wide-ranging effects on patients' lives. To review systematically the effects of gastro-oesophageal reflux disease on work productivity. Studies of gastro-oesophageal reflux disease and work productivity were identified in a systematic literature search and their results were valued in US dollars using the human capital method. Work productivity loss was defined as absence from work (absenteeism) plus reduced effectiveness while working (presenteeism). Eight eligible studies were included. Reported work productivity loss among individuals with gastro-oesophageal reflux disease ranged from 6% to 42% and was primarily because of presenteeism (6-40%) rather than absenteeism (<1% to 7%). Reported losses were greatest in patients experiencing sleep disturbance because of gastro-oesophageal reflux disease, and lowest in individuals from the general population taking appropriate prescription medication. Work productivity impairment correlated with symptom severity and responded to acid-suppressive therapy. Assuming a 40-h working week and average wages in the US, the weekly mean productivity loss per employee with gastro-oesophageal reflux disease can be estimated between 2.4 (62 dollars) and 16.6 h (430 dollars), depending on the population studied. Gastro-oesophageal reflux disease has a substantial impact on employee productivity, primarily by impairing productivity while working. Further studies are needed to confirm that this impact can be decreased by acid-suppressive therapy.


Prognostic Relevance of Metabolic Dysfunction-associated Steatohepatitis for Patients with Chronic Hepatitis B.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is prevalent in patients with chronic hepatitis B (CHB). The effect of the histologic MAFLD phenotype on long-term CHB outcomes is unknown. We performed a longitudinal study to determine the prognostic relevance of biopsy-proven hepatic steatosis and steatohepatitis for CHB patients. Clinical and laboratory data were obtained from CHB patients who underwent liver biopsy during 2002-2008 and were treated with antiviral drugs. A hepatopathologist reviewed the biopsy specimens. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (aHR) of outcomes, including all-cause mortality, liver transplantation, and liver-related events. In accordance with Brunt's classification, 408 patients had steatohepatitis (n=34), "steatosis but not steatohepatitis" (n=118), or "non-steatosis" (n=256). All steatohepatitis patients had features of metabolic dysfunction. Over a mean follow-up of 13.8±3.1 years, 18 patients died or underwent liver transplantation. In multivariate-adjusted analysis, steatohepatitis (aHR, 6.37; 95% confidence interval [CI]: 1.59-25.5) compared with non-steatosis and advanced fibrosis (aHR, 11.3; 95% CI: 1.32-96.3) compared with no fibrosis were associated with overall mortality/liver transplantation. Thirty-five patients developed 43 liver-related events, among which 32 were hepatocellular carcinoma. These events were associated with steatohepatitis (aHR, 5.55; 95% CI: 2.01-15.3) compared with non-steatosis and advanced fibrosis (aHR, 6.23; 95% CI: 1.75-22.2) compared with no fibrosis. The steatosis but not steatohepatitis group had a non-significantly higher risk of overall mortality and liver-related events. Metabolic dysfunction-associated steatohepatitis increased the risk of long-term mortality/transplantation and liver-related events in CHB patients.


Preparation of visible-light-excited europium biolabels for time-resolved luminescence cell imaging application.
By using a visible-light-excited ternary Eu(3+) complex, BHHBCB-Eu(3+)-BPT (BHHBCB: 1,2-bis[4'-(1",1",1",2",2",3",3"-heptafluoro-4″,6″-hexanedion-6″-yl)-benzyl]-4-chlorosulfobenzene; BPT: 2-(N,N-diethylanilin-4-yl)-4,6-bis(pyrazol-1-yl)-1,3,5-triazine), as a luminophore, two kinds of novel visible-light-excited europium materials, the silica-encapsulated BHHBCB-Eu(3+)-BPT (Eu@SiO2) nanoparticles and BHHBCB-Eu(3+)-BPT-conjugated bovine serum albumin (BSA-BHHBCB-Eu(3+)-BPT), were prepared for biolabeling and time-resolved luminescence cell imaging applications. The Eu@SiO2 nanoparticles, prepared by the copolymerization of 3-aminopropyl(triethoxy)silane-BHHBCB-Eu(3+)-BPT conjugate, free 3-aminopropyl(triethoxy) silane and tetraethyl orthosilicate in a water-in-oil reverse microemulsion, are monodispersed, spherical and uniform in size, and strongly luminescent with an excitation peak at ≈ 400 nm and a long luminescence lifetime of 346 μs. The BSA-BHHBCB-Eu(3+)-BPT, prepared by covalent binding of BHHBCB-Eu(3+)-BPT to BSA, shows also strong visible-light-excited luminescence with a excitation peak at ≈ 400 nm and a long luminescence lifetime of 402μs. The two materials were used for labeling transferrin and folic acid. Using the time-resolved luminescence imaging of living HeLa cells, the cell-surface receptors of transferrin and folic acid were successfully visualized by the prepared biolabels based on the ligand-receptor affinity binding interaction. The results demonstrated the feasibility of the new materials as visible-light-excited biolabels for the time-resolved luminescence cell imaging.


Hand washing behavior change effect of community-based hygiene and sanitation intervention in low resource setting.
Lack of hygiene and sanitation causes significant disease, disability and death. Majority of diarrheal diseases are related to hygiene and drinking water. Hand washing with soap after toilet use and before eating reduces these risks significantly. This report is based on a behavior change project in the rural community setting (union council Nahqi), Peshawar, Pakistan aimed to improve hygiene- and sanitation-related behavior. A pre-intervention survey was conducted at household level (n = 958), followed by a structured behavior change communication program with motivational and educational material and key health messages for three months. Lastly, an end-line survey was conducted measuring change in practice domains. All the domains of hygiene and sanitation showed statistically significant improvement (11-59% P < 0.001), including handwashing before meals (28.2%), before cooking (54.1%), before child feeding (21.2%), after defecation (30.6%); tooth brushing twice daily (7.3%); nail clipping at least weekly (16.3%); bathing daily (11.3%); change of clothing twice weekly (24.7%); covering the water containers (59.3%) and house orderliness (30.6%). The findings conclude that a behavior change communication program that is in accord with community needs, level of their understanding, beliefs and sociocultural norms is well received for positive behavior change.


Autoreactive B cell responses targeting nuclear antigens in systemic sclerosis: Implications for disease pathogenesis.
A hallmark of disease pathogenesis of systemic sclerosis (SSc) is the presence of autoreactive B cell responses targeting nuclear proteins. Almost all SSc-patients harbour circulating antinuclear autoantibodies of which anti-topoisomerase 1, anti-centromere protein, anti-RNA polymerase III and anti-fibrillarin autoantibodies (ATA, ACA, ARA and AFA, respectively) are the most common and specific for SSc. In clinical practice, autoantibodies serve as diagnostic biomarkers and can aid in the identification of clinical phenotypes of the disease. However, factors driving disease progression in SSc are still poorly understood, and it is difficult to predict disease trajectories in individual patients. Moreover, treatment decisions remain rather empirical, with variable response rates in clinical trials due to patient heterogeneity. Current evidence has indicated that certain patients may benefit from B cell targeting therapies. Hence, it is important to understand the contribution of the antinuclear autoantibodies and their underlying B cell response to the disease pathogenesis of SSc.


RANIBIZUMAB VERSUS VERTEPORFIN PHOTODYNAMIC THERAPY IN ASIAN PATIENTS WITH MYOPIC CHOROIDAL NEOVASCULARIZATION: BRILLIANCE, a 12-Month, Randomized, Double-Masked Study.
To evaluate the efficacy and safety of 2 dosing regimens of ranibizumab 0.5 mg versus verteporfin photodynamic therapy in Asian patients with visual impairment due to myopic choroidal neovascularization. Eligible patients (aged ≥18 years) were randomized 2:2:1 to Group I (n = 182; ranibizumab treatment guided by visual acuity stabilization criteria); Group II (n = 184; ranibizumab treatment guided by disease activity); or Group III (n = 91; verteporfin photodynamic therapy on Day 1; from Month 3, ranibizumab/verteporfin photodynamic therapy/both treatment guided by disease activity). The mean average best-corrected visual acuity change from baseline to Month 1 through Month 3 was significantly higher in Groups I/II versus Group III (Group I/II: +9.5/+9.8 letters vs. Group III: +4.5 letters; both P < 0.001). Group II was statistically noninferior to Group I for the mean average best-corrected visual acuity change from baseline to Month 1 through Month 6 (10.7 vs. 10.4 letters; P < 0.001). Over 12 months, the mean number of ranibizumab injections received by Groups I/II/III was 4.6/3.9/3.2. In Asian patients, ranibizumab treatments demonstrated superior efficacy versus verteporfin photodynamic therapy at Month 3, and the beneficial treatment effects persisted at Month 12. Ranibizumab was well-tolerated and demonstrated a good safety profile.


Electrochemical oxidation combined with UV irradiation for synergistic removal of perfluorooctane sulfonate (PFOS) in water.
The effect of electrochemical degradation on Magnéli phase Ti4O7 anode combined with UV irradiation on the removal of PFOS was systematically evaluated in the present study. A synergistic effect of electrolysis and UV irradiation rather than a simple additive effect for PFOS degradation was demonstrated experimentally and theoretically. The short wavelength irradiation within 400 nm is the main contribution to enhance the electrochemical degradation of PFOS, while the initial pH of the solution has little effect on the PFOS degradation. The increase of current density accelerates the removal of PFOS either by electrolysis treatment or the joint process. The time-dependent density functional theory (TD-DFT) calculation indicates that the synergistic effect of the electrolysis and UV irradiation is most likely due to the involvement of the excited PFOS induced under UV irradiation in the electrochemical reaction. This study provides the first mechanistic explanation for the electrochemical degradation of PFOS enhanced by UV irradiation.


A method for cellular stimulation of thyroid transplant for correction of thyroid system function.
The efficiency of autotransplantation of the thyroid tissue into the greater omentum was demonstrated in experiments on rats. High viability of the transplant and restoration of the hormonal thyroid activity were attained after a single injection of the cell suspension of autologous adherent bone marrow cells directly into the transplant.


No effect of subperiosteal growth factor application on periosteal neo-chondrogenesis in osteoperiosteal bone grafts for osteochondral defect repair.
The purpose of this study was to examine the effect of subperiosteal injection of chondroinductive growth factors on the histological and biomechanical outcome of autologous osteoperiosteal grafts. Thirty six standardised osteochondral defects were created in the trochlear groove of 18 Göttinger Minipigs and evaluated after six, 12 and 52 weeks. Defects were treated with press-fit implantation of autologous osteoperiosteal cylindrical block-grafts with or without subperiosteal injection of a chondroinductive growth factor mixture (GFM). Histomorphological analysis showed complete osseointegration of all grafts from six weeks. The periosteum remained in place in 35 of 36 cases. Fibrocartilagineous repair tissue formation occurred at the cambium layer with a maximum at 12 weeks in both groups. Histomorphological grading and biomechanical testing showed highest values at 12 weeks, with signs of tissue degradation at one year. There was no significant difference between both groups. Transplantation of autologous osteoperiosteal grafts is an effective method to restore subchondral bone defects, but not the overlying cartilage as the repair tissue deteriorates in the long term. Subperiosteal growth factors injection did not stimulate tissue differentiation on a biomechanical and histomorphological level.


High mobility group AT-hook 2 regulates osteoblast differentiation and facial bone development.
The mutation and deletion of high mobility group AT-hook 2 (Hmga2) gene exhibit skeletal malformation, but almost nothing is known about the mechanism. This study examined morphological anomaly of facial bone in Hmga2-/- mice and osteoblast differentiation of pre-osteoblast MC3T3-E1 cells with Hmga2 gene knockout (A2KO). Hmga2-/- mice showed the size reduction of anterior frontal part of facial bones. Hmga2 protein and mRNA were expressed in mesenchymal cells at ossification area of nasal bone. A2KO cells differentiation into osteoblasts after reaching the proliferation plateau was strongly suppressed by alizarin red and alkaline phosphatase staining analyses. Expression of osteoblast-related genes, especially Osterix, was down-regulated in A2KO cells. These results demonstrate a close association of Hmga2 with osteoblast differentiation of mesenchymal cells and bone growth. Although future studies are needed, the present study suggests an involvement of Hmga2 in osteoblast-genesis and bone growth.


Fibrin glue for the prevention of epithelial ingrowth after laser in situ keratomileusis.
We present 3 cases of recurrent epithelial ingrowth following laser in situ keratomileusis. All patients consented to flap lifting, epithelial ingrowth removal, and placement of fibrin glue (Tisseel(R) VH, Baxter) at the flap edges. Two of 3 eyes had no evidence of recurrent epithelial ingrowth within a relatively short follow-up. One eye that also had had radial keratotomy had a small nest of stable epithelial cells that had not progressed. Fibrin glue may be a useful adjunct to prevent recurrent epithelial ingrowth. There were no complications associated with its use.


The equations of the inserted length of percutaneous central venous catheters on neonates in NICU.
In neonatal intensive care units, a percutaneous central venous catheter (PCVC) is inserted peripherally and threaded into a central venous location, when intravenous access is anticipated for an extended period of time. The tip location of PCVCs should be checked by an X-ray after the procedure. The present study aimed to determine an equation to estimate the optimal insertion length of PCVCs in neonates prior to the procedure. The data of all neonates who had PCVC insertion between May 1st 2015 and April 30th 2016 was reviewed. Their gender, body weight and body length at the insertion date, any complications and the tip culture of their PCVCs were recorded. The tip location of the PCVC, which was confirmed by X-ray, was either in the inferior vena cava near to the diaphragm or in the superior vena cava before the right atrial junction, depending on the insertion site. We analyzed the correlation among inserted length of PCVCs, body weight and body length by linear regression to determine an equation for estimating the optimal insertion length of PCVCs. The accuracy of the equations was evaluated prospectively by Pearson's correlation analysis, and the adjusting rate of PCVCs after the initial insertion was compared between the traditional method and using the equation. The equation of PCVCs inserted in the foot was "insertion length (cm) = 16 + 4.27 × body weight (kg)", in the femoral vein was "inserted length (cm) = 9.8 + 1.7 × body weight (kg)", in the popliteal vein was "inserted length (cm) = -0.3 + 0.45 × body length (cm)", in the hand was "inserted length (cm) = 4.46 + 0.32 × body length (cm)", and in the axillary vein was inserted length (cm) = 1 + 0.18 × body length (cm). The adjusting rate of PCVCs after initial insertion was decreased from 73.5% to 53% following use of the equation. Equations provided a convenient and accurate method to estimate the optimal insertion length of PCVCs before their placement.


Pathogenesis of Pancreatitis in Chickens after Experimental Infection with 9a5b Newcastle Disease Virus Mutant Isolate.
The aim of this study was to investigate the effect of Newcastle disease virus (NDV) on the chicken pancreas. A virulent 9a5b mutant NDV isolate was inoculated intranasally into 32-day-old specific pathogen-free white Leghorn chickens. The pancreas was examined grossly and fixed for histopathological, immunohistochemical and electron microscopical investigations. Inflammatory changes were observed in the peripancreatic tissue at the early stage of infection (12 h post infection) and became more prevalent towards the end of the experiment. Multifocal areas of necrotizing inflammation were detected in the exocrine portion of the pancreas by 5 days post infection (dpi) and became more severe at 10 dpi. The endocrine islets were generally preserved, but slight degenerative changes were observed at 10 dpi. Immunohistochemically, NDV-nucleoprotein (NDV-NP) signals were detected in the peripancreatic tissues (associated with macrophages and other lymphoid cells) by 1 dpi. In the exocrine portion of the pancreas, NDV-NP signals were detected at 5 dpi and increased in intensity and distribution by 10 dpi. NDV particles were confirmed in the cytoplasm of exocrine acinar cells by transmission electron microscopy. CD3-positive cells were observed in the peripancreatic tissues earlier than in the pancreatic tissue. Moreover, in comparison with control chickens, insulin immunoexpression was unchanged, except on the last day of the experiment, when it was slightly reduced. The 9a5b NDV infection induced an inflammatory reaction and viral replication in the peripancreatic tissues earlier than in the pancreatic tissue. Furthermore, necrosis affected mainly the exocrine portion of the pancreas, while the endocrine portion was generally unaffected.


The dynamics of microsaccade amplitude reflect shifting of covert attention.
Attention flexibly shifts between spatial locations to accommodate task demands. The present study examined if the dynamics of attentional shifting are seen in microsaccades whose direction has been shown to accompany the shifts of covert attention. In a spatial cueing task, the cue predicted the target location on 100%, 75%, or 50% of the trials. The results revealed that microsaccade rate and amplitude were both reduced following cue onset and then rebounded. Both microsaccade rate and amplitude were biased towards the opposite direction of the cue and then returned to the cued direction. Importantly, the cue validity modulated the temporal profile of microsaccade amplitude but had little impact on the temporal profile of microsaccade rate. In line with this, the cueing effect measured with target response accuracy was correlated with the microsaccade amplitude only. These results indicate that the temporal dynamics of microsaccade amplitude reflect shifting of covert attention.


Current Approaches to Quantifying Tonic and Reflex Autonomic Outflows Controlling Cardiovascular Function in Humans and Experimental Animals.
The role of the autonomic nervous system in the pathophysiology of human and experimental models of cardiovascular disease is well established. In the recent years, there have been some rapid developments in the diagnostic approaches used to assess and monitor autonomic functions. Although most of these methods are devoted for research purposes in laboratory animals, many have still found their way to routine clinical practice. To name a few, direct long-term telemetry recording of sympathetic nerve activity (SNA) in rodents, single-unit SNA recording using microneurography in human subjects and spectral analysis of blood pressure and heart rate in both humans and animals have recently received an overwhelming attention. In this article, we therefore provide an overview of the methods and techniques used to assess tonic and reflex autonomic functions in humans and experimental animals, highlighting current advances available and procedure description, limitations and usefulness for diagnostic purposes.


Randomized controlled trial of vaginal misoprostol versus vaginal misoprostol and isosorbide dinitrate for termination of pregnancy at 13-29 weeks.
When compared to the use of 12 hourly 200 microg vaginal misoprostol on its own, the addition of a single dose of 5 mg did not significantly increase the abortion or delivery rate in pregnancy termination at 13-29 weeks gestation. All patients were given intravenous syntocinon at 30 mU/min from the first dose of misoprostol onwards.


Event-related potentials in complex partial seizures.
Both early (N1 and P2) and late (N2 and P3) event-related potentials (ERP) were obtained in 16 patients with complex partial seizures, 12 with left hemispheric ictal focus and 4 with right, to see if they help in lateralizing the seizure focus, and also to determine if they correlate with behavioral (MMPI, Bear-Fedio), attentional (Trails A and B), cognitive (WAIS-R, Boston Naming, Warrington Word and Face recognition) and mental speed (Stroop color naming and reading) tasks. Early waves were more often lateralized than late waves but both were often falsely lateralizing. Early waves were better correlated with behavioral tasks whereas late waves were better with those measuring mental speed, attention and cognition. These data tentatively discourage the utility of ERP in preoperative lateralization of seizure focus but argue for their potential value in psychophysiological correlations.


Cancer genes generated by rare chromosomal rearrangements rather than activation of oncogenes.
The 20 known transforming onc genes of retroviruses are defined by sequences that are transduced from cellular genes, termed proto-oncogenes or cellular oncogenes. Based on these sequences, viral onc genes have been postulated to be transduced cellular cancer genes and proto-onc genes have been postulated to be latent cancer genes that can be activated from within the cell to cause virus-negative tumors. The hypothesis is popular because it promises direct access to cellular cancer genes. However, the existence of latent cancer genes presents a paradox since such genes are clearly undesirable. The hypothesis predicts (i) that viral onc genes and proto-onc genes are isogenic, (ii) that expression of proto-onc genes induces tumors, (iii) that activated proto-onc genes transform diploid cells upon transfection, like viral onc genes, and (iv) that diploid tumors exist that differ from normal cells only in transcriptionally or mutationally activated proto-onc genes. As yet, none of these predictions is confirmed. Moreover, the probability of spontaneous transformation in vivo is at least 10(9) times lower than predicted from the mechanisms thought to activate proto-onc genes. Therefore the hypothesis, that proto-onc genes are latent cellular oncogenes, appears to be an overinterpretation of sequence homology to structural and functional homology with viral onc genes. Here it is proposed that only rare truncations and illegitimate recombinations that alter the germline configuration of cellular genes, generate viral and possibly cellular cancer genes. The clonal chromosome abnormalities that are consistently found in tumor cells are microscopic evidence for rearrangements that may generate cancer genes. The clonality indicates that the tumors are initiated with, and possibly by, these abnormalities as predicted by Boveri in 1914 (Zur Frage der Entstehung maligner Tumoren, Jena, Fischer).


Gluconeogenesis and glucuronidation in liver in vivo and the heterogeneity of hepatocyte function.
In order to examine metabolic zonation in human liver, [2-14C]glycerol, which labels carbons 2 and 5 of glucose-6-P, and [1-14C]lactate, which labels carbons 3 and 4 of glucose-6-P, in the process of gluconeogenesis, were infused intravenously into healthy subjects who ingested acetaminophen and had fasted 36 h. Distributions of 14C were determined in glucose in blood and in the glucuronic acid moiety of acetaminophen glucuronide excreted in urine. Ratios of 14C in carbons 2 and 5 to 14C in carbons 3 and 4 were significantly higher in blood glucose than in glucuronide. Since glucose and glucuronic acid are formed from glucose-6-P in liver without randomization of carbon, the differences in the ratios indicate that the pool of glucose-6-P in liver is not homogeneous. The glucuronide sampled glucose-6-P with more label from lactate than glycerol compared to the glucose-6-P sampled by the glucose. The apparent explanation is the greater decrease in glycerol compared with lactate concentration as blood streams from the periportal to the perivenous zones of the liver lobule. Glucuronidation is then expressed in humans relatively more in the perivenous than periportal zones and gluconeogenesis from glycerol more in the periportal than perivenous zones.


Alleviation of D-gal-induced senile liver injury by Rg3, a signature component of red ginseng.
To investigate the mechanism by which ginsenoside Rg3 regulates oxidative stress (OS) and inflammation through NF/KB pathway to delay mouse liver injury. This work randomized Balbc mice as four groups: Normal, D-gal, Rg3-L, Rg3-H. Paraffin-embedded liver tissue sections were prepared, later, BAX/BCL-2 protein expression was observed by HE, Sirius red, TUNEL and immunofluorescence to detect apoptotic injury and α-SMA/TGF-β protein expression to detect fibrosis, and liver inflammation-related protein NF-KB was detected. HE and TUNEL staining showed that Rg3 reduced necrotic cells and fibrosis in liver-injured mice, Rg3 increased anti-inflammatory cytokine IL-18 and reduced TNF-α, IL-1β and IL-6 expression. Conclusion: Ginsenoside Rg3 can effectively antagonize D-gal's role in mouse liver injury, and its mechanism may be associated with regulating inflammatory pathway by Rg.


Assignment of nucleoside phosphorylase gene to q2.1----q2.2 region of chromosome 7 in the pig, Sus scrofa domestica L.
Using in situ hybridization with a human probe, we have mapped the nucleoside phosphorylase gene on pig chromosome 7. These results are in agreement with those obtained by other groups, but give a more precise localization in the q2.1----q2.2 region of chromosome 7.


Are patients with chronic renal failure (CRF) deficient in Biotin and is regular Biotin supplementation required?
In 23 patients with chronic renal failure (CRF), 23 patients on chronic intermittent hemodialysis treatment (DP), 22 patients after renal transplantation (RT) and 40 normal persons (NP), Biotin plasma levels and the urinary excretion were analysed and compared to the dietary Biotin intake. Unsupplemented DP had lower intake of Biotin than the CRF, RT, NP and DP with supplementation. DP excreted only 1.6-6.3% of the daily intake as compared to 39.7% in NP, 27.6% in CRF and 24.3% in RT. In unsupplemented DP patients, Biotin plasma levels were elevated by 4 times and in supplemented patients by 6 times compared to NP. During hemodialysis treatment, the Biotin plasma level dropped by about 30% in DP with and by 33% in DP without vitamine supplementation. However, after 44 hours, the initial concentration was reached again in those receiving vitamine supplementation (99% of basal level) and in DP without substitution (97% of basal level). Only in male DP significantly higher Biotin plasma levels before HD were detected irrespective of the supplementation dose as compared to female patients (30 micrograms and 300 micrograms Biotin after each dialysis session). Biotin plasma concentration did not vary with respect to the underlying renal disease, the serum creatinine concentration and the length and frequency of dialysis treatment, including the type of dialyzer (low- vs high flux) used and the blood flow rate (QB 180-260 vs 270-280 vs 300 ml/min). There were no major effects of the age of the patients (< 60 years vs > 60 years), the BMI, nicotine abuse, or alcohol intake on Biotin blood concentration. Our results showed normal Biotin plasma levels which reflect a normal functional status and exclude a functional deficit, therefore there is no reason for a regular Biotin supplementation in patients with chronic renal failure.


PAS-positive inclusions in the alveolar type II cells of the caprine lung.
Histochemical analysis of inclusions in the alveolar type II cells was done with the alcian blue-PAS technique. PAS-positive inclusions, which were absent in the sheep and buffalo, were detected in the alveolar type II cells of the goat lung. Mixed diamine-sodium chloride did not stain these inclusions which also showed orthochromatic blue reaction with toluidine blue. The high percentage of alveolar type II cells showing these inclusions suggested that this difference could be explained by the environmental habitat of the goat.


Effect of cyclic compressive loading on the bond strength of an adhesive system to dentin after collagen removal.
The objective of this study was to verify the effect of cyclic compressive loading on the shear bond strength of an adhesive system following collagen removal. Sixty bovine teeth were divided into 4 groups based on the adhesive procedure used: groups 1 and 2--etching with 35% phosphoric acid and application of the Single Bond adhesive system; groups 3 and 4--after etching, a 10% sodium hypochlorite solution was applied for 1 min before the application of the adhesive. In all the specimens, a Z100 resin cylinder was built up over the bond area. Groups 2 and 4 were submitted to 500,000 cycles with a load of 100 N. The mean values for the shear bond test (MPa) were: group 1: 7.37 +/- 1.15; group 2: 5.72 +/- 1.66; group 3: 5.95 +/- 1.21; group 4: 3.66 +/- 1.12. There was no difference between groups 1 and 2 (p > 0.01). Between groups 1 and 3, 2 and 4, and 3 and 4 there was a significant difference (p < 0.01). The majority of the specimens demonstrated an adhesive failure. The application of sodium hypochlorite on dentin decreased the values of shear bond strength, as did the load cycling in the group treated with sodium hypochlorite.


Protein nanotechnology: what is it?
Protein nanotechnology is an emerging field that is still defining itself. It embraces the intersection of protein science, which exists naturally at the nanoscale, and the burgeoning field of nanotechnology. In this opening chapter, a select review is given of some of the exciting nanostructures that have already been created using proteins, and the sorts of applications that protein engineers are reaching towards in the nanotechnology space. This provides an introduction to the rest of the volume, which provides inspirational case studies, along with tips and tools to manipulate proteins into new forms and architectures, beyond Nature's original intentions.


Giant negative linear compressibility in zinc dicyanoaurate.
The counterintuitive phenomenon of negative linear compressibility (NLC) is a highly desirable but rare property exploitable in the development of artificial muscles, actuators and next-generation pressure sensors. In all cases, material performance is directly related to the magnitude of intrinsic NLC response. Here we show the molecular framework material zinc(II) dicyanoaurate(I), Zn[Au(CN)(2)](2), exhibits the most extreme and persistent NLC behaviour yet reported: under increasing hydrostatic pressure its crystal structure expands in one direction at a rate that is an order of magnitude greater than both the typical contraction observed for common engineering materials and also the anomalous expansion in established NLC candidates. This extreme behaviour arises from the honeycomb-like structure of Zn[Au(CN)(2)](2) coupling volume reduction to uniaxial expansion, and helical Au…Au 'aurophilic' interactions accommodating abnormally large linear strains by functioning as supramolecular springs.


Complement therapeutics are coming of age in rheumatology.
The complement system was described over 100 years ago, and it is well established that activation of this pathway accompanies the great majority of autoimmune and inflammatory diseases. In addition, over three decades of work in murine models of human disease have nearly universally demonstrated that complement activation is upstream of tissue injury and the engagement of pro-inflammatory mechanisms such as the elaboration of cytokines and chemokines, as well as myeloid cell recruitment and activation. With that background, and taking advantage of advances in the development of biologic and small-molecule therapeutics, the creation and clinical evaluation of complement therapeutics is now rapidly expanding. This article reviews the current state of the complement therapeutics field, with a focus on their use in diseases cared for or consulted upon by rheumatologists. Included is an overview of the activation mechanisms and components of the system, in addition to the mechanisms by which the complement system interacts with other immune system constituents. The various therapeutic approaches to modulating the system in rheumatic and autoimmune diseases are reviewed. To understand how best to clinically assess the complement system, methods of its evaluation are described. Finally, next-generation therapeutic and diagnostic advances that can be envisioned for the future are discussed.


Concise review: Anemia caused by viruses.
Most of the viruses known to be associated with anemia in human tend to persistently infect their host and are noncytopathic or poorly cytopathic for blood cell progenitors. Infections with Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human herpes virus 6 (HHV-6), B19 parvovirus, human immunodeficiency virus, hepatitis A and C viruses and the putative viral agent associated with non-A-G post-hepatitis aplastic anemia have been reported in association with anemia. Nevertheless, a direct cytotoxic effect on erythroid progenitors has been clearly demonstrated only for human parvovirus B19 and evocated for HHV-6. A major role for destructive immunity is strongly suspected in the pathogenesis of anemia associated with the other viral infections. Host genes play a role in the occurrence of virus-induced anemia in animal models, and there are some evidences that genetic background could also influence the occurrence of virus-associated anemia in human.