Experimental replacement of the cervical esophagus in rats with a jejunal free transplantation.
Hypopharynx and cervical-esophageal reconstruction after malignant-lesion removal has been a challenging problem for head and neck surgeons. The reconstructive technique has been developed over the years through several ingenious methods of replacement. As a result of recent refinements in microvascular anastomosis techniques, many studies concerning one-stage, immediate cervical-esophagus reconstruction have been reported. An experimental study on esophageal reconstruction has been developed using a free intestinal transplantation in two distinct strains of rats. One of the groups consisted of a heterogeneous population of Wistar rats and the other an inbred Lewis strain. In our study the Wistar group reacted as in allograft transplantations and developed an immunological rejection process. The Lewis strain reacted according to isogenic transplantations. The surviving rats were killed and microscopical studies of the reconstructed esophagus were performed. This study is a low-cost, practical experimental model to achieve a better knowledge of the behavior of the transplanted organs.


The Effects of Antisense miRNA-20a Alone or in Combination with Imatinib on K562 Cell Proliferation.
Objective: The effects of microRNA-20a (miR-20a) antisense oligonucleotides (ASODNs) on the proliferation and apoptosis of K562 cells were investigated, and the effects of these ASODNs in combination with imatinib on K562 cells were preliminarily observed. Methods: miR-20a ASODNs and scrambled oligonucleotides (SODNs) were chemically synthesized, and the later was used as the control. miR-20a ASODNs were transfected into K562 cells using Lipofectamine 2000 transfection reagent, and the expression of miR-20a was detected using real-time quantitative RT-PCR (qRT-PCR). The CCK8 assay was performed to detect the inhibition of the cell growth rate. The cells were stained by Hoechst 33258 to detect apoptotic cell morphology. Annexin V/PI double staining was used to detect the cell apoptosis rate using flow cytometry. The protein expression levels of E2F1, P21, and Bim in the K562 cell line were detected using western blotting. Results: The qRT-PCR results showed that the expression level of miR-20a in K562 cells transfected with miR-20a ASODNs was lower than those in the normal control, SODN and blank transfection groups (p < 0.05). miR-20a ASODNs significantly inhibited the growth of K562 cells as compared to the controls (p < 0.05). The Hoechst staining results showed morphological changes, suggesting apoptosis. The cell apoptosis rates in the ASODN group was (13.9 ± 1.5)%, which was significantly higher than that in the normal control group (1.84 ± 0.21)%, blank transfection group (3.21 ± 0.32)%, and SODN group (3.72 ± 0.44)% (p < 0.05). The protein expression of E2F1 and P21 in K562 cells transfected with miR-20a ASODNs were higher, while the level of Bim protein was significantly lower than that in the control groups. When miR-20a ASODNs were combined with imatinib, the growth of K562 cells was significantly inhibited as compared to the ASODN treatment alone, imatinib alone, and SODN+imatinib groups (p < 0.05). Conclusions: miR-20a ASODNs could induce apoptosis and inhibit the proliferation of K562 cells. In addition, imatinib combined with miR-20a ASODNs can increase the inhibitory effect on K562 cell proliferation.


Effects of the resistance plasmid R124 on the level of the OmpF outer membrane protein and on the response of Escherichia coli to environmental agents.
The introduction of the F-like resistance plasmid R124 into an ompC mutant of Escherichia coli K12 conferred altered sensitivity to a wide range of inhibitory agents. Sensitivity to ampicillin, chloramphenicol, ethionine, copper ions, deoxycholate, two fatty acids and colicins L and M was decreased by the plasmid. In contrast the plasmid-bearing ompC derivatives were more sensitive than the plasmid-free ompC mutant to erythromycin, cetyltrimethylammonium bromide and phenol. Introduction of R124 into the ompC strain also decreased the level of the OmpF protein and some (but not all) of the changed sensitivities listed above clearly resulted from this outer membrane protein deficiency. The presence in the ompC mutant of R124 (rather than the more efficient introduction of the plasmid into variants of the ompC strain) led to at least most of the changes described above because those tested were accentuated by the presence of a copy mutant of R124 and reversed by plasmid curing.


Gal repressor-operator-HU ternary complex: pathway of repressosome formation.
DNA transaction reactions require formation of nucleoprotein complexes that involve multifaceted DNA-protein and protein-protein interactions. Genetic and biochemical studies suggested that the higher order Gal repressosome structure, which governs the transcription of two tandem galpromoters in Escherichia coli, involves sequence-specific binding of GalR repressor dimers to two operators, O(E) and O(I), located 113 bp apart, binding of GalR to the sequence-nonspecific DNA binding protein HU, interaction of HU with an architecturally critical DNA site between the two operators, and interaction between two DNA-bound GalR dimers generating a loop of the intervening DNA segment. In this paper, we demonstrate and determine the thermodynamic parameters of several of these interactions, GalR dimer-O(E), GalR tetramerization, HU-GalR, and HU-GalR-O(E) interactions, by analytical ultracentrifugation, fluorescence anisotropy, and fluorescence resonance energy transfer. The physiological significance of several of these interactions was confirmed by the finding that a mutant HU, which is unable to form the repressosome in vivo and in vitro, failed to show the HU-GalR interaction. The results help to construct a pathway of Gal repressosome assembly.


Regulation of CRAC channels by protein interactions and post-translational modification.
Store-operated Ca(2+) entry (SOCE) is a widespread mechanism to elevate the intracellular Ca(2+) concentrations and stimulate downstream signaling pathways affecting proliferation, secretion, differentiation and death in different cell types. In immune cells, immune receptor stimulation induces intracellular Ca(2+) store depletion that subsequently activates Ca(2+)-release-activated-Ca(2+) (CRAC) channels, a prototype of store-operated Ca(2+) (SOC) channels. CRAC channel opening leads to activation of diverse downstream signaling pathways affecting proliferation, differentiation, cytokine production and cell death. Recent identification of STIM1 as the endoplasmic reticulum Ca(2+) sensor and Orai1 as the pore subunit of CRAC channels has provided the much-needed molecular tools to dissect the mechanism of activation and regulation of CRAC channels. In this review, we discuss the recent advances in understanding the associating partners and posttranslational modifications of Orai1 and STIM1 proteins that regulate diverse aspects of CRAC channel function.


Enhancing cellular cancer vaccines.
Various strategies have been used to generate cellular cancer vaccines with the expectation that they will become an effective part of the overall management of cancer patients. However, with few notable exceptions, immunization has not resulted in significant long-term therapeutic benefits. Tumor growth has continued and patient survival has been at best only modestly prolonged. One possible explanation is that as only a small proportion of the constituents of malignant cells are "tumor specific" and the vast majority are the products of nonantigenic, normal "housekeeping" genes, the immune response in patients immunized with cellular cancer vaccines is not sufficient to result in tumor rejection. Here, we review and characterize various types of cellular cancer vaccines. In addition, in a mouse breast cancer model system, we describe a unique strategy designed to enrich cellular vaccines for cells that induce tumor immunity. Numerous advantages and disadvantages of cancer immunotherapy with cellular vaccines are also presented.


Insulin Bolus Calculator in a Pediatric Hospital. Safety and User Perceptions.
Insulin dosing in hospitalized pediatric patients is challenging and requires dosing to be matched with the specific clinical and nutritional circumstances. We implemented a customized subcutaneous insulin bolus dose calculator tool integrated with the electronic health record to improve patient care. Here we describe this tool, its utilization and safety, and assess user satisfaction and perceptions of the tool. Blood glucose results for all patients who received insulin with and without the calculator tool were compared to assess safety. To assess user perceptions and satisfaction, a survey was sent to all identified users who interacted with the tool during the period from May 2015 to the end of November 2015. Survey responses were summarized, mean user satisfaction calculated, and correlation of Likert scale items with overall satisfaction assessed. Hypoglycemia rates (2.2% and 2.9%, p = 0.17) and severe hypoglycemia rates (0.04% and 0.1%, p = 0.21) were similar for the groups that received insulin with and without the calculator tool. Overall satisfaction for all survey respondents was high (4.05, SD = 0.83). Physicians indicated a slightly higher satisfaction than nurses (4.33 versus 3.94, p = 0.04). User agreement with improvement of quality of care showed the highest correlation with overall satisfaction (r = 0.80, 95% CI 0.7 - 0.87). Implementation of an insulin calculator tool streamlined ordering and administration of insulin in a pediatric academic institution while maintaining patient safety. Users indicated high overall satisfaction with the tool.


Tap water as a natural vehicle for microorganisms shaping the human gut microbiome.
Fresh potable water is an indispensable drink which humans consume daily in substantial amounts. Nonetheless, very little is known about the composition of the microbial community inhabiting drinking water or its impact on our gut microbiota. In the current study, an exhaustive shotgun metagenomics analysis of the tap water microbiome highlighted the occurrence of a highly genetic biodiversity of the microbial communities residing in fresh water and the existence of a conserved core tap water microbiota largely represented by novel microbial species, representing microbial dark matter. Furthermore, genome reconstruction of this microbial dark matter from water samples unveiled homologous sequences present in the faecal microbiome of humans from various geographical locations. Accordingly, investigation of the faecal microbiota content of a subject that daily consumed tap water for 3 years provides proof for horizontal transmission and colonization of water bacteria in the human gut.


Seasonal variation in mineralization rates (C-N-P-Si) of mussel Mytilus edulis biodeposits.
To determine seasonal variability in mineralization dynamics of mussel biodeposits, we applied a multiple-element approach measuring mineralization rates of carbon (C), nitrogen (N), phosphorus (P) and silicate (Si) during three periods (March, August and November). The results of this study showed that mineralization rates vary between seasons and between elements and that mineralization dynamics were influenced by both temperature and biodeposit nutrient composition. Mineralization rates were 3.2 ± 0.4 mmol C, 0.17 ± 0.04 mmol N, 0.06 ± 0.02 mmol P and 3.91 ± 3.75 mmol Si per gram biodeposit (DW) per day, which represented 24 % of the particulate organic C and 17 % of the particulate organic N in mussel biodeposits. Seasonal variability was largest for Si mineralization with 60-80-fold higher rates measured in March compared to August and November. This difference is most likely related to the difference in biodeposit nutrient composition. It was furthermore shown that the labile fraction of biodeposits became mineralized after, respectively, 18, 9 and 13 days during the experimental periods in March, August and November. This indicates that temperature enhances biodeposit decomposition with approximately 2-3 times faster turnover at a 10 °C temperature interval (Q10 ).


Comparison of multiple and novel measures of dietary glycemic carbohydrate with insulin resistant status in older women.
Previous epidemiological investigations of associations between dietary glycemic intake and insulin resistance have used average daily measures of glycemic index (GI) and glycemic load (GL). We explored multiple and novel measures of dietary glycemic intake to determine which was most predictive of an association with insulin resistance. Usual dietary intakes were assessed by diet history interview in women aged 42-81 years participating in the Longitudinal Assessment of Ageing in Women. Daily measures of dietary glycemic intake (n = 329) were carbohydrate, GI, GL, and GL per megacalorie (GL/Mcal), while meal based measures (n = 200) were breakfast, lunch and dinner GL; and a new measure, GL peak score, to represent meal peaks. Insulin resistant status was defined as a homeostasis model assessment (HOMA) value of >3.99; HOMA as a continuous variable was also investigated. GL, GL/Mcal, carbohydrate (all P < 0.01), GL peak score (P = 0.04) and lunch GL (P = 0.04) were positively and independently associated with insulin resistant status. Daily measures were more predictive than meal-based measures, with minimal difference between GL/Mcal, GL and carbohydrate. No significant associations were observed with HOMA as a continuous variable. A dietary pattern with high peaks of GL above the individual's average intake was a significant independent predictor of insulin resistance in this population, however the contribution was less than daily GL and carbohydrate variables. Accounting for energy intake slightly increased the predictive ability of GL, which is potentially important when examining disease risk in more diverse populations with wider variations in energy requirements.


Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR-375/JAK2.
In this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through Gene Expression Omnibus data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT-PCR along with the low expression of its downstream miRNA miR-375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR-375 overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2 was identified as a downstream mRNA target of miR-375 by RNA pull-down and dual-luciferase reporter gene assays, its expression in HCC cell lines were positively regulated by hsa_circ_101280 and negatively by miR-375 expression. Furthermore, the silencing of hsa_circ_101280 significantly inhibited the growth of HCC xenografts in nude mice, with the downregulated expression of JAK2. Overall, both the in vitro and in vivo studies revealed that hsa_circ_101280 largely facilitated the tumorigenesis of HCC, characterized by the promoted proliferation and suppressed apoptosis of HCC cells, by sponging miR-375 and upregulating JAK2.


A selective hydrolytic and restructuring approach through a Schiff base design on a coumarin platform for "turn-on" fluorogenic sensing of Zn2.
A new Schiff base, CMD, designed based on a coumarin platform was synthesized and fully characterized through single crystal X-ray diffraction studies. CMD underwent selective Zn2+-triggered hydrolysis in ethanolic medium followed by restructuring of its fragments, resulting in a "turn-on" green fluorogenic response. This response was confirmed through various physico-chemical measurements along with single crystal X-ray diffraction studies. This selective hydrolytic fluorogenic event was exploited for the successful optical detection and live cell imaging of Zn2+ in SiHa cells. The above restructured products were characterized as two new Schiff bases, viz.CM and NSA, of which NSA was highly fluorescent (green). Hence, the formation of this green fluorogenic product accounted for the above fluorogenic "turn-on" sensing of Zn2+ with a sub-nanomolar detection limit. Spectroscopic evidence along with mass determinations indicated that the Zn-CMD ensemble took the form of CM-Zn-CM in solution, supporting our above proposal of hydrolysis and restructuring. However, the X-ray diffraction studies of the Zn-CMD ensemble further revealed it to consist of NSA and CM-Zn-CM', where CM' is yet another new Schiff base formed in situ during the process of developing single crystals.


Production of H2 from combined endothermic and exothermic hydrogen carriers.
One of the major limitations to the use of fuel cell systems in vehicular transportation is the lack of hydrogen storage systems that have the required hydrogen storage density and moderate enthalpy of dehydrogenation. Organic liquid H(2) carriers that release H(2) endothermically are easier to handle with existing infrastructure because they are liquids, but they have low storage densities and their endothermicity consumes energy in the vehicle. On the other hand, inorganic solid H(2) carriers that release H(2) exothermically have greater storage densities but are unpumpable solids. This paper explores combinations of an endothermic carrier and an exothermic carrier, where the exothermic carrier provides some or all of the necessary heat required for dehydrogenation to the endothermic system, and the endothermic carrier serves as a solvent for the exothermic carrier. The two carriers can be either physically mixed or actually bonded to each other. To test the latter strategy, a number of chemically bound N-heterocycle:BH(3) adducts were synthesized and in turn tested for their ability to release H(2) by tandem hydrolysis of the BH(3) moiety and dehydrogenation of the heterocycle. To test the strategy of physically mixing two carriers, the hydrolysis of a variety of amine-boranes (H(3)N:BH(3), Me(2)HN:BH(3), Et(3)N:BH(3)) and the catalytic dehydrogenation of indoline were carried out together.


The novel melphalan prodrug J1 inhibits neuroblastoma growth in vitro and in vivo.
Neuroblastoma is the most common extracranial solid tumor of childhood. The activity of J1 (l-melphalanyl-p-l-fluorophenylalanine ethyl ester), an enzymatically activated melphalan prodrug, was evaluated in neuroblastoma models in vitro and in vivo. Seven neuroblastoma cell lines with various levels of drug resistance were screened for cytotoxicity of J1 alone or in combination with standard cytotoxic drugs, using a fluorometric cytotoxicity assay. J1 displayed high cytotoxic activity in vitro against all neuroblastoma cell lines, with IC(50) values in the submicromolar range, significantly more potent than melphalan. The cytotoxicity of J1, but not melphalan, could be significantly inhibited by the aminopeptidase inhibitor bestatin. J1 induced caspase-3 cleavage and apoptotic morphology, had additive effects in combination with doxorubicin, cyclophosphamide, carboplatin, and vincristine, and synergistically killed otherwise drug-resistant cells when combined with etoposide. Athymic rats and mice carrying neuroblastoma xenografts [SH-SY5Y, SK-N-BE(2)] were treated with equimolar doses of melphalan, J1, or no drug, and effects on tumor growth and tissue morphology were analyzed. Tumor growth in vivo was significantly inhibited by J1 compared with untreated controls. Compared with melphalan, J1 more effectively inhibited the growth of mice with SH-SY5Y xenografts, was associated with higher caspase-3 activation, fewer proliferating tumor cells, and significantly decreased mean vascular density. In conclusion, the melphalan prodrug J1 is highly active in models of neuroblastoma in vitro and in vivo, encouraging further clinical development in this patient group.


A ventricular septum filleted down the middle.
Trauma inflicted by sharp penetrating objects can cause unusual and complex injuries to the heart. We present a case where penetrating trauma caused an unusual ventricular laceration that filleted the ventricular septum into two separate sections creating an artificial chamber in between. The ventricular septal defect was clearly displayed with echocardiography and required special cardiac surgical intervention.


[A Case of Localized Amyloidosis of the Right Ureter Treated Effectively by Occulusive Dressing Technique Therapy Using Dimethyl Sulfoxide : Long-Term Follow-Up of Eight Years].
The patient was a 56-year-old female. She was referred to our department for further examination of right hydronephrosis in 2010. Computed tomography (CT) showed right hydronephrosis, and retrograde pyelography (RP) revealed stenosis of the right lower ureter. Urine cytology was negative. Transurethral biopsy of the right ureter was performed using ureteroscopic cup forceps and the histopathlogical diagnosis was ureteral amyloidosis. A whole-body search was performed, including rectal biopsy, but no evidence of amyloidosis was obtained. She was diagnosed with localized amyloidosis of the right ureter. A ureteral stent was indwelled and the patient was given occulusive dressing technique (ODT) therapy using dimethyl sulfoxide (DMSO) for 1 year. After ODT therapy, right hydronephrosis improved. After a 2-year followup, it worsened. ODT therapy was restarted and continued for 2 years. She consulted our department because of fever and right lumbago in April 2017 after a 4-month interruption of ODT therapy. CT revealed progression of the right hydronephrosis. A ureteral stent was indwelled and ODT therapy was restarted. The right hydronephrosis improved after 1 year. ODT therapy using DMSO was effective for localized ureteral amyloidosis, but periodic follow-up was necessary and ODT therapy was also effective when it recurred after the interruption of treatment.


Systematic review and meta-analysis of the risk of major cardiovascular events with etoricoxib therapy.
To determine the risk of thromboembolic cardiovascular events associated with the use of etoricoxib, a COX-2 inhibitor. Systematic review and meta-analysis of placebo-controlled randomised double-blind clinical trials of etoricoxib that were of at least 6 weeks duration and presented data on cardiovascular thromboembolic events. Six databases including Medline and EMBASE. The main outcome measure was cardiovascular thromboembolic events. A secondary analysis was undertaken to identify the presence or absence of predefined features that allowed determination of major cardiovascular events in a clinical trial. There were five studies with a total of 2,919 subjects included in the meta-analysis. There were 7 cardiovascular thromboembolic events in 1,441 patients (0.5%) treated with etoricoxib, and 1 event in 906 patients (0.1%) on placebo. A pooled fixed effect estimate of the absolute risk difference was 0.5% (95% CI 0.1-1.0). The odds ratio for the risk of cardiovascular events with etoricoxib was 1.49 (0.42-5.31). The clinical trials of etoricoxib provide limited data on major cardiovascular thromboembolic events as they were neither designed nor powered to assess the potential cardiovascular risks with etoricoxib therapy. However, the limited data that were available provide weak evidence of an increased cardiovascular risk with etoricoxib consistent with a class effect for COX-2 inhibitors.


PIN1 inhibits apoptosis in hepatocellular carcinoma through modulation of the antiapoptotic function of survivin.
PIN1, a peptidyl-prolyl-isomerase, binds a specific motif comprising a phosphorylated serine or threonine preceding a proline (p-Ser/Thr-Pro) residue in proteins. Through cis-trans isomerization, it induces conformational changes and modulates functions of many proteins that are involved in cell cycle progression, cell proliferation, and oncogenesis. PIN1 is overexpressed in hepatocellular carcinomas (HCC) and contributes to hepatocarcinogenesis. We investigated the role of PIN1 and the significance of its interaction with the inhibitor of apoptosis protein survivin in evading apoptosis in HCC cells. Using cell line and xenograft models, we determined that PIN1 overexpression inhibits apoptosis through suppression of caspase-3 and caspase-9 activity. In addition, down-regulation of survivin in PIN1-overexpressing cells attenuated the antiapoptotic effect induced by PIN1, suggesting that the inhibition of apoptosis is mediated through PIN1-survivin interaction. Coimmunoprecipitation assays showed that PIN1 interacted with survivin via the phosphorylated Thr34-Pro35 motif and enhanced binding among survivin phosphorylated at Thr34, hepatitis B X-interacting protein (HBXIP), and pro-caspase-9. Taken together, these results suggest that the inhibition of apoptosis by PIN1 in HCC cells is mediated through modulation of the antiapoptotic function of survivin by increasing its binding to pro-caspase-9 via HBXIP. Such functional interaction between PIN1 and survivin may therefore play an important role in hepatocarcinogenesis and chemoresistance.


The timing of herbivore-induced volatile emission in black poplar (Populus nigra) and the influence of herbivore age and identity affect the value of individual volatiles as cues for herbivore enemies.
The role of herbivore-induced plant volatiles as signals mediating the attraction of herbivore enemies is a well-known phenomenon. Studies with short-lived herbaceous plant species have shown that various biotic and abiotic factors can strongly affect the quantity, composition and timing of volatile emission dynamics. However, there is little knowledge on how these factors influence the volatile emission of long-lived woody perennials. The aim of this study was to investigate the temporal dynamics of herbivore-induced volatile emission of black poplar (Populus nigra) through several day-night cycles following the onset of herbivory. We also determined the influence of different herbivore species, caterpillars of the gypsy moth (Lymantria dispar) and poplar hawkmoth (Laothoe populi), and different herbivore developmental stages on emission. The emission dynamics of major groups of volatile compounds differed strikingly in response to the timing of herbivory and the day-night cycle. The emission of aldoximes, salicyl aldehyde, and to a lesser extent, green leaf volatiles began shortly after herbivore attack and ceased quickly after herbivore removal, irrespective of the day-night cycle. However, the emission of most terpenes showed a more delayed reaction to the start and end of herbivory, and emission was significantly greater during the day compared to the night. The identity of the caterpillar species caused only slight changes in emission, but variation in developmental stage had a strong impact on volatile emission with early instar L. dispar inducing more nitrogenous volatiles and terpenoids than late instar caterpillars of the same species. The results indicate that only a few of the many herbivore-induced black poplar volatiles are released in tight correlation with the timing of herbivory. These may represent the most reliable cues for herbivore enemies and, interestingly, have been shown in a recent study to be the best attractants for an herbivore enemy that parasitizes gypsy moth larvae feeding on black poplar.


Family medicine capability in medical disaster response.
Every disaster often holds a potential for significant impacts on human health and life. Every new threat presents new challenges to health risk management. However, family medicine faces an uncertainty on the specific roles it can assume to support urgent efforts at disaster surge response. Its preparedness level remains unknown. This research project, designed to explore issues of family medicine competency in this changed disaster response environment, conducted a disaster preparedness and response workshop among 28 family medicine physicians, testing their learning rate using a pre-test-post-test data collection method. Pre-test results (38.11 percent, x = 10.67) indicate that family medicine practitioners as a group were not ready by competency to respond to a disaster event and may instead increase the life risks of disaster victims. Post-test results (x = 21.67, 77.39 percent) showed an average doubling of their learning levels, indicating the workshop effectiveness in improving their disaster preparedness and response competency.


Role of graduate mental health workers within primary care.
The concept of primary healthcare graduate mental health workers came into being following the implementation of The NHS Plan (Department of Health, 2000) and the National Service Framework for Mental Health (DH, 1999). It is now generally agreed that service users must be consulted in order to fully understand and judge the effectiveness of this new role. It is this knowledge that can then position precisely where this new role will fit within the NHS's mental health organisational structure.


Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system.
Although many bacterial pathogens use specialized secretion systems for virulence, no such systems have been described for Mycobacterium tuberculosis, a major pathogen of humans that proliferates in host macrophages. In a screen to identify genes required for virulence of M. tuberculosis, we have discovered three components and two substrates of the first Sec-independent secretion pathway described in M. tuberculosis, which we designate the Snm pathway. Here we demonstrate that the proteins Snm1, -2, and -4 are required for the secretion of ESAT-6 and CFP-10, small proteins previously identified as major T cell antigens. Snm2, a member of the AAA ATPase family, interacts with substrates and with Snm1, another AAA ATPase. We show that M. tuberculosis mutants lacking either the Snm system or these substrates exhibit defects in bacterial growth during the acute phase of a mouse infection and are attenuated for virulence. Strikingly, snm mutants fail to replicate in cultured macrophages and to inhibit macrophage inflammatory responses, two well established activities of wild-type M. tuberculosis bacilli. Thus, the Snm secretion pathway works to subvert normal macrophage responses and is a major determinant of M. tuberculosis virulence.


The organization and implementation of relationship management.
The relationship management approach to public relations has much to offer practitioners in the health field. Public relations practitioners operate in an increasingly complex environment, and a relational approach provides professionals with a method of managing organization-public relationships in a coordinated manner to help health organizations achieve their goals. In addition, the adoption of a relational approach will allow public relations practitioners to work more closely with their marketing counterparts, who are increasingly using relational approaches in their jobs.


Determination of putrescine, spermine and spermidine in human tissues of prostate and kidney.
Polyamines react with o-phthalaldehyde forming intensely blue fluorescing condensation products with an activation maximum at 340 nm. Tissue concentrations of polyamines can be detected by cation exchange analysis and putrescine, spermine and spermidine were assayed in specimens of benign hyperplasia of prostate and renal adenocarcinoma and in normal control tissues. Comparison of results on polyamines in normal prostate and kidney tissues revealed significant differences, and changes of polyamines are discussed in relation to hyperplastic and neoplastic growth.


Role of apoptosis and cell proliferation in the testicular dynamics of seasonal breeding mammals: a study in the Iberian mole, Talpa occidentalis.
Apoptosis and cell proliferation are two important cellular processes known to be involved in the normal functioning of the testis in nonseasonally breeding mammals, but there is some controversy concerning their roles in the gonads of males from seasonally breeding species. We have studied the processes of apoptosis and cell proliferation in the testes of males of the Iberian mole (Talpa occidentalis), a species showing a strict seasonal reproduction pattern. Both males and females are sexually active during the winter and completely inactive in the summer, with two transitional periods, in the autumn and the spring. Adult males from these four reproductive stages were captured, and their testes were immunohistochemically studied for the presence of apoptotic and proliferation molecular markers as well for other testicular and meiotic cell-specific markers. We found that apoptosis varies in a season-dependent manner in the testes of male moles, affecting mainly late zygotene and pachytene cells during the period of sexual inactivity, but it does not differentially affect the number of Sertoli cells. More interestingly, apoptosis is not responsible for the massive germ-cell depletion occurring during mole testis regression. In addition, a wave of spermatogonial cell proliferation appears to restore the number of spermatogonia lost during the period of testis inactivity. According to current knowledge, data from moles indicate that mammals do not form a homogeneous group regarding the mechanisms by which the cell-content dynamics are regulated in the testes of males from seasonally breeding species.


[Clinical and epidemiological analysis of bone marrow transplantation in a pediatric oncology unit].
To describe the demographics and the most important acute clinical complications in patients undergoing bone marrow transplantation in the Pediatric Oncology Unit at Hospital de Clínicas de Porto Alegre, Brazil. A retrospective analysis was performed including 41 patients treated between August 1997 and June 2002. Twenty patients received allogeneic transplants (AG) and 21 received autologous transplants (AT). The mean age of AG patients was 8.9 +/- 5.4 years. Twelve patients were male. Stem cell sources were: bone marrow in 12 patients; peripheral blood in five; and unrelated cord blood in three. The diseases were acute lymphoid leukemia in seven patients; acute myeloid leukemia in four; chronic myeloid leukemia in two; myelodysplastic syndrome in two; Burkitt's lymphoma in one; severe combined immunodeficiency in one; Chediaki-Higashi syndrome in one; Fanconi anemia in one; and aplastic anemia in one. One patient developed grade II acute graft-versus-host-disease (GVHD), and three patients had grade IV GVHD. Three patients developed chronic GVHD. In all of them, the cell source was peripheral blood. Survival in this group was 70.0 +/- 10.3%. The main cause of death was GVHD in three patients and sepsis in another three. All deaths occurred before day 100. One of the patients who received unrelated cord blood is alive 3.5 years after the transplantation. In AG patients, mean age was 8.7 +/- 4.3 years. Eleven patients were male. The stem cell sources were: peripheral blood in 16; bone marrow in three; and peripheral blood + bone marrow in two. The diseases were: Wilms' tumor in five patients; Ewing's sarcoma family tumors in four; neuroblastoma in three; Hodgkin's disease in three; non-Hodgkin's lymphoma in one; rhabdomyosarcoma in two; neuroectodermic tumor of the central nervous system in two; acute myeloid leukemia in one. Survival in this group was 59.4 +/- 11.7%. Five patients died due to tumor relapse, two patients due to sepsis and one patient died in remission 20 months after bone marrow transplantation due to infection. In the whole group, the most common toxicities were vomiting, mucositis, diarrhea and abdominal pain. Infections were recorded in 58.5% of the patients. In 46.9%, at least one pathogen was isolated in the blood culture. The time required for neutrophil and platelet engraftment was correlated to the number of hematopoietic stem cell infused. The overall survival in our patients is similar to that reported in the literature. We did not find differences between AT and AG patients regarding acute toxicities and infections.


Target-Driven Design of Deep-UV Nonlinear Optical Materials via Interpretable Machine Learning.
The development of a data-driven science paradigm is greatly revolutionizing the process of materials discovery. Particularly, exploring novel nonlinear optical (NLO) materials with the birefringent phase-matching ability to deep-ultraviolet (UV) region is of vital significance for the field of laser technologies. Herein, a target-driven materials design framework combining high-throughput calculations (HTC), crystal structure prediction, and interpretable machine learning (ML) is proposed to accelerate the discovery of deep-UV NLO materials. Using a dataset generated from HTC, an ML regression model for predicting birefringence is developed for the first time, which exhibits a possibility of achieving fast and accurate prediction. Essentially, crystal structures are adopted as the only known input of this model to establish a close structure-property relationship mapping birefringence. Utilizing the ML-predicted birefringence which can affect the shortest phase-matching wavelength, a full list of potential chemical compositions based on an efficient screening strategy is identified. Further, eight structures with good stability are discovered to show potential applications in the deep-UV region, owing to their promising NLO-related properties. This study provides a new insight into the discovery of NLO materials and this design framework can identify desired materials with high performances in the broad chemical space at a low computational cost.


Anemia: a continuing problem following kidney transplantation.
Cardiovascular disease is a leading cause of death among kidney transplant recipients. Anemia, a risk factor for cardiovascular complications among patients with chronic kidney disease, has not been well characterized in kidney transplant recipients. We performed a retrospective cohort study of the prevalence of and factors associated with anemia among 240 patients who underwent kidney transplantation at our institution. The mean hematocrit (Hct) rose from 33% at 1 month after transplantation to 40% at 12 months after transplantation. The proportion of patients with Hct < 36% was 76% at transplantation and 21% and 36%, 1 year and 4 years after transplantation, respectively. Six months after transplantation, women had higher likelihood (OR = 3.61) of Hct < 36%, while higher Hct at 3 months (OR = 0.67 for 1% higher Hct) and diabetes (OR = 0.14) were associated with a lower likelihood of Hct < 36%. Similar associations were seen 12 months after transplantation. Even among patients with Hct < 30%, only 36% had iron studies, 46% received iron supplementation and 40% received recombinant human erythropoietin. Awareness of factors associated with a lower Hct may prompt better anemia screening and management, potentially improving cardiovascular outcomes among kidney transplant recipients.


gem-Diborylalkanes: recent advances in their preparation, transformation and application.
Recently, gem-diborylalkanes have attracted much attention as versatile building blocks and fundamental intermediates in organic synthesis, because they enable multiple C-C bond construction and further transformation at C-B bonds. Importantly, gem-diborylalkanes can be utilised as bisnucleophilic partners in a variety of chemo-selective C-C bond-forming reactions. This review describes recent developments in synthesising gem-diborylalkanes in complex molecules along with their chemical transformation. In the first part of the review the different synthetic approaches used to synthesise gem-diborylalkanes are described. In the second part, an overview of the chemoselective transformation of gem-diborylalkanes into various functionalized materials is discussed along with one-carbon homologation of diborylmethane via a selective uni- and bidirectional method.


KNOX2 genes regulate the haploid-to-diploid morphological transition in land plants.
Unlike animals, land plants undergo an alternation of generations, producing multicellular bodies in both haploid (1n: gametophyte) and diploid (2n: sporophyte) generations. Plant body plans in each generation are regulated by distinct developmental programs initiated at either meiosis or fertilization, respectively. In mosses, the haploid gametophyte generation is dominant, whereas in vascular plants-including ferns, gymnosperms, and angiosperms-the diploid sporophyte generation is dominant. Deletion of the class 2 KNOTTED1-LIKE HOMEOBOX (KNOX2) transcription factors in the moss Physcomitrella patens results in the development of gametophyte bodies from diploid embryos without meiosis. Thus, KNOX2 acts to prevent the haploid-specific body plan from developing in the diploid plant body, indicating a critical role for the evolution of KNOX2 in establishing an alternation of generations in land plants.


Regulatory potential for concerted modulation of Nrf2- and Nfkb1-mediated gene expression in inflammation and carcinogenesis.
Many studies have implicated nuclear factor E2-related factor 2 (Nrf2) and nuclear factor-kappaB1 (Nfkb1) in inflammation and cancer. However, the regulatory potential for crosstalk between these two important transcription factors in inflammation and carcinogenesis has not been explored. To delineate conserved transcription factor-binding site signatures, we performed bioinformatic analyses on the promoter regions of human and murine Nrf2 and Nfkb1. We performed multiple sequence alignment of Nrf2 and Nfkb1 genes in five mammalian species - human, chimpanzee, dog, mouse and rat - to explore conserved biological features. We constructed a canonical regulatory network for concerted modulation of Nrf2 and Nfkb1 involving several members of the mitogen-activated protein kinase (MAPK) family and present a putative model for concerted modulation of Nrf2 and Nfkb1 in inflammation/carcinogenesis. Our results reflect potential for putative crosstalk between Nrf2 and Nfkb1 modulated through the MAPK cascade that may influence inflammation-associated etiopathogenesis of cancer. Taken together, the elucidation of potential relationships between Nrf2 and Nfkb1 may help to better understand transcriptional regulation, as well as transcription factor networks, associated with the etiopathogenesis of inflammation and cancer.


Spindle cell squamous cell carcinoma arising in Bowen's disease: Case report and review of the published work.
A 79-year-old Japanese woman presented with an ulcerated, brown-red nodule in the center of a sharply demarcated, tan-brown plaque situated on the left side of her right breast. Histologically, the plaque demonstrated an acanthosis with an intraepidermal epithelioma of Borst-Jadassohn. Small oval nests of bland-appearing basophilic cells in the periphery gradually enlarged into nests of various sizes and irregular shapes, composed of densely cohesive, atypical basophilic cells above the central nodule. The atypical keratinocytes shifted to atypical spindle cells beneath the acanthotic epidermis, penetrating deep into the subcutaneous tissue. In addition to vimentin and p63, the spindle cells were positive for several cytokeratin (CK) markers, including AE1/AE3, 34βE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34βE12 and CK5/6. The MIB-1 index was estimated at approximately 40-50% in both the bland-appearing and the atypical basophilic cells. We describe the first case of spindle cell squamous cell carcinoma arising in an intraepidermal epithelioma expressed by clonal Bowen's disease, which was difficult to differentiate from clonal seborrheic keratosis.


Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma.
Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways. Recent studies demonstrated that PD-L1 expression is significantly correlated to the mutation status of EGFR, and activation of EGFR signaling can also induce the expression of PD-L1. However, the real linker between PD-L1 and EGFR signaling remains to be revealed. Our previous study revealed that the Hippo pathway effector YAP confers EGFR-TKI resistance in lung adenocarcinoma, and inhibition of YAP restores sensitivity to EGFR-TKIs. Thus, we examined whether PD-L1 is relevant, in terms of conferring EGFR-TKI resistance and whether YAP directly regulates the expression of PD-L1 in this context. First, we compared the expression levels of PD-L1 and YAP between EGFR-TKI-resistant PC9 cells and the parental PC9 adenocarcinoma cells. The expression levels of both YAP and PD-L1 were markedly higher in the EGFR-TKI-resistant cells compared to the parental cells, suggesting differential expression pattern between two cell types. YAP knockdown significantly decreased the expression of PD-L1 in the EGFR-TKI-resistant cells, while YAP overexpression increased the expression of PD-L1 in the parental PC9 cells. Then, our results revealed that YAP regulates the transcription of PD-L1, and the YAP/TEAD complex binds to the PD-L1 promoter. Surprisingly, knockdown of PD-L1 was sufficient to decrease cell proliferation and wound healing in the EGFR-TKI-resistant PC9 cells. These data suggest a PD1-independent oncogenic function of PD-L1. The Hippo effector YAP plays a crucial role in linking the PD-L1 and EGFR-TKI resistance by directly regulating the expression of PD-L1 in lung cancer. Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung adenocarcinoma.


[Screening and identification of proteins interacting with RAR alpha-V via yeast two-hybrid system].
To screen the protein interacting with retinoic acid receptor variant protein (RAR alpha-V) via the yeast two-hybrid technique (YTHT) and to find out the targets protein and study its biological function. The bait vector of pGBKT7-RAR alpha-V was constructed for screening proteins interacting with RAR alpha-V in K562 cell cDNA expression library via YTHT. The protein-protein interaction was confirmed with re-transformation in yeast and GST pull-down in vitro. The bait vector was successfully constructed without toxicity, leakage and self-activation. Sixteen proteins were screened by YTHT and eight positive clones were identified by re-transformation in yeast. The interaction between RAR alpha-V and JTV-1 was confirmed by GST pull-down in vitro. There are some kinds of proteins interacting with RAR alpha-V in cell. The biological dysfunction caused by certain protein-protein interaction may be involved in the pathogenesis of leukemia.


Ionizing radiation and chemical oxidant exposure impacts on Cryptococcus neoformans transfer RNAs.
Cryptococcus neoformans is a fungus that is able to survive abnormally high levels of ionizing radiation (IR). The radiolysis of water by IR generates reactive oxygen species (ROS) such as H2O2 and OH-. C. neoformans withstands the damage caused by IR and ROS through antioxidant production and enzyme-catalyzed breakdown of ROS. Given these particular cellular protein needs, questions arise whether transfer ribonucleic acids molecules (tRNAs) undergo unique chemical modifications to maintain their structure, stability, and/or function under such environmental conditions. Here, we investigated the effects of IR and H2O2 exposure on tRNAs in C. neoformans. We experimentally identified the modified nucleosides present in C. neoformans tRNAs and quantified changes in those modifications upon exposure to oxidative conditions. To better understand these modified nucleoside results, we also evaluated tRNA pool composition in response to the oxidative conditions. We found that regardless of environmental conditions, tRNA modifications and transcripts were minimally affected. A rationale for the stability of the tRNA pool and its concomitant profile of modified nucleosides is proposed based on the lack of codon bias throughout the C. neoformans genome and in particular for oxidative response transcripts. Our findings suggest that C. neoformans can rapidly adapt to oxidative environments as mRNA translation/protein synthesis are minimally impacted by codon bias.


Can neutrophil-lymphocyte ratio and mean platelet volume be used to predict metastasis in individuals with lung cancer?
Chronic inflammation plays an important role in the etiopathogenesis of many life-threatening chronic diseases, including cancer. Currently, the relationship between inflammation, native immunity and cancer is widely accepted; however, many of the mechanisms mediating this relationship remain undetermined and the clinical significance of these markers is unclear. The purpose of this study was to investigate the potential of neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) to indicate the existence of metastasis in lung cancer. This retrospective cross-sectional study evaluated patients with lung cancer of any pathological type who was admitted to the Palliative Care Unit of the referral hospital in the region between January 2019 and February 2020. Patient characteristics, distant organ metastasis, treatments, NLR and MPV values were noted. Patients were grouped as with or without metastasis. Characters, NLR, MPV values were compared. One hundred twenty-six patients were included. The mean age of the patients was 61.17 ± 9.4 years and 7.9% (n = 10) were female. The patients with a history of chemotherapy were 47% (n = 60) and distant organ metastases were present in 38.9% (n = 49) of the patients. The mean MPV value of 49 patients with distant metastasis was 8.34 ± 0.8 fL. MPV values of those with metastasis were found to be significantly higher than those without (P = .010). There was no significant difference in NLR values between groups (P = .920). Lung cancer patients with metastasis were found with higher MPV values. MPV can be effective and most accessible test in prediction of metastasis in lung cancer patients regardless of the pathological type.


Two-way partial AUC and its properties.
Simultaneous control on true positive rate and false positive rate is of significant importance in the performance evaluation of diagnostic tests. Most of the established literature utilizes partial area under receiver operating characteristic (ROC) curve with restrictions only on false positive rate (FPR), called FPR pAUC, as a performance measure. However, its indirect control on true positive rate (TPR) is conceptually and practically misleading. In this paper, a novel and intuitive performance measure, named as two-way pAUC, is proposed, which directly quantifies partial area under ROC curve with explicit restrictions on both TPR and FPR. To estimate two-way pAUC, we devise a nonparametric estimator. Based on the estimator, a bootstrap-assisted testing method for two-way pAUC comparison is established. Moreover, to evaluate possible covariate effects on two-way pAUC, a regression analysis framework is constructed. Asymptotic normalities of the methods are provided. Advantages of the proposed methods are illustrated by simulation and Wisconsin Breast Cancer Data. We encode the methods as a publicly available R package tpAUC.


In-Plane Ultrasound-Guided Botulinum Toxin Injection to Lumbrical and Interosseus Upper Limb Muscles: Technical Report.
This technical report presents an innovative approach utilizing in-plane ultrasound-guided injections to precisely target the lumbrical and interosseous muscles within the upper limb. The report also elucidates the rationale and advantages of incorporating ultrasound guidance in the administration of Botulinum toxin (BTX) injections, encompassing the real-time visualization of needle trajectory and accurate localization of the target muscle groups while delving into the pertinent anatomical details of these muscles and their significance in diverse neuromuscular conditions. The step-by-step procedure for conducting in-plane ultrasound-guided BTX injections to the lumbrical and interosseous muscles is delineated, emphasizing critical technical considerations and potential pitfalls to be vigilant of during the procedure. Furthermore, the article addresses the significance of selecting appropriate BTX dosages and injection sites based on individual patient presentations and clinical indications. Overall, the in-plane ultrasound-guided BTX injection technique presents a promising approach for providing precise and targeted treatment to the lumbrical and interosseous muscles in the upper limb. It offers clinicians an alternative to injections performed without guidance or out-of-plane ultrasound-guided injections, potentially decreasing the likelihood of complications and enhancing treatment outcomes for patients with a range of neuromuscular conditions. However, further research and comparative studies are necessary to establish the long-term efficacy and safety of this technique, thus confirming its role in clinical practice.


The effects of platelet receptor GPIIb/IIIa polymorphism (Leu Pro33) on the receptor expression and platelet aggregation in patients with ischaemic stroke.
Platelet hyperaggregation in ischaemic stroke patients is a proven finding, and associated with increased expression of the platelet surface GPIIb/IIIa receptor. The polymorphism occurs at nucleotide position 1565 of the GPIIIa gene resulting a 33Leu-Pro change. Data are conflicting regarding the abnormal function of the PlA1/A2 receptor in stroke. The aim of the study was to address the difference of platelet receptor function in ischemic stroke patients with the wild PlA1/A1 and heterozygous PlA1/A2 genotype. A total of 51 patients with PA1/A1 and 54 patients with PlA1/A2 genotypes were enrolled. Polymerase chain reaction was used for genotyping of platelets. Platelet aggregation was measured in whole blood and in platelet rich plasma (PRP). Flow cytometry was used for measuring surface molecule expression (CD42b, CD41a, CD61, CD62P) and fibrinogen binding capacity of cells with phosphate buffer solution (PBS) in comparison with activation by ristocetin in whole blood as well as by adenosine diphosphate (ADP) in PRP. In comparison with wild types, platelets carrying the PlA1/A2 genotypes showed hyperaggregation measured in whole blood and induced by ristocetin (p< 0.05). Using whole blood flow cytometry with ristocetin induction, the CD62P+/FIB- (P selectin) and the CD62P+/FIB+ were more expressed in heterozygous platelets as compared to wild types (p< 0.01 and p< 0.05), respectively. According to mean fluorescence intensity with ADP induction, an increased expression of CD61+, CD61+/CD41+ and CD62P+ in PlA1/A2 platelets were detected as compared to the group carrying the wild type (p< 0.0001, p= 0.006, p= 0.0001), respectively. These findings support the possibility that in ischaemic stroke patients, platelets carrying PlA1/A2 genotypes can be activated by different inductors in a way, which leads to permanent hyperfunction of platelet surface receptor GPIIIa.


AirPen: A Wearable Monitor for Characterizing Exposures to Particulate Matter and Volatile Organic Compounds.
Exposure to air pollution is a leading risk factor for disease and premature death, but technologies for assessing personal exposure to particulate and gaseous air pollutants, including the timing and location of such exposures, are limited. We developed a small, quiet, wearable monitor, called the AirPen, to quantify personal exposures to fine particulate matter (PM2.5) and volatile organic compounds (VOCs). The AirPen combines physical sample collection (PM onto a filter and VOCs onto a sorbent tube) with a suite of low-cost sensors (for PM, VOCs, temperature, pressure, humidity, light intensity, location, and motion). We validated the AirPen against conventional personal sampling equipment in the laboratory and then conducted a field study to measure at-work and away-from-work exposures to PM2.5 and VOCs among employees at an agricultural facility in Colorado, USA. The resultant sampling and sensor data indicated that personal exposures to benzene, toluene, ethylbenzene, and xylenes were dominated by a specific workplace location. These results illustrate how the AirPen can be used to advance our understanding of personal exposure to air pollution as a function of time, location, source, and activity, even in the absence of detailed activity diary data.


Radioimmunotherapy for Non-Hodgkin's Lymphoma.
Non-Hodgkin's lymphoma (NHL) is the most common hematological malignancy in the United States with a rapidly increasing incidence. Most follicular NHL is indolent but incurable, whereas the more aggressive varieties do respond to therapy. Most patients with follicular NHL who transform to an aggressive NHL are very difficult to treat successfully. Treatment options have included chemotherapy, radiation, immunotherapy with monoclonal antibodies, alone or in combination, and hematopoietic stem cell transplantation. The efficacy of monoclonal antibodies is augmented when they are combined with a radioisotope like iodine-131 or yttrium-90. There have been a number of studies done in recent years studying the efficacy of this form of therapy, i.e., radioimmunotherapy (RIT) in patients with NHL. This review attempts to integrate the information from the various clinical trials done using RIT in patients with relapsed/refractory or newly diagnosed NHL and in hematopoietic stem cell transplantation. It also includes updates on the use of RIT in elderly patients and in patients with significant bone marrow involvement among other recent advances made in this field.


First hydrolysis constants of hexaaquacobalt(III) and -manganese(III): longstanding issues resolved.
The acid dissociation constants, Kh, of the hexaaquacobalt(III) and -manganese(III) ions are reported under conditions which minimize the problems of instability of these species at modest acidities (pH 1-4). A rapid and convenient preparation of aqueous Co(III) has been used, and the latter has been reacted with aqueous Mn(II) to form aqueous Mn(III). The noncoordinating buffer H2PIPPS (1,4-bis(3-sulfopropyl)piperazine) has been used to react with H+ and provide some control of the pH. Spectrophotometric changes, after stopped-flow mixing for Co(III) and conventional mixing for Mn(III), were used to determine the Kh values. The pKh values are as follows: Co(III), 3.10 +/- 0.07 (6.0 degrees C) and 2.92 +/- 0.04 (20.0 degrees C) in 1.0 M H+, Na+, ClO4-; Mn(III), 0.22 +/- 0.04 (7.6 degrees C) and 0.08 +/- 0.04 (20.0 degrees C) in approximately 4 M H+, Mn2+, ClO4-. Global fits of the data for each metal have been used to estimate the DeltaH degree and DeltaS degree values for Kh. It is suggested that the unusually high acidity of Mn(OH2)6(3+) may be due to a Jahn-Teller distortion effect.


Differential diagnosis of benign and malignant intraductal papillary mucinous tumors of the pancreas: MR cholangiopancreatography and MR angiography.
To compare the usefulness of magnetic resonance cholangiopancreatography (MRCP) and MR angiography (MRA) in differentiating malignant from benign intraductal papillary mucinous tumors of the pancreas (IPMTs), and to determine the findings which suggest malignancy. During a 6-year period, 46 patients with IPMT underwent MRCP. Morphologically, tumor type was classified as main duct, branch duct, or combined. The diameter of the main pancreatic duct (MPD), the extent of the dilated MPD, and the location and size of the cystic lesion, septum, and communicating channel were assessed. For all types of IPMTs, enhanced mural nodules and portal vein narrowing were evaluated at MRA. Combined-type IPMTs were more frequently malignant (78%) than benign (42%) (p < 0.05). Compared with benign lesions, malignant lesions were larger, and the caliber of the communicating channel was also larger (p < 0.05). Their dilated MPD was more extensive and of greater diameter (p < 0.05), and the presence of mural nodules was more frequent (p < 0.001). Combined MRCP and MRA might be useful for the differential diagnosis of malignant and benign IPMTs of the pancreas.


Macrophage-derived extracellular vesicles regulates USP5-mediated HDAC2/NRF2 axis to ameliorate inflammatory pain.
Emerging research has highlighted the capacity of microRNA-23a-3p (miR-23a-3p) to alleviate inflammatory pain. However, the molecular mechanism by which miR-23a-3p attenuates inflammatory pain is yet to be fully understood. Hence, the current study aimed to elucidate the mechanism by which miR-23a-3p influences inflammatory pain. Bioinformatics was initially performed to predict the inflammatory pain related downstream targets of miR-23a-3p in macrophage-derived extracellular vesicles (EVs). An animal inflammatory pain model was established using Complete Freund's Adjuvant (CFA). The miR-23a-3p expression was downregulated in the microglia of CFA-induced mice, after which the inflammatory factors were determined by ELISA. FISH and immunofluorescence were performed to analyze the co-localization of miR-23a-3p and microglia. Interestingly, miR-23a-3p was transported to the microglia via M2 macrophage-EVs, which elevated the mechanical allodynia and the thermal hyperalgesia thresholds in mice model. The miR-23a-3p downstream target, USP5, was found to stabilize HDAC2 via deubiquitination to promote its expression while inhibiting the expression of NRF2. Taken together, the key findings of the current study demonstrate that macrophage-derived EVs containing miR-23a-3p regulates the HDAC2/NRF2 axis by decreasing USP5 expression to alleviate inflammatory pain, which may provide novel therapeutic targets for the treatment of inflammatory pain.


How should we categorise self-reported data on subsequent injuries?
Classifying subsequent injuries is of high importance in injury epidemiology since a previous injury has been reported to increase the risk of a new injury or increase the risk of a more severe injury. Multiple reports have shown that self-reported data provide an extensive view of an injury problem and add valuable information to the understanding of the athlete's health. The purpose of this study was to display a method that can be used to facilitate classification of subsequent injuries and to discuss challenges faced when categorising subsequent injuries based on self-reported data. The suitability of a new model for Subsequent Injuries Adjusted for Self-reported data (SIAS model) was demonstrated with sport injury data from a cohort of 101 adolescent elite track & field athletes, followed over 52 weeks. A total number of 71 subsequent injuries were identified. Of all subsequent injuries, recurrent injuries represented 69.0% (n = 49) and 31.0% (n = 22) were classified as new injuries. The majority of subsequent injuries (n = 60, 84.5%) occurred after athletes had recovered from a previous injury. Of all subsequent injuries, 15.5% (n = 11) represented injuries where athletes had not fully recovered from a previous injury. Application of the SIAS model allows for classification of subsequent injuries based on self-reported data on the recovery level of the athletes, the injury onset and injury type. The developed SIAS model follows the consensus recommendations of injury definition, injury classification and is an attempt to increase the understanding of the complex relationship of subsequent injuries in self-reported data sets.


Association of sexual abstinence in adolescence with mental health in adulthood.
We examined whether adolescent sexual abstinence predicts better adult mental health. 1,917 adolescents, recruited from middle schools at age 13, were surveyed at ages 13, 18, 23, and 29. In bivariate analyses, adolescent sexual abstinence was associated with better mental health at age 29 for females, but not males; three adolescent factors, educational prospects, family bonding, and unconventionality were investigated as explanatory variables of this relationship. The abstinence-mental health relationship was nonsignificant when educational prospects was included in multivariate models, and marginally significant when family bonding and unconventionality were included; all three explanatory factors accounted for significant proportions of the variance in adult mental health. Girls who are uninvolved in school, have weak family backgrounds, and exhibit unconventionality may have poor adult mental health, whether or not they abstain from sex in adolescence. Interventions that strengthen adolescents' connections to families and schools may reduce risk for long-term mental health problems.


Sustained Release Bilayer Tablet of Ibuprofen and Phenylephrine Hydrochloride: Preparation and Pharmacokinetics in Beagle Dogs.
Cold is a global common infectious disease accompanied by symptoms such as headache and stuffy nose. Ibuprofen (IBU) and phenylephrine hydrochloride (PE) were commonly used for common cold due to their different effects in relieving fever and the main symptoms such as nasal congestion and high sinus pressure. However, the commercial tablets of IBU and PE have to be administered 2 to 3 times per day due to their short half-life, with inconvenience for patient and fluctuations of plasma concentration. Bilayer tablet technology was utilized to design the IBU-PE sustained release tablets because of the significantly different solubility of IBU and PE in release media. The formulations of IBU layer and PE layer contain different viscosity grades of hydroxypropyl methylcellulose (HPMC) as sustained-release matrix, hydrophilic diluent, and traditional glidant and lubricant. The sustained release bilayer tablet exhibited satisfying sustained release performance with the mechanisms of diffusion and matrix erosion. Compared with the conventional tablets, the IBU-PE sustained release bilayer tablet expressed significantly sustained-release behavior with decreased Cmax and prolonged Tmax in fasted conditions for IBU and PE. Though IBU of IBU-PE sustained release bilayer tablet was bioequivalent to the commercial IBU tablet, the relative bioavailability of PE from the bilayer tablets was 87.49 ± 20.00% (90% confidence interval was 72.3 to 102.5%), indicating bioinequivalence probably due to the "first pass" effect.


Health promotion or pharmacological treatment for chronic diseases?
Over the last years medicine has progressed very rapidly. Communicable diseases, which were the leading causes of mortalities, are not anymore, especially in developed countries. Currently, non-communicable diseases are more prevalent, and most of them are related to changes in our daily habits and degenerative processes. Most of these diseases are chronic, need continuous care and treatment with limited improvement and high costs. The General Assembly of the United Nations in its resolution 65/238 recognized the primary role and responsibility of Governments in responding to the challenge of non-communicable diseases and the essential need for the efforts and engagement of all sectors of society to generate an effective response. Special emphasis has been concentrated on pharmacological treatments for most of chronic non-communicable diseases with the challenge to discover new drugs for treating, in most cases, chronic irreversible degenerative diseases associated with aging. Little care was given to non-pharmacological lines of treatment.


Determinants of Risk Perception Related to Exposure to Endocrine Disruptors during Pregnancy: A Qualitative and Quantitative Study on French Women.
Endocrine disruptors (EDCs) are known as environmental exposure factors. However, they are rarely reported by health professionals in clinical practice, particularly during pregnancy, even though they are associated with many deleterious consequences. The objectives of this study were to estimate the risk perception of pregnant women related to EDC exposure and to evaluate its determinants. A qualitative study based on the Health Belief Model was carried out through interviews of pregnant women and focus group with perinatal, environmental health and prevention professionals in 2015 in the city of Poitiers, France. Then, determinants of risk perception were included in a questionnaire administered to 300 women in the perinatal period through a quantitative study. Scores were subsequently calculated. Perception of EDC risk was defined as perceived severity for different stages of the infant's development and perceived susceptibility to EDC exposure. The determinants reported in the qualitative study were: age, strong maternal figure, socio-professional category, level of knowledge, and involuntariness of exposure. Age and level of knowledge were confirmed in our statistical model as determinants. Mean score of EDC risk perception was 55.0 ± 18.3 on 100 points. Our study should guide healthcare providers when advising pregnant women about EDC and environmental exposure. Our score for perceived EDC risk and assessment of its known determinants may help to assess the impact and the relevance of prevention programs dedicated to reducing exposure to EDC during pregnancy.


Synthesis of lanthanum-doped MCM-48 molecular sieves and its catalytic performance for the oxidation of styrene.
Lanthanum-doped MCM-48 molecular sieves with different La contents were synthesized hydrothermally and characterized by X-ray diffraction (XRD), nitrogen sorption, transmission electron microscopy (TEM), UV-visible spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy. The results show that the majority of La cations have been incorporated into the framework of MCM-48 molecular sieves. When the molar ratio of La/Si is >0.039 in the sample, some of lanthanum species exist in the extraframework. Compared with pure silicate MCM-48, lanthanum-doped MCM-48 samples show the medium strong acidity that is due to the incorporation of La in the framework of silica. In the oxidation of styrene with H(2)O(2) as the oxidant over the lanthanum-doped MCM-48 catalysts, benzaldehyde is the main product with a small amount of styrene oxide. The La content in the catalysts, reaction temperature, reaction time, and solvent affect greatly the catalytic oxidation of styrene. The conversion of styrene and the selectivity to styrene oxide increase noticeably when a small amount of NaOH aqueous solution is added into the reaction mixture. Ln-doped MCM-48 catalysts with 14 kinds of rare earth elements were synthesized hydrothermally and evaluated for the oxidation of styrene. The results show that their catalytic performance is tremendously different and depends on the nature of rare earth elements doped in the MCM-48 mesoporous materials.


Initiation and termination of calcium sparks in skeletal muscle
Three main paths to derive the Ca2+ release flux underlying Ca2+ sparks are reviewed here: Some properties of release flux can be inferred from an examination of spark morphology. Others from model simulations, which generate sparks assuming an ion source within a cytoplasm-like medium. Finally, the release flux can be derived from the fluorescence transient by generalizing an algorithm developed earlier for global or whole cell signals. The transient and spatially limited nature of sparks adds many uncertainties to the process. These methods yield estimates between 1.4 and 30 pA, not clearly greater in skeletal than in cardiac muscle. At their low end, the estimates are consistent with generation of sparks by one or two ryanodine receptor channels, but the results are easier to explain if several channels, from as little as four to as many as 60, cooperate in their generation. How release flux determines spark shape and time course has been understood largely through simulations. The rise time of sparks corresponds to active release time. Both release flux and release time may vary among individual sparks, leading to their varied size and shape. Release flux turns off abruptly, therefore the decay of sparks is determined by Ca2+ removal and diffusion. Spatial width increases with release time (rise time). That its experimentally determined value is too large compared with simulations, remains the single most important question in the interpretation of shape. Sparks are not the sole form of local fluorescence transients. When channel opening drugs are present, or sometimes spontaneously, sparks may be prolonged by embers. If the release flux calculated during an ember corresponds to a single open channel, then the release underlying a spark must require many open channels. The continued examination of Ca2+ release flux appears to be an essential requisite for the interpretation of sparks and their place in calcium signaling.


Psychomotor delay, a possible rare presentation of moyamoya disease.
Moyamoya disease is a rare, chronic cerebrovascular occlusive disease of unknown etiology. It is characterized by progressive stenosis of the arteries of the circle of Willis leading to ischemic strokes in young people and cerebral hemorrhage, which is more frequent in adults. Secondarily, an abnormal network of fine collateral vessels arises at the base of the brain. The term moyamoya refers to the angiographic appearance of the cerebral vasculature. We present such a disease in an 18-month-old Iranian girl with global developmental delay, which is a very rare presentation of moyamoya disease. She was diagnosed by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA).


Promethazine-montmorillonite inclusion complex to enhance drug photostability.
The capability of montmorillonite as a matrix (MONT) to improve the photostability of photolabile drugs has been recently reported. Herein promethazine (PRO), which was chosen as a model drug because of its photodegradation mechanism, was intercalated into this inorganic matrix, and the effects on drug photoprotection were evaluated as well. The hybrid material (MONT-PRO) was successfully prepared with high drug loading and then was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and FTIR spectroscopy. The spectrophotometric measurements as a function of light exposure time showed that PRO intercalation into montmorillonite markedly improved the drug photostability because a 5-fold-slower degradation rate was determined compared to that measured for PRO in homogeneous solutions; nanosecond transient absorption measurements highlighted that the interaction with the inorganic matrix made negligible the photoionization process of the drug, and its efficiency in producing singlet oxygen was strongly reduced. The MONT-PRO intercalation compound could be easily formulated in gel or ointment media without losing its photostability.


Aberrant Clinical Appearance and Pathomorphology Noticed During an Outbreak of Histomonosis Indicates a Different Pathogenesis of Histomonas meleagridis Genotype 2.
The present case report describes a remarkable feature of Histomonas meleagridis characterized by aberrant clinical appearance and pathomorphologic lesions, which were mainly confined to the ceca, noticed during a field outbreak of histomonosis. In a flock of meat turkey toms, sudden death was noticed at the end of week 5 in the absence of specific clinical signs. Instead of the well-known sulfur-colored feces, some caseous cores were found in the litter. Mortality up to 17% per week was noticed in the first 2 wk of observation, after which it declined to approximately 1% per week. In the 10th week of life roughly 31% of the birds had died before the remaining birds were killed to preclude further economic losses due to insufficient growth or continuing mortality. Necropsy of affected birds on the farm and during a more detailed investigation of 15 birds prior to the killing of the flock revealed severe lesions in the ceca characterized by thickened cecal walls filled with necrotic and caseous material. Additionally, some ruptured and necrotic ceca were noticed together with localized peritonitis. Despite such severe typhlitis, only one of the sectioned birds showed pathomorphologic changes in the liver. Test tube flotation from collected fecal samples revealed only sporadic occurrence of coccidial oocysts and no nematodes. However, the presence of H. meleagridis was confirmed by PCR and/or immunohistochemistry, with specific antibodies against the parasite in a majority of the investigated ceca and in four liver samples. Remarkably, genetic characterization revealed H. meleagridis genotype 2, about which no detailed investigations have been reported so far. Although PCR detected a concurrent presence of Tetratrichomonas gallinarum, an involvement in the lesions could be excluded based upon histologic investigations. Finally, infection with Escherichia coli and Gallibacterium anatis was demonstrated by bacteriologic smears of internal organs, most likely a secondary infection. Altogether, the results demonstrate an aberrant clinical appearance and pathomorphology in turkeys suffering from histomonosis. Pathomorphologic changes were characterized by severe inflammation of the ceca with minimal liver involvement, indicating a different pathogenesis of H. meleagridis genotype 2.


Biodegradable polylactide microspheres enhance specific immune response induced by Hepatitis B surface antigen.
Hepatitis B (HB) infection caused by Hepatitis B virus (HBV) is the most common liver disease in the world. HB vaccine, when administered in conjunction with alum adjuvants, induces Th2 immunity that confers protection against HBV. However, currently available vaccine formulations and adjuvants do not elicit adequate Th1 and CTL responses that are important for prevention of maternal transmission of the virus. Microspheres synthesized from poly (D, L-lactide-co-glycolide) (PLGA) or poly (D, L-lactide) (PLA) polymers have been considered as promising tools for in vivo delivery of antigens and drugs. Here we describe PLA microspheres synthesized by premix membrane emulsification method and their application in formulating a new microsphere based HB vaccine. To evaluate the immunogenicity of this microsphere vaccine, BALB/c mice were immunized with microsphere vaccine and a series of immunological assays were conducted. Results of Enzyme-linked ImmunoSpot (ELISPOT) assays revealed that the number of interferon-gamma (IFN-γ)-producing splenocytes and CD8(+) T cells increased significantly in the microsphere vaccine group. Microsphere vaccine group showed enhanced specific cell lysis when compared with HB surface antigen (HBsAg) only group in (51)Cr cytotoxicity assays. Moreover, microsphere vaccine elicited a comparable level of antibody production as that of HB vaccine administered with alum adjuvant. We show that phagocytosis of HBsAg by dendritic cells is more pronounced in microsphere vaccine group when compared with other control groups. These results clearly demonstrate the potential of using PLA microspheres as effective HB vaccine adjuvants for an enhanced Th1 immune response.


Mesalamine in ulcerative colitis.
Sulfasalazine has been used for many years in the management of ulcerative colitis. As many as 20 percent of patients treated with it experience intolerable adverse effects usually attributed to its sulfapyridine component. The other active component is 5-aminosalicylic acid (5-ASA); the only 5-ASA enema preparation currently available in the U.S. is mesalamine (Rowasa, Reid-Rowell) containing 5-ASA 4 g in 60 mL. In clinical trials, mesalamine has proved efficacious in treating refractory cases of distal ulcerative colitis, proctitis, and proctosigmoiditis. Because of its high cost compared with more conventional treatment modalities, it should be reserved for cases that are either refractory or intolerant to conventional treatment.


[5-FU concentration in blood and tissue of patients with primary lung cancer after oral administration of UFT].
Concentration of FT-207, 5-FU and Uracil in blood and normal lung tissue were estimated for lung cancer patients to whom UFT was orally administered. The histological types of these cases were as follows: 10 squamous cell carcinomas, 10 adenocarcinomas, 2 large cell carcinomas and 1 small cell carcinoma. Average concentration of 5-FU in these tumor tissues was 0.101 +/- 0.107 microgram/g. This was a significantly higher 5-FU concentration in comparison to those in serum and normal lung tissue. Comparison of 5-FU concentration between squamous cell carcinomas and adenocarcinomas showed no significant difference. Between metastasis-positive lymph nodes and metastasis-negative lymph nodes, there was also no significant difference in 5-FU concentration, but there was a significant difference in Uracil concentration. This result showed an effective transition of 5-FU from serum to tumor tissues with oral administration of UFT. It was therefore concluded that UFT would be expected to have an antitumor effect in primary lung cancer patients.


DBR1 siRNA inhibition of HIV-1 replication.
HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1) expression would specifically inhibit HIV-1 replication. We designed three short interfering RNA (siRNA) molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.


The small-hole technique in endoscopic sinus surgery.
It may be that the uncinate process, the posteromedial wall of the agger nasi, and the medial wall of the ethmoid bulla are the critical anatomic components in recalcitrant sinus disease. The basal lamella may be a fourth component. It may be that addressing these "transition spaces" is all that is required in cases of sinusitis requiring surgical treatment. Quantitative studies and outcome studies are necessary. Minimally invasive, "small hole" sinus surgery may offer the prospect of reversibility of disease in the paranasal sinuses with limited surgical intervention.


Reversal by naloxone of the antihypertensive action of clonidine: involvement of the sympathetic nervous system.
The effects of clonidine, naloxone, and their combination on arterial blood pressure (BP), heart rate (HR), and hemodynamic and biochemical parameters were examined in 29 patients with essential hypertension. Treatment for 3 days with 0.3 mg/day clonidine reduced BP and HR, and these effects were quickly reversed by a single injection of 0.4 mg iv naloxone in 17 of the patients (responders), but not in the remaining 12 (nonresponders). Responders had higher control values for cardiac output, stroke index, plasma renin activity (PRA), and plasma epinephrine levels than did nonresponders. Basal BP was similar in the two groups, but clonidine decreased BP, PRA, and plasma epinephrine more in responders than in nonresponders. Naloxone given during placebo treatment had no significant effects. During clonidine treatment naloxone increased BP, HR, total peripheral resistance, PRA, and plasma epinephrine and norepinephrine, and decreased stroke volume in responders, whereas in nonresponders its only effect was a small increase in HR. It is concluded that in a subset of hyperadrenergic, hypertensive patients the antihypertensive effect of clonidine involves a naloxone-reversible inhibition of central sympathetic outflow, probably mediated by the release of an endogenous opioid.


Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS.
HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservoirs are needed. One such agent, auranofin, has recently been shown to decrease the memory T-cell reservoir in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize with a fully suppressive ART protocol and induce a drug-free post-therapy containment of viremia. We administered buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis currently in clinical trials for cancer, in combination with auranofin to chronically SIVmac251-infected macaques under highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was followed, after therapy suspension, by a significant decrease of viral RNA and DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy control of the infection was achieved in animals with pre-therapy viral loads ranging from values comparable to average human set points to levels largely higher. This control was dependent on the presence CD8+ cells and associated with enhanced levels of cell-mediated immune responses. The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current "ART for life" plight.


Area-level income inequality and oral health among Australian adults-A population-based multilevel study.
A lack of evidence exists on the association between area-level income inequality and oral health within Australia. This study examined associations between area-level income inequality and oral health outcomes (inadequate dentition (<21 teeth) and poor self-rated oral health) among Australian adults. Variations in the association between area-level income inequality and oral health outcomes according to area-level mean income were also assessed. Finally, household-income gradients in oral health outcomes according to area-level income inequality were compared. For the analyses, data on Australian dentate adults (n = 5,165 nested in 435 Local Government Areas (LGAs)) was obtained from the National Dental Telephone Interview Survey-2013. Multilevel multivariable logistic regression models with random intercept and fixed slopes were fitted to test associations between area-level income inequality and oral health outcomes, examine variations in associations according to area-level mean income, and examine variations in household-income gradients in outcomes according to area-level income inequality. Covariates included age, sex, LGA-level mean weekly household income, geographic remoteness and household income. LGA-level income inequality was not associated with poor self-rated oral health and inversely associated with inadequate dentition (OR: 0.64; 95% CI: 0.48, 0.87) after adjusting for covariates. Inverse association between income inequality and inadequate dentition at the individual level was limited to LGAs within the highest tertile of mean weekly household income. Household income gradients in both outcomes showed poorer oral health at lower levels of household income. The household income gradients for inadequate dentition varied according to the LGA-level income inequality. Findings suggest that income inequality at the LGA-level in Australia is not positively associated with poorer oral health outcomes. Inverse association between income inequality and inadequate dentition is likely due to the contextual differences between Australia and other high-income countries.


Nanoscale investigations on interchain organization in thin films of polymer-liquid crystal blend.
Optimized nanomorphology in organic thin active layers is crucial for good performance in organic solar cells. However, the relation between morphology and electronic properties at nanoscale remains not completely understood. Here, we study the effect of film thickness and temperature annealing on the ordering of poly(3-hexylthiophene) chains when the polymer is blended with a columnar liquid crystalline molecule. Electronic absorption, atomic force microscopy measurements, and Raman spectroscopy show that morphology and chain ordering of the blend depend on the film thickness. We highlight the benefit of using a liquid crystal in organic blends, opening the way to use simple processing methods for the fabrication of organic electronic devices.


Bacterial diversity across a highly stratified ecosystem: A salt-wedge Mediterranean estuary.
Highly stratified Mediterranean estuaries are unique environments where the tidal range is low and the tidal currents are almost negligible. The main characteristics of these environments are strong salinity gradients and other environmental parameters. In this study, 454 pyrosequencing of the 16S rRNA gene in combination with catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH) was used to estimate the bacterial diversity across the Krka estuary in February and July 2013. The comparison of the data derived from these two techniques resulted in a significant but weak positive correlation (R=0.28) indicating a substantial difference in the bacterial community structure, depending on the applied method. The phytoplankton bloom observed in February was identified as one of the main factors shaping the bacterial community structure between the two environmentally contrasting sampling months. Roseobacter, Bacteroidetes and Gammaproteobacteria differed substantially between February and July. Typical freshwater bacterial classes (Actinobacteria and Betaproteobacteria) showed strong vertical distribution patterns depending on the salinity gradient. Cyanobacteria decreased in abundance in February due to competition with phytoplankton, while the SAR11 clade increased its abundance in July as a result of a better adaptation toward more oligotrophic conditions. The results provided the first detailed insight into the bacterial diversity in a highly stratified Mediterranean karstic estuary.


Association of atrial fibrillation and obstructive sleep apnea.
Obstructive sleep apnea (OSA) is associated with recurrent atrial fibrillation (AF) after electrocardioversion. OSA is highly prevalent in patients who are male, obese, and/or hypertensive, but its prevalence in patients with AF is unknown. We prospectively studied consecutive patients undergoing electrocardioversion for AF (n=151) and consecutive patients without past or current AF referred to a general cardiology practice (n=312). OSA was diagnosed with the Berlin questionnaire, which is validated to identify patients with OSA. We also assessed its accuracy compared with polysomnography in a sample of the study population. Groups were compared with the 2-tailed t, Wilcoxon, and chi2 tests. Logistic regression modeled the association of AF and OSA after adjustment for relevant covariates. Patients in each group had similar age, gender, body mass index, and rates of diabetes, hypertension, and congestive heart failure. The questionnaire performed with 0.86 sensitivity, 0.89 specificity, and 0.97 positive predictive value in our sample. The proportion of patients with OSA was significantly higher in the AF group than in the general cardiology group (49% versus 32%, P=0.0004). The adjusted odds ratio for the association between AF and OSA was 2.19 (95% CI 1.40 to 3.42, P=0.0006). The novel finding of this study is that a strong association exists between OSA and AF, such that OSA is strikingly more prevalent in patients with AF than in high-risk patients with multiple other cardiovascular diseases. The coinciding epidemics of obesity and AF underscore the clinical importance of these results.


The validity of predicted body fat percentage from body mass index and from impedance in samples of five European populations.
To test and compare the validity of a body mass index (BMI)-based prediction equation and an impedance-based prediction equation for body fat percentage among various European population groups. Cross-sectional observational study. The study was performed in five different European centres: Maastricht and Wageningen (The Netherlands), Milan and Rome (Italy) and Tampere (Finland), where body composition studies are routinely performed. A total of 234 females and 182 males, aged 18-70 y, BMI 17.0-41.9 kg/m(2). The reference method for body fat percentage (BF%(REF)) was either dual-energy X-ray absorptiometry (DXA) or densitometry (underwater weighing). Body fat percentage (BF%) was also predicted from BMI, age and sex (BF%(BMI)) or with a hand-held impedance analyser that uses in addition to arm impedance weight, height, age and sex as predictors (BF%(IMP)). The overall mean (+/-s.e.) bias (measured minus predicted) for BF%(BMI) was 0.2+/-0.3 (NS) and-0.7+/-0.3 (NS) in females and males, respectively. The bias of BF%(IMP) was 0.2+/-0.2 (NS) and 1.0+/-0.4 (P<0.01) for females and males, respectively. There were significant differences in biases among the centres. The biases were correlated with level of BF% and with age. After correction for differences in age and BF% between the centres the bias of BF%(BMI) was not significantly different from zero in each centre and was not different among the centres anymore. The bias of BF%(IMP) decreased after correction and was significant from zero and significant from the other centres only in males from Tampere. Generally, individual biases can be high, leading to a considerable misclassification of obesity. The individual misclassification was generally higher with the BMI-based prediction. The prediction formulas give generally good estimates of BF% on a group level in the five population samples, except for the males from Tampere. More comparative studies should be conducted to get better insight in the generalisation of prediction methods and formulas. Individual results and classifications have to be interpreted with caution.


Laser Doppler anemometer measurements using nonorthogonal velocity components: error estimates.
Laser Doppler anemometers (LDAs) that are arranged to measure nonorthogonal velocity components (from which orthogonal components are computed through transformation equations) are more susceptible to calibration and sampling errors than are systems with uncoupled channels. In this paper uncertainty methods and estimation theory are used to evaluate, respectively, the systematic and statistical errors that are present when such devices are applied to the measurement of mean velocities in turbulent flows. Statistical errors are estimated for two-channel LDA data that are either correlated or uncorrelated. For uncorrelated data the directional uncertainty of the measured velocity vector is considered for applications where mean streamline patterns are desired.


Centennial of Metchnikoff's discovery.
Phagocytosis was discovered by Elie Metchnikoff (Ilia Mechnikov) in 1882. Although the phenomenon of endocytosis by the leukocytes (more related to the pinocytosis) had been described 30 years earlier [8], it was Metchnikoff who explained its function, and alerted the scientific community to the importance of phagocytosis in immunity. He devoted most of his life to studying different aspects of phagocytosis and related immunological phenomena. It required 25 years of intense effort to achieve recognition of the phagocytosis theory, the first experimentally based theory in immunology. This struggle culminated in 1908 with the awarding of the Nobel Prize to Metchnikoff and Ehrlich for their two theories of immunity, "cellular" and "humoral," respectively. That was an official recognition of the existence and importance of immunology, but modern immunology began at the moment of Metchnikoff's discovery, which is why 1982 may be considered the 100th year anniversary of immunology.


Transient silencing of CHALCONE SYNTHASE during fruit ripening modifies tomato epidermal cells and cuticle properties.
Tomato (Solanum lycopersicum) fruit ripening is accompanied by an increase in CHALCONE SYNTHASE (CHS) activity and flavonoid biosynthesis. Flavonoids accumulate in the cuticle, giving its characteristic orange color that contributes to the eventual red color of the ripe fruit. Using virus-induced gene silencing in fruits, we have down-regulated the expression of SlCHS during ripening and compared the cuticles derived from silenced and nonsilenced regions. Silenced regions showed a pink color due to the lack of flavonoids incorporated to the cuticle. This change in color was accompanied by several other changes in the cuticle and epidermis. The epidermal cells displayed a decreased tangential cell width; a decrease in the amount of cuticle and its main components, cutin and polysaccharides, was also observed. Flavonoids dramatically altered the cuticle biomechanical properties by stiffening the elastic and viscoelastic phase and by reducing the ability of the cuticle to deform. There seemed to be a negative relation between SlCHS expression and wax accumulation during ripening that could be related to the decreased cuticle permeability to water observed in the regions silencing SlCHS. A reduction in the overall number of ester linkages present in the cutin matrix was also dependent on the presence of flavonoids.