Exploring the Aggressiveness of Sarcomatoid Carcinoma of the Oral Cavity - an Institutional Experience.
Background: Sarcomatoid variant of squamous cell carcinoma in the oral cavity is a rare biphasic variant of squamous cell carcinoma. This aggressive variant of squamous cell carcinoma is characterized by invasive growth with marked local recurrence and distant metastasis resulting in poor prognosis. Sarcomatoid carcinoma can occur over a wide age range, incidence increases with older age and is a male-predominant disease. Methods: 23 patients with histologically proven Sarcomatoid SCC or with a sarcomatoid component (Group A) were compared with 23 randomly chosen patients with clinical stage IV (Group B) disease at the time of diagnosis, within the same time period and comparison was made between disease free survival and overall survival. Results: In group A, the mean DFS was found to be 12.4 months raging from 1 month to 36 months. 6 patients were therafter lost to follow follow up, in 11 patients the mean overall survival was found to be 8.72 months (ranging from 2 to 18 months) whereas 6 patients are alive till date. In group B, the mean DFS was found to be 19.56 months ranging from 6 months to 33 months. 4 patients succumbed to the disease with a mean overall survival of 24.25 years (ranging from 18 to 33 months), 4 patients were lost to follow up and the rest are alive till date. Conclusion: Sarcomatoid carcinoma of the oral cavity is an extremely rare but aggressive variant of conventional squamous cell carcinoma. We have to systematically understand their clinical, morphological and immunohistochemical features which is critical for their accurate diagnosis which aids in correct patient management. After radical surgery and adjuvant radiation therapy, strict follow up for development of recurrence and distant metastasis should be done.


New bacterial and archaeal lineages discovered in organic rich sediments of a large tropical Bay.
The nutrient and oxygen gradient present in marine sediments promotes high levels of microbial diversity. We applied metagenomics and biogeochemical tools to analyze microbial communities in different sediment depths (0-4 m below sea floor, mbsf) from Guanabara Bay, Brazil, a brackish tropical ecosystem with a history of massive anthropogenic impacts, and a largely unknown sediment microbial diversity. Methanogens (e.g. Methanosarcinales, Methanomicrobiales) were more abundant at 1 mbsf, while sulphate-reducing microbes (Desulfurococcales, Thermoprotales, and Sulfolobales) were more abundant at deeper layers (4 mbsf; corresponding to 3 K Radiocarbon years before present, Holocene Epoch). Taxonomic analyzes and functional gene identification associated with anaerobic methane oxidation (e.g. monomethylamine methyltransferase (mtmB), trimethylamine methyltransferase (mttB) and CO dehydrogenase/acetyl-CoA synthase delta subunit) and sulfate reduction indicated the dominance of Campylobacteria (Sulfurimonas) at deeper sediment layers. Gene sequences related to assimilation of inorganic sulfur increased with depth, while organic sulfur related sequences decrease, accompanying the clear reduction in the concentration of sulfur, organic carbon and chla torwards deeper layers. Analyzes of metagenome assembled genomes also led to the discovery of a novel order within the phylum Acidobacteriota, named Guanabacteria. This novel order had several in silico phenotyping features that differentiate it from closely related phylogenetic neighbors (e.g. Acidobacteria, Aminicenantes, and Thermoanaerobaculum), including several genes (carbon monoxide dehydrogenase, CO dehydrogenase/CO-methylating acetyl-CoA synthase complex subunit beta, heterodisulfide reductase, sulfite exporter TauE/SafE family protein, sulfurtransferase) that relevant for the S and C cycles. Furthermore, the recovered Bathyarchaeota genome SS9 illustrates the methanogenic potential in deeper sediment layer.


Plasma protein regulation of platelet function and metabolism.
This reviews summarizes our evidence suggesting that the plasma protein enviroment influences platelet aggregation potential and metabolic activity. Cationic proteins are capable of restoring the aggreation potential of washed human platelets. The aggregation restoring effect of gamma globulin is inhibited by more anionic proteins in subfractions of Cohn fraction IV and fractions V and VI. Artificial enhancement of the net negative charge of plasma proteins through acylation produces derivatives capable of inhibiting platelet rich plasma. The oxygen consumption of washed human platelets is lower than in platelet rich plasma while the lactate production is identical. Autologus plasma, albumin or IgG immunoglobulin restores the oxygen consumption of washed platelets to values comparable to those obtained for platelet rich plasma, while the lactate production is unaffected. Fibrinogen on IgA myeloma protein increases the lactate production, but not the oxygen consumption. Cyclic AMP levels are considerably lower in washed platelets than in platelet rich plasma. Gamma globulin and albumin causes a futher decrease, which is progressive with time. Fibrinogen causes no change in platelet cyclic AMP content. It is suggested that these observations may in part be explained by the equilibriun between anionic and cationic proteins in the platelet microenvironment. This hypothesis appears applicable in certain situations.


PD-L1 near Infrared Photoimmunotherapy of Ovarian Cancer Model.
(1) Background: Despite advances in surgical approaches and drug development, ovarian cancer is still a leading cause of death from gynecological malignancies. Patients diagnosed with late-stage disease are treated with aggressive surgical resection and chemotherapy, but recurrence with resistant disease is often observed following treatment. There is a critical need for effective therapy for late-stage ovarian cancer. Photoimmunotherapy (PIT), using an antibody conjugated to a near infrared (NIR) dye, constitutes an effective theranostic strategy to detect and selectively eliminate targeted cell populations. (2) Methods: Here, we are targeting program death ligand 1 (PD-L1) using NIR-PIT in a syngeneic mouse model of ovarian cancer. PD-L1 PIT-mediated cytotoxicity was quantified in RAW264.7 macrophages and ID8-Defb29-VEGF cells in culture, and in vivo with orthotopic ID8-Defb29-VEGF tumors. (3) Results: Treatment efficacy was observed both in vitro and in vivo. (4) Conclusions: Our data highlight the need for further investigations to assess the potential of using NIR-PIT for ovarian cancer therapy to improve the treatment outcome of ovarian cancer.


Visible optical nonlinearity of vanadium dioxide dispersions.
Vanadium dioxide (VO2), a correlated oxide compound, is one of the functional materials extensively studied in solid state physics due to its attractive physical properties. However, the nonlinear optical response of VO2 and related all-optical applications have been paid less attention. Here, the nonlinear refractive index (n 2) and third-order nonlinear susceptibility (χ (3)) of VO2 dispersions have been acquired to be 3.06 × 10-6 cm2 W-1 and 1.68 × 10-4 esu at a wavelength of 671 nm, and 5.17 × 10-6 cm2 W-1 and 2.83 × 10-4 esu at a wavelength of 532 nm via the spatial self-phase modulation (SSPM) and spatial cross-phase modulation (SXPM) effects in the visible regime, respectively. Based on the excellent nonlinear optical properties of VO2 dispersions, the proof-of-principle functions such as optical logic or-gates, all-optical switches, and inter-channel information transfer are implemented in the visible wavelength. The experimental results on the response time of VO2 to light indicate that the formation of diffraction rings is mainly an electronically coherent third-order nonlinear optical process. The experimental results show that the VO2 dispersions exhibit an excellent nonlinear optical response and may lay the foundation for the application of VO2-based all-optical devices.


14C characteristics of organic carbon in the atmosphere and at glacier region of the Tibetan Plateau.
As an important component of carbonaceous aerosols (CA), organic carbon (OC) exerts a strong, yet insufficiently constrained perturbation of the climate. In this study, we reported sources of OC based on its natural abundance radiocarbon (14C) fingerprinting in aerosols and water-insoluble organic carbon (WIOC) in snowpits across the Tibetan Plateau (TP) - one of the remote regions in the world and a freshwater reservoir for billions of people. Overall, the proportions from 14C-based non-fossil fuel contribution (fnon-fossil) for OC in aerosols was 74 ± 10%, while for WIOC in snowpits was 81 ± 10%, both of which were significantly higher than that of elemental carbon (EC). These indicated sources of OC (WIOC) and EC were different at remote TP. Spatially, high fnon-fossil of WIOC of snowpit samples appeared at the inner part of the TP, indicating the important contribution of local non-fossil sources. Therefore, local non-fossil sources rather than long-range transportation OC dominants its total amount of the TP. In addition, the contribution of local non-fossil sourced WIOC increased during the monsoon period because heavy precipitation removed a high ratio of long-range transportation WIOC. The results of this study showed that not only OC and EC but also their different fuel sources should be treated separately in models to investigate their sources and atmospheric transportation.


Cellular distribution of retinoic acid receptor-alpha in benign hyperplastic and malignant human prostates: comparison with androgen, estrogen and progesterone receptor status.
Retinoids are unique modulators of gene activity, cell growth and differentiation by binding to a series of nuclear receptors, i.e. all-trans-retinoic acid receptors (RAR) or 9-cis-retinoid receptors (RXR). In this study, the expression of RARalpha was immunohistochemically evaluated in benign, hyperplastic and malignant prostatic tissue and correlated with sex steroid receptor status. Twenty-four cases of BPH and 139 cases of primary prostatic carcinoma were evaluated for RARalpha expression in correlation with androgen (AR), estrogen (ER) and progesterone (PGR) receptor staining, as well as with tumor grade. RARalpha was detected in the nuclei of epithelial cells in both BPH and prostate carcinoma cases. A modest inverse relationship with grade was present, especially for grade I and grade II tumors. AR staining was intense and a strong inverse relationship with grade was revealed. Although ER and PGR showed nuclear staining in prostatic epithelium, the overall expression for these receptors was low. When RARalpha content was compared to the nuclear AR expression, at least two-fold higher RARalpha levels were observed in AR+ grade II and grade III tumors. RARalpha expression can be immunohistochemically evaluated in formalin-fixed paraffin-embedded prostatic tissue. RARalpha expression is significantly elevated in AR+ moderately and poorly differentiated prostate carcinomas. Immunohistochemical determination of RARalpha content may be useful in defining the patient subsets in which retinoid-based treatment may be of clinical value.


New therapeutic opportunities for hepatitis C based on small RNA.
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease, including cirrhosis and liver cancer and is therefore, the most common indication for liver transplantation. Conventional antiviral drugs such as pegylated interferon-alpha, taken in combination with ribavirin, represent a milestone in the therapy of this disease. However, due to different viral and host factors, clinical success can be achieved only in approximately half of patients, making urgent the requirement of exploiting alternative approaches for HCV therapy. Fortunately, recent advances in the understanding of HCV viral replication and host cell interactions have opened new possibilities for therapeutic intervention. The most recent technologies, such as small interference RNA mediated gene-silencing, anti-sense oligonucleotides (ASO), or viral vector based gene delivery systems, have paved the way to develop novel therapeutic modalities for HCV. In this review, we outline the application of these technologies in the context of HCV therapy. In particular, we will focus on the newly defined role of cellular microRNA (miR-122) in viral replication and discuss its potential for HCV molecular therapy.


Classification study of skin sensitizers based on support vector machine and linear discriminant analysis.
The support vector machine (SVM), recently developed from machine learning community, was used to develop a nonlinear binary classification model of skin sensitization for a diverse set of 131 organic compounds. Six descriptors were selected by stepwise forward discriminant analysis (LDA) from a diverse set of molecular descriptors calculated from molecular structures alone. These six descriptors could reflect the mechanic relevance to skin sensitization and were used as inputs of the SVM model. The nonlinear model developed from SVM algorithm outperformed LDA, which indicated that SVM model was more reliable in the recognition of skin sensitizers. The proposed method is very useful for the classification of skin sensitizers, and can also be extended in other QSAR investigation.


Explainable artificial intelligence in skin cancer recognition: A systematic review.
Due to their ability to solve complex problems, deep neural networks (DNNs) are becoming increasingly popular in medical applications. However, decision-making by such algorithms is essentially a black-box process that renders it difficult for physicians to judge whether the decisions are reliable. The use of explainable artificial intelligence (XAI) is often suggested as a solution to this problem. We investigate how XAI is used for skin cancer detection: how is it used during the development of new DNNs? What kinds of visualisations are commonly used? Are there systematic evaluations of XAI with dermatologists or dermatopathologists? Google Scholar, PubMed, IEEE Explore, Science Direct and Scopus were searched for peer-reviewed studies published between January 2017 and October 2021 applying XAI to dermatological images: the search terms histopathological image, whole-slide image, clinical image, dermoscopic image, skin, dermatology, explainable, interpretable and XAI were used in various combinations. Only studies concerned with skin cancer were included. 37 publications fulfilled our inclusion criteria. Most studies (19/37) simply applied existing XAI methods to their classifier to interpret its decision-making. Some studies (4/37) proposed new XAI methods or improved upon existing techniques. 14/37 studies addressed specific questions such as bias detection and impact of XAI on man-machine-interactions. However, only three of them evaluated the performance and confidence of humans using CAD systems with XAI. XAI is commonly applied during the development of DNNs for skin cancer detection. However, a systematic and rigorous evaluation of its usefulness in this scenario is lacking.


Mechanisms underlying satiation of feeding behavior of the mollusc Aplysia.
Animals filled almost to satiation by nonnutritive bulk do not satiate when they ingest a small amount of seaweed. This suggests that satiation is not triggered by chemostimulation of an anteriorly located "hot spot." Inflation of a balloon placed in the gut of the animal results in satiation as reflected in a number of different parameters of feeding behavior. The suppressive effect of a relatively brief inflation is rapidly and fully reversible, although repeated inflation and deflation appeared to produce slowly reversible or irreversible effects. The parameters of the changes in feeding during gut inflation are comparable to those of normal animals that are slowly fed individual pieces of food. The inflation volume needed to satiate the animal is a function of the rate of inflation--more rapid inflations requiring larger volumes. Cutting of the esophageal nerves results in a significant increase in the volume needed to satiate the animals, but nevertheless they eventually cease feeding and generally do not show a burst gut. The evidence indicates that the satiation that eventually occurs in nerve-sectioned animals, at least in part, is due to depression of feeding following very prolonged sensory stimulation. The data suggest that for a rapidly consumed meal, satiation results primarily due to distension-related gut signals conveyed by the esophageal nerves, whereas for very slowly consumed meals, the former factor interacts with a process associated with sensory stimulation, such as receptor adaptation. The current results indicate that balloon distension can serve as a reasonable stimulus in experiments in simplified preparations in which the nervous system can be studied.


Leukotriene C4 is a tight-binding inhibitor of microsomal glutathione transferase-1. Effects of leukotriene pathway modifiers.
Microsomal glutathione transferase-1 (MGST-1) is an abundant protein that catalyzes the conjugation of electrophilic compounds with glutathione, as well as the reduction of lipid hydroperoxides. Here we report that leukotriene C4 is a potent inhibitor of MGST-1. Leukotriene C4 was found to be a tight-binding inhibitor, with a Ki of 5.4 nM for the unactivated enzyme, and 9.2 nM for the N-ethylmaleimide activated enzyme. This is the first tight-binding inhibitor characterized for this enzyme. Leukotriene C4 was competitive with respect to glutathione and non-competitive toward the second substrate, CDNB. Analysis of stoichiometry supports binding of one molecule of inhibitor per homotrimer. Leukotrienes A4, D4, and E4 were much weaker inhibitors of the purified enzyme (by at least 3 orders of magnitude). Leukotriene C4 analogues, which have been developed as antagonists of leukotriene receptors, were found to display varying degrees of inhibition of MGST-1. In particular, the cysteinyl-leukotriene analogues SKF 104,353, ONO-1078, and BAYu9773 were strong inhibitors (IC50 values: 0.13, 3. 7, and 7.6 microM, respectively). In view of the partial structural similarity between MGST-1, leukotriene C4 synthase, and 5-lipoxygenase activating protein (FLAP), it was of interest that leukotriene C4 synthesis inhibitors (which antagonize FLAP) also displayed significant inhibition (e.g. IC50 for BAYx1005 was 58 microM). In contrast, selective 5-lipoxygenase inhibitors such as zileuton only marginally inhibited activity at high concentrations (500 microM). Our discovery that leukotriene C4 and drugs developed based on its structure are potent inhibitors of MGST-1 raises the possibility that MGST-1 influences the cellular processing of leukotrienes. These findings may also have implications for the effects and side-effects of drugs developed to manipulate leukotrienes.


The Mr 24,000 phosphoprotein from developing bone is the NH2-terminal propeptide of the alpha 1 chain of type I collagen.
Using nondegradative isolation procedures, we have purified and characterized the Mr 24,000 phosphoprotein from developing bovine and human bone where it constitutes 5% of the noncollagenous protein in the mineral compartment. This hydroxyproline-containing protein could not be cleaved by cyanogen bromide. The purified, intact product spontaneously formed a complex consistent with a collagen-like trimer that remained a trimer even in sodium dodecyl sulfate-polyacrylamide gels. The ability to form the complex was lost upon treatment with bacterial collagenase, a treatment that resulted in an NH2-terminally blocked fragment of Mr 17,000. After deblocking, the NH2-terminus of the intact, Mr 24,000 bovine product was shown to have virtually the same amino acid sequence (residues 1-24 with asparagine rather than aspartic acid at position 20 as reported earlier by Horlein et al. (Horlein, D., Fietzek, P. P., Wachter, E., Lapiere, C. M., and Kuhn, K. (1979) Eur. J. Biochem. 90, 31-38) as the amino-terminal segment of dermatosparatic calf skin alpha 1 type I procollagen. Furthermore, pulse-chase studies showed a precursor-product relationship between procollagen and the Mr 24,000 protein. Anti-serum made against the bovine bone protein bound to bands on electrotransfers that were consistent with the positions of both alpha 1(I) procollagen and the procollagen chain missing its COOH-terminal extension peptide (pN-alpha 1(I), as well as the original Mr 24,000 product in extracts of bone, skin, tendon, cornea, and other type I collagen-containing tissues. Fetal calf serum contained an average of 106 micrograms/ml of the Mr 24,000 protein as determined by quantitative enzyme-linked immunosorbent assay. The only serine residue in the bovine bone protein was phosphorylated. It is unknown whether the corresponding collagen NH2-terminal pro-peptides in other tissues and serum are similarly phosphorylated.


Large Copy-Number Variants in UK Biobank Caused by Clonal Hematopoiesis May Confound Penetrance Estimates.
Large copy-number variants (CNVs) are strongly associated with both developmental delay and cancer, but the type of disease depends strongly on when and where the mutation occurred, i.e., germline versus somatic. We used microarray data from UK Biobank to investigate the prevalence and penetrance of large autosomal CNVs and chromosomal aneuploidies using a standard CNV detection algorithm not designed for detecting mosaic variants. We found 160 individuals that carry >10 Mb copy number changes, including 56 with whole chromosome aneuploidies. Nineteen (12%) individuals had a diagnosis of Down syndrome or other developmental disorder, while 84 (52.5%) individuals had a diagnosis of hematological malignancies or chronic myeloproliferative disorders. Notably, there was no evidence of mosaicism in the blood for many of these large CNVs, so they could easily be mistaken for germline alleles even when caused by somatic mutations. We therefore suggest that somatic mutations associated with blood cancers may result in false estimates of rare variant penetrance from population biobanks.


Variable responses to high density of female Mus musculus: A merger of two population regulation hypotheses.
Grouping of female Mus musculus resulted in an increase in mean estrous cycle length from 4 to 12 days, yet some short cycles were still observed. Short cycles were attributed to certain females who consistently maintained a short cycling pattern as well as females who exhibited both short and long cycles. Upon breeding, females that continued to show a short cycle when grouped produced and weaned more young than females with suppressed cycles. No differences in mean weaning weight or sex ratio of the litters was observed. The ecological and evolutionary implications of these findings are discussed.


Trouble from the abdominal cavity: an unusual foreign body secondary to laparoscopic cholecystectomy.
Gastric foreign bodies are frequently seen in children and the elderly. In adults, most foreign bodies are caused by accidental ingestion and 80 % or more of them are likely to pass spontaneously. Herein, we report an interesting case of a gastric foreign body in a healthy adult with no apparent risk factors, such as psychiatric disorders, mental retardation and alcohol consumption, nor a history of accidental ingestion.


[Antimicrobial effects of fentanyl and bupivacaine].
In this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case of combined use. In vitro prospective study. University Clinical Microbiology Laboratory. In our study, in vitro antimicrobial effect of 0.05 mg.mL-1 fentanyl citrate, 5 mg.mL-1 bupivacaine were tested against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231 as Group F (Fentanyl Citrate) and Group B (Bupivacaine), respectively. S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 25922 were cultured onto Mueller Hinton agar (Oxoid, UK) plates and Candida albicans ATCC 10231 were cultured onto Sabouraud dextrose agar (Oxoid, UK) plates for 18-24 hours at 37°C. In terms of inhibition zone diameters, S. Aureus ATCC 29213, P. aeruginosa ATCC 27853, and C. albicans ATCC10231 values obtained after 12 and 24 hours of incubation were significantly higher in Group F than Group B (p < 0.001). In terms of inhibition zone diameters, E. coli ATCC 25922, and K. pneumomiae ATCC 13883 values obtained after 12 and 24hours of incubation were significantly higher in Group B than Group F (p < 0.001, E. coli 12ª hour p = 0.005). Addition of fentanyl to Local Anesthetics (LAs) is often preferred in regional anesthesia applications in today's practice owing especially to its effect on decreasing the local anesthetic dose and increasing analgesia quality and patient satisfaction. However, when the fact that fentanyl antagonized the antimicrobial effects of LAs in the studies is taken into account, it might be though that it contributes to an increase in infection complications. When the fact that fentanyl citrate, which was used in our study and included hydrochloric acid and sodium hydroxide as protective agents, broadened the antimicrobial effect spectrum of LAs, had no antagonistic effect and showed a synergistic antimicrobial effect against E. Coli is considered, we are of the opinion that the addition of fentanyl to LAs would contribute significantly in preventing the increasing regional anesthesia infection complications.


Decreased oxidative stress index of urine in patients with urinary tract infection.
To investigate the oxidative and antioxidative status of urine and serum of patients with urinary tract infection (UTI) and to compare them with those of controls. The antioxidative status of urine and serum were evaluated by measuring total antioxidant capacity (TAC) and plasma vitamin C concentration. The oxidative status of the samples was assessed by measuring the total peroxide and the oxidative stress index (OSI) levels. The means of the parameters were compared and the relationships among them were determined. Total peroxide and OSI levels were found to be lower and TAC was found to be higher in the urine of patients with UTI. On the contrary, while the plasma vitamin C concentration and TAC of serum was lower, the total peroxide and OSI levels were higher in patients than controls. There was a negative correlation between serum TAC and urine TAC values. There was also a positive correlation between plasma vitamin C concentration and serum TAC levels. The urine of the patients with UTI have higher TAC and lower total peroxide and OSI levels. However, lower TAC and plasma vitamin C concentration and higher total peroxide and OSI levels were observed in UTI. This condition may be a factor which facilitates the development of the infection or is secondary to UTI.


Smooth muscle cell arachidonic acid release, migration, and proliferation are markedly attenuated in mice null for calcium-independent phospholipase A2beta.
Pharmacologic evidence suggests that the lipid products generated by one or more calcium-independent phospholipases A(2) (iPLA(2)s) participate in the regulation of vascular tone through smooth muscle cell (SMC) Ca(2+) signaling and the release of arachidonic acid. However, the recent identification of new members of the iPLA(2) family, each inhibitable by (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one, has rendered definitive identification of the specific enzyme(s) mediating these processes difficult. Accordingly, we used iPLA(2)beta(-/-) mice to demonstrate that iPLA(2)beta is responsible for the majority of thapsigargin and ionophore (A23187)-induced arachidonic acid release from SMCs. Both thapsigargin and A23187 stimulated robust [(3)H]arachidonate (AA) release from wild-type aortic SMCs that was dramatically attenuated in iPLA(2)beta(-/-) mice (>80% reduction at 5 min; p < 0.01). Moreover, iPLA(2)beta(-/-) mice displayed defects in SMC Ca(2+) homeostasis and decreased SMC migration and proliferation in a model of vascular injury. Ca(2+)-store depletion resulted in the rapid entry of external Ca(2+) into wild-type aortic SMCs that was significantly slower in iPLA(2)beta-null cells (p < 0.01). Furthermore, SMCs from iPLA(2)beta-null mesenteric arterial explants demonstrated decreased proliferation and migration. The defects in migration and proliferation in iPLA(2)beta-null SMCs were restored by 2 mum AA. Remarkably, the cyclooxygenase-2-specific inhibitor, NS-398, prevented AA-induced rescue of SMC migration and proliferation in iPLA(2)beta(-/-) mice. Moreover, PGE(2) alone rescued proliferation and migration in iPLA(2)beta(-/-) mice. We conclude that iPLA(2)beta is an important mediator of AA release and prostaglandin E(2) production in SMCs, modulating vascular tone, cellular signaling, proliferation, and migration.


Combining anaerobic bacterial oncolysis with vaccination that blocks interleukin-10 signaling may achieve better outcomes for late stage cancer management.
Late stage solid tumors cause significant cancer mortality rates worldwide and effective therapy remains a big challenge. Cancer therapeutic vaccines elicit tumor specific T cells that kill tumor cells yet often fail to result in tumor destruction because of the limited T cell response and the local immune-suppressive environment. Blocking interleukin 10 (IL-10) signaling at the time of therapeutic vaccination elicits much stronger T cell responses than vaccination without IL-10 blocking. Anaerobic oncolytic bacteria target hypoxic regions of the late stage tumor tissues which not only stops tumor growth but also provides a pro-inflammatory environment that may increase the effectiveness of a therapeutic vaccine by recruiting more effector T cells to tumor site. In this review, we argue that combining both bacterial and vaccine therapies may improve the efficiency of late stage cancer management.


Pneumoperitoneum, omental emphysema and intramural barium perforation following double contrast barium enema.
Perforation above the peritoneal reflection is a rare complication of a barium enema. We describe a case in which perforation in the transverse colon during a double contrast study resulted in intramural extravasation of barium, pneumoperitoneum and omental emphysema.


[Age-related changes in the mucocutaneous junction and the conjunctivochalasis in the lower lid margins].
We investigated the age-related changes in the mucocutaneous junction and the conjunctivochalasis at the lower lid margin, and whether there is a correlation between the two or not. Sixty eyes of sixty patients without ocular surface disorders were examined and they were divided into six groups by age (20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years old) and sex(five males and five females in each age group). The lower lid margins were divided into three parts(the temporal third, the middle third, and the nasal third) and the anteroplacement of the mucocutaneous junction and the conjunctivochalasis were graded 0, 1, 2 and 3. In each part of the lower lid margins, there were significant age-related increases in both parameters(p < 0.005, p < 0.0001 respectively). Also, the grade of the anteroplacement of mucocutaneous junction increased with the grade of conjunctivochalasis. These findings suggest that there is a relationship between the anteroplacement of the mucocutaneous junction and the conjunctivochalasis with aging.


Comparison of mechanisms controlling uptake and accumulation of 2,4-dichlorophenoxy acetic acid, naphthalene-1-acetic acid, and indole-3-acetic acid in suspension-cultured tobacco cells.
Accumulation of radiolabelled naphthalene-1-acetic acid (1-NAA), 2,4-dichlorophenoxyacetic acid (2,4-D), and indole-3-acetic acid (IAA) has been measured in suspension-cultured tobacco (Nicotiana tabacum) cells. In this paper is presented a simple methodology allowing activities of the auxin influx and efflux carriers to be monitored independently by measuring the cellular accumulation of [3H]NAA and [14C]2,4-D. We have shown that 1-NAA enters cells by passive diffusion and has its accumulation level controlled by the efflux carrier. By contrast, 2,4-D uptake is mostly ensured by the influx carrier and this auxin is not secreted by the efflux carrier. Both auxin carriers contribute to IAA accumulation. The kinetic parameters and specificity of each carrier have been determined and new information concerning interactions with naphthylphthalamic acid, pyrenoylbenzoic acid, and naphthalene-2-acetic acid are provided. The relative contributions of diffusion and carrier-mediated influx and efflux to the membrane transport of 2,4-D, 1-NAA, and IAA have been quantified, and the data indicate that plant cells are able to modulate over a large range their auxin content by modifying the activity of each carrier.


Commercialization of gene therapy--the evolution of licensing and rights issues.
The scientific community and the general public are intrigued by the potential use of gene therapy to tackle disease at its origin, and the resulting benefits to the quality of lif. At the same time, pharmaceutical researchers are beginning to appreciate how an understanding of the genetic basis of disease, and its associated technologies may revolutionize the discovery process for new drugs. Therefore, companies must understand and anticipate how licensing and rights issues are likely to evolve with the science.


Multiplex real-time PCR and high-resolution melting analysis for detection of white spot syndrome virus, yellow-head virus, and Penaeus monodon densovirus in penaeid shrimp.
A multiplex real-time PCR and high-resolution melting (HRM) analysis was developed to detect simultaneously three of the major viruses of penaeid shrimp including white spot syndrome virus (WSSV), yellow-head virus (YHV), and Penaeus monodon densovirus (PmDNV). Plasmids containing DNA/cDNA fragments of WSSV and YHV, and genomic DNAs of PmDNV and normal shrimp were used to test sensitivity of the procedure. Without the need of any probe, the products were identified by HRM analysis after real-time PCR amplification using three sets of viral specific primers. The results showed DNA melting curves that were specific for individual virus. No positive result was detected with nucleic acids from shrimp, Penaeus monodon nucleopolyhedrovirus (PemoNPV), Penaeus stylirostris densovirus (PstDNV), or Taura syndrome virus (TSV). The detection limit for PmDNV, YHV and WSSV DNAs were 40fg, 50fg, and 500fg, respectively, which was 10 times more sensitive than multiplex real-time PCR analyzed by agarose gel electrophoresis. In viral nucleic acid mixtures, HRM analysis clearly identified each virus in dual and triple infection. To test the capability to use this method in field, forty-one of field samples were examined by HRM analysis in comparison with agarose gel electrophoresis. For HRM analysis, 11 (26.83%), 9 (21.95%), and 4 (9.76%) were infected with WSSV, PmDNV, and YHV, respectively. Agarose gel electrophoresis detected lesser number of PmDNV infection which may due to the limit of sensitivity. No multiple infection was found in these samples. This method provides a rapid, sensitive, specific, and simultaneous detection of three major viruses making it as a useful tool for diagnosis and epidemiological studies of these viruses in shrimp and carriers.


Immunohistochemical demonstration of renin in the juxtaglomerular apparatus of three Bufo species.
The cellular localization of renin was examined in the kidneys of some amphibians of the genus Bufo by immunoperoxidase and immunofluorescence techniques with an antiserum to renin isolated from the submandibular gland of the mouse. Immunoreactivity could be demonstrated in the media cells of the afferent arterioles (juxtaglomerular cells) close to as well as at great distance from the glomeruli. Occasionally, media cells of larger arterial vessels were also stained. The immunohistochemical data seem to be in accordance with earlier results obtained with a modified silver impregnation technique (Movat's staining procedure) used for the visualization of juxtaglomerular cells in non-mammalian vertebrates. Mouse kidney tissue, studied for purposes of comparison, showed renin-immunoreactivity as described by earlier investigators, i.e., immunoreactive staining in the afferent arterioles near the glomeruli and in the proximal tubule cells.


Potential effects of chocolate on human pregnancy: a randomized controlled trial.
This trial was undertaken to evaluate the effects of high-cocoa-content chocolate supplementation in pregnancy on several haematochemical and clinical parameters. The study had as reference population the pregnant women requesting an obstetric control at Outpatient Clinic of Obstetrics and Gynaecology of the S. Maria della Misericordia University Hospital, Perugia, Italy. Candidates who participated in this study were all Caucasian women aged 18-40 years, who had a single gestation pregnancy between 11th + 0 and 13th + 0 week gestational age. We conducted a single-center randomized controlled trial. The pregnant women selected were randomized into Group A, which received daily doses of 30 g of chocolate (70% cocoa), and Group B, which was free to increase their diet with other foods. Ninety women were randomized. Significant difference was found between the two groups for diastolic blood pressure (p = 0.05), systolic (p < 0.0001) and levels of liver enzymes, with values lower in Group A than in Group B. Total cholesterol levels and weight gain in Group A did not increase more than in Group B. A modest daily intake of high-cocoa-content chocolate contributes to reduce blood pressure, glycemic and liver pattern during pregnancy without affecting the weight gain.


Incidence of Listeria monocytogenes in two milk processing environments, and assessment of Listeria monocytogenes blood agar for isolation.
A year-long survey of two Northern Ireland milk processing plants for Listeria monocytogenes was carried out. Sample sites included the milk processing environment (walls, floors, drains, and steps), processing equipment, raw and pasteurised milk. The FDA listeria-selective enrichment procedure was used to process samples and an additional agar medium, L. monocytogenes Blood Agar (LMBA), was utilized as part of the isolation procedure in order to compare its performance to that of the recommended Oxford and Palcam agars. LMBA proved to be a very useful tool and was able to detect L. monocytogenes from 94.1% of sites compared to the 76.5% and 79.4% detection rate displayed by Oxford and Palcam agars, respectively. The overall incidence of listeria on equipment was 18.8% (6.3% L. monocytogenes), in the environment was 54.7% (40.6% L. monocytogenes) and in raw milk 44.4% (22.2% L. monocytogenes). On one occasion, L. welshimeri was isolated from pasteurised milk, probably demonstrating post-pasteurisation contamination of product. The main environmental sources of L. monocytogenes were considered to be a floor drain and stainless steel steps.


Risk of predation and feeding rate in tropical freshwater fishes: field evidence.
In a previous study (A. Prejs and K. Prejs in press) we found that at the end of the dry season small fish species trapped together with piscivorous fish in small, shallow pool varied in their level of food intake. The two smallest of these species fed little, whereas larger species fed at high rate. By examining the species and size composition of the diet and gape limitations of predatory species, I found that the decreased feeding rate of small fish was in response to a high risk of predation by gape-limited predators. The reduction of feeding rate was very substantial when compared to that of the same species in predator free area.


Inhibitory effect of lactoferrin against gray mould on tomato plants caused by Botrytis cinerea and possible mechanisms of action.
Lactoferrin (LF), an 80 kDa iron binding glycoprotein, was effective in the control of gray mould caused by Botrytis cinerea on tomato. LF strongly inhibited spore germination and germ tube elongation of B. cinerea in vitro, especially at 100 mg/L. When viewed by fluorescence microscopy following staining with propidium iodide, the membrane integrity of B. cinerea conidia treated with LF (50 mg/L) decreased to 68% at 2 h. The leakage of carbohydrate and protein from mycelia increased as the dose of LF increased compared with the untreated controls. Furthermore, methane dicarboxylic aldehyde (MDA) content in B. cinerea spores exposed to LF increased markedly. The activities of superoxide dismutase and catalase in spores treated with LF were also 1.3, twice as high as those in the control at 6 h, whereas ATP content was 1.5 times lower. In planta assays demonstrated that LF exhibited significant curative effect (76.3%, 100 mg/L) against gray mould, compared with the preventive effect (52.6%, 100 mg/L). The mechanisms by which LF decreased gray mould decay of tomato plant may be directly related to the severe damage to the conidia plasma membrane and loss of cytoplasmic materials from the hyphae. These findings suggest that LF has potential as an antifungal agent to reduce the severity of gray mould of tomato plants.


Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis.
Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non-alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans. To analyse the effect of cocoa polyphenols on NADPH oxidase isoform 2 (NOX2) activation, oxidative stress and hepatocyte apoptosis in a population affected by NASH. In a cross-sectional study comparing 19 NASH and 19 controls, oxidative stress, as assessed by serum NOX2 activity and F2-isoprostanes, and hepatocyte apoptosis, as assessed by serum cytokeratin-18 (CK-18) levels, were measured. Furthermore, the 19 NASH patients were randomly allocated in a crossover design to 40 g/day of dark chocolate (>85% cocoa) or 40 g/day of milk chocolate (<35% cocoa), for 2 weeks. sNOX2-dp, serum isoprostanes and CK-18 were assessed at baseline and after 2 weeks of chocolate intake. Compared to controls, NASH patients had higher sNOX2-dp, serum isoprostanes and CK-18 levels. A significant difference for treatments was found in subjects with respect to sNOX2-dp, serum isoprostanes and serum CK-18. The pairwise comparisons showed that, compared to baseline, after 14 days of dark chocolate intake, a significant reduction in sNOX2-dp serum isoprostanes and CK-18 M30 was found. No change was observed after milk chocolate ingestion. A simple linear regression analysis showed that ∆ of sNOX2-dp was associated with ∆ of serum isoprostanes. Cocoa polyphenols exert an antioxidant activity via NOX2 down-regulation in NASH patients.


Development of LnMnO3+σ perovskite on low temperature Hg0 removal.
LnMnO3+σ (Ln = La, Pr, Nd, Sm, Eu, Gd or Dy) perovskites synthesized by sol-gel method were employed for gaseous elemental mercury (Hg0) removal from coal-fired flue gas. Characterization results revealed the structure of the perovskites presented a phase transition process from rhombohedral system to O- and O'-orthorhombic structure with the change of A-site rare earth elements. The perovskites showed satisfactory Hg0 removal capacity in a narrow temperature range of 100-150°C. NdMnO3+σ with an O-O' orthorhombic structure presented the best Hg0 removal performance, which markedly depends on four factors: crystal structure, oxygen vacancy density, Mn4+/Mn3+ ratio and surface element segregation. The Hg0 removal mechanism was illustrated based on the mercury temperature programmed desorption experiment and X-ray photoelectron spectroscopy characterization. Both chemisorption and catalytic oxidation played a role in the Hg0 removal process. Chemisorption dominated the Hg0 removal, due to the slow catalytic oxidation rate at low temperature. This work preliminarily established the relation between the structure of rare earth manganese perovskite and Hg0 removal performance.


Long-term follow-up of generalized anxiety disorder.
The diagnostic stability and long-term prognosis of generalized anxiety disorder (GAD) remain the subjects of considerable controversy. We report the results of an investigation of the long-term outcome of an original sample of 44 subjects who participated in a medication trial. Subjects were reinterviewed approximately 16 months after completion of the study, using structured interviews. Fifty percent continued to fulfill criteria for GAD. Other concurrent axis I diagnoses were as follows: dysthymia, 11%; major depression, 7%; and social phobia, 7%. Regarding axis II comorbidity, subjects with chronic GAD were more likely to fulfill criteria for one or more personality disorders, especially in clusters B and C. In addition, follow-up subjects with GAD and with remitted GAD reported a statistically equivalent number of recent life events, although subjects with chronic GAD were more likely to report significant dissatisfaction with life. The findings indicate that although many subjects with GAD do not follow a chronic course, many others remain symptomatic. The results also suggest that GAD symptoms are not simply the result of a subject's recent negative experiences, and that life satisfaction measures are an accurate reflection of GAD outcome.


Management of patients with low-grade gliomas.
The accurate diagnosis and management of patients who have infiltrating low-grade gliomas is increasing in importance. Recent advances in molecular characterization, imaging, and treatment of these tumors underscore this current focus of investigations.


Pyrroloquinoline quinone-dependent dehydrogenases of acetic acid bacteria.
Pyrroloquinoline quinone (PQQ)-dependent dehydrogenases (quinoproteins) of acetic acid bacteria (AAB), such as the membrane-bound alcohol dehydrogenase (ADH) and the membrane-bound glucose dehydrogenase, contain PQQ as the prosthetic group. Most of them are located on the periplasmic surface of the cytoplasmic membrane, and function as primary dehydrogenases in cognate substance-oxidizing respiratory chains. Here, we have provided an overview on the function and molecular architecture of AAB quinoproteins, which can be categorized into six groups according to the primary amino acid sequences. Based on the genomic data, we discuss the types of quinoproteins found in AAB genome and how they are distributed. Our analyses indicate that a significant number of uncharacterized orphan quinoproteins are present in AAB. By reviewing recent experimental developments, we discuss how to characterize the as-yet-unknown enzymes. Moreover, our bioinformatics studies also provide insights on how quinoproteins have developed into intricate enzymes. ADH comprises at least two subunits: the quinoprotein dehydrogenase subunit encoded by adhA and the cytochrome subunit encoded by adhB, and the genes are located in a polycistronic transcriptional unit. Findings on stand-alone derivatives of adhA encourage us to speculate on a possible route for ADH development in the evolutional history of AAB. A combination of bioinformatics studies on big genome sequencing data and wet studies assisted with genetic engineering would unravel biochemical functions and physiological role of uncharacterized quinoproteins in AAB, or even in unculturable metagenome.


Mitogenicity of human fibroblasts in vivo for human breast cancer cells.
Stromal factors have been implicated in the regulation of mammary epithelial cell behaviour, but their influence on human breast cancer is unknown. Fibroblasts were grown in monolayer cell culture from explants of benign and malignant breast tissue and normal skin. MCF7 human breast cancer cells alone (2 X 10(6) cells) or in combination with live fibroblasts (MCF7 + F) were inoculated into the mammary fat pads of 6-8-week-old female nude mice. After 5 weeks tumours were excised, weighed and fixed for histological examination. Addition of live breast fibroblasts significantly increased the retrieval (127/135 versus 52/106, P less than 0.01, chi 2 test) and growth (tumour weight 174 +/- 11 versus 41 +/- 4 mg, mean +/- s.e.m., P less than 0.01, Mann-Whitney U test) of subsequent tumours. Histological examination did not reveal any morphological difference between the two tumour groups. Injection of fibroblasts alone did not produce tumours. Addition of skin fibroblasts was also stimulatory. Glutaraldehyde-killed fibroblasts increased tumour take but did not stimulate tumour growth. Mononuclear blood leucocytes were ineffective. The results demonstrate that, in this model, fibroblasts exert stimulatory influences on human breast cancer xenograft growth and development.


Detection of Borrelia lusitaniae, Rickettsia sp. IRS3, Rickettsia monacensis, and Anaplasma phagocytophilum in Ixodes ricinus collected in Madeira Island, Portugal.
A total of 300 Ixodes ricinus ticks were tested by polymerase chain reaction (PCR) for the presence of Borrelia spp., Rickettsia spp., and Anaplasma phagocytophilum. Sequence analysis demonstrated 8 (2.7%) ticks infected with B. lusitaniae, 60 (20%) with Rickettsia spp., and 1 (0.3%) with A. phagocytophilum. Seven (2.3%) ticks were coinfected with B. lusitaniae and Rickettsia spp., 2 (0.6%) with R. monacensis, and 5 (1.7%) with Rickettsia sp. IRS3. The results of this study suggest simultaneous transmission of multiple tick-borne agents on Madeira Island, Portugal.


Gonadal development and gametogenesis in the hypogonadal mouse are restored by gene transfer.
These results describe controlled regulation of a mammalian neural gene in transgenic mice. Analysis of truncated GnRH-GAP genes in transgenic mice will enable us to define the DNA sequences responsible for this control. Furthermore, by separate mutation of the GnRH and GAP coding sequences we will be able to determine the relative importance of these two peptides in the development and maintenance of reproductive function.


Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid peroxidation.
Iron and aluminum complexes of nitrilotriacetic acid cause severe nephrotoxicity in Wistar rats. In addition, a high incidence of renal cell carcinoma is seen in ferric nitrilotriacetate-treated animals. The present study was performed to see if lipid peroxidation is involved in ferric nitrilotriacetate toxicity. Ferric nitrilotriacetate had more bleomycin-detectable 'free' iron than any ferric salt, while iron complexed with desferrioxamine or ferric chondroitin sulfate had none. The toxicity of ferric nitrilotriacetate in vivo was more pronounced in vitamin E-deficient rats. A thiobarbituric acid-reactive substance was present in the kidneys of vitamin E-deficient rats in amounts markedly elevated compared to vitamin E-sufficient, or vitamin E-supplemented rats. Non-complexed nitrilotriacetate or aluminum nitrilotriacetate did not produce any thiobarbituric acid-reactive substance in vitamin E-sufficient rats died by the 58th day of administration. We suggest that the iron-stimulated production of free radicals leading to lipid peroxidation is the major cause of ferric nitrilotriacetate-mediated renal toxicity. Vitamin E, a known scavenger of free radicals, is effective in protecting against this iron-induced toxicity.


Gender and smoking-related risk reduction of periodontal disease with variant myeloperoxidase alleles.
Myeloperoxidase (MPO) is an oxidative enzyme expressed in polymorphonuclear leukocytes. It is involved in the defence against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in periodontal disease. A G/A polymorphism in the promoter region of the MPO gene at position -463 has been assumed to exert profound effects on the expression of the enzyme. It is the aim of this study to evaluate whether this polymorphism may influence the risk of periodontal diseases. A total of 3148 subjects were randomly selected from the general population in the SHIP study (Study of Health in Pomerania). Periodontal status, health-related and socio-economic items were assessed. All subjects aged 40-60 years (n = 1103) were included in this study, and 1083 genotyped for the MPO -463 G/A polymorphism by PCR and RFLP methods. The genotype frequencies determined were homozygous wild type G/G 65.9% (95% CI 63.5-68.6), heterozygous A/G 31.4% (28.8-34.4), and homozygous variant A/A 2.7% (2.0-3.8). Only female subjects have a significantly reduced risk of severe periodontal disease when bearing the variant genotypes A/G or A/A. In female subjects the reduction in periodontal risk was significant for non-smokers (OR = 0.48; 95% CI 0.23-0.96); the smoke-related increase in risk was also reduced (OR = 0.50; 95% CI 0.22-1.10). When adjusted for age, smoking, and education the odds ratios were calculated as 0.52 (P = 0.01) and 0.97 (P = 0.90) for female and male subjects, respectively. The results of this study confirm the assumption that the MPO -463A allele variants are protective in the pathogenesis of periodontal diseases. This holds true only with women but not with men. The results are discussed with respect to the known influences of sexual hormones on MPO activity.


R on T or R on P phenomenon? Relation to the genesis of ventricular tachycardia.
Continuous electrocardiographic monitoring of 225 patients with acute myocardial infarction was performed during the initial 48 hours after admission. Two hundred twelve episodes of ventricular tachycardia occurred in 49 subjects, and 8 patients had primary ventricular fibrillation. Most cases of ventricular tachycardia were associated with late coupling of premature ventricular complexes. Of the 212 instances of ventricular tachycardia, 42 (20 percent) were initiated by a premature complex on the T wave (R on T) (R-R'/Q-T less than 1), and 93 (44 percent) had initiating premature complexes that occurred directly after onset of the sinus P wave (R on P). Of eight episodes of ventricular fibrillation, seven were initiated by a premature ventricular complex and in four of these there was associated R on T phenomenon. The influence of atrial contraction and myocardial stretch on reentry or ectopy is proposed as a possible explanation for the relatively high incidence rate of ventricular tachycardia observed after the onset of the sinus P wave.


Computer applications in analysis, mapping and cataloging of proteins separated by two dimensional electrophoresis.
Two dimensional electrophoretic separation of complex mixtures of proteins can only be exploited to its fullest potential using sophisticated computerized spot detection, quantification, pattern recognition, pattern normalization, data reduction and data storage. We present a discussion of some of the technical problems and of the options available which will ultimately lead toward full computerization of the data.


Inferences about radionuclide mobility in soils based on the solid/liquid partition coefficients and soil properties.
To assist transport modeling in assessments of the radiological impact of a geological repository for radioactive wastes, the mobility of various elements was studied in arable and wetland soils in the Forsmark region, Sweden. Pore water and total element contents were determined for five types of unconsolidated deposits (regolith), spanning a wide range of soil properties with respect to pH and organic matter content. Two soil depths were sampled to capture element mobility in regolith layers affected and unaffected by soil-forming processes. The solid/liquid partition coefficients (K d values) for most elements varied significantly among regolith types. For most elements, the observed variations in K d values could be explained by variations in soil properties. For many elements, mobility increased with decreasing soil pH. The results provide a significant addition of data on radionuclide retention in soils, taking account of soil properties and processes.


Application of a Nanotechnology-Based, Point-of-Care Diagnostic Device in Diabetic Kidney Disease.
Early detection of diabetes mellitus (DM) and diabetic kidney disease (DKD) is important for preventing end-stage renal failure and reducing cardiovascular complications. Availability of a validated point-of-care (PoC) device that can measure various DKD markers would be useful in this respect, especially in resource-poor parts of the world. We validated a novel nanotechnology-based multianalyte PoC device (minimally invasive and does not require trained medical personnel) against laboratory gold standard tests for the detection of 5 biomarkers related to management of DM and DKD. The prospective study was funded by an International Society of Nephrology American Nephrologists of Indian Origin grant in 2 phases: (i) proof of concept: random samples were tested for the analytes with the PoC device and correlated with the laboratory gold standard; and (ii) clinical validation in a well-characterized cohort of patients. A nonenzymatic- and nonantibody-based electrochemical PoC device for quantitative measurement of markers-glycosylated hemoglobin (HbA1c), hemoglobin, serum albumin, microalbuminuria, urine creatinine, and albumin-to-creatinine ratio-was developed and used in this study. The disposable strips were interfaced with a multipotentiostat hand-held PoC device (3.7-V rechargeable lithium battery, 5-inch touch screen, Bluetooth enabled) working in amperometry mode, which provided the results in <1 minute. Data were analyzed using linearity plots and Bland-Altman difference plot analysis. A total of 4717 individuals were screened during the study (phase 1: 2576 and phase 2: 2141.) In phase 2, samples were tested in 529 subjects (346 females)-120 subjects with type 1 DM, 255 subjects with type 2 DM, 54 subjects without DM, 400 subjects with stage 2 chronic kidney disease, and 30 subjects with stage 3 chronic kidney disease. A nanotechnology-based PoC device for quantitative measurement of HbA1c, hemoglobin, serum albumin, microalbuminuria, and the urine albumin-to-creatinine ratio was developed for detection of early DKD and showed excellent correlation between the device and laboratory results. This device has the potential for early detection of DM and/or DKD, especially in remote communities in underserved areas of the world where prevalence of diabetes is rapidly increasing.


Cyclic Martensitic Transformations Influence on the Diffusion Of Carbon Atoms in Fe-18 wt.%Mn-2 wt.%Si alloy.
A significant carbon diffusion mobility acceleration as a result of cyclic γ↔ε martensitic transformations in iron-manganese alloy is determined by one- and two-dimensional structure defects of ε-martensite with face-centered close-packed lattice. Such defects (dislocations, low angle sub-boundaries of dislocations, chaotic stacking faults) were formed during cyclic γ↔ε martensitic transformations. Peak carbon diffusion coefficient increase was observed under thermocycling when maximum quantity of lattice defects increase was fixed.


Non-random arrangement of synonymous codons in archaea coding sequences.
Non-random arrangement of synonymous codons in coding sequences has been recently reported in eukaryotic and bacterial genomes, but the case in archaeal genomes is largely undetermined. Here, we systematically investigated 122 archaeal genomes for their synonymous codon co-occurrence patterns. We found that in most archaeal coding sequences, the order of synonymous codons is not arranged randomly, but rather some successive codon pairs appear significantly more often than expected. Importantly, such codon pairing bias (CPB) pattern in archaea does not seem to completely follow the co-tRNA codon pairing (CCP) rule previously reported for eukaryotes, but largely obeys an identical codon pairing (ICP) rule. Further, synonymous codon permutation test demonstrated that in many archaeal genomes, random mutation alone is unable to cause the observed high level of ICP bias, which strongly indicates that selection force has been involved to shape synonymous codon orders, potentially meeting a global requirement to optimize translation rate.


Degradation of acetochlor by four microbial communities.
Four microbial communities capable of degrading acetochlor, designated A, D, E, and J, were obtained from acetochlor-contaminated soil and sludge. Acetochlor at an initial concentration of 55mg/L was completely degraded by the four mixed cultures after 4 days. At 80 mg/L acetochlor, more than 99% degradation was observed with D, 84% with A and E, and 88% with J after 9 days. There are primary eight strains of bacteria in community A, three in community D, E, and J, respectively. No single isolate was able to degrade acetochlor efficiently. The acetochlor biodegradation products were identified by gas chromatography-mass spectrometry. The probable degradative pathways of acetochlor involved dechlorination, hydroxylation, deethoxymethylation, cyclization, carboxylation, and decarboxylation. Propachlor, alachlor, and metolachlor, which are also the main components of the chloroacetanilide herbicide, could be degraded by the four mixed cultures to some degree. Given the high degradation rates observed here, the four mixed cultures obtained may be useful in the degradation processes of acetochlor.


Automated selection of relevant information for notification of incident cancer cases within a multisource cancer registry.
The aim of this study was to develop and evaluate a selection algorithm of relevant records for the notification of incident cases of cancer on the basis of the individual data available in a multi-source information system. This work was conducted on data for the year 2008 in the general cancer registry of Poitou-Charentes region (France). The selection algorithm hierarchizes information according to its level of relevance for tumoral topography and tumoral morphology independently. The selected data are combined to form composite records. These records are then grouped in respect with the notification rules of the International Agency for Research on Cancer for multiple primary cancers. The evaluation, based on recall, precision and F-measure confronted cases validated manually by the registry's physicians with tumours notified with and without records selection. The analysis involved 12,346 tumours validated among 11,971 individuals. The data used were hospital discharge data (104,474 records), pathology data (21,851 records), healthcare insurance data (7508 records) and cancer care centre's data (686 records). The selection algorithm permitted performances improvement for notification of tumour topography (F-measure 0.926 with vs. 0.857 without selection) and tumour morphology (F-measure 0.805 with vs. 0.750 without selection). These results show that selection of information according to its origin is efficient in reducing noise generated by imprecise coding. Further research is needed for solving the semantic problems relating to the integration of heterogeneous data and the use of non-structured information.


Yoga therapy for military personnel and veterans: Qualitative perspectives of yoga students and instructors.
Millions of military personnel and veterans live with chronic mental and physical health conditions that often do not respond well to pharmacological treatments. Serious side effects and lack of treatment response have led to widespread efforts to study and promote non-pharmacological and behavioral health treatments for many chronic health conditions. Yoga is an increasingly popular mind-body intervention that has growing research support for its efficacy and safety. Our objective was to explore the attitudes, perspectives, and preferences of military personnel and veterans toward yoga as a therapeutic modality, thus providing needed information for designing and promoting yoga interventions for this population. Participants included 24 individuals with yoga experience and current or past military service and 12 instructors who have taught yoga for military personnel and/or veterans. A semi-structured set of questions guided interviews with each participant. Five themes emerged from the interviews: (1) mental health benefits experienced from yoga practice; (2) physical health benefits experienced from yoga practice; (3) important yoga elements and conditions that support effective practice; (4) facilitators for engaging military in yoga practice; and (5) challenges and barriers to yoga practice for military. The study highlights consistent reports of mental and physical benefits of yoga practice, ongoing stigma resulting in the need for combatting and demystifying yoga and other complementary and integrative health (CIH) practices, the importance of designing interventions to address the unique mental health issues and perspectives of this population, and the importance of efforts by military leadership to bring CIH to military personnel and veterans. Rigorous research addressing these findings, along with further research on the efficacy and effectiveness of yoga interventions for treating various conditions are needed.


Awakening the endogenous Leloir pathway for efficient galactose utilization by Yarrowia lipolytica.
Production of valuable metabolites by Yarrowia lipolytica using renewable raw materials is of major interest for sustainable food and energy. Galactose is a monosaccharide found in galactomannans, hemicelluloses, gums, and pectins. Yarrowia lipolytica was found to express all the Leloir pathway genes for galactose utilization, which encode fully functional proteins. Gene organization and regulation in Y. lipolytica resembles filamentous fungi rather than Saccharomyces cerevisiae. After Y. lipolytica was grown on mixture of glucose and galactose, it was then able to metabolize galactose, including when glucose concentrations were higher than 4 g/L. However, glucose was still the preferred carbon source. Nonetheless, a strain overexpressing the four ylGAL genes of the Leloir pathway was able to efficiently use galactose as its sole carbon source. This mutant was used to produce citric acid and lipids from galactose; the yields were comparable to or greater than that obtained for the parental strain (W29) on glucose. The construction of a Y. lipolytica strain able to produce citric acid and lipids from galactose is a very important step in bypassing issues related to the use of food-based substrates in industrial applications.


Directions of single-leg landing affect multi-segment foot kinematics and dynamic postural stability in male collegiate soccer athletes.
Understanding lower limb kinematics and postural control in different directions of single-leg landings is critical to evaluate postural control and prevent lower limb injuries. However, foot and ankle kinematics and postural control during single-leg landings in different directions are less known. Does the difference in the direction of single-leg landing affect the foot kinematics on the frontal plane and dynamic postural stability? A cross-sectional study was conducted. Forty-nine male collegiate soccer players performed single-leg forward (FL), 45° lateral (LL), and medial (ML) direction landings. The lower limb, foot (rearfoot, midfoot, forefoot), and ankle kinematics during an impact phase were evaluated, and a curve analysis was performed using a statistical parametric mapping method to compare the three landings. The three landings were compared in terms of postural control parameters, including time to stabilization (TTS), peak of ground reaction forces (GRFs), root-mean-square of the mediolateral GRFs for 0-0.4 s (GRFML0.4), loading rate, and magnitude of horizontal GRFs from 0-0.4 s (HGRF-0.4), 0.4-2.4 s (HGRF-2.4), and 3.0-5.0 s. Ankle and rearfoot kinematics in LL exhibited smaller eversion and pronation positions than FL and ML (p < 0.01). The TTS-mediolateral (TTS-ML) was longer in the LL than in FL and ML (p < 0.001). The GRFML0.4, HGRF-0.4, and -2.4 in the LL and ML were greater than those in the FL (p < 0.001). Directions of single-leg landing affect foot and ankle kinematics and postural stability. Specifically, the LL exhibits more inverted ankle and supinated rearfoot positions, and longer TTS-ML. Thus, the LL may induce stretching of the lateral ankle ligament. These findings can help understand foot kinematics and assess dynamic postural control.


3D optoelectronic analysis of interfractional patient setup variability in frameless extracranial stereotactic radiotherapy.
To investigate size and frequency of interfractional patient setup variability in hypofractionated stereotactic extracranial radiotherapy. Infrared optical 3D tracking of surface markers was applied to quantify setup variability on 51 patients. Isocenter position repeatability was assessed by means of frameless anatomic calibration and was compared with portal image evaluation. Specific data analysis allowed for compensation of patients' breathing movements and for separation of the effects of operator-dependent misalignments and respiration-induced displacements. Effects of patient position (supine vs. prone) and treatment table configuration were investigated. Patient positioning assisted by the optical tracking device allowed reducing displacements of surface control points within the 3-mm range. Errors in isocenter localization were in the range of a few millimeters. This was in agreement with the portal image evaluation. Breathing motion introduced appreciable errors, which increased control points and isocenter 3D variability. This effect was significantly higher than those related to other investigated factors. The role of infrared optical tracking devices for patient positioning is assessed on a large patient population. Their use in the frame of high-precision radiotherapy is emphasized by the application of related methodologies for breathing phase detection and frameless isocenter localization.


A Preliminary Study on the Feasibility of the Quantitative Parameters of Dual-Energy Computed Tomography Enterography in the Assessment of the Activity of Intestinal Crohn's Disease.
To investigate the value of dual energy CT enterography (DECTE) in evaluating the activity of Crohn's disease (CD). The endoscopy and imaging data of 29 patients with CD confirmed by clinic and pathology were analyzed retrospectively. The clinical CD activity index (CDAI) was used as the disease activity grouping standard, 29 patients with CD were grouped into activity groups, 18 patients in the active group (CDAI ≥ 150) with 36 intestinal segments, and 11 patients in the remission group (CDAI < 150) with 20 intestinal segments.The virtual single energy CT value, slope of energy spectrum curve and iodine content were analyzed to evaluate the evaluation of intestinal CD activity by DECTE. There were statistically significant differences in virtual single energy CT value (except 90 keV and 100 keV virtual single energy CT value), curve slope and iodine content between remission group and active group (P < 0.05), and has more diagnostic value for active phase (AUC > 0.5). ① Virtual single energy CT value: the AUC of 60 keV in arterial phase was the highest (0.924). The specificity of diagnosing CD in active stage was high (95%). ② Curve slope: the AUC of portal vein phase was the largest (0.731). The specificity of diagnosing CD in active stage was higher (85%). ③ Iodine content: the AUC of arterial phase was the highest (0.885). The specificity of diagnosing CD lesions in the active stage was 100%. The virtual single energy CT value, energy spectrum curve slope and iodine content can provide reference for clinical accurate diagnosis of CD activity.


On the enterohepatic cycle of triiodothyronine in rats; importance of the intestinal microflora.
Until 70 h after a single iv injection of 10 uCi [125I]triiodothyronine (T3), normal rats excreted 15.8 +/- 2.8% of the radioactivity with the feces and 17.5 +/- 2.7% with the urine, while in intestine-decontaminated rats fecal and urinary excretion over this period amounted to 25.1 +/- 7.2% and 23.6 +/- 4.0% of administered radioactivity, respectively (mean +/- SD, n = 4). In fecal extracts of decontaminated rats 11.5 +/- 6.8% of the excreted radioactivity consisted of T3 glucuronide (T3G) and 10.9 +/- 2.8% of T3 sulfate (T3S), whereas no conjugates were detected in feces from normal rats. Until 26 h after ig administration of 10 uCi [125I]T3, integrated radioactivity in blood of decontaminated rats was 1.5 times higher than that in normal rats. However, after ig administration of 10 uCi [125I]T3G or [125I]T3S, radioactivity in blood of decontaminated rats was 4.9- and 2.8-fold lower, respectively, than in normal rats. The radioactivity in the serum of control animals was composed of T3 and iodide in proportions independent of the tracer injected, while T3 conjugates represented less than 10% of serum radioactivity. These results suggest an important role of the intestinal microflora in the enterohepatic circulation of T3 in rats.


The determiner congruency effect in language production investigated with functional MRI.
In language production, naming a picture with a gender-marked determiner phrase is faster in the presence of a distractor noun with the same grammatical gender (congruent condition) as compared with a different grammatical gender (incongruent condition). We investigated the neural correlates of this determiner congruency effect in German with functional magnetic resonance imaging (fMRI). Participants named pictures of real objects with determiner phrases (e.g. "der Tisch"-the table) in the presence of a gender-congruent or gender-incongruent distractor noun. Different comparisons allow the following functional segregation within the prefrontal cortex. First, the comparison between picture naming versus rest revealed a steeper slope of the haemodynamic response function (HRF) in the gender-congruent than the gender-incongruent condition in the left BA 44, suggesting the involvement of BA 44 in determiner selection. HRF amplitude differences between the congruent and the incongruent condition were observed outside the language network in the right fronto-median wall (congruent > incongruent), and in the left premotor cortex, middle frontal gyrus, cerebellum, and inferior parietal lobe (incongruent > congruent). The latter regions are known to be involved in the processing of incongruence and conflict in general. The data thus reveal the involvement of the left BA 44 in the selection of determiners for language production.


In vitro production of llama (Lama glama) embryos by intracytoplasmic sperm injection: effect of chemical activation treatments and culture conditions.
Assisted reproductive technologies in the llama (Lama glama) are needed to provide alternative methods for the propagation, selection and genetic improvement; however, recovery of adequate quantity and quality of spermatozoa for conventional IVF is problematic. Therefore, an effort was made to adapt the intracytoplasmic sperm injection (ICSI) procedure for the in vitro production of llama embryos. The specific objectives of this study were: (1) to determine in vitro maturation rates of oocytes recovered by transvaginal ultrasound-guided oocyte aspiration (TUGA) or flank laparotomy; (2) to evaluate the effects of activation treatments following ICSI; (3) to evaluate the development of llama ICSI embryos in CR1aa medium or in an oviduct cell co-culture system. Llamas were superstimulated by double dominant follicle reduction followed by oFSH administered in daily descending doses over a 3-day interval. Oocytes were harvested by flank laparotomy or TUGA and matured in vitro for 30 h. Mature oocytes were subjected to ICSI followed by no chemical activation (Treatment A), ionomycin only (Treatment B) or ionomycin/DMAP activation (Treatment C). More oocytes were recovered by flank laparotomy procedure compared with TUGA (94% versus 61%, P<0.05) and a greater number of oocytes harvested by flank laparotomy reached the metaphase-II stage (77% versus 44%, P<0.05). After ICSI, the proportion of cleaved and 4-8-cell stages embryos was significantly greater when injected oocytes were activated with ionomycin/DMAP combination (63% and 38%, respectively, P<0.05). The co-culture of ICSI embryos with llama oviduct epithelial cells resulted in progression to morula (25%) and blastocyst (12%) stages; whereas, all embryos cultured in CR1aa medium arrested at the 8-16-cell developmental stage.


Characteristics and clinical significance of ambulatory myocardial ischemia in men and women in the general population presenting with angina pectoris.
The aim of this study was to determine the frequency and prognostic importance of ambulatory myocardial ischemia and its association with cardiovascular risk factors in men and women in the general population presenting for the first time with typical angina pectoris. Previous studies in selected "low" and "high" risk patients with stable coronary heart disease report a wide range in the frequency of ischemia (24% to 82%) and there is no agreement about whether ambulatory ischemia is of prognostic importance for the generality of patients with stable angina. Consecutive patients < or = 70 years of age from a randomly selected population with no previous coronary heart disease were assessed prospectively, and 96 patients with typical angina and 95 age-, gender- and practice-matched asymptomatic control subjects underwent 24-h ambulatory ST segment monitoring before antianginal therapy. All recordings were analyzed in blinded fashion. Follow-up evaluation of patients with angina to assess for revascularization, myocardial infarction and death was undertaken at a mean of 15.8 months (range 7 to 30) after the initial evaluation. Transient episodes of ischemic ST segment depression were detected in 50 patients (52%) with angina and 9 control subjects (9%). In patients with angina, 159 episodes (71%) were silent, median duration of ischemia was 66 min (range 1 to 782) and mean +/- SD ST depression was 2.4 +/- 1.1 mm. In logistic regression analysis, serum cholesterol (p < 0.05) and ischemia on exercise (p < 0.01) were independently associated with the presence of ambulatory ischemia in men with angina, but only the latter was significant in women; this may reflect a different pathophysiologic basis for ambulatory ischemia in women. During follow-up, there were 29 events. Kaplan-Meier survival analysis revealed no significant difference in event-free survival between patients with angina who did and did not have ischemic episodes (66% vs. 72%, p = NS). This is the first study representative of new patients with angina pectoris in the general population and shows that ischemia during daily living activities is present in > 50% of these patients but appears to be of no prognostic value.


Penetrating Vascular Injury: Diagnosis and Management Updates.
Penetrating vascular injury is becoming increasingly common in the United States and abroad. Much of the current research and treatment is derived from wartime and translation to the civilian sector has been lacking. Penetrating vascular injury can be classified as extremity, junctional, or noncompressible. Diagnosis can be obvious but at other times subtle and difficult to diagnose. Although there are numerous modalities, computed tomography angiography is the diagnostic study of choice. It is hoped that care will be improved by using an algorithmic approach integrating experience from military and civilian research.


Long-term effects of neovaginal reconstruction with sigmoid loop technique on sexual function and self image in patients with gynecologic malignancies: results of a prospective study.
We evaluated the long-term results of sigmoid vaginoplasty in women with gynecologic malignancies after radical pelvic surgery, with specific focus on safety and effects of the procedure on patients' sexuality and self image. This prospective study included women with gynecologic malignancies who underwent partial or complete colpectomy as part of the cancer treatment. In all cases a pedicled sigmoid loop was used for the neovaginal reconstruction. Systematic clinical examination was performed and validated questionnaires about sexuality (Female Sexual Function Index), quality of life (SF-12) and susceptibility to depression (ADSk-15) were answered by all patients at the earliest 6 months after vaginoplasty. Seven patients with sigmoid vaginoplasty, recruited between 11/2003 and 02/2008, were evaluated in the present analysis. Mean patients age was 48+/-8.49 years. Mean neovaginal length was 6.4 cm (range: 2-12 cm). The mean Female Sexual Function Index (FSFI)-score of all patients was 16.6+/-12.6. In the subset of sexually active patients the mean FSFI-score was 22.5+/-9.4 higher. Regarding early operative morbidity and complications, sigmoid vaginal reconstruction appears to be a safe procedure, though in a long-term assessment 85% of the patients developed a vaginal stenosis with the need for operative bougienage. The vaginal reconstruction using a sigmoid loop is a safe and well accepted procedure in patients with gynecologic malignancies. However lower sexuality scores seem to be achieved than in non-cancer patients after equivalent vaginoplasty. Cancer-related physical and psychological comorbidity seem to have negative effects on the overall outcome and patient's satisfaction.


Development and optimization of a novel 384-well anti-malarial imaging assay validated for high-throughput screening.
With the increasing occurrence of drug resistance in the malaria parasite, Plasmodium falciparum, there is a great need for new and novel anti-malarial drugs. We have developed a 384-well, high-throughput imaging assay for the detection of new anti-malarial compounds, which was initially validated by screening a marine natural product library, and subsequently used to screen more than 3 million data points from a variety of compound sources. Founded on another fluorescence-based P. falciparum growth inhibition assay, the DNA-intercalating dye 4',6-diamidino-2-phenylindole, was used to monitor changes in parasite number. Fluorescent images were acquired on the PerkinElmer Opera High Throughput confocal imaging system and analyzed with a spot detection algorithm using the Acapella data processing software. Further optimization of this assay sought to increase throughput, assay stability, and compatibility with our high-throughput screening equipment platforms. The assay typically yielded Z'-factor values of 0.5-0.6, with signal-to-noise ratios of 12.


Bacteriological characteristics of Histophilus ovis and its relationship to similar bacteria.
Seventeen strains of Histophilus ovis were obtained from a variety of pathological conditions and geographical areas and were examined to determine the bacteriological characteristics of the organism. All were Gram-negative pleomorphic rods which only grew under micro-aerophilic conditions in media enriched with blood, serum or meat particles. All strains were catalase negative, indole positive and nitrate positive while most produced acid from glucose, fructose, galactose, mannose, xylose, mannitol and sorbitol. Eight strains were examined serologically and compared with two strains of Actinobacillus seminis. In agglutination and precipitation tests, all strains of H ovis appeared antigenically identical and showed antigenic relationships to A seminis. Results of complement fixation tests confirmed the close, if not identical, antigenic relationship of H ovis and A seminis. It is suggested that H ovis and A seminis are biochemical variants of the same organism.


Knowledge, attitudes, and practice towards allergic rhinitis in patients with allergic rhinitis: a cross-sectional study.
The knowledge, attitude, and practice (KAP) of Chinese patients with allergic rhinitis (AR) on AR is poorly known. This study investigated the KAP towards AR in patients with this disease and explored the factors associated with KAP. This cross-sectional study enrolled patients with AR in Zhangjiagang Hospital of Traditional Chinese Medicine between October 2022 and March 2023. This study included 656 valid questionnaires. Most participants were 26-35 years old (36.13%) and were female (55.18%). The knowledge, attitude, and practice scores were 5.70 ± 2.88 (possible range: 0-12), 29.51 ± 3.52 (possible range: 9-45), and 34.13 ± 7.55 (possible range: 9-45), indicating poor knowledge, unfavorable attitudes, and proactive practice. AR history of 3-5 years (adjusted odds ratio (adjOR) = 1.62, 95% confidence interval (CI): 1.03-2.54, P = 0.037), AR history of > 6 years (adjOR = 1.64, 95%CI: 1.06-2.54, P = 0.027), and know their own allergens (adjOR = 2.34, 95%CI: 1.28-4.25, P = 0.005) were independently associated with the sufficient knowledge. AR history of ≥ 6 years (adjOR = 0.60, 95%CI: 0.37-0.96, P = 0.035), and liking sports (adjOR = 1.58, 95%CI = 1.07-2.33, P = 0.020) were independently associated with the positive attitude. The knowledge scores (adjOR = 1.14, 95%CI: 1.05-1.22, P = 0.001), attitude scores (adjOR = 1.24, 95%CI: 1.17-1.32, P < 0.001), age 36-45 (adjOR = 2.13, 95%CI: 1.19-3.82, P = 0.011), employed (adjOR = 0.59, 95%CI: 0.37-0.94, P = 0.026), and liking sports (adjOR = 2.11, 95%CI: 1.43-3.14, P < 0.001) were independently associated with the proactive practice. Patients with AR have poor knowledge and unfavorable attitudes but good practice toward AR. Continuous quality teaching interventions and education on patients for AR were recommended.


The Predictive Link between Matrix and Metastasis.
Cancer spread (metastasis) is responsible for 90% of cancer-related fatalities. Informing patient treatment to prevent metastasis, or kill all cancer cells in a patient's body before it becomes metastatic is extremely powerful. However, aggressive treatment for all non-metastatic patients is detrimental, both for quality of life concerns, and the risk of kidney or liver-related toxicity. Knowing when and where a patient has metastatic risk could revolutionize patient treatment and care. In this review, we attempt to summarize the key work of engineers and quantitative biologists in developing strategies and model systems to predict metastasis, with a particular focus on cell interactions with the extracellular matrix (ECM), as a tool to predict metastatic risk and tropism.


Increased incidence of neoplasia in patients with pituitary adenomas. The Pituitary Study Group.
The goal of our study was to determine the rate of neoplasms in patients with other pituitary adenomas (non-functioning and prolactinomas) in comparison with acromegaly which is known to favour the development of neoplasia. We reviewed clinical records for 220 patients with acromegaly, 151 patients with non-functioning pituitary adenoma (NF) and 98 patients with prolactinomas. Incidence rates of cancer for patients with pituitary tumours were calculated per person-years of follow-up study. These rates were then compared with sex and age adjusted incidence rates reported by National Tumour Registry. An internal control group of 163 subjects with a non-neoplastic condition, i.e. Graves' disease followed chronically in the same clinic was also studied. The ratios observed to expected were expressed as standardized incidence rates (SIR). The only significant difference between the acromegalic and other pituitary tumours patients was in hypopituitarism, present in 18.2% (acromegaly) 47% (NF) and 18.6% (prolactinomas). Twenty-three malignant tumours were registered in 19 acromegalics (1 Hodgkin disease, 1 myelogenous leukaemia, 1 lymphocytic leukaemia, 3 papillary thyroid carcinomas, 1 ovarian carcinoma, 2 colorectal carcinoma, 1 renal cell carcinoma, 4 cervical carcinoma, 2 skin cancers, 2 pancreatic carcinoma, 4 breast carcinoma, 1 bladder carcinoma). Three acromegalics harboured two malignancies. Patients with acromegaly had a 3.39-fold increased rate of malignant tumours compared with the general population and a 3.21-fold increased rate compared with our internal control group. Eleven malignant tumours were found in patients with NF-pituitary adenomas and 2 in prolactinoma patients (1 lymphoma, 1 multiple myeloma, 1 colonic cancer, 1 renal cell cancer, 1 stomach cancer, 2 lung cancers, 1 cervix carcinoma, 1 breast cancer, 1 testicular carcinoma and 3 melanoma). Patients with NF pituitary adenomas had a 3.91-fold increased rate of malignant tumours compared with the general population and 4.07-fold increase compared with the internal control group. Patients harbouring prolactinomas did not have an increased incidence rate of malignancy compared with the general population or our internal controls. Female patients with acromegaly and male patients with NF-pituitary adenoma had higher incidences of neoplasia. We have demonstrated that the overall incidence of malignant tumours in patients with non-functioning pituitary adenomas and acromegaly is significantly higher than expected for general population and for our internal control group.


3D Carbon Foam Supported Edge-Rich N-Doped MoS2 Nanoflakes for Enhanced Electrocatalytic Hydrogen Evolution.
Molybdenum disulfide (MoS2 ) is one of the most promising alternatives to the Pt-based electrocatalysts for the hydrogen evolution reaction (HER). However, its performance is currently limited by insufficient active edge sites and poor electron transport. Hence, enormous efforts have been devoted to constructing more active edge sites and improving conductivity to obtain enhanced electrocatalytic performance. Herein, the 3D carbon foam (denoted as CF) supported edge-rich N-doped MoS2 nanoflakes were successfully fabricated by using the commercially available polyurethane foam (PU) as the 3D substrate and PMo12 O40 3- clusters (denoted as PMo12 ) as the Mo source through redox polymerization, followed by sulfurization. Owing to the uniform distribution of nanoscale Mo sources and 3D carbon foam substrate, the as-prepared MoS2 -CF composite possessed well-exposed active edge sites and enhanced electrical conductivity. Systematic investigation demonstrated that the MoS2 -CF composite showed high HER performance with a low overpotential of 92 mV in 1.0 m KOH and 155 mV in 0.5 m H2 SO4 at a current density of 10 mA cm-2 . This work offers a new pathway for the rational design of MoS2 -based HER electrocatalysts.


Distinct roles of pH and organic ligands in the dissolution of goethite by cysteine.
Electron shuttles such cysteine play an important role in Fe cycle and its availability in soils, while the roles of pH and organic ligands in this process are poorly understood. Herein, the reductive dissolution process of goethite by cysteine were explored in the presence of organic ligands. Our results showed that cysteine exhibited a strong reactivity towards goethite - a typical iron minerals in paddy soils with a rate constant ranging from 0.01 to 0.1 hr-1. However, a large portion of Fe(II) appeared to be "structural species" retained on the surface. The decline of pH was favorable to generate more Fe(II) ions and enhancing tendency of Fe(II) release to solution. The decline of generation of Fe(II) by increasing pH was likely to be caused by a lower redox potential and the nature of cysteine pH-dependent adsorption towards goethite. Interestingly, the co-existence of oxalate and citrate ligands also enhanced the rate constant of Fe(II) release from 0.09 to 0.15 hr-1; nevertheless, they negligibly affected the overall generation of Fe(II) in opposition to the pH effect. Further spectroscopic evidence demonstrated that two molecules of cysteine could form disulfide bonds (S-S) to generate cystine through oxidative dehydration, and subsequently, inducing electron transfer from cysteine to the structural Fe(III) on goethite; meanwhile, those organic ligands act as Fe(II) "strippers". The findings of this work provide new insights into the understanding of the different roles of pH and organic ligands on the generation and release of Fe induced by electron shuttles in soils.


Histopathological and scintigraphic features of condylar hyperplasia.
This investigation was undertaken to correlate the scintigraphic and histological features of condylar hyperplasia to identify consistent diagnostic findings. A series of 34 surgically excised condyles were examined from a 5 year period. Of these, 20 were diagnosed clinically and histologically as condylar hyperplasia. In 18 of these the presentation was one of increasing facial asymmetry. In all 20 cases there was an increased uptake of Technetium 99 as determined by gamma scintigraphy. The thickness of the fibrous articular layer, undifferentiated germinal mesenchyme layer and the hyperplastic cartilage layer were measured using an eyepiece graticule and the presence and frequency of islands of cartilage in the subchondral bone were noted. 7 patients received tetracycline hydrochloride 14 and 4 days pre-operatively in an attempt to quantify the calcification rate. An uninterrupted layer of undifferentiated germinal mesenchyme is a consistent feature of condylar hyperplasia. An increased uptake on scintigraphy is proportionally related to the thickness of the hypertrophic cartilage and not only to the presence but also the frequency of cartilage islands in the subchondral bone.


Characterization and expression analysis of laboratory of genetics and physiology 2 gene in sea perch, Lateolabrax japonicus.
LGP2 (laboratory of genetics and physiology 2) as a key component of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), plays a predominant role in modulating RLRs-mediated cellular antiviral signaling during viral infection. In the present study, we cloned the LGP2 gene from the sea perch (Lateolabrax japonicus) (LjLGP2), an economically important farmed fish. The complete cDNA sequence of LjLGP2 was 2790 nt and encoded a polypeptide of 682 amino acids which contains four main structural domains: one DEAD/DEAH box helicase domain, one conserved restriction domain of bacterial type III restriction enzyme, one helicase superfamily c-terminal domain and one C-terminal domain of RIG-I, similar to most vertebrate LGP2. Subcellular localization analysis showed that LjLGP2 spanned the entire cytosol. The LjLGP2 mRNA was widespread expressed in the tested 10 tissues of healthy fish and significantly up-regulated post NNV infection. Furthermore, time course analysis showed that LjLGP2 transcripts significantly increased in the spleen, kidney and liver tissues after NNV infection. LjLGP2 mRNA expression was rapidly and significantly up-regulated in LJB cells after poly I:C stimulation and NNV infection. The present results suggest that LjLGP2 may be involved in recognization of NNV and play a role in antiviral innate immune against NNV in sea perch.


Pets and the elderly. A social work perspective.
Pets can provide companionship, affection, and psychosocial stimulus for elderly people in a program that is planned and supervised by professionals who are knowledgeable about both the humans and the animals and who are clear about the goals to be achieved. Ineffective programs, or programs with negative effects, have developed when the proponents assumed that any pet would be good for elderly persons either living alone or in a residential center. A much-needed aspect of any people-pet program is the collection, analysis, and reporting of social data to provide a better information base for planning the use of pets in a therapeutic setting.


New partners of acyl carrier protein detected in Escherichia coli by tandem affinity purification.
We report the first use of tandem affinity purification (TAP) in a prokaryote to purify native protein complexes, and demonstrate its reliability and power. We purified the acyl carrier protein (ACP) of Escherichia coli, a protein involved in a myriad of metabolic pathways. Besides the identification of several known partners of ACP, we rediscovered ACP/MukB and ACP/IscS interactions already detected but previously disregarded as due to contamination. Here, we demonstrate the specificity of these interactions and characterize them. This suggests that ACP is involved in additional previously unsuspected pathways. Furthermore, this study shows how the TAP method can be simply used in prokaryotes such as E. coli to identify new partners in protein-protein interactions under physiological conditions and thereby uncover novel protein functions.


Modeling ant foraging: A chemotaxis approach with pheromones and trail formation.
We consider a continuous mathematical description of a population of ants and simulate numerically their foraging behavior using a system of partial differential equations of chemotaxis type. We show that this system accurately reproduces observed foraging behavior, especially spontaneous trail formation and efficient removal of food sources. We show through numerical experiments that trail formation is correlated with efficient food removal. Our results illustrate the emergence of trail formation from simple modeling principles.


Community involvement and socialization among individuals with mental retardation.
Mental retardation, a condition characterized by significantly lower than average intellectual ability and adaptive behavior deficits, currently affects between 2% and 3% of the population. Individuals with mental retardation experience many difficulties throughout their lives, with one such difficulty being that they have few opportunities for community involvement and often have few social relationships. To determine if increased community involvement and increased socialization are among the most common desires expressed by individuals with mental retardation, we conducted a study examining pre-existing data of 1348 individuals. The study focused on specific desires expressed by individuals with mental retardation--including, but not limited to, increased community involvement and increased socialization. Although these individuals expressed a wide variety of desires, they expressed a desire for increased community involvement most frequently. Individuals also frequently expressed a desire for increased socialization, change of residence, work-related changes, increased personal belongings, and increased personal activities. We discuss the importance of community involvement and socialization, the link between the two, interactions that could potentially exist among other expressed desires, and ways of increasing community involvement while addressing other desires that individuals with mental retardation expressed.