Functional profile of human influenza virus-specific cytotoxic T lymphocyte activity is influenced by interleukin-2 concentration and epitope specificity.
The ability of influenza A virus-specific cytotoxic T lymphocytes (CTL) to degranulate and produce cytokines upon antigenic restimulation was studied in four HLA-A*0101 and HLA-A*0201 positive subjects. Peripheral blood mononuclear cells of these subjects were stimulated with influenza A virus in the presence of high or low interleukin (IL)-2 concentrations. CD8(+) T cell populations specific for the HLA-A*0101 restricted epitope NP(44-52) and the HLA-A*0201 restricted epitope M1(58-66) were identified by positive staining with tetramers of peptide major histocompatibility complexes (MHC) (NP-Tm and M1-Tm, respectively). Within these populations, the proportion of cells mobilizing CD107a, or expressing interferon (IFN)-gamma and tumour necrosis factor-(TNF)-alpha upon short-term peptide restimulation was determined by flow cytometry. Independent of IL-2 concentrations, large subject-dependent differences in the mobilization of CD107a and expression of IFN-gamma and TNF-alpha by both NP- and M1-specific T cells were observed. In two of the four subjects, the functional profile of NP-Tm(+) and M1-Tm(+) cells differed considerably. Overall, no difference in the proportion of NP-Tm(+) or M1-Tm(+) cells expressing CD107a was observed. The proportion of M1-Tm(+) cells that produced IFN-gamma (P < 0.05) was larger than for NP-Tm(+) cells, independent of IL-2 concentration. When cultured under IL-2(hi) concentrations higher TNF-alpha expression was also observed in M1-Tm(+) cells (P < 0.05). The IL-2 concentration during expansion of virus-specific cells had a profound effect on the functionality of both M1-Tm(+) and NP-Tm(+) cells.


Sustainable and health claims vs sensory properties: Consumers' opinions and choices using a vegetable dip as example product.
New foods development is always challenging, and including consumers' opinion during the design process is crucial to increase a successful welcome of the product in the market. During the present study, a whole product design and development process is described, including consumers' insights collected from focus groups, a national online survey, and a final sensory consumer study of the developed vegetable dip. The aim of the study was to determine if some of the extrinsic properties of a product developed using discarded parts of fruits and vegetables had an impact on the final product acceptance, or if the intrinsic properties were the main drivers of the acceptance. The experimental design included four focus groups to study consumers' ideas about products made with sustainable ingredients and which may have health benefits. Then, a national survey was conducted to test the best messages associated to the new food. A vegetable dip was developed, using consumers' insights, and a consumer study was conducted to test the impact of three different messages associated with the product. Results of the survey showed three consumers' segments with different interests on the concepts associated with the products, being two of the clusters potential consumers of the new vegetable dip. Results of the consumer study showed that, although consumers belonged to these segments in which the extrinsic properties seemed to be important, the 3 tested messages were similarly accepted.


A survey of the knowledge, perceptions of and attitudes to digital health of healthcare professionals in 14 Bulgarian hospitals: First large-scale study on digital health in Bulgarian inpatient facilities.
To explore the knowledge, perceptions of and attitudes to digital health of Bulgarian hospital professionals in the first study of digital health in this professional group. A paper-based questionnaire was administered to doctors, trainee doctors, nurses, midwives, and laboratory assistants working in multiprofile or specialized hospitals. Topics included the following: state, objectives, benefits, and future of digital health; data storage, access, security, and sharing; main software used; patient-held Personal Information System (PIS); and telemedicine. A total of 1187 participants from 14 hospitals completed the survey in two phases: September 2013-April 2014 and May 2015-April 2017. Data were analyzed through descriptive statistics and multilevel logistic regression. Three-quarters of participants evaluated the state of development of digital health in Bulgaria as subpar (36.0% negative; 38.9% passable; 24.5% positive). 27.2% (323) endorsed patients having unconditional access to their data. In contrast, 89.5% (1062) of participants considered it appropriate to have full access to patient data recorded by colleagues. Doctors were more likely to endorse patients having access to their data than healthcare specialists (OR = 1.79 at facility, OR = 1.77 at location). The largely negative or lukewarm attitudes toward the state of development of digital health in Bulgaria are likely to result from the high number of failed projects, unmet expectations, misunderstood benefits, and unforeseen challenges. This study provides a much-needed stimulus and baseline for researching the ways in which the digital health landscape in Bulgaria has matured-or not.


NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis.
NGM282, an engineered fibroblast growth factor 19 analogue, rapidly and significantly reduced liver fat content in a multicenter, randomized, double-blind, placebo-controlled study in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH). However, it is unclear whether these changes would be accompanied by histological improvement. In this open-label study, we assessed the histological efficacy of NGM282 in patients with biopsy-confirmed nonalcoholic steatohepatitis. Paired liver biopsies from 43 patients who received subcutaneous NGM282 (1 mg, n = 24; 3 mg, n = 19) once daily for 12 weeks were evaluated blinded to time point, subject, and clinical information. At week 12, NGM282 significantly reduced nonalcoholic fatty liver disease activity score (NAS; -1.9; 95% confidence interval, -2.6 to -1.2; P < 0.001 in the 1 mg group; -2.2, -3.1 to -1.3; P < 0.001 in the 3 mg group) and fibrosis (-0.5; -0.9 to 0; P = 0.035 in the 3 mg group) scores. Overall, 50% and 63% of the patients receiving NGM282 1 mg or 3 mg, respectively, improved NAS by 2 or more points without fibrosis worsening. Of the patients receiving NGM282 1 mg or 3 mg, 25% and 42%, respectively, improved liver fibrosis by one stage or more without worsening of steatohepatitis. Treatment with NGM282 led to relative reductions in liver fat content (-58% and -67% in the 1 mg and 3 mg groups, respectively), corrected T1 (cT1; -8% and -9%), alanine aminotransferase (ALT) (-67% and -60%), aspartate aminotransferase (-57% and -52%), and fibrogenesis biomarkers neoepitope-specific N-terminal propeptide of type III collagen (Pro-C3; -22% and -33%) and enhanced liver fibrosis score (ELF; -3% and -6%) at week 12. Greater reductions in Pro-C3, ELF, and cT1, but not in liver fat content, 7alpha-hydroxy-4-cholesten-3-one, or ALT, were observed in histological responders than in nonresponders. Conclusion: In this open-label study, NGM282 improved the histological features of NASH in 12 weeks with significant reductions in NAS and fibrosis scores, accompanied by improvements in noninvasive imaging and serum markers.


Cyclophosphamide/antithymocyte globulin conditioning of patients with severe aplastic anemia for marrow transplantation from HLA-matched siblings: preliminary results.
Many approaches have been taken to reducing the rate of graft failure and the incidence of graft-versus-host disease (GVHD) in bone marrow transplantation (BMT) of patients with severe aplastic anemia (SAA). The combination of cyclophosphamide with irradiation has had unequivocal success in reconstituting a sustained engraftment, but this procedure has severe associated risks such as second malignancies. Recently, cyclophosphamide (CYC) plus antithymocyte globulin (ATG) has been shown to be an effective alternative to irradiation-based programs in retransplants. Based on these experiences, the current clinical trial was started to prepare patients suffering from SAA for marrow transplantation from HLA-identical siblings with ATG plus CYC. Nine patients have been enrolled into the study so far. They received a total dose of 200 mg/kg CYC and concomitantly 120 mg/kg or 90 mg/kg ATG, followed by cyclosporine plus methotrexate as post-transplantation GVHD prophylaxis. Eight of nine patients survived without any transplant-associated complications; i.e., they had a documented stable engraftment without rejection and without acute or chronic GVHD. One patient died due to an Aspergillus sepsis prior to a definite engraftment. Although our data are preliminary because of the small number of patients enrolled and a follow-up of only 30 months, CYC plus ATG appears to be an effective preparative regimen for BMT in patients with SAA, resulting in a favorable outcome.


Two novel transposable elements in a cytochrome P450 gene govern anthocyanin biosynthesis of commercial petunias.
The gene Hf1 plays a key role in the expression of floral color in petunias. Hf1 encodes a flavonoid-3',5'-hydroxylase (F3'5'H). The recessive allele (hf1) in an inbred line of petunia is known to be generated by the insertion of a transposable element (Psl). We isolated a novel Mutator-like transposable element (named dTph9) from the hf1 allele of a commercial petunia with red flowers. Another novel transposable element (named rTph1) was found in hf1 of another red petunia. rTph1 shared features with the copia-like retrotransposable element family. These novel elements were inserted independently in the third exon of the Hf1 gene, at different positions. The hf1 allele harboring dTph9 or rTph1 cannot produce an active F3'5'H enzyme because there are stop codons in the dTph9 and rTph1 sequences. Southern analysis showed that these elements were present in relatively low copy numbers and that mutation of the Hf1 locus was associated with the transposition of both elements. We conclude that a loss-of-function mutation of the petunia Hf1 gene is caused by the insertion of at least two different transposable elements, other than Psl, within the Hf1 gene.


Systematical analyses of variants in DNase I hypersensitive sites to identify hepatocellular carcinoma susceptibility loci in a Chinese population.
Although several variants located at coding and non-coding regions were evaluated by previous studies, the evidence for associations between variants located in DNase I-hypersensitive sites (DHSs) and hepatocellular carcinoma (HCC) risk was still limited. Recent advances using ENCODE data indicated that genetic variants in DHSs played an important role in carcinogenesis. Therefore, systematically investigating the associations between regulatory variants in DHSs and HCC risk should be put on the agenda. We conducted a case-control design (1538 HCC cases vs 1465 normal controls) to evaluate the effects on HCC for the variants located at the uniform DNase I hypersensitive sites sequencing peaks in a Chinese population. We found two novel single nucleotide polymorphisms rs12309362 (odds ratio = 0.64, P = 5.61 × 10-6 ) and rs9970827 (odds ratio = 0.73, P = 7.23 × 10-6 ) significantly associated with decreased risk of HCC. Conditional analysis proved that both of them independently contributed to the susceptibility of HCC. Expression quantitative trait loci analysis found that A allele of rs12309362 was significantly associated with an elevated expression of phosphatase phosphoglycerate mutase 5 in liver tissues. In addition, gene-based analysis indicated that CEBPB (P = 1 × 10-4 ) was associated with the risk of HCC, and the expression of CEBPB was significantly lower in 50 The Cancer Genome Atlas HCC tumor tissues compared with matched normal tissues. Our results indicated that rs12309362 (G > A), rs9970827 (A > G) in DHSs, and elevated expression of CEBPB were associated with a decreased risk of HCC. These results may contribute us to understand the function of regulatory DNA sequences in HCC development.


Assessment of Histopathological Grade and Ki-67 Expression in Tobacco and Non-tobacco Habitual Buccal Mucosa Cancer.
Although there are various risk factors in the literature, the established primary risk factor for oral cancer is tobacco and betal-nut chewing habits. It is believed that pathogenesis of oral cancer depends on the aetiology. To assess the histopathological grade and Ki-67 expression in tobacco (smoking/smokeless) and non-tobacco (betal nut/pan masala) habitual buccal mucosa cancer. The cross-sectional study was carried out in Regional cancer centre, Tamilnadu. Proliferative marker, Ki-67 expression was determined by immunohistochemistry using biotin-streptavidin method. The study includes 117 buccal mucosa cancer patients (61 male and 56 female). According to WHO grading system, high frequency observed with well differentiated squamous cell carcinoma 48 (41%) followed by moderate 46 (39.3%) and poorly differentiated 23 (19.7%). The cut-off value 50% was used to categorize Ki-67 expression into low and high labelling index (LI); 96 (82%) buccal mucosa cancer and 4 (3.4%) adjacent normal mucosa patients showed high Ki-67 expression. The present study showed highly significant association of histopathological tumor grade and Ki-67 expression by Chi square and paired t test p < 0.05. All the patients were grouped as tobacco 87 (74.4%) and non-tobacco habitual 30 (25.6%) in 3:1, respectively. Further, the risk habits identified with significant differences of tumor grade (p = 0.028) and Ki-67 at p < 0.05. Thus, the study revealed that the nature of cell differentiation and proliferation was strongly related to consumption of carcinogen in both tobacco and non-tobacco form. Therefore, histopathological grade and Ki-67 could be used as a reliable biomarker to understand the biological behaviour of risk habits which might helpful for further treatment therapeutics.


The time-course of recovery from interruption during reading: eye movement evidence for the role of interruption lag and spatial memory.
Two experiments examined how interruptions impact reading and how interruption lags and the reader's spatial memory affect the recovery from such interruptions. Participants read paragraphs of text and were interrupted unpredictably by a spoken news story while their eye movements were monitored. Time made available for consolidation prior to responding to the interruption did not aid reading resumption. However, providing readers with a visual cue that indicated the interruption location did aid task resumption substantially in Experiment 2. Taken together, the findings show that the recovery from interruptions during reading draws on spatial memory resources and can be aided by processes that support spatial memory. Practical implications are discussed.


Expression of cellular prion protein in activated hepatic stellate cells.
Suppression subtractive hybridization was used to clone genes associated with the activation of hepatic stellate cells and 13 genes were found to be dominantly expressed in activated stellate cells. Among them, one was identical to the 421-837th base pairs of cDNA sequence reported for rat prion-related protein (PrP). In cultured stellate cells, PrP mRNA expression increased in a time-dependent manner in parallel with smooth muscle (SM) alpha-actin mRNA expression. In situ hybridization demonstrated that PrP mRNA was localized in and around the fibrous septa of carbon tetrachloride (CCl4)-treated liver. Cellular PrP (PrPc) was produced by culture-activated stellate cells, and immunohistochemically detected in the fibrous septa of CCl4-damaged liver and sinusoidal linings of common bile duct-ligated liver, consistent with the localization of SM alpha-actin. Immunoelectron microscopy revealed that PrPc resided on the plasma membrane of stellate cells. These results indicate that PrP expression is closely related to stellate cell activation associated with fibrogenic stimuli.


Behavior analysis and neuroscience.
Darwin proposed a powerful functional principle-natural selection-to interpret phylogenetic diversity and complexity. Nevertheless, some 70 years elapsed before even biologists embraced his account. The triumph of natural selection required two additional factors: (a) biological mechanisms that implemented the functional principle (i.e. genetics); and (b) quantitative procedures that traced its cumulative effects (i.e. population genetics). Thorndike and, later, Skinner proposed a functional principle-selection by reinforcement-that interpreted ontogenetic diversity and complexity. This principle has been substantially refined by subsequent experimental and theoretical work and now provides an equally powerful functional account. However, a purely functional principle has once again not persuaded most scientists (apart from the behavior-analytic minority) that complex behavior can be understood by a selection principle. If the history of ontogeny recapitulates the history of phylogeny, the biological mechanisms that implement selection by reinforcement must be discovered and quantitative techniques that trace its effects must be devised. In short, the triumph of reinforcement may await the integration of behavior analysis with the neurosciences and the development of coordinated quantitative procedures. This article identifies specific interrelations with neuroscience that form the basis for a behavior-analytically faithful interpretation of reinforcement using neural-network techniques. Implications for the architecture of networks and for the learning algorithm are emphasized.


The safety and effectiveness of adenosine diphosphate receptor inhibitor pretreatment among acute myocardial infarction patients treated with percutaneous coronary intervention in community practice: Insights from the TRANSLATE-ACS study.
To understand the optimal timing of adenosine diphosphate (ADP) receptor inhibitor pretreatment prior to percutaneous coronary intervention (PCI) among acute myocardial infarction (MI) patients. The role of ADP receptor inhibitor pretreatment in this population is unclear. A total of 9,251 ADP receptor inhibitor-naïve MI patients undergoing PCI at 229 TRANSLATE-ACS sites were evaluated. Adjusted risks of in-hospital major adverse cardiovascular events (MACE) and major bleeding were compared among patients with and without pretreatment using inverse probability-weighted propensity adjustment. Of 9,251 patients treated with either prasugrel or clopidogrel during the index MI hospitalization, 4,056 (44%) received pretreatment (ST-segment elevation MI [STEMI] 54.9%, non-STEMI 45.1%); pretreatment was used more commonly among those receiving clopidogrel than prasugrel (52% vs. 20%, P < 0.0001). MACE risks were not significantly different between patients with and without pretreatment (clopidogrel 2.1% vs. 2.2%, adjusted hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.70-1.43; prasugrel 2.1% vs. 2.3%, adjusted odds ratio [OR] 0.82, 95% CI 0.42-1.60). No differences in major bleeding were observed among those receiving versus not receiving pretreatment (clopidogrel 3.1% vs. 3.5%, adjusted HR 0.94, 95% CI 0.65-1.36; prasugrel 2.5% vs. 2.7%, adjusted OR 0.93, 95% CI 0.42-2.02); results were similar when stratified by MI type. ADP receptor inhibitor pretreatment (44%) is commonly used among acute MI patients undergoing PCI in contemporary practice, but no significant differences were found in in-hospital MACE and/or bleeding risks between patients receiving versus not receiving pretreatment, regardless of ADP receptor inhibitor type.


Identification and characterization of DNA aptamers specific to VP2 protein of canine parvovirus.
Canine parvovirus-2 (CPV-2) is ubiquitously distributed in dog population worldwide causing a severe and often fatal gastroenteritis. Owing to its highly contagious nature, rapid detection of CPV is crucial in effective control of the disease. Aptamers have emerged as potential alternative to antibodies as affinity reagents in diagnostic field. Present study was aimed to select and validate ssDNA aptamers specific to CPV. Systematic evolution of ligands through exponential enrichment (SELEX) method was employed for selection of CPV structural protein (VP2) specific DNA aptamers. SELEX was performed using a pool of ssDNA library comprising 30 random nucleotide region. A total of seven rounds of SELEX were performed using VP2 protein as target antigen which yielded ten aptamers (1A-10A) with distinct sequences. Target binding of all ten aptamers was assessed by dot blot and enzyme-linked oligonucleotide assay (ELONA) which revealed that 5A, 6A, 9A, and 10A were superior binders. In silico analysis of the aptamers revealed the existence of binding site on VP2 protein, and binding pattern was similar to in vitro findings. The affinity (KD) of all these four binders against CPV was evaluated by ELONA indicating relatively higher affinity of 6A and 10A than remaining two DNA sequences. Out of which, aptamer 6A displayed cross-reactivity with canine distemper virus and canine corona virus. Hence, aptamer 10A was considered as better binding sequence having high specificity and affinity for CPV. The study confirms the future utility of selected aptamers in development of a reliable diagnostic for rapid detection of CPV. KEY POINTS: • Canine parvovirus-specific ssDNA aptamers were identified with nanomolar affinity (100-150 nM). • Three aptamers displayed negligible cross-reactivity with other related viruses. • Aptamer 10A displayed high binding affinity and specificity to CPV.


A Rho-signaling pathway mediates cortical granule translocation in the sea urchin oocyte.
Cortical granules are secretory vesicles of the egg that play a fundamental role in preventing polyspermy at fertilization. In the sea urchin egg, they localize directly beneath the plasma membrane forming a compact monolayer and, upon fertilization, undergo a Ca(2+)-dependent exocytosis. Cortical granules form during early oogenesis and, during maturation, translocate from the cytosol to the oocyte cortex in a microfilament-mediated process. We tested the hypothesis that these cortical granule dynamics were regulated by Rho, a GTPase of the Ras superfamily. We observed that Rho is synthesized early in oogenesis, mainly in a soluble form. At the end of maturation, however, Rho associates with cortical granules. Inhibition of Rho with the C3 transferase from C. botulinum blocks cortical granule translocation and microfilaments undergo a significant disorganization. A similar effect is observed by GGTI-286, a geranylgeranyl transferase inhibitor, suggesting that the association of Rho with the cortical granules is indispensable for its function. In contrast, the anchorage of the cortical granules in the cortex, as well as their fusion at fertilization, are Rho-independent processes. We conclude that Rho association with the cortical granules is a critical regulatory step in their translocation to the egg cortex.


Impact of organochlorine pesticide residues and PCBs on otters (Lutra lutra): a study from western Britain.
A study of otter (Lutra lutra) populations and levels of organochlorine (OC) pesticide residues and PCBs in otter droppings (spraints) was made on eight stretches of river in three catchments in Wales and West Midland England. Population and contaminant levels were compared against target values. The otter populations (as measured by an index) remained stable on one stretch over 11 years, while they increased rapidly to equilibrium on four other stretches. The three lower stretches of rivers showed more erratic trends and on only one stretch did the index exceed, occasionally, the target value. Marking intensity at spraint sites was also lower at the three lowland sites. Concentrations of dieldrin, DDE and PCBs were significantly greater in spraint samples from the three lowland stretches. Over 50% of samples from the three lowland stretches had OC concentrations above the maximum allowable concentration, whereas most samples from the upland stretches had concentrations below the 'no effects level'. It is suggested that the colonization, by otters, of their former lowland range is inhibited by OC contamination of their food chain but, if contaminant levels can be reduced, spread will occur rapidly.


Quantitative proteomics and phosphoproteomics of urinary extracellular vesicles define putative diagnostic biosignatures for Parkinson's disease.
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been recognized as genetic risk factors for Parkinson's disease (PD). However, compared to cancer, fewer genetic mutations contribute to the cause of PD, propelling the search for protein biomarkers for early detection of the disease. Utilizing 138 urine samples from four groups, healthy individuals (control), healthy individuals with G2019S mutation in the LRRK2 gene (non-manifesting carrier/NMC), PD individuals without G2019S mutation (idiopathic PD/iPD), and PD individuals with G2019S mutation (LRRK2 PD), we applied a proteomics strategy to determine potential diagnostic biomarkers for PD from urinary extracellular vesicles (EVs). After efficient isolation of urinary EVs through chemical affinity followed by mass spectrometric analyses of EV peptides and enriched phosphopeptides, we identify and quantify 4476 unique proteins and 2680 unique phosphoproteins. We detect multiple proteins and phosphoproteins elevated in PD EVs that are known to be involved in important PD pathways, in particular the autophagy pathway, as well as neuronal cell death, neuroinflammation, and formation of amyloid fibrils. We establish a panel of proteins and phosphoproteins as novel candidates for disease biomarkers and substantiate the biomarkers using machine learning, ROC, clinical correlation, and in-depth network analysis. Several putative disease biomarkers are further partially validated in patients with PD using parallel reaction monitoring (PRM) and immunoassay for targeted quantitation. These findings demonstrate a general strategy of utilizing biofluid EV proteome/phosphoproteome as an outstanding and non-invasive source for a wide range of disease exploration.


Effects of early undernutrition on the brain insulin-like growth factor-I system.
Undernutrition reduces circulating concentrations of insulin-like growth factor (IGF)-I, but how it affects the brain IGF system, especially during development, is largely unknown. We have studied IGF-I, IGF-II, IGF receptor and IGF binding protein (BP)-2 mRNA expression in the hypothalamus, cerebellum and cerebral cortex of neonatal rats that were food restricted beginning on gestational day 16. One group was refed starting on postnatal day 14. Rats were killed on postnatal day 8 or 22. Undernutrition did not produce an overall reduction in brain weight at either age but, at 22 days, both the cerebellum and hypothalamus weighed significantly less. At 8 days, no change was detected in the central IGF axis in response to undernutrition. However, in 22-day-old undernourished rats, IGF-I and IGF receptor mRNA expression were increased in both the hypothalamus and cerebellum, while IGFBP-2 was decreased, but only in the hypothalamus. Refeeding had no effect on any of these parameters. These results suggest that the hypothalamus and cerebellum respond to malnutrition and the decrease in circulating IGF-I, a peptide fundamental for growth and development, by increasing the local production of both the growth factor and its receptor in attempt to maintain normal development.


Utilization of [11C]phosgene for radiosynthesis of N-(2-{3-[3,5-bis(trifluoromethyl)]phenyl[11C]ureido}ethyl)glycyrrhetinamide, an inhibitory agent for proteasome and kinase in tumors.
N-(2-{3-[3,5-Bis(trifluoromethyl)]phenylureido}ethyl)glycyrrhetinamide (2), an ureido-substituted derivative of glycyrrhetinic acid (1), has been reported to display potent inhibitory activity for proteasome and kinase, which are overexpressed in tumors. In this study, we labeled this unsymmetrical urea 2 using [(11)C]phosgene ([(11)C]COCl(2)) as a labeling agent with the expectation that [(11)C]2 could become a positron emission tomography ligand for the imaging of proteasome and kinase in tumors. The strategy for the radiosynthesis of [(11)C]2 was to react hydrochloride of 3,5-bis(trifluoromethyl)aniline (4·HCl) with [(11)C]COCl(2) to possibly give isocyanate [(11)C]6, followed by the reaction of [(11)C]6 with N-(2-aminoethyl)glycyrrhetinamide (3).


MNPmApp: An image analysis tool to quantify mononuclear phagocyte distribution in mucosal tissues.
Mononuclear phagocytes (MNPs) such as dendritic cells and macrophages perform key sentinel functions in mucosal tissues and are responsible for inducing and maintaining adaptive immune responses to mucosal pathogens. Positioning of MNPs at the epithelial interface facilitates their access to luminally-derived antigens and regulates MNP function through soluble mediators or surface receptor interactions. Therefore, accurately quantifying the distribution of MNPs within mucosal tissues as well as their spatial relationship with other cells is important to infer functional cellular interactions in health and disease. In this study, we developed and validated a MATLAB-based tissue cytometry platform, termed "MNP mapping application" (MNPmApp), that performs high throughput analyses of MNP density and distribution in the gastrointestinal mucosa based on digital multicolor fluorescence microscopy images and that integrates a Monte Carlo modeling feature to assess randomness of MNP distribution. MNPmApp identified MNPs in tissue sections of the human gastric mucosa with 98 ± 2% specificity and 76 ± 15% sensitivity for HLA-DR+ MNPs and 98 ± 1% specificity and 85 ± 12% sensitivity for CD11c+ MNPs. Monte Carlo modeling revealed that mean MNP-MNP distances for both HLA-DR+ and CD11c+ MNPs were significantly lower than anticipated based on random cell placement, whereas MNP-epithelial distances were similar to randomly placed cells. Surprisingly, H. pylori infection had no significant impact on the number of HLA-DR and CD11c MNPs or their distribution within the gastric lamina propria. However, our study demonstrated that MNPmApp is a reliable and user-friendly tool for unbiased quantitation of MNPs and their distribution at mucosal sites.


Possible indirect interactions between transient and resident killer whales: implications for the evolution of foraging specializations in the genus Orcinus.
Two distinct forms of killer whale (Orcinus orca) occur off the coast of British Columbia, Alaska and Washington State. These have different diets, and may be reproductively isolated. Because the primary food of transient whales (pinnipeds) is a potential competitor for the primary food of resident whales (salmon), or for the smaller fishes on which salmon feed, there should be an indirect interaction between the two forms of killer whale. We use simple mathematical models to show that this interaction will be either of a "plus-minus" type, or a "plus-plus" type (indirect mutualism), depending on whether or not pinnipeds and residents are on the same trophic level. In the case of the "plus-minus" interaction, increasing the population density or improving the environmental conditions of transients will increase the population density of residents, while increasing resident populations will reduce the equilibrium population size of transients. In the case of the "plus-plus" interaction, increasing the population density or improving the environmental conditions of transients will increase the population density of residents, while increasing resident populations will reduce the equilibrium population size of transients. In the case of the "plus-plus" interaction, increasing the population density or improving the environmental conditions of transients will increase the population density of residents, and vice versa. Such effects may not be currently manifest due to reduced populations at most levels in the food web. Regardless, considering such indirect interactions may be important for the management of many of the species involved, and can also provide a valuable framework for examining the evolution of the two forms of killer whales. Frequency-dependent indirect interactions, acting in concert with density-dependence within populations and disruptive selection on prey-type specific foraging characteristics, may have favoured reproductive isolation of the two forms of killer whales. We suggest that these two forms of whale are in the process of speciating, i.e., the two forms are incipient species.


Compensation mechanisms for fishermen quit fishing: A case of Jiangsu province, China.
The 'Ten-year Ban on Fishing' policy was designed by the Chinese government to protect the biodiversity of the Yangtze River basin. Fishermen are the ultimate implementers of the fishing ban policy. Therefore, a scientific compensation mechanism for fishers to stop fishing is the basis for ensuring the continuous implementation of the policy. First, we conducted a survey with 309 fishermen in eight cities along the Yangtze River in Jiangsu province. We also analyzed living conditions of fishermen before and after quitting fishing based on descriptive statistical analysis. Based on the theory of sustainable livelihood, a binary logistic regression model was used to analyze the relationship between fishermen's willingness to quit fishing and five types of livelihood capital (natural, material, human, financial, and social capital). The results showed that fishermen face severe livelihood sustainability issues after ceasing to fish and that their willingness to quit is closely related to the five types of livelihood capital. Based on this, and according to different age groups, this study constructed a compensation mechanism for retired fishermen from two aspects: monetary and social security compensation. The research results can provide a theoretical framework for other provinces in the Yangtze River basin to formulate a compensation system for fishermen.


Association of polyunsaturated fatty acids in breast milk with fatty acid desaturase gene polymorphisms among Chinese lactating mothers.
The fatty acid desaturase (FADS) controls polyunsaturated fatty acid (PUFA) synthesis in human tissues and breast milk. Evaluate the influence of 10 single nucleotide polymorphisms (SNPs) and various haplotypes in the FADS gene cluster (FADS1, FADS2, FADS3) on PUFA concentration in the breast milk of 209 healthy Chinese women. PUFA concentrations were measured in breast milk using gas chromatography and genotyping was performed using the Sequenom Mass Array system. A SNP (rs1535) and 2-locus haplotypes (rs3834458-rs1535, rs1535-rs174575) in the FADS2 gene were associated with concentrations of γ-linoleic acid (GLA) and arachidonic acid (AA) in breast milk. Likewise, in the FADS1 gene, a 2-locus constructed haplotype (rs174547-rs174553) also affected GLA and AA concentration (P<0.05 for all). Minor allele carriers of the SNP and haplotypes described above had lower concentrations of GLA and AA. In the FADS2 gene, the 3-locus haplotype rs3834458-rs1535-rs174575, significantly affected concentrations of GLA but not AA. Pairwise comparison showed that individuals major homozygous for the SNP rs1000778 in the FADS3 gene had lower concentrations of ALA and linoleic acid (LA) in their breast milk. Polymorphisms in the FADS gene cluster influence PUFA concentrations in the breast milk of Chinese Han lactating women.


Acetyl-CoA synthetase is activated as part of the PDH-bypass in the oleaginous green alga Chlorella desiccata.
In a recent study, it has been shown that biosynthesis of triacylglycerol (TAG) in the oleaginous green alga Chlorella desiccata is preceded by a large increase in acetyl-coenzyme A (Ac-CoA) levels and by upregulation of plastidic pyruvate dehydrogenase (ptPDH). It was proposed that the capacity to accumulate high TAG critically depends on enhanced production of Ac-CoA. In this study, two alternative Ac-CoA producers-plastidic Ac-CoA synthase (ptACS) and ATP citrate lyase (ACL)-are shown to be upregulated prior to TAG accumulation under nitrogen deprivation in the oleaginous species C. desiccata, but not in the moderate TAG accumulators Dunaliella tertiolecta and Chlamydomonas reinhardtii. Measurements of endogenous acetate production and of radiolabelled acetate incorporation into lipids are consistent with the upregulation of ptACS, but suggest that its contribution to the overall TAG biosynthesis is negligible. Induction of ACS and production of endogenous acetate are correlated with activation of alcohol dehydrogenase, suggesting that the upregulation of ptACS is associated with activation of PDH-bypass in C. desiccata. It is proposed that activation of the PDH-bypass in C. desiccata is needed to enable a high rate of lipid biosynthesis under nitrogen deprivation by controlling the level of pyruvate reaching ptPHD and/or mtPDH. This may be an important parameter for massive TAG accumulation in microalgae.


Thalamocortical and thalamo-amygdaloid projections from the parvicellular division of the posteromedial ventral nucleus in the cat.
Projections from the parvicellular division of the posteromedial ventral thalamic nucleus (VPMpc) of the cat were examined. After injection of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) into the VPMpc, both anterogradely labeled axon terminals and retrogradely labeled neuronal cell bodies were found ipsilaterally in three discrete regions of the cerebral cortex, i.e., in the orbital cortex, caudoventral part of the infralimbic cortex, and medial part of the fundus of the posterior rhinal sulcus (perirhinal area); in the subcortical regions, anterogradely labeled axon terminals were seen ipsilaterally in the rostrodorsal part of the lateral amygdaloid nucleus. Neuronal connections between these VPMpc-recipient regions were further verified by injecting WGA-HRP into each of the three cortical and the lateral amygdaloid regions. After injection of WGA-HRP into each of the three cortical regions, labeled neuronal cell bodies and axon terminals were seen ipsilaterally in the VPMpc, especially in its medial part, and in the other two of the three VPMpc-recipient cortical regions. In the rostrodorsal part of the lateral amygdaloid nucleus, both axon terminals and neuronal cell bodies were labeled after WGA-HRP injection into the perirhinal area, and only axon terminals were labeled after WGA-HRP injection into the orbital cortex, but no labeling was observed after WGA-HRP injection into the infralimbic cortex. After injection of WGA-HRP into the rostrodorsal portion of the lateral amygdaloid nucleus, both axon terminals and neuronal cell bodies were labeled ipsilaterally in the perirhinal area and the ectorhinal area, and only neuronal cell bodies were labeled ipsilaterally in the VPMpc (especially in its medial part) and orbital cortical region; no labeling was observed in the infralimbic cortex. The present results indicate that the VPMpc of the cat is connected reciprocally with the orbital, infralimbic, and perirhinal cortical regions on the ipsilateral side, that the three VPMpc-recipient cortical regions are reciprocally connected with each other, that the VPMpc sends fibers ipsilaterally to the rostrodorsal part of the lateral amygdaloid nucleus, which may relay information from the VPMpc to the perirhinal cortical area, and that the VPMpc-recipient area in the lateral amygdaloid nucleus receives cortical fibers from the orbital and perirhinal cortical regions.


Skin lesions by Scedosporium apiospermum and Nocardia pulmonary infection in an oncologic patient: a case report.
Fungal infections, other than candidiasis and aspergillosis, are an uncommon entity. Despite this, emerging pathogens are a growing threat. In the following case report, we present the case of an immunocompromised patient suffering from two serious opportunistic infections in the same episode: the first of these, Nocardia multilobar pneumonia; and the second, skin infection by Scedosporium apiospermum. These required prolonged antibacterial and antifungal treatment. This case is a 71-year-old oncological patient admitted for recurrent pneumonias that was diagnosed for Nocardia pulmonary infection. Nervous system involvement was discarded and cotrimoxazole was started. Haemorrhagic skin ulcers in the lower limbs appeared after two weeks of hospital admission. We collected samples which were positive for Scedosporium apiospermum and we added voriconazole to the treatment. As a local complication, the patient presented a deep bruise that needed debridement. We completed 4 weeks of intravenous treatment with slow improvement and continued with oral treatment until the disappearance of the lesions occurs. Opportunistic infections are a rising entity as the number of immunocompromised patients is growing due to more use of immunosuppressive therapies and transplants. Clinicians must have a high suspicion to diagnose and treat them. A fluid collaboration with Microbiology is necessary as antimicrobial resistance is frequent.


Cilnidipine improves spontaneously hypertensive rat coronary hemodynamics without altering cardiovascular mass and collagen.
The present study was designed to determine the effects of prolonged treatment with cilnidipine, a novel dihydropyridine calcium antagonist which blocks both L-type and N-type calcium channels, on systemic, regional and coronary hemodynamics, cardiovascular mass and collagen content in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Male 23-week-old WKY and SHR rats were divided into two groups for each strain. One group received cilnidipine (10 mg/kg per day), whereas their respective controls were given no therapy. Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular and aortic mass, and hydroxyproline concentration were determined after 12 weeks treatment. The data demonstrated that cilnidipine neither affected systemic hemodynamics nor cardiovascular mass and collagen content in WKY rats. The same treatment in the SHR reduced arterial pressure and total peripheral resistance without changes in heart rate and cardiac index. Ventricular and aortic mass indices as well as ventricular collagen content remained unchanged. There were no differences in organ blood flows between two SHR groups, whereas renal, liver and left ventricular coronary vascular resistances were reduced by cilnidipine. After dipyridamole infusion left ventricular minimal coronary vascular resistance decreased further in cilnidipine-treated SHR as compared with control SHR rats. These data suggest that cilnidipine, an L- and N- type calcium channel antagonist, exerted beneficial effects on coronary hemodynamics without altering cardiovascular mass or collagen content in SHR.


Association of blepharitis with Demodex: a meta-analysis.
To conduct a meta-analysis to confirm the association between Demodex infestation and blepharitis. We conducted a comprehensive and quantitative analysis of relevant published case-control studies which were found from the ISI Web of Knowledge, MEDLINE and CNKI from January 1950 to December 2010. Meta-analysis was applied for 13 of these and included matched data sets, using odds ratio (OR) as the effect indicator. Sensitivity was assessed. Eleven articles (13 matched data sets) covering four different countries and reporting 4741 participants (2098 blepharitis and 2643 controls) were eligible. The pooled OR in random effect models was 4.89 (95% confidence interval, 3.00-7.97). Sensitivity analysis showed that results of pooled ORs in different effect models, language, sample size, and control groups were completely consistent, which demonstrated a stable association between Demodex infestation and blepharitis by meta-analysis. The association between Demodex infestation and blepharitis was statistically significant. The conclusion implies that when conventional treatments for blepharitis fail, examination of Demodex mites and acaricidal therapy should be considered.


Prevalence and risk factors for Helicobacter pylori infection in Chinese populations.
The prevalence of Helicobacter pylori is higher in developing countries. The aim of this study was to investigate the prevalence and risk factors of H. pylori infection in areas with high prevalence of gastric cancer in Jiangsu Province, China. A prospective epidemiologic survey of H. pylori infection was accomplished in a natural population of 1457 individuals in Xiangshui and Gaoyou counties, Jiangsu Province, China. Questionnaires and laboratory tests for H. pylori infection ((13)C-urea breath test and serum IgG antibodies to H. pylori) were used and performed, respectively. Among 1371 subjects who completed questionnaires and H. pylori detection, 851 (62%) were H. pylori positive. The prevalence reached a peak at the age of 30-40 years (67%). There was no sex difference. The annual family income level was shown to be positively correlated with the risk of H. pylori infection. The prevalence of H. pylori infection was also associated with family size, education level, and several diet-related factors, such as the number of times cooked rice and potatoes eaten per week, and a family history of stomach diseases. Compared to nonsymptomatic individuals, people with dyspeptic symptoms (nausea, vomiting, and belching) presented a low prevalence of H. pylori infection. No association between H. pylori prevalence and smoking or drinking was found. Using multivariate logistic regression analysis, annual family income and education level were the independent predictors for H. pylori infection. High prevalence of H. pylori infection was found in areas with a high risk of gastric cancer and was related to several risk factors. The underlying mechanisms need to be further investigated.


Comparison of clinical outcomes between peripheral blood stem cells and peripheral blood stem cells plus bone marrow in myelodysplastic syndrome patients with haploidentical transplantation.
The comparison of haploidentical G-CSF-mobilized peripheral blood and bone marrow transplantation (HBMT) for patients with myelodysplastic syndrome (MDS) and haploidentical G-CSF-primed peripheral blood stem cell transplantation (HPBSCT) remains unclear. We performed a retrospective analysis using a propensity score method on 140 MDS patients who received HPBSCT (n = 46) or HBMT (n = 94) with BU/CY as a conditioning regimen prior to transplantation at our center between June 2016 and June 2021. HBMT recipients were associated with a reduced incidence of grade III-IV acute GVHD (17.22% vs. 30.57%, p = 0.019) within 100 days, reduced 2-year transplant-related mortality (TRM) (14.29% vs. 28.94%, p = 0.045) and superior 2-year overall survival (OS) (81.6% vs. 66.0%, p = 0.027), progression-free survival (PFS) (80.9% vs. 61.2%, p = 0.015), and GVHD relapse-free survival (GRFS) (64.6% vs. 53.3%, p = 0.062) compared with HPBSCT, but 2-year relapse incidence (RI) (5.96% vs. 9.39%, p = 0.445) was not affected. Multivariate analysis revealed that a GPB/GBM mixture was the independent factor for a reduced incidence of grade III-IV acute GVHD (p = 0.018) and TRM (p = 0.048), improved OS (p = 0.029), PFS (p = 0.019) and GRFS (p = 0.072). Collectively, the use of a GPB/GBM mixture as stem cell grafts for haplo-HSCT in patients with MDS appears to be an optimal choice.


Augmented analgesic effects of enkephalinase inhibitors combined with transcranial electrostimulation.
The analgesic effects of very low current transcranial electrostimulation are naloxone-reversible and thus presumably mediated by endogenous opioid activity. The present experiments indicate that blocking enkephalinase activity by i.c.v. thiorphan or i.p. acetorphan results in an increased analgesic effect of electrostimulation as measured by the 50 degrees C wet tail flick test. In the case of each drug, rats receiving both drug and electrostimulation displayed significantly more analgesia than rats receiving electrostimulation and injection vehicle alone, rats receiving drug and sham stimulation or rats receiving vehicle and sham stimulation.


Calcified pericardial cyst--a case report and the roentgenologic and pathologic differentiation from other calcified mediastinal cysts.
A case of calcified pericardial cyst is reported and is differentiated from calcified bronchogenic, enteric, thymic, terato-dermoid, and hydatid cysts by means of roentgenology and pathology.


Carbon nanohorns as a high-performance carrier for MnO2 anode in lithium-ion batteries.
MnO(2) nanoflakes coated on carbon nanohorns (CNHs) has been synthesized via a facile solution method and evaluated as anode for lithium-ion batteries. By using CNHs as buffer carrier, MnO(2)/CNH composite displays an excellent capacity of 565 mA h/g measured at a high current density of 450 mA/g after 60 cylces.


Reading the Fine Print: State Considerations for Medicaid Buy-In Plans.
States that are pursuing Medicaid buy-in plans have considerable options in designing a plan to meet their goals. Buy-in plans will reflect key decisions on four major issues: 1) whether plans are sold on or off exchange, 2) whether plans are run by the state or a Medicaid Managed Care Organization, 3) who is eligible to purchase plans, and 4) which benefits and providers will be covered and at what payment rates. Our goal is to clarify the implications of these choices with respect to the goals and with respect to the tradeoffs each choice would involve.


Application of solid waste of ductile cast iron industry for treatment of wastewater contaminated by reactive blue dye via appropriate nano-porous magnesium oxide.
The solid waste of ductile iron industry, which contains at least 88.0% magnesium oxide, is one of the toxic materials, leading to land contamination. On the other hand, the removal of reactive dyes from wastewaters is difficult required effective adsorbent like nano-porous MgO. The novelty of present investigation is based on nano-porous magnesium oxide production by precipitation from the solid waste to treat the wastewaters contaminated by reactive dye which is abundantly used in the textile industry. In order to improve the adsorptive properties of extracted MgO powder, the combinations of surfactants, containing cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS) and polyoxyethylene octyl phenyl ether (TX100) were applied based on the mixture design algorithm in the precipitation. The effects of processing factors such as surfactant composition, powder calcination temperature, surfactant dose and pH were evaluated on the removal efficiency. The results revolved that the combination of SDS and TX100, 1:1, plays an effective role in the production of particles with the appropriate average pore size, 16 nm. The adsorbent prepared in the optimum condition indicated a significant affinity for the removal of reactive dye which shows relatively pH-independent efficiency in the range of 3-9. The applied producer for fabrication of adsorbent eventually overcomes the pH-dependent problem for the toxic dye uptake, leading to produce the adsorbent with maximal adsorption capacity of 1000 mg g-1.


A portable multi-syringe flow system for spectrofluorimetric determination of iodide in seawater.
A miniaturized analyzer encompassing a poly(methyl methacrylate) chip with integrated spectrofluorimetric detection and solutions propelling by a multi-syringe module is proposed. Iodide was determined through its catalytic effect on the reaction between Ce(IV) and As(III). Matrix isopotential synchronous fluorescence was explored to set the excitation and emission wavelengths. A two-level full factorial design allowed to evaluate the significance of variables (Ce(IV), As(III) and H2SO4 concentrations) and their interaction effects in the experimental domain. A Doehlert Matrix was applied to identify the critical values. The optimized procedure showed a linear response from 1 to 100 μg L(-1) (S=53.7+2.61C, in which S is the net fluorescence and C is iodide concentration in μg L(-1)). Detection limit, coefficient of variation (n=6) and sampling rate were estimated at 0.3 μg L(-1), 0.8% and 20 h(-1), respectively. Recoveries within 90-117% were estimated for iodide spiked to seawater samples. The proposed procedure stands out because of the portability, robustness, and simplicity for in-field analysis of iodide in seawater.


Intravenous ganaxolone in pediatric super-refractory status epilepticus: A single hospital experience.
Synaptic GABAA receptor (GABAAR) internalization contributes to the drug resistant nature of super-refractory status epilepticus (SRSE). Ganaxolone is a 3β-methylated synthetic analog of the endogenous neuroactive steroid, allopregnanolone, that has positive allosteric modulatory activity on synaptic and extrasynaptic GABAA receptors. Ganaxolone is currently in clinical trials to treat rare pediatric seizure disorders and established and refractory SE. Two pediatric patients with SRSE (age 17 and age 7) were treated under emergency investigational new drug (E-IND) applications with intravenous (IV) ganaxolone administered as an initial bolus and a maintenance infusion for up to 4.5 days with intermittent IV boluses as-needed followed by taper on day 5 and transitioned to chronic treatment using ganaxolone suspension. Adjunctive ganaxolone was effective in terminating SRSE in both patients, safely permitting IV anesthetics to be weaned. Seizure control has been maintained after transitioning to enteric ganaxolone. Further investigation of ganaxolone as a safe and effective treatment for SRSE is warranted.


In vitro alanine utilization by rat interscapular brown adipose tissue.
The in vitro oxidation to CO2 and tissue incorporation of alanine label by pieces of rat interscapular brown adipose tissue (IBAT) has been investigated. Insulin increased both uptake and oxidation of alanine, as well as the incorporation of alanine label into tissue. This effect only was observed in the presence of glucose in the incubation medium. Noradrenaline hampered alanine incorporation, not affecting its rate of oxidation. IBAT from 4-h cold-exposed rats showed a higher alanine utilization than that of controls; however, IBAT pieces from both 36-h starved and 30-day cold-exposed rats presented lower rates of alanine utilization. The main fate of alanine taken up by the IBAT pieces was its oxidation to CO2. Part of the label was also incorporated into the fatty acid fraction of lipids. The results obtained in this study agree with a possible role of alanine as alternative energetic substrate for IBAT.


Differential role of CD97 in interleukin-8-induced and granulocyte-colony stimulating factor-induced hematopoietic stem and progenitor cell mobilization.
CD97 is broadly expressed on hematopoietic cells and is involved in neutrophil migration. Since neutrophils are key regulators in HSC/HPC mobilization, we studied a possible role for CD97 in interleukin-8 and granulocyte-colony stimulating factor-induced HSC/HPC mobilization. Mobilization was absent in mice receiving CD97 mAb followed by interleukin-8, while granulocyte-colony stimulating factor-induced mobilization remained unaltered following anti-CD97 administration. Furthermore, combined administration of CD97 mAb and IL-8 induced a significant reduction in the neutrophilic compartment. We hypothesize that the absence of interleukin-8-induced HSC/HPC mobilization after CD97 mAb administration is due to its effect on neutrophil function.


Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability.
Pembrolizumab is a novel immune-checkpoint inhibitor used for treatment of microsatellite instability-high (MSI-H) colorectal cancer. Several studies have reported clinical complete response (CR) after treatment with pembrolizumab, but none has confirmed pathological CR. Here we provide the first description of pathological CR with R0 resection after immune-checkpoint therapy. A 45-year-old man presented at our hospital with abdominal distention and highly elevated tumor markers. Contrast-enhanced abdominal CT showed a 110 × 75 mm bulky mass with markedly swollen lymph nodes and an isolated peritoneal metastasis in the pelvic space. Biopsy revealed poorly differentiated adenocarcinoma. We diagnosed ascending colon cancer cT4aN2bM1c Stage IVc. A biopsy specimen obtained during systemic chemotherapy (FOLFOXIRI) was confirmed pathologically as MSI-H, after which the treatment was changed to pembrolizumab. The tumor markers rapidly decreased to within normal ranges after three courses of treatment. After twenty courses, CT revealed shrinkage of the main tumor, lymph node metastases, and the peritoneal metastasis, and we performed extended right hemi-colectomy with dissection of the peritoneal metastasis. No residual tumor cells were found histologically. The patient achieved pathological CR and the postoperative course was uneventful. An accurate diagnosis and appropriate follow up are crucial for obtaining sufficient therapeutic effect of pembrolizumab.


Evaluation of Cerebellar Ataxic Patients.
Cerebellar ataxia results from damage to the cerebellum and presents as movement incoordination and variability, gait impairment, and slurred speech. Patients with cerebellar ataxia can also have cognitive and mood changes. Although the identification of causes for cerebellar ataxia can be complex, age of presentation, chronicity, family history, and associated movement disorders may provide diagnostic clues. There are many genetic causes for cerebellar ataxia, and the common autosomal dominant and recessive ataxia are due to genetic repeat expansions. Step-by-step approach will lead to the identification of the causes. Symptomatic and potential disease-modifying therapies may benefit patients with cerebellar ataxia.


Transbronchial biopsy of peripheral lung lesions using fluoroscopic guidance combined with an enhanced ray-summation display.
The aim of this study was to investigate the effectiveness of guidance assistance during transbronchial biopsy (TBB) to achieve an appropriate pathway to small and peripheral pulmonary lesions (PPLs) using a combination of fluoroscopy and specialized ray-summation (Ray-sumTBB) images, which were processed from preprocedural lung computed tomography (CT) images. To improve the visibility of the correct pathway to the PPLs, three-dimensional spatial resolution enhancement and CT number conversion processes were applied to the original CT images. The Ray-sumTBB images reconstructed from the processed CT images were used as additional guides. We compared the rates of successful tumor localization and biopsy (arrival rate) between the trial (with Ray-sumTBB) and control (without Ray-sumTBB) groups. The fluoroscopy and examination times were also compared. The arrival rate of the trial group (73.1%) was significantly better than that of the control group (42.3%) (p = 0.048). The fluoroscopy and examination times did not differ significantly between the trial and control groups. No complications were identified in the trial group. Our results suggest that Ray-sumTBB improves the diagnostic accuracy of TBB.


In-well cell lysis technique reveals two new megaplasmids of 103.0 and 212.6 MDa in the multiple plasmid-containing strain V517 of Escherichia coli.
Identification of two new plasmids in the multiple plasmid-containing strain V517 of Escherichia coli. By using an in-well mild cell lysis technique suitable for megaplasmids observation, two plasmids of 103.0 and 212.6 MDa were detected in the multiplasmid-containing E. coli V517. The two new megaplasmids that were completely overlooked when standard disruptive procedures were used, can now be added to the list of eight plasmids with molecular size from 1.36 to 35.84 MDa reported earlier. This finding allows to use the strain V517 not only as a size reference of small and moderately large plasmids but as a size reference of megaplasmids as well.


Formate-Bicarbonate Cycle as a Vehicle for Hydrogen and Energy Storage.
In recent years, hydrogen has been considered a promising energy carrier for a sustainable energy economy in the future. An easy solution for the safer storage of hydrogen is challenging and efficient methods are still being explored in this direction. Despite having some progress in this area, no cost-effective and easily applicable solutions that fulfill the requirements of industry are yet to be claimed. Currently, the storage of hydrogen is largely limited to high-pressure compression and liquefaction or in the form of metal hydrides. Formic acid is a good source of hydrogen that also generates CO2 along with hydrogen on decomposition. Moreover, the hydrogenation of CO2 is thermodynamically unfavorable and requires high energy input. Alkali metal formates are alternative mild and noncorrosive sources of hydrogen. On decomposition, these metal formates release hydrogen and generate bicarbonates. The generated bicarbonates can be catalytically charged back to alkali formates under optimized hydrogen pressure. Hence, the formate-bicarbonate-based systems being carbon neutral at ambient condition has certain advantages over formic acid. The formate-bicarbonate cycle can be considered as a vehicle for hydrogen and energy storage. The whole process is carbon-neutral, reversible, and sustainable. This Review emphasizes the various catalytic systems employed for reversible formate-bicarbonate conversion. Moreover, a mechanistic investigation, the effect of temperature, pH, kinetics of reversible formate-bicarbonate conversion, and new insights in the field are also discussed in detail.


Gender and age influence the association between gait speed and mild cognitive impairment in community-dwelling Japanese older adults: from the Japan Prospective Studies Collaboration for Ageing and Dementia (JPSC-AD).
Studies have shown that decreased gait speed is associated with impaired cognitive function. However, whether this association is equivalent across ages or genders in the older population remains unclear. Thus, we examined the association between mild cognitive impairment (MCI) and gait speed emphasising the influence of age and gender. Overall, 8233 Japanese participants aged ≥65 years were enrolled in this cross-sectional study between 2016 and 2018. After stratification by gender and age group, the participants' gait speeds were divided into quintiles, and the difference in MCI prevalence at each gait speed quintile was calculated. Logistic regression analyses were performed to assess the odds of MCI for each quintile and to assess the influence of age and gender. Males had a consistently higher prevalence of MCI than females. The odds of MCI were increased as gait speed decreased. Logistic regression analyses revealed that in the multivariable-adjusted model 2, the odds ratios (95% confidence interval; CI) for MCI were 2.02 (1.47-2.76) for females and 1.75 (1.29-2.38) for males in the slowest gait speed quintiles compared to the fastest quintile. In the stratified analyses, only males showed an age-dependent increase in the associations between gait speed and MCI, while females exhibited comparable associations across age groups. Reduced gait speed was associated with increased odds of MCI, and this association may vary according to gender and age. Therefore, gait speed could serve as a valuable screening tool for MCI, with gender- and age-dependent clinical implications.


Discovering hidden viral piracy.
Viruses and developers of anti-inflammatory therapies share a common interest in proteins that manipulate the immune response. Large double-stranded DNA viruses acquire host proteins to evade host defense mechanisms. Hence, viral pirated proteins may have a therapeutic potential. Although dozens of viral piracy events have already been identified, we hypothesized that sequence divergence impedes the discovery of many others. We developed a method to assess the number of viral/human homologs and discovered that at least 917 highly diverged homologs are hidden in low-similarity alignment hits that are usually ignored. However, these low-similarity homologs are masked by many false alignment hits. We therefore applied a filtering method to increase the proportion of viral/human homologous proteins. The homologous proteins we found may facilitate functional annotation of viral and human proteins. Furthermore, some of these proteins play a key role in immune modulation and are therefore therapeutic protein candidates.


Antibiotic prophylaxis for dental treatment after prosthetic joint replacement: exploring the orthopaedic surgeon's opinion.
Antibiotic prophylaxis before dental treatment is routinely recommended by orthopaedic surgeons to prevent prosthetic joint infection (PJI). This recommendation is at odds with current guidelines. A postal survey of 9 checkbox or short-answer questions was completed by 633 orthopaedic surgeons. The majority of respondents (n = 186 of 260, 72%) believe that antibiotic prophylaxis is required indefinitely for dental treatment. A small number (n = 43, 15%) seek a dentist's opinion before elective joint replacement. The surgeons reported low numbers of PJIs, although 24% (n = 68 of 280) believed that they were associated with dental treatment. Australian orthopaedic surgeons continue to recommend antibiotic prophylaxis for dental treatment. The recording of PJI in relation to dental procedures into clinical registries would enable the development of consistent guidelines between professional groups responsible for the care of this patient group.


Implications of VEGF gene sequence variations and its expression in recurrent pregnancy loss.
What is the association between VEGF gene sequence variants and its mRNA expression in recurrent pregnancy loss (RPL)? Vascular endothelial growth factor (VEGF) has a prominent role in pregnancy and affects pregnancy outcome. The association of VEGF gene 1154G>A, 634G>C and 583C>T polymorphic variations with cases of RPL and full-term fertile women as controls was investigated. Two hundred women with RPL and 240 women healthy controls were included. The restriction fragment length polymorphism method was used for genotyping and quantitative real-time polymerase chain reaction was used for analysis of mRNA expression. In VEGF 1154G>A, significant differences were found in homozygous AA genotype between case and control participants. The variant allele A frequency was significantly more abundant in RPL cases (0.41) than controls (0.19) (P < 0.0001). Only RPL cases with the multi-generation family history of miscarriages and those without any history showed significant differences of combined genotype GA+AA (P < 0.0001). In VEGF 634 G>C, CC genotype and allele C showed significantly increased frequency in RPL cases compared with healthy controls (P < 0.0001). The association between VEGF-1154 G>A SNP and VEGF-A mRNA expression levels was significant in RPL cases (P = 0.004). Also in VEGF-583 C>T, CT genotypes were seen significantly associated with cases (P = 0.003). The heterozygous genotype GA was significantly (P = 0.03) associated with upregulation and downregulation of VEGF mRNA, whereas the homozygous variant genotype AA only leads to low expression levels of VEGF mRNA in patients with RPL. All the variants of VEGF play a vital role in an increased susceptibility to RPL. Also, VEGF-1154, AA genotypes are associated with its altered low mRNA expression in women with RPL and seem to affect pregnancy outcome.


Relative infectivity of the SARS-CoV-2 Omicron variant in human alveolar cells.
With the continuous emergence of highly transmissible SARS-CoV-2 variants, the comparison of their infectivity has become a critical issue for public health. However, a direct assessment of the viral characteristic has been challenging because of the lack of appropriate experimental models and efficient methods. Here, we integrated human alveolar organoids and single-cell transcriptome sequencing to facilitate the evaluation. In a proof-of-concept study with four highly transmissible SARS-CoV-2 variants, including GR (B.1.1.119), Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.1), a rapid evaluation of the relative infectivity was possible. Our system demonstrates that the Omicron variant is 5- to 7-fold more infectious to human alveolar cells than the other SARS-CoV-2 variants at the initial stage of infection. To our knowledge, for the first time, this study measures the relative infectivity of the Omicron variant under multiple virus co-infection and provides new experimental procedures that can be applied to monitor emerging viral variants.


Isozymes as bioprobes for genetic analysis of nonhuman primates.
The identification and the utilization of genetically determined electrophoretic differences of enzymes between the individuals of species as well as between cell lines have played an important role in the advancement of mammalian genetics during the past quarter of a century. In an explicit search we found a number of red cell enzyme polymorphisms in each of the following four species: chimpanzees, orang utans, rhesus monkeys and brown capuchins. Allelic distribution patterns among populations have indicated trends of subspeciation among chimpanzees and orang utans due to geographic barriers leading to reproductive isolation. Investigations of quantitative levels of red cell glucose-6-phosphate dehydrogenase have suggested that relative activity profiles of certain enzymes among species may be helpful in studies of the evolution of physiological traits and their biological significance during speciation. A large number of biochemical genetic markers in primate-rodent (i.e., chimpanzee-, gorilla-, orang utan-, rhesus monkey- and African green monkey-Chinese hamster) somatic cell hybrids have been identified and are useful for primate genetic analysis. Some of the biologically relevant observations on the enzyme markers in the above mentioned primate species are discussed.


Anti-inflammatory action following liver damage in the rat.
A high molecular weight protein fraction, obtained by column chromatography of saline extracts of the livers of rats that had previously been treated with dimethylnitrosamine, was found to have anti-inflammatory activity against carrageenin induced inflammation in the rat. Evidence was presented that the anti-inflammatory activity may be due to a protein fragment produced by proteolysis of a larger molecule.


Potential for selective oxidation of aniline in soil washing effluent by active chlorine and testing its practicality.
Recovery of surfactants in the soil washing effluent (SWE) can significantly reduce the cost of the soil washing (SW) technology. This paper consists of two parts experiments. The first part constructed a selective oxidation system of active chlorine by electrochemical technology to treat SWE. Three factors, current density, NaCl concentration and TW 80 to aniline concentration ratio (T/A), were set up for a total of nine sets of experiments after orthogonal design. The results of ANOVA analysis and visual analysis showed that the NaCl concentration greatly affected the aniline removal efficiency (ARE) and the TW 80 retention efficiency (TW 80 RE), and the effects were in opposite directions. The biotoxicity of the SWE decreased as the experiment progressed, and at the end of the experiment, 30%-45% of TW 80 was still present in each set. And the oxidation group quenching experiments determined that the degradation of aniline was mainly contributed by active chlorine. Because active chlorine slowed the loss rate of TW 80, the electrochemical treatment of SWE + soil in-situ sequential batch recirculation washing method was designed, and 50% of aniline in the soil was washed out after 125h. At the end of the experiment, the less biotoxic SWE was collected where no aniline and TW 80 were present, and only small organic acids were present after the GC-MS test. The method has a great potential to be applied as it shows good results in the treatment of soil pollution incidents.


Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Pulsatile assistance for circulatory arrest, low-flow perfusion, and moderate-flow perfusion.
The brain tissue pH, oxygen tension, and carbon dioxide tension were experimentally examined during profoundly hypothermic cardiopulmonary bypass with core cooling and core rewarming. Sixty-minute circulatory arrests (n = 28, group I), 120-minute low-flow perfusions (25 ml/kg/min; n = 16, group II), and 120-minute moderate-flow perfusions (50 ml/kg/min; n = 16, group III) were accomplished with and without pulsatile flow. In group I, progressive brain tissue acidosis and hypercapnia were recovered with pulsatile assistance. In group II, brain tissue acidosis and hypercapnia were recovered completely with pulsatile assistance but incompletely without it. In group III mild acidosis was eliminated with pulsatile assistance where the pH was significantly higher than in groups I and II, and brain tissue carbon dioxide pressure was significantly lower than in groups I and II with and without pulsatile assistance. Brain tissue hypoxia was severe in group I, slight in group II, but not found in group III. We concluded that a perfusion flow rate will decide the safe period, and a pulsatile assistance will promote brain protection at any flow rate in profoundly hypothermic cardiopulmonary bypass.


[Fluid therapy in cardiac surgery. An update].
The anesthetist has 2 major tools for optimizing haemodynamics in cardiac surgery: Vasoactive drugs and the intravascular volume. It is necessary to identify which patients would benefit from one or the other therapies for a suitable response to treatment. Hemodynamic monitoring with the different existing parameters (pressure, volumetric static, volumetric functional and echocardiography) allows the management of these patients to be optimized. In this article a review is presented on the most recent and relevant publications, and the different tools available to control the management of the fluid therapy in this context, and to suggest a few guidelines for the haemodynamics monitoring of patients submitted to cardiac surgery. A systematic search has been made in PubMed, limiting the results to the publications over the last five years up to February 2012.


The characteristics of men who have sex with men (MSM) using post-exposure prophylaxis for sexual exposure (PEPSE) in the pre-exposure prophylaxis (PrEP) era.
HIV pre-exposure prophylaxis (PrEP) is now available in the UK. However, some men who have sex with men (MSM) continue to use HIV post-exposure prophylaxis following sexual exposure (PEPSE) and are not using PrEP. It is important to characterize MSM having condomless anal sex who are not using PrEP. In a cross-sectional analysis, we compared the characteristics of MSM who used PEPSE in 2021 with MSM using PEPSE in 2017. Overall, 126 MSM used PEPSE in January to June 2017 and 28 MSM used PEPSE in January to June 2021, a 78% decline in PEPSE use. Those MSM using PEPSE in 2021 were significantly younger (27 vs. 35 years, p < 0.01), more likely to identify as black or from another minority ethnic group [29% (8/28) vs. 8% (10/126); p < 0.01], more likely to attend as a result of a group sex encounter [35% (10/28) vs. 16% (10/126); p = 0.03], more likely to attend following sex involving recreational drug use [32% (9/28) vs. 13% (16/126); p = 0.02], and more likely to initiate PEPSE in the emergency department [35% (10/28) vs. 19% (24/126); p = 0.04] compared with MSM attending in 2017. Those MSM using PEPSE in 2021 were significantly less likely to attend follow-up appointments compared with the 2017 cohort [71% (20/28) vs. 87% (110/126); p < 0.05]. Ninety-five per cent of MSM using PEPSE in 2021 were initiated on PrEP at follow-up. Despite PrEP being readily available, some MSM continue using PEPSE and these MSM are significantly more likely to be younger, from black or minority ethnic groups, to engage in group sex involving recreational drugs and to attend the emergency department for PEPSE compared with MSM attending in 2017. Increasing the accessibility of PrEP for this group of MSM is important in order to optimize HIV prevention strategies.


Using Compound Specific Isotope Analysis to decipher the 1,2,3-trichloropropane-to-Allyl chloride transformation by groundwater microbial communities.
1,2,3-trichloropropane (TCP), a refractory contaminant, can be reductive dehalogenated to allyl chloride (AC) by microorganisms, which has been shown a potential in situ bioremediation (ISB) strategy for TCP remediation in groundwater. In practice, however, it is hard to monitor the bioreduction extent because the TCP concentrations may also be decreased by non-biodegradation processes. Compound specific isotope analysis (CSIA) can be promising in determining the extent of degradation by quantifying the isotope enrichment factors (ε) of relevant degradation mechanisms. To date, no CSIA study has been reported on TCP degradation. In this study, a novel TCP-to-AC transformation enrichment culture (dominated by Azotobacter, Parabacteroides, Fusibacter, Hydrogenophaga, Trichococcus Desulfovibrio, etc) in the absence of the already identified TCP anaerobic reductive dechlorinating microorganisms (e.g., Dehalogenimonas) was derived from a chlorinated hydrocarbon-contaminated aquifer. A TCP degradation experiment was carried out by adding yeast extract to produce hydrogen as an electron donor. The TCP-to-AC transformation was found to conform to zero-order conversion kinetics with the rate constant 11 ± 0.34 μmol L-1 d-1 during the main biodegradation stage. The bulk carbon isotope enrichment factor (εbulk) of the TCP-to-AC transformation was firstly evaluated as -5.2 ± 0.1‰. This study for the first time characterized the carbon isotope fractionations during TCP biodegradation using a novel enrichment culture, which would provide a promising tool for the incorporation of ISB for TCP removal in the future.


Clinico-Radiological-Pathologic Profile and Outcomes of Lung Transplant in Post-COVID-19 Phenotype: A Single Center Experience.
Lung transplantation (LTx) has come as hope for select patients with post-COVID acute respiratory distress syndrome (ARDS). It has a different phenotype with unique challenges. We aimed to bring out our experience with and outcomes of LTx for post-COVID ARDS. This study is retrospective case series from a single center in India. All the patients with post-COVID end stage lung disease (ESLD) who underwent bilateral LTx between 1st May 2020 and 30th August 2021 were included. LTx was performed following no improvement with optimal medical management with adequate time provided for recovery. Information relating to demographics, comorbidities, pretransplant status, perioperative parameters, gross and histopathological findings of explanted lungs, posttransplant morbidity, and mortality were analyzed. This study included 23 patients. The median age of the patients in this study was 42 years and 20 participants were men (87%). The mean duration of intensive care unit stay was 15.83 ± 6.61 days. Mortality was observed among 8 participants (34.78%). Mean survival time was 34.54 weeks. Among the 8 patients who expired, the cause of death was sepsis for 6 patients (75.0%), neurologic cerebrovascular accident for 1 patient (12.5%), and cytomegalovirus for 1 patient (12.5%). All the deaths were reported in primary graft dysfunction grade 2 & 3 category. No rejections were observed on first and third month surveillance biopsies. LTx is the definitive option for survival in select patients with severe post-COVID-19-associated ESLD. This study brings out various challenges involved in such phenotypes and also observations in postoperative recovery.


Multifarious aspects of the chaos game representation and its applications in biological sequence analysis.
Chaos game representation (CGR) has been successfully applied in bioinformatics for over 30 years. Since then, many further extensions were announced. Numerical encoding of biological sequences is especially convenient in the visualisation process, free-alignment methods and input preparation for machine learning techniques. The development and applications of CGR have embraced mainly linear nucleotide sequences. However, there were also some attempts to create a representation of proteins. The latter need to be more sophisticated, as arbitrary coordinates for amino acids do not reflect their properties which is crucial during the encoding process. In this paper, the authors summarised various variations of CGRs and their limitations. We began by studying the PROSITE motifs and showed the immense number of amino acid properties employed by different proteins. To this aim, we harnessed the Principal Component Analysis (PCA) and studied the relation between explained variance and the number of features that describe them. It appeared that even after many reductions, about 50 features are non-redundant. This was the reason we introduced an embedding concept from natural language processing which enables adjusting features for a given list of sequences. We presented a simple neural network architecture with one hidden layer and one neuron within it and showed it provides satisfactory results in phylogenetic tree construction in ND5 and SPARC protein cases. To this aim, we transformed CGR representations for all considered sequences using Discrete Fourier Transform (DFT) and applied Unweighted Pair Group Method with Arithmetic Mean (UPGMA) algorithm. Moreover, we indicated some similarities between CGR and Recurrent Neural Networks (RNN). In the end, we attempted to include information about the RNA secondary structure and defined some measures to validate biological significance. We studied their properties and showed on ALMV-3 example its usefulness.


Significance of Fas receptor protein expression in epithelial ovarian cancer.
Fas receptor (FasR) is a cell surface receptor that, when activated, triggers apoptosis. It has been postulated that this receptor may be involved in the clearance of benign ovarian epithelial inclusion cysts (IC). In this study, we test the hypothesis that the expression of FasR changes among IC, cystadenoma (AD), tumors of low malignant potential (LMP), and invasive cancer (cystadenocarcinoma, CA). Formalin-fixed paraffin-embedded sections from 53 oophorectomy specimens representing 26 IC, 17 AD, 17 LMP, and 24 CA were stained using the immunohistochemical avidin-biotin-peroxidase method. We used a mouse antihuman monoclonal antibody Apo-1/Fas (Dako), at 1:5 dilution, after antigen retrieval. The stain was semiquantitatively scored by 3 observers evaluating the intensity of the stain and percentage of positive tumor cells. Statistical analysis was performed using the Wilcoxon rank sum test. Strong (score 6+/7+) and diffuse (>75%) luminal FasR stain was identified in 22 (85%) of 26 IC and 16 (94%) of 17 AD, but only in 6 (35%) of 17 LMP and 1 (4%) of 24 CA. Conversely, weak (score 2+/3+) and focal (<25%) FasR staining was observed in 7 (29%) of 24 CA, but in none of the IC, AD, or LMP. These differences were statistically significant (P < .05). The decreased expression of FasR in malignant ovarian epithelial neoplasms as compared with benign ovarian epithelial lesions suggests that a decreased sensitivity to Fas-mediated apoptosis may be involved in ovarian epithelial carcinogenesis.


Toxicity of the alkylating agent bendamustin.
In acute toxicity studies the maximum tolerated dose (MTD), the LD50 and the LD100 of Bendamustin were determined in rats and mice after i.v. and oral administration. In a subchronic study male rats were given Bendamustin for 28 days at oral dose levels of 5, 10, 20 or 40 mg/kg/day. Chlorambucil was used as a standard at dose levels of 1, 5 and 10 mg/kg/day. Bodyweight gain, food and water intake, hematology, clinical chemistry and histopathology were evaluated. With quantitative differences the main target organs for both compounds were the bone marrow, the kidney, the intestine and the lymphatic system. Additionally, Chlorambucil caused a significant atrophy of the testes and a slight atrophy of the pancreas at a dose of 5 mg/kg/day. In conclusion, the data obtained may be used as a base to evaluate the therapeutic range of Bendamustin compared to Chlorambucil for the oral route.


Augmentation of atrial contribution to left ventricular filling in IDDM subjects as assessed by Doppler echocardiography.
Left ventricular diastolic function was assessed by pulsed Doppler echocardiography in 21 subjects (mean age 48 yr) with insulin-dependent diabetes mellitus (IDDM) and without evidence of ischemic heart disease and in 21 healthy control subjects of similar age and sex distribution. The peak mitral valve flow velocities during the early rapid filling phase (E) and during late atrial filling (A) were measured, and the ratio of these peak flow velocities (E:A) was calculated. E was similar in both groups, but A was higher (P less than .01) in the diabetic group. Thus, E:A was lower (1.19 +/- 0.24 vs. 1.65 +/- 0.67; P less than .01) in the diabetic subjects than in the control subjects. On subgroup analysis, 6 patients with cardiac autonomic neuropathy had lower E:A than the patients with no such disorder (0.99 +/- 0.15 vs. 1.29 +/- 0.25; P less than .05). E:A was not related to the duration of diabetes, presence of retinopathy, HbA1, or blood glucose levels. In conclusion, the atrial contribution to left ventricular filling seems to be augmented in diabetic subjects. This finding indirectly supports the view that left ventricular compliance is already reduced in asymptomatic diabetic subjects.


Survey of anti-human T-cell leukemia virus type I antibody in family members of patients with adult T-cell leukemia.
To evaluate the intrafamilial clustering of HTLV-I, we examined the sera or plasma of 296 healthy family members of patients with adult T-cell leukemia (ATL) for anti-HTLV-I antibodies. Of 296 subjects, 132 (44.6%) had anti-HTLV-I antibodies. Fifty-nine (41.0%) out of 144 males and 73 (48.0%) out of 152 females were seropositive. The positive rates of antibody to HTLV-I increased with age, especially between the 30-39 and the 40-49 age groups. Five out of 6 fathers, 3 out of 4 mothers, 31 (60.8%) out of 51 spouses, 40 (63.5%) out of 63 siblings and 46 (33.8%) out of 136 children of patients with ATL had anti-HTLV-I antibodies. Of 74 children with an ATL father, 14 (18.9%) were seropositive, while 32 (51.6%) out of 63 children with an ATL mother were seropositive. This difference was statistically significant (P less than 0.001). Of those children with an ATL father, 12 (26.1%) out of 46 whose mothers were HTLV-I carriers had antibodies to HTLV-I. In contrast, none of the 13 children whose mothers were not carriers were seropositive. These results supported the hypothesis that the mother-to-child transmission is one of the most important modes of HTLV-I transmission. In wives of male patients with ATL, the positive rate of antibody to HTLV-I was 65.6% (21/32), and in husbands of female patients, it was 52.6% (10/19). The high positive rate of antibody to HTLV-I not only in wives of male patients but also in husbands of female patients suggests that either HTLV-I is more frequently transmitted from wives to their husbands than we had originally expected, or that ATL may develop even in wives who acquire HTLV-I from their husbands after marriage.


Radiologist use of and perceived need for patient data access.
Given the increasing volume of radiological exams, the decreasing frequency of direct communication with the referring provider, and the distribution of patient data over many clinical systems, radiologists often do not have adequate clinical information at the time of interpretation. We have performed a survey of radiologists to determine the need and actual utilization of patient data at the time of image interpretation. Our findings demonstrate that most radiologists want more clinical information when interpreting images and that this information would impact their report, but they are discouraged by the time it takes to access this information. In addition, current mechanisms for monitoring necessary patient follow-up are inadequate.


Incidence of nephrolithiasis in relation to environmental exposure to lead and cadmium in a population study.
Whether environmental exposure to nephrotoxic agents that potentially interfere with calcium homeostasis, such as lead and cadmium, contribute to the incidence of nephrolithiasis needs further clarification. We investigated the relation between nephrolithiasis incidence and environmental lead and cadmium exposure in a general population. In 1302 participants randomly recruited from a Flemish population (50.9% women; mean age, 47.9 years), we obtained baseline measurements (1985-2005) of blood lead (BPb), blood cadmium (BCd), 24-h urinary cadmium (UCd) and covariables. We monitored the incidence of kidney stones until October 6, 2014. We used Cox regression to calculate multivariable-adjusted hazard ratios for nephrolithiasis. At baseline, geometric mean BPb, BCd and UCd was 0.29µmol/L, 9.0nmol/L, and 8.5nmol per 24h, respectively. Over 11.5 years (median), nephrolithiasis occurred in 40 people. Contrasting the low and top tertiles of the distributions, the sex- and age-standardized rates of nephrolithiasis expressed as events per 1000 person-years were 0.68 vs. 3.36 (p=0.0016) for BPb, 1.80 vs. 3.28 (p=0.11) for BCd, and 1.65 vs. 2.95 (p=0.28) for UCd. In continuous analysis, with adjustments applied for sex, age, serum magnesium, and 24-h urinary volume and calcium, the hazard ratios expressing the risk associated with a doubling of the exposure biomarkers were 1.35 (p=0.015) for BPb, 1.13 (p=0.22) for BCd, and 1.23 (p=0.070) for UCd. In conclusion, our results suggest that environmental lead exposure is a risk factor for nephrolithiasis in the general population.


Pathogenesis of extrahepatic bile duct atresia (EHBA): comprehension from a surgical point of view.
The aim of the study is to establish a complete comprehension of the pathogenesis of Biliary Atresia, and to explain both the variable and redundant pathomorphological, as well as, histological findings. The pathomorphological and histological findings in 223 patients with histologically evident EHBA were recorded retrospectively (72 patients) or prospectively (151 patients), according to a projected ascending study. These findings were compared with histological findings in human and rat embryos. 1) The pathomorphological findings recorded in patients with EHBA were also found in stages of normal embryogenesis of the bile duct system in human and rat embryos. 2) Each histological finding in Biliary Atresia corresponds to a finding in an interrupted stage of the normal development in human and rat embryos. 3) The findings in patients and embryos can be explained completely by a disturbed intrinsic epithelium/mesoderm interaction. 4) Some findings in Biliary Atresia cannot be explained easily by the assumption of an extrinsic factor. There is no finding in Biliary Atresia which cannot be completely explained as the result of an intrinsic developmental error, probably due to disturbances or interruption of epithelium/mesoderm interaction during embryogenesis.


Tetrahydrofolate enzyme levels in Acetobacterium woodii and their implication in the synthesis of acetate from CO2.
Acetate synthesis from CO2 by Acetobacterium woodii may occur as in homoacetate-fermenting clostridia, as indicated by high levels of enzymes of the tetrahydrofolate pathway and by pyruvate-dependent formation of acetate from methyl-B12 and methyltetrahydrofolate.


Effects of disease resistance genes on Rhizobium symbiosis in an annual legume.
The evolution of disease resistance in plants may be constrained if genes conferring resistance to pathogens interfere with plant responses toward other, nonpathogenic organisms. To test for such effects, we compared symbiotic nitrogen fixation in Amphicarpaea bracteata plants that differed at a major locus controlling resistance to the pathogen Synchytrium decipiens. Both resistant and susceptible plant genotypes nodulated successfully and grew significantly better in the presence of Rhizobium, although growth enhancement by Rhizobium was altered by different levels of nitrate fertilization. Plants homozygous for disease resistance achieved 2% higher growth than susceptible homozygotes across all treatments, but this difference was not significant. Resistant and susceptible plant genotypes did not differ in the mean number of nodules formed per plant or in nodule diameter. However, there was highly significant variation among replicate families within each disease resistance category for both nodulation characteristics. These results imply that genetic variation exists among A. bracteata plants both for diease resistance and for traits affecting symbiotic nitrogen fixation. However, there were no evident pleiotropic effects of disease resistance genes on the plant-Rhizobium symbiosis.


Characterization of a putative Plasmodium falciparum SAC1 phosphoinositide-phosphatase homologue potentially required for survival during the asexual erythrocytic stages.
Despite marked reductions in morbidity and mortality in the last ten years, malaria still takes a tremendous toll on human populations throughout tropical and sub-tropical regions of the world. The absence of an effective vaccine and resistance to most antimalarial drugs available demonstrate the urgent need for new intervention strategies. Phosphoinositides are a class of lipids with critical roles in numerous processes and their specific subcellular distribution, generated through the action of kinases and phosphatases, define organelle identity in a wide range of eukaryotic cells. Recent studies have highlighted important functions of phosphoinositide kinases in several parts of the Plasmodium lifecycle such as hemoglobin endocytosis and cytokinesis during the erythrocytic stage however, nothing is known with regards to the parasite's putative phosphoinositide phosphatases. We present the identification and initial characterization of a putative homologue of the SAC1 phosphoinositide phosphatase family. Our results show that the protein is expressed throughout the asexual blood stages and that it localises to the endoplasmic reticulum and potentially to the Golgi apparatus. Furthermore, conditional knockdown and knockout studies suggest that a minimal amount of the protein are likely required for survival during the erythrocytic cycle.


A systematic review of the relationship between physical activities in sports or daily life and postural sway in upright stance.
In many sports, maintaining balance is necessary to compete at a high level. Also, in many health problems, balance is impaired. Postural sway (PS) is often used as an indicator of upright balance control, and physical activity (PA) might enhance balance control. However, the relationship between PS and PA has never been systematically reviewed. Our objective was to summarize the evidence regarding the relationship between PS in upright bipedal and unipedal standing and PA. We conducted a literature search in MEDLINE, EmBase, CINAHL, the Cochrane Database, and PEDro, up to March 2012, with no limit on the starting date. Characteristics and methodological aspects of each article were extracted by two reviewers. We used centre of pressure (CoP) velocity, and variables related to the CoP area, to compare studies. A total of 39 articles were reviewed from an initial yield of 2,058. Of these 39 studies, 37 used a comparative design, one was a cohort study, and one was a randomized controlled trial. The main conclusion was that in general, sport practitioners sway less than controls, and high-level athletes sway less than low-level athletes. Additionally, we identified specific effects dependent on the use of vision, sport-specific postures, and frequency and duration of the (sports) activity. PS in unperturbed bipedal stance appears to have limited sensitivity to detect subtle differences between groups of healthy people.


Identification of an amino acid sequence motif in the cytoplasmic domain of the NCAM-140 kDa isoform essential for its neuritogenic activity.
The functions of the extracellular domains of neural cell adhesion molecule (NCAM) have been studied extensively, whereas the roles of the cytoplasmic domains of the transmembrane forms of NCAM are less elucidated. We investigated the importance of the cytoplasmic domain of the 140-kDa NCAM isoform (cytNCAM-140) and of the 180-kDa NCAM isoform (cytNCAM-180) in NCAM-induced neurite extension by estimating NCAM-dependent neurite outgrowth from PC12-E2 cells grown in coculture with NCAM-negative or NCAM-positive fibroblasts. PC12-E2 cells were transiently transfected with expression plasmids encoding cytNCAM-140, cytNCAM-180, the constitutively active form of the mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase kinase (MEK2), and the enhanced variant of the green fluorescent protein (EGFP). EGFP expression was used for identification of transfected cells. We found that expression of cytNCAM-180 had no effect on NCAM-stimulated neuritogenesis, whereas expression of cytNCAM-140 strongly inhibited this process. However, if MEK2 was expressed concomitantly with cytNCAM-140, neurite outgrowth was rescued, indicating that cytNCAM-140 is involved in signaling via the Ras-MAP kinase pathway. PC12-E2 cells were subsequently transiently transfected with constructs encoding a series of fragments of cytNCAM-140 and various full-length cytNCAM-140 mutants, and the residues Thr-Glu-Val-Lys-Thr (839-843) were identified as essential in NCAM-stimulated neuritogenesis. The combined substitution of Glu(840) and Lys(842) with Ala abrogated the effect of the construct, assigning a critical role to these two residues.