Contribution to the knowledge of the andean stonefly genus Claudioperla illies, with description of new apterous and micropterous species (Plecoptera: Gripopterygidae).
The genus Claudioperla (Plecoptera: Gripopterygidae), which has been reported from Chile and Argentina to Colombia, was until now monospecific. The study of adults from various localities of the Bolivian Altiplano has resulted in the discovery of four distinct species. Three are new and described: Claudioperla rosalesi n. sp., Claudioperla moyai n. sp., and Claudioperla ruhieri n. sp. The fourth, Claudioperla tigrina (Klapálek), presents morphological variations with previous descriptions that are exposed and discussed. One of the new species, C. ruhieri, is apterous. The male of C. moyai is micropterous. Among South American stoneflies, they are the first cases of aptery and microptery reported outside of Patagonia. Adapted to extreme conditions of temperature and altitude, C. moyai and C. ruhieri are particularly threatened by the recent evolution of Bolivian glaciers.


Drug Treatment of Heart Failure in Children: Focus on Recent Recommendations from the ISHLT Guidelines for the Management of Pediatric Heart Failure.
The International Society of Heart and Lung Transplantation (ISHLT) recently updated consensus pediatric heart failure guidelines from those published in 2004 with an aim to provide a practical evidence-based resource whilst recognizing the influence of adult heart failure practice. The new guidelines were formed from published evidence for heart failure management and used parallels with adult literature where pediatric evidence was lacking. This is a summary of the pharmacological therapies discussed in the new 2014 guidelines, emphasizing changes from the previous recommendations with regards to treatment of chronic heart failure with reduced ejection fraction, chronic heart failure with preserved ejection fraction, and acute decompensated heart failure. Each recommendation is classified according to strength and level of evidence. We also discuss future perspectives in the pharmacological treatment of heart failure. The 2014 ISHLT guidelines have evolved considerably from those published in 2004 with extensive information surrounding the underlying pathophysiology, investigations and recommended treatment. The new guidelines contain a modest amount of new pediatric data on pharmacological therapies and extrapolate adult data when appropriate. It is likely that most new recommendations for pediatric heart failure will continue to be based on therapies of proven benefit in adult heart failure studies.


Photosynthetic CO2 uptake in seedlings of two tropical tree species exposed to oscillating elevated concentrations of CO2.
Do short-term fluctuations in CO2 concentrations at elevated CO2 levels affect net CO2 uptake rates of plants? When exposed to 600 microl CO2 l(-1), net CO2 uptake rates in shoots or leaves of seedlings of two tropical C3 tree species, teak (Tectona grandis L. f.) and barrigon [Pseudobombax septenatum (Jacq.) Dug.], increased by 28 and 52% respectively. In the presence of oscillations with half-cycles of 20 s, amplitude of ca. 170 microl CO2 l(-1) and mean of 600 microl CO2 l(-1), the stimulation in net CO2 uptake by the two species was reduced to 19 and 36%, respectively, i.e. the CO2 stimulation in photosynthesis associated with a change in exposure from 370 to 600 microl CO2 l(-1) was reduced by a third in both species. Similar reductions in CO2-stimulated net CO2 uptake were observed in T. grandis exposed to 40-s oscillations. Rates of CO2 efflux in the dark by whole shoots of T. grandis decreased by 4.8% upon exposure of plants grown at 370 microl CO2 l(-1) to 600 microl CO2 l(-1). The potential implications of the observations on CO2 oscillations and dark respiration are discussed in the context of free-air CO2 enrichment (FACE) systems in which short-term fluctuations of CO2 concentration are a common feature.


Oil gavage effects on tumor incidence in the National Toxicology Program's 2-year carcinogenesis bioassay.
Numerous studies have reported a positive relationship between dietary fat and chemically induced tumor incidence. The results of the 2-year carcinogenesis bioassay used by the National Toxicology Program (NTP), in which test compounds were administered to rodents by corn oil gavage, provide an opportunity to compare the effects of fat on chemically induced and naturally occurring tumors. Oil gavage increases the fat intake about threefold, equivalent to a 15% fat diet. Only 2 oil gavage effects were observed in the NTP carcinogenesis bioassay. First, pancreatic hyperplasia was increased from 2.6% in untreated controls to 12.6% in male Fischer 344/N vehicle control rats; however, this sporadic and weak effect did not influence the outcome of carcinogenesis bioassays. Second, leukemia/lymphoma incidence was about 50% lower in male vehicle controls than in the untreated control rats; in contrast, this strong effect increased survival by 8-10%. Therefore, oil gavage had an apparent protective effect in male Fischer 344/N rats. The absence of growth enhancement for the relatively high background level of tumors in oil gavage-treated rats was remarkable and is inconsistent with observations in rat mammary tumor model studies. Because it is impossible to extrapolate the enhancing effect of a high fat diet on tumor growth from rodent tumor models to the NTP carcinogenesis bioassay, great caution should be used in extrapolating from rodent tumor model studies to the human situation.


Video-assisted thoracoscopic pericardial fenestration for tuberculous pericardial effusion.
A 72-year-old woman was admitted with chest discomfort and general fatigue. She was diagnosed as having cardiac tamponade with massive pericardial effusion. Percutaneous pericardiocentesis yielded bloody effusion. Tuberculous pericarditis was suspected owing to the adenosine deaminase level in this fluid. Video-assisted thoracoscopic pericardial fenestration (VATSPF) was performed for the diagnosis and treatment. Polymerase chain reaction detected Mycobacterium tuberculosis DNA in the pericardial tissues, confirming the diagnosis of tuberculous pericarditis. She received a combination of three-kind medication and anti-tuberculous regimen, and a follow-up check up for more than 2 years, exhibiting a good postoperative course. We conclude that VATSPF can be a useful procedure not only for diagnosis but for release of tuberculous pericarditis with cardiac tamponade and for prophylaxis of constrictive pericarditis.


Neural correlates of the energetic value of food during visual processing and response inhibition.
Previous research showed that human brain regions involved in reward and cognitive control are responsive to visually presented food stimuli, in particular high-energy foods. However, it is still to be determined whether the preference towards high-energy foods depends on their higher energy density (kcal/gram), or is based on the difference in energy content of the food items (total amount of kcal). Here we report the results of an fMRI study in which normal-weight healthy participants processed food images during a one-back task or were required to inhibit their response towards food stimuli during a Go/No-Go task. High-energy density (HD) and low-energy density (LD) foods were matched for energy content displayed. Food-related kitchen objects (OBJ) were used as control stimuli. The lateral occipital complex and the orbitofrontal cortex showed consistent higher activity in response to HD than LD foods, both during visual processing and response inhibition. This result suggests that images of HD foods, even when the amount of food shown is not associated with a higher energy content, elicit preferential visual processing - possibly involving attentional processes - and trigger a response from the reward system. We conclude that the human brain is able to distinguish food energy densities of food items during both active visual processing and response inhibition.


Effects of sevoflurane on lung epithelial permeability in experimental models of acute respiratory distress syndrome.
Preclinical studies in acute respiratory distress syndrome (ARDS) have suggested that inhaled sevoflurane may have lung-protective effects and clinical trials are ongoing to assess its impact on major clinical outcomes in patients with ARDS. However, the underlying mechanisms of these potential benefits are largely unknown. This investigation focused on the effects of sevoflurane on lung permeability changes after sterile injury and the possible associated mechanisms. To investigate whether sevoflurane could decrease lung alveolar epithelial permeability through the Ras homolog family member A (RhoA)/phospho-Myosin Light Chain 2 (Ser19) (pMLC)/filamentous (F)-actin pathway and whether the receptor for advanced glycation end-products (RAGE) may mediate these effects. Lung permeability was assessed in RAGE-/- and littermate wild-type C57BL/6JRj mice on days 0, 1, 2, and 4 after acid injury, alone or followed by exposure at 1% sevoflurane. Cell permeability of mouse lung epithelial cells was assessed after treatment with cytomix (a mixture of TNFɑ, IL-1β, and IFNγ) and/or RAGE antagonist peptide (RAP), alone or followed by exposure at 1% sevoflurane. Levels of zonula occludens-1, E-cadherin, and pMLC were quantified, along with F-actin immunostaining, in both models. RhoA activity was assessed in vitro. In mice after acid injury, sevoflurane was associated with better arterial oxygenation, decreased alveolar inflammation and histological damage, and non-significantly attenuated the increase in lung permeability. Preserved protein expression of zonula occludens-1 and less increase of pMLC and actin cytoskeletal rearrangement were observed in injured mice treated with sevoflurane. In vitro, sevoflurane markedly decreased electrical resistance and cytokine release of MLE-12 cells, which was associated with higher protein expression of zonula occludens-1. Improved oxygenation levels and attenuated increase in lung permeability and inflammatory response were observed in RAGE-/- mice compared to wild-type mice, but RAGE deletion did not influence the effects of sevoflurane on permeability indices after injury. However, the beneficial effect of sevoflurane previously observed in wild-type mice on day 1 after injury in terms of higher PaO2/FiO2 and decreased alveolar levels of cytokines was not found in RAGE-/- mice. In vitro, RAP alleviated some of the beneficial effects of sevoflurane on electrical resistance and cytoskeletal rearrangement, which was associated with decreased cytomix-induced RhoA activity. Sevoflurane decreased injury and restored epithelial barrier function in two in vivo and in vitro models of sterile lung injury, which was associated with increased expression of junction proteins and decreased actin cytoskeletal rearrangement. In vitro findings suggest that sevoflurane may decrease lung epithelial permeability through the RhoA/pMLC/F-actin pathway.


Pre-operative and post-operative ultrasound evaluation of Budd Chiari syndrome due to coarctation of the inferior vena cava.
Coarctation of the inferior vena cava (IVC) is being increasingly recognised as a congenital and operable cause for chronic Budd Chiari syndrome. It is necessary to distinguish this entity from other causes of Budd Chiari syndrome because of a more favourable outcome after surgery. Early diagnosis would result in surgical intervention before irreversible liver damage and also possibly avoid the onset of hepatocellular carcinoma. Real time ultrasound has proved valuable in pre-operative diagnosis in nine patients with coarctation of the IVC. It has also been found useful to confirm patency of dorsal cavo-atrial bypass using polytetrafluoroethylene grafts in five patients and isthmusplasty of the IVC in one patient. Ultrasound is recommended for routine screening of high risk population.


Fatigue and Recovery Time Course After Female Soccer Matches: A Systematic Review And Meta-analysis.
This study aimed to analyze the extent of fatigue responses after female soccer matches and the ensuing recovery time course of performance, physiological, and perceptual responses. Three databases (PubMed, Web of Science, and SPORTDiscus) were searched in October 2020 and updated in November 2021. Studies were included when participants were female soccer players, regardless of their ability level. Further, the intervention was an official soccer match with performance, physiological, or perceptual parameters collected pre- and post-match (immediately, 12 h, 24 h, 48 h, or 72 h-post). A total of 26 studies (n = 465 players) were included for meta-analysis. Most performance parameters showed some immediate post-match reduction (effect size [ES] = - 0.72 to - 1.80), apart from countermovement jump (CMJ; ES = - 0.04). Reduced CMJ performance occurred at 12 h (ES = - 0.38) and 24 h (ES = - 0.42) and sprint at 48 h post-match (ES = - 0.75). Inflammatory and immunological parameters responded acutely with moderate-to-large increases (ES = 0.58-2.75) immediately post-match. Creatine kinase and lactate dehydrogenase alterations persisted at 72 h post-match (ES = 3.79 and 7.46, respectively). Small-to-moderate effects were observed for increased cortisol (ES = 0.75) and reduced testosterone/cortisol ratio (ES = -0.47) immediately post-match, while negligible to small effects existed for testosterone (ES = 0.14) and estradiol (ES = 0.34). Large effects were observed for perceptual variables, with increased fatigue (ES = 1.79) and reduced vigor (ES = - 0.97) at 12 h post-match, while muscle soreness was increased immediately post (ES = 1.63) and at 24 h post-match (ES = 1.00). Acute fatigue exists following female soccer matches, and the performance, physiological, and perceptual parameters showed distinctive recovery timelines. Importantly, physical performance was recovered at 72 h post-match, whereas muscle damage markers were still increased at this time point. These timelines should be considered when planning training and match schedules. However, some caution should be advised given the small number of studies available on this population. The protocol for this systematic review was pre-registered on the International Prospective Register of Systematic Reviews (PROSPERO, Registration Number: CRD42021237857).


Complementary and alternative medicine use among Mauritian women.
To assess CAM usage among women in Mauritius. Cross-sectional survey with a nationally-representative sample (n = 384). Quantitative indices included informant-consensus factor, use-value, fidelity-value and use-mentions were calculated. Thirteen therapies were identified and currently are used to treat or manage 26 ailments. These were phytotherapy (30%); yoga (13%); deep-breathing (12%); massage therapy (11%); ayurvedic medicine (8%); meditation (6%); zootherapy (6%); homeopathy (5%); exercise (3%) and reiki (3%). The most prevalent CAM was phytotherapy. Based on the quantitative ethnobotanical indices, plants commonly used were Acalphya spp., (Copper leaf), Curcuma longa (Tumeric), Cymbopogon citratus (Lemon grass), Erythroxylum hypericifolium (Bois ronde), Lens culinaris (Lentil) and Mentha piperita (Mentha). Interestingly, the present study is the first attempt to record CAM management of women's health in Mauritius. This study can be considered as a primary information resource recording the current use of CAM by women in Mauritius.


Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model.
The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model. One hundred female nude BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 of these mice were injected intraperitoneally with ~2.7 MBq of (213)Bi-MX35 (n=20) or ~0.44 MBq of (211)At-MX35 (n=20). Four weeks after inoculation, 40 new OVCAR-3-inoculated mice were injected with the same activities of (213)Bi-MX35 (n=20) or (211)At-MX35 (n=20). Presence of tumors and ascites was investigated 8 weeks after therapy. Biodistributions of intraperitoneally injected (213)Bi-MX35 and (211)At-MX35 were studied in tumor-free nude BALB/c (nu/nu) mice (n=16). The animals injected with (213)Bi-MX35 or (211)At-MX35 2 weeks after cell inoculation had tumor-free fractions (TFFs) of 0.60 and 0.90, respectively. The untreated reference group had a TFF of 0.20. The groups treated with (213)Bi-MX35 or (211)At-MX35 4 weeks after inoculation both had TFFs of 0.25, and the reference animals all exhibited evidence of disease. The biodistributions of (213)Bi-MX35 and (211)At-MX35 were very similar to each other and displayed no alarming activity levels in the investigated organs. Micrometastatic growth of an ovarian cancer cell line was reduced in nude mice after treatment with (213)Bi-MX35or (211)At-MX35. Treatment with (211)At-MX35 provided a non-significantly better result for the chosen activity levels. The radiolabeled MX35 did not accumulate to a high extent in the investigated organs. No considerable signs of toxicity were observed.


Construction and validation of a prognostic model for colon adenocarcinoma based on bile acid metabolism-related genes.
Colon adenocarcinoma (COAD), one of the common clinical cancers, exhibits high morbidity and mortality, and its pathogenesis and treatment are still underdeveloped. Numerous studies have demonstrated the involvement of bile acids in tumour development, while the potential role of their metabolism in the tumor microenvironment (TME) has not been explored. A collection of 481 genes related to bile acid metabolism were obtained, and The Cancer Genome Atlas-based COAD risk model was developed using the least absolute shrinkage selection operator (LASSO) regression analysis. The Gene Expression Omnibus dataset was used to validate the results. The predictive performance of the model was verified using column line plots, principal component analysis and receiver operating characteristic curves. Then, we analysed the differences between the high- and low-risk groups from training set based on clinical characteristics, immune cell infiltration, immune-related functions, chemotherapeutic drug sensitivity and immunotherapy efficacy. Additionally, we constructed a protein-protein interaction network to screen for target genes, which were further investigated in terms of differential immune cell distribution. A total of 234 bile acids-related differentially expressed genes were obtained between normal and tumour colon tissues. Among them, 111 genes were upregulated and 123 genes were down-regulated in the tumour samples. Relying on the LASSO logistic regression algorithm, we constructed a model of bile acid risk score, comprising 12 genes: CPT2, SLCO1A2, CD36, ACOX1, CDKN2A, HADH, GABRD, LEP, TIMP1, MAT1A, SLC6A15 and PPARGC1A. This model was validated in the GEO-COAD set. Age and risk score were observed to be independent prognostic factors in patients with COAD. Genes related to bile acid metabolism in COAD were closely related to bile secretion, intestinal transport, steroid and fatty acid metabolism. Furthermore, the high-risk group was more sensitive to Oxaliplatin than the low-risk group. Finally, the three target genes screened were closely associated with immune cells. We identified a set of 12 genes (CPT2, SLCO1A2, CD36, ACOX1, CDKN2A, HADH, GABRD, LEP, TIMP1, MAT1A, SLC6A15, and PPARGC1A) associated with bile acid metabolism and developed a bile acid risk score model using LASSO regression analysis. The model demonstrated good predictive performance and was validated using an independent dataset. Our findings revealed that the bile acid risk score were independent prognostic factors in COAD patients.


High-Energy Batteries: Beyond Lithium-Ion and Their Long Road to Commercialisation.
Rechargeable batteries of high energy density and overall performance are becoming a critically important technology in the rapidly changing society of the twenty-first century. While lithium-ion batteries have so far been the dominant choice, numerous emerging applications call for higher capacity, better safety and lower costs while maintaining sufficient cyclability. The design space for potentially better alternatives is extremely large, with numerous new chemistries and architectures being simultaneously explored. These include other insertion ions (e.g. sodium and numerous multivalent ions), conversion electrode materials (e.g. silicon, metallic anodes, halides and chalcogens) and aqueous and solid electrolytes. However, each of these potential "beyond lithium-ion" alternatives faces numerous challenges that often lead to very poor cyclability, especially at the commercial cell level, while lithium-ion batteries continue to improve in performance and decrease in cost. This review examines fundamental principles to rationalise these numerous developments, and in each case, a brief overview is given on the advantages, advances, remaining challenges preventing cell-level implementation and the state-of-the-art of the solutions to these challenges. Finally, research and development results obtained in academia are compared to emerging commercial examples, as a commentary on the current and near-future viability of these "beyond lithium-ion" alternatives.


Binding of chimeric metal-binding green fluorescent protein to lipid monolayer.
Membrane-based bioanalytical devices for metal determination using green fluorescent protein as the sensor molecule may be a useful future biomimetic material. However, in order to develop such a device, it is necessary first to understand the interaction of the protein with lipid membranes. Thus we have investigated the interaction between chimeric cadmium-binding green fluorescent proteins (CdBPGFPs) and lipid monolayers, using a film-balance technique complemented with epifluorescence microscopy. The binding avidity was monitored from the surface pressure vs. area isotherms or from the measured increase in the lateral pressure upon injection of the chimeric CdBPGFPs beneath the lipid monolayer. Increased fluidization as well as expansion of the surface area were shown to depend on the concentration of the CdBPGFPs. The kinetics of the protein-induced increase in lateral pressure was found to be biphasic. The chimeric CdBPGFPs possessed high affinity to the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayer with a dissociation constant of Kd = 10(-8)M. Epifluorescence measurements showed that this affinity is due to the presence of the Cd-binding peptide, which caused the GFP to incorporate preferentially to the liquid phase and defect part of the rigid domain at low interfacial pressure. At high compression, the Cd-binding peptide could neither incorporate nor remain in the lipid core. However, specific orientation of the chimeric CdBPGFPs underneath the air-water interface was achieved, even under high surface pressure, when the proteins were applied to the metal-chelating lipid-containing surfaces. This specific binding could be controlled reversibly by the addition of metal ions or metal chelator. The reversible binding of the chimeric CdBPGFPs to metal-chelating lipids provided a potential approach for immobilization, orientation and lateral organization of a protein at the membrane interface. Furthermore, the feasibility of applying the chelator lipids for the codetermination of metal ions with specific ligands was also revealed. Our finding clearly demonstrates that a strong interaction, particularly with fluid lipid domains, could potentially be used for sensor development in the future.


A comparison of multiple sclerosis disease activity after discontinuation of fingolimod and placebo.
Cases of higher-than-expected disease activity have been reported following fingolimod discontinuation. The objective of this paper is to assess the risk of substantially higher-than-expected disease activity post-study drug discontinuation (SDD) at the individual patient level using data from the Phase III, placebo-controlled FREEDOMS and FREEDOMS II trials. Baseline gadolinium-enhancing T1-lesion volumes were used to statistically model the expected level of MRI disease activity post-SDD. Patients exceeding this level were classed as "MRI outliers." Patients with an unusually high increase in Expanded Disability Status Scale score, hospitalization for relapse, severe relapse, or relapse with incomplete recovery post-SDD were classed as "clinical outliers." In FREEDOMS, the number of MRI outliers post-SDD was 2/69 (2.9%), 1/65 (1.5%) and 7/83 (8.4%) for the placebo, fingolimod 0.5 mg, and fingolimod 1.25 mg groups, respectively. In FREEDOMS II, the corresponding numbers were 4/72 (5.6%), 6/79 (7.6%) and 3/73 (4.1%). The number of clinical outliers across both trials was low. No consistent evidence of placebo vs fingolimod, dose-related or inter-trial patterns was discernable. The low number of clinical and MRI outliers and lack of any discernible pattern within and between trials, including between placebo and fingolimod, argues against a systematic risk of higher-than-expected recurrence of disease activity following discontinuation of fingolimod.


Carotenoid glucosides and menaquinones from the gliding bacterium Herpetosiphon giganteus Hp a2.
The gliding bacterium Herpetosiphon giganteus Hp a2 was shown to contain gamma-carotene, one monoglucosyloxy and two new diglucosyloxy carotenoids with a x-O-acyldiglucosyloxy carotenoid as main component. Flexirubin-like pigments could not be detected in this organism. As in the Myxobacterales and Cytophagales (Kleinig et al., 1974) menaquinones (MK-6 and MK-7) were found to be the only isoprenoid quinones present in Herpetosiphon. The chemosystematic implications of these findings are briefly discussed.


The glycosaminoglycans of normal and hyperplastic prostate.
A study has been made of the glycosaminoglycans (GAG) of the fetus, normal adult, and benign hyperplastic prostate. In the adult normal prostate dermatan sulphate (DS) is the predominant GAG. The central zone has a slightly higher chondroitin sulphate (Ch AC) content than the peripheral zone. Fetal prostates (22-27 weeks gestation) contain no heparan sulphate (HS). Benign prostatic hyperplasia (BPH) has an increased content of Ch AC. On separation of BPH stroma and epithelium, the epithelial fraction contains only Ch AC and DS. HS and hyaluronic acid (HA) are confined to the prostatic stroma.


Two new species of Elachistocleis Parker, 1927 (Anura: Microhylidae: Gastrophryninae) from Colombia.
The genus Elachistocleis consists of small to medium size species of Neotropical microhylids. It is the second largest genus of New World microhylids and an important component of the anuran diversity in the Neotropical region. Herein, based on morphological, acoustical, and molecular evidence, we describe two new species and their advertisement calls. The new species have reticulated venter and inhabit the Orinoco basin of Colombia.


Apoptosis in the rat lens after in vivo threshold dose ultraviolet irradiation.
To investigate DNA damage in the rat lens after in vivo close-to-threshold exposure to ultraviolet radiation (UVR). Sprague-Dawley rats received 5 kJ/m2 UVR (lambdaMAX = 300 nm, lambda0.5 = 10 nm) unilaterally for 15 minutes. Animals were killed at 1, 6, and 24 hours and at 1 week after exposure. DNA-strand breaks were investigated in sagittal paraffin sections using the TdT-dUTP terminal nick-end labeling (TUNEL) technique and propidium iodide for counterstaining. Other lenses were prepared for transmission electron microscopy (TEM). TUNEL-positive nuclei were found at only 24 hours after UVR exposure. About one tenth of the epithelial cell nuclei were TUNEL positive, and affected cells were scattered over the entire epithelium. No TUNEL-positive cells were found at 1 or 6 hours or at 1 week after UVR exposure or in the nonexposed lenses. TEM verified the occurrence of programmed cell death and showed the breakdown of the apoptotic cells by adjacent cells. No signs of necrosis were found. Threshold-dose UVR induces programmed cell death that peaks 24 hours after exposure and involves the entire epithelium. Dead cells are removed from the epithelium by phagocytosis.


Influence of tumor thrombus location on the outcome of external-beam radiation therapy in advanced hepatocellular carcinoma with macrovascular invasion.
The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher α-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.


Isolation and phosphorylation of the Bacillus subtilis degS and degU gene products.
The Bacillus subtilis sacU locus consists of two genes, degS and degU, which positively regulate the synthesis of several extracellular enzymes including the neutral and alkaline proteases. Both the DegS and DegU proteins have been purified from overproducing Escherichia coli strains harboring degS or degU gene-carrying plasmids, and the following results were obtained. DegS was autophosphorylated in the presence of [gamma-32P]ATP, and transferred the phosphoryl group to DegU. The transfer reaction was rapid in contrast to the autophosphorylation reaction. The phosphoryl groups incorporated into DegS and DegU were released at their own specific rates, the latter being twice faster than the former. The linkage between DegS and the phosphoryl moiety was unstable at acidic pH, whereas reverse was the case for the linkage between DegU and its phosphoryl group, suggesting that His and Asp are involved in the formation of DegS-phosphate and DegU-phosphate, respectively. Deletion of degS resulted in the reduced expression of the exocellular alkaline protease gene, aprE. These results suggest that phosphorylation of DegS by its own kinase activity and subsequent transfer of the phosphoryl group to DegU play a role in the activation of the aprE gene.


Incomplete degradation of linear alkylbenzene sulfonate surfactants in Brazilian surface waters and pursuit of their polar metabolites in drinking waters.
In Brazil more than 90% of the population are not connected to municipal wastewater treatment plants. As a consequence, surface waters receive continuously considerable amounts of untreated domestic sewage containing surfactants as a major constituent. Such polluted waters gave rise to special interest if they are used as a source for the production of drinking water. In this work, the river Rio Macacu (State Rio de Janeiro, Brazil) was monitored for the occurrence of the most widely used anionic surfactant linear alkylbenzene sulfonate (LAS) together with its main degradative product, sulfophenyl carboxylates (SPC). In order to pursue the fate of both compounds after emission into the river, samples were collected at several locations along the river bank, and analyzed applying liquid chromatography-mass spectrometry after enrichment by solid-phase extraction. The LAS concentrations ranged between 14 and 155 microg l(-1) and the levels of their metabolic intermediates were found from 1.2 to 14 microg l(-1). The self-purification capacity of the water was impressively demonstrated in the upper course of the river downstream of a town considered as one major discharge point, whereas in the lower course the relative constant concentrations of both analytes were detected which was explained with an overall increasing level of pollution. Furthermore, a series of drinking water samples from Niterói and São Gonçalo, supplied by the same waterworks treating surface waters from the Rio Macacu, were taken during two sampling periods and examined for the presence of the strongly polar SPC which is suspected of by-passing the purification processes. The levels detected in the drinking water ranged between 1.6 and 3.3 microg l(-1). For the analyses of drinking and surface waters the peak pattern of a selected SPC homologue composed by several positional isomers served as an indicator to describe the progression of SPC degradation occurred in the river and could be used to distinguish drinking waters of different origins.


Effect of HDL-raising drugs on cardiovascular outcomes: a systematic review and meta-regression.
Substantial residual cardiovascular risk remains after optimal LDL lowering in patients of established coronary artery disease. A number of therapeutic agents that raise HDL-C have been tested in clinical trials to cover this risk. However, the results of clinical trials are conflicting. To determine whether raising HDL-C with pharmacologic therapies translates into beneficial cardiovascular outcomes and to find out if this change was proportional to the percentage change in HDL levels. Electronic and printed sources were searched up to August, 2013 for randomised controlled trials (RCTs) using at least one of the HDL raising therapies for secondary prevention of adverse cardiovascular events over optimal LDL levels. Data from eligible studies were pooled for the following outcomes: all cause mortality, cardiovascular disease mortality, hospitalization for unstable angina, non-fatal myocardial infarction, coronary revascularization and ischemic stroke. Mantel Haensnzel fixed effect model was used preferentially. Meta-regression was done to see the correlation of change in HDL levels and cardiovascular outcomes. Pooled odds ratios with 95% confidence interval (CI) were calculated. A total of 12 RCTs including 26,858 patients with follow up period ranging from 1 year to 6.2 years were included in the analysis. Pooled analysis showed no significant difference in all-cause mortality between the treatment and control group (Pooled OR 1.07; 95% CI 0.98-1.16, p = 0.15). No significant difference was found between the groups for any of the secondary outcomes. Similarly no correlation was seen between percentage change in HDL and adverse cardiovascular outcomes on meta-regression analysis. Increasing HDL levels via pharmacological manipulation beyond optimal lipid lowering therapy for secondary prevention is not beneficial.


Accumbal opioid receptors modulate cue competition in one-trial overshadowing.
The contribution of opioid receptors in the nucleus accumbens to contextual and auditory fear conditioning was examined. Impairment in contextual fear conditioning was found when training occurred under accumbal infusions of the opioid receptor agonist morphine in a dose-dependent and receptor specific fashion, only when shock onset coincided with auditory stimulus offset. Contextual fear conditioning was spared, however when the delivery of shock was not signalled by an auditory stimulus, the auditory stimulus was of low intensity (70dB), or an interval (10s or 30s) was interpolated between auditory stimulus offset and shock onset. These results provide evidence that opioid receptors in the nucleus accumbens regulate competition between contextual and discrete auditory stimuli for association formation.


4,977-bp human mitochondrial DNA deletion is associated with asthenozoospermic infertility in Jordan.
Male infertility is commonly associated with sperm abnormalities including asthenozoospermia. The molecular basis of asthenozoospermia was linked to mitochondrial DNA (mtDNA) mutations. The 4,977-bp human mtDNA deletion is one of the most common mutations of spermatozoa and results in loss of about 33% of the mitochondrial genome. In this preliminary study, we aimed to investigate the presence of 4,977-bp mtDNA deletion in asthenozoospermic infertile men in Jordan. Semen specimens of 120 asthenozoospermic infertile men and 80 normozoospermic individuals were collected at the in vitro fertilization unit. MtDNA was extracted after the enrichment of spermatozoa; then, polymerase chain reaction was performed using 4,977-bp mtDNA deletion-specific primers. The deletion of 4,977-bp mtDNA was detected in 79.2% of asthenozoospermic patients compared to 10% in normozoospermic controls. The results showed a significant association between the presence of 4,977-bp mtDNA deletion and the asthenozoospermia and infertility (OR = 34.2000, 95% CI = 14.57-80.26, p-value < .001). In conclusion, our findings underscored a strong association between 4,977-bp mtDNA deletion and asthenozoospermia in the Jordanian population.


The Acoustic and Perceptual Correlates of Gender in Children's Voices.
This study investigates the perceptual and acoustic correlates of gender in prepubertal voices. The study is part of a longitudinal project analyzing recordings of circa 60 German primary school children from the first to fourth grades (6- to 10-year-olds). Spontaneous and content-controlled audio recordings were made of 62 first-grade children (29 girls, 33 boys; age: 6- to 7-year-olds) from two German primary schools. Information on gender conformity was also recorded. A total of 167 listeners judged the gender of the voices on a 7-point scale. The results of the listening experiments and gender conformity ratings were related to a range of typical acoustic parameters. Measures of self-reported gender conformity differ significantly between the boys and the girls. Sixteen of the 62 children show unambiguous gender attributions in the listening experiment. A hierarchical cluster analysis including gender perception, gender conformity, and acoustic parameters shows four different types of speakers. Two multiple regression models revealed a significant main effect of fundamental frequency on the gender perception ratings of the listening experiment across and within gender. Significant correlations were found between the center of gravity and skewness of the sibilants and gender conformity, especially for the male speakers. Fundamental frequency plays an important role in influencing perceptual judgments, whereas sibilant spectra are correlated with gender conformity. In further listening experiments, we will examine in more detail the role of individual acoustic parameters and analyze how the vocal expression of gender and gender conformity in individual children develops before reaching puberty.


Resistance is futile? Mucosal immune mechanisms in the context of microbial ecology and evolution.
In the beginning it was simple: we injected a protein antigen and studied the immune responses against the purified protein. This elegant toolbox uncovered thousands of mechanisms via which immune cells are activated. However, when we consider immune responses against real infectious threats, this elegant simplification misses half of the story: the infectious agents are typically evolving orders-of-magnitude faster than we are. Nowhere is this more pronounced than in the mammalian large intestine. A bacterium representing only 0.1% of the human gut microbiota will have a population size of 109 clones, each actively replicating. Moreover, the evolutionary pressure from other microbes is at least as profound as direct effects of the immune system. Therefore, to really understand intestinal immune mechanisms, we need to understand both the host response and how rapid microbial evolution alters the apparent outcome of the response. In this review we use the examples of intestinal inflammation and secretory immunoglobulin A (SIgA) to highlight what is already known (Fig. 1). Further, we will explore how these interactions can inform immunotherapy and prophylaxis. This has major implications for how we design effective mucosal vaccines against increasingly drug-resistant bacterial pathogens Fig. 1 THE IMMUNE RESPONSE SHAPES THE FITNESS LANDSCAPE IN THE GASTRO-INTESTINAL TRACT.: The red arrows depict possible evolutionary paths of a novel colonizer along adaptive peaks in the intestinal fitness landscapes that change with the status of the host immune system. The flat surfaces represent the non-null fitness baselines (values x or y) at which a bacterium can establish at minimum carrying capacity. a In the healthy gut, metabolic competence, resistance to aggressions by competitors and predators, swift adaptation to rapid fluctuations as well as surviving acidic pH and the flow of the intestinal content, represent potent selective pressures and as many opportunities for bacteria to increase fitness by phenotypic or genetic variations. b When pathogens trigger acute inflammation, bacteria must adapt to iron starvation, killing by immune cells and antimicrobial peptides, and oxidative stress, while new metabolic opportunities emerge. c When high-affinity SIgA are produced against a bacterium, e.g., after oral vaccination, escape of SIgA by altering or losing surface epitopes becomes crucial for maximum fitness. However, escaping polyvalent SIgA responses after vaccination with "evolutionary trap" vaccines leads to evolutionary trade-offs: A fitness maximum is reached in the vaccinated host gut that represents a major disadvantage for transmission into naïve hosts (fitness diminished below x) (d).


Sterigmatocystin - incidence, fate and production byA versicolor in ras cheese.
Sterigmatocystin (STG) is a toxic metabolite produced by severalAspergillus species. Because of its toxic and carcinogenic properties the occurrence of STG in food is considered to represent a potential hazard to man. The present study was designed to investigate following points: 1 A survey of STG incidence in Ras cheese on local markets. Ras cheese samples were collected from Cairo, Giza and Kalubia governorates. Thirty five percent of the samples contained the toxin with a mean value of 22.23 μg /kg 2 Fate of STG contaminating milk during Ras cheese processing. Milk was artificially contaminated with 125 μg/kg and processed into Ras cheese. Eighty percent of the toxin was distributed into the curd and 20% into the whey. Cheese ripening effected toxin content and the effect was temperature dependent. At 6°C: toxin concentration was slightly affected; at 20°C the toxin was reduced by 16% after 90 days when low toxin concentration was used. 3 Formation of STG byA versicolor mold on Ras cheese. Ras cheese blocks were contaminated with spores of the mold. Toxin production started after 45 days of ripening and reached a maximum at 90 days and then declined. Cow's milk favoured toxin production over buffaloe's. Aged cheese inhibited toxin production.


Emergence of high-level tigecycline resistance due to the amplification of a tet(A) gene variant in clinical carbapenem-resistant Klebsiella pneumoniae.
To investigate the prevalence of a tet(A) gene variant and its role in developing high-level tigecycline resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates. The mechanism of high-level tigecycline resistance in CRKP mediated by a tet(A) variant was explored by induction experiments, antimicrobial susceptibility testing, whole-genome sequencing and bioinformatics analysis. The amplification and overexpression of the tet(A) variant were measured by the determination of sequencing depth, gene copy numbers, and qRT-PCR. A high rate (62.1%, 998/1607) of tet(A) variant carriage was observed among 1607 CRKP clinical isolates from Henan Province, China. High-level tigecycline resistance could rapidly develop by the amplification of the tet(A) variant in these isolates. The analysis of the raw sequencing data and the plasmid mapping depth revealed that the ΔtnpA homologous sequence of Tn1721 supports the amplification of the region that harbours the tet(A) variant by forming a large number of repeat arrays through translocatable units (TUs). Moreover, the epidemiological analysis of tet(A) variant-carrying structures among 1607 clinical CRKPs showed that the TU structure is widely present. The presence of a tigecycline resistance-mediating tet(A) variant in CRKP clinical isolates represents a greater health concern than initially thought and should be monitored consistently.


Effective antimicrobial therapies of urinary tract infections among children in low- and middle-income countries: A systematic review.
Urinary tract infection (UTI) is one of the most common infections encountered in infancy and childhood. Despite the emerging problem of antibiotic resistance in recent years, the use of antibiotics for better management of UTIs is inevitable. This study aims to explore the efficacy and adverse effects of the available antimicrobial agents that are used in pediatric UTIs in low- and middle-income countries (LMICs). Five electronic databases were searched to identify relevant articles. Two reviewers independently performed screening, data extraction, and quality assessment of the available literature. Randomized controlled trials providing antimicrobial interventions in both male and female participants within the age range of 3 months to 17 years in LMICs were included. Six randomized controlled trials from 13 LMICs were included in this review (four trials explored the efficacy). Due to high heterogeneity across the studies, a meta-analysis was not performed. Other than attrition and reporting bias, the risk of bias was moderate to high due to poor study designs. The differences in the efficacy and adverse events of different antimicrobials were not found to be statistically significant. This review indicates the necessity for additional clinical trials on children from LMICs with more significant sample numbers, adequate intervention periods, and study design.


A nationwide cross-sectional study using a web-based questionnaire survey of the duration of isolation of COVID-19 inpatients with cancer at Japanese cancer centers.
There is no clear consensus regarding the optimal isolation duration for immunocompromised patients with coronavirus disease 2019 (COVID-19). Therefore, we conducted a questionnaire survey at eight Japanese cancer centers to investigate the practices of infectious disease specialists regarding the duration of isolation for COVID-19 inpatients with cancer. For asymptomatic to severely ill COVID-19 inpatients without severe immunodeficiency, four centers reported at least 10 days of isolation without testing, and two reported at least 20 days. Two centers incorporated polymerase chain reaction (PCR) as a criterion for terminating the isolation of inpatients without severe immunodeficiency. For severely immunocompromised COVID-19 inpatients, at least 20 days of isolation were required in seven facilities, regardless of illness severity. Additionally, seven centers had implemented Ct or antigen quantification test values as criteria for de-isolating severely immunocompromised inpatients. No cases caused nosocomial outbreaks after isolation was terminated based on each facility's criteria for isolation termination. Thus, cancer patients required longer isolation periods than the general population in most facilities, and for those with severe immunodeficiency, the isolation periods were longer and more tightly controlled with tests.


MiR-92b-3p regulates oxygen and glucose deprivation-reperfusion-mediated apoptosis and inflammation by targeting TRAF3 in PC12 cells.
What is the central question of this study? MiR-92b-3p was found to be reduced in a rat model of middle cerebral artery occlusion: what are the functions of miR-92b-3p in oxygen and glucose deprivation-reperfusion (OGD/R)? What is the main finding and its importance? MiR-92b-3p abated apoptosis, mitochondrial dysfunction and inflammation caused by OGD/R via targeting TRAF3, suggesting that miR-92b-3p may serve as a potential therapeutic target in ischaemic stroke treatment. Stroke is the most common cause of human neurological disability. MiR-92b-3p has been shown to be decreased in a rat model of middle cerebral artery occlusion, but its effects in cerebral ischaemic insult are unknown. In this study, PC12 cells were exposed to oxygen and glucose deprivation-reperfusion (OGD/R) to establish cerebral ischaemic injury in vitro. Quantitative real time-PCR analysis demonstrated that OGD/R exposure led to down-regulation of miR-92b-3p and increased mRNA and protein levels of tumour necrosis factor receptor-associated factor 3 (TRAF3). Gain of miR-92b-3p expression facilitated cell survival; attenuated lactate dehydrogenase leakage, cell apoptosis, caspase 3 activity and cleaved-caspase 3 (c-caspase 3) expression; and decreased the Bax/Bcl-2 ratio. Furthermore, miR-92b-3p repressed mitochondrial membrane potential depolarization, reactive oxygen species production, cytochrome c protein expression, inflammatory cytokine production and the reduction of ATP content. MiR-92b-3p directly targeted the 3'-untranslated region of TRAF3 and decreased TRAF3 expression. Reinforced expression of TRAF3 partly abrogated the biological activity of miR-92b-3p during OGD/R. Hence, miR-92b-3p abated apoptosis, mitochondrial dysfunction and inflammatory responses induced by OGD/R by targeting TRAF3.


On the Dynamical Regimes of Pattern-Accelerated Electroconvection.
Recent research has established that electroconvection can enhance ion transport at polarized surfaces such as membranes and electrodes where it would otherwise be limited by diffusion. The onset of such overlimiting transport can be influenced by the surface topology of the ion selective membranes as well as inhomogeneities in their electrochemical properties. However, there is little knowledge regarding the mechanisms through which these surface variations promote transport. We use high-resolution direct numerical simulations to develop a comprehensive analysis of electroconvective flows generated by geometric patterns of impermeable stripes and investigate their potential to regularize electrokinetic instabilities. Counterintuitively, we find that reducing the permeable area of an ion exchange membrane, with appropriate patterning, increases the overall ion transport rate by up to 80%. In addition, we present analysis of nonpatterned membranes, and find a novel regime of electroconvection where a multivalued current is possible due to the coexistence of multiple convective states.


A QSAR review on melanoma toxicity.
Melanoma is one of the most aggressive forms of skin cancer and is currently attracting our attention particularly in the area of quantitative structure-activity relationships (QSAR). In the present review, an attempt has been made to collect the data for different sets of compounds and to discuss their toxicities toward melanoma cells by the formulation of a total number of 36 QSAR.


Reduced expression of endothelial cell markers after 1 year treatment with simvastatin and atorvastatin in patients with coronary heart disease.
The study was aimed at investigating the effects, after treatment for 1 year, of two different statins on the levels of circulating biochemical markers of endothelial function in patients with established coronary heart disease, with the hypothesis that statins might reduce these levels. Twenty-eight patients were randomized to treatment with atorvastatin and 30 to simvastatin for 1 year. The starting dose in both groups was 20 mg/day. Soluble forms of P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined to assess inflammatory activity of the endothelium, and tissue plasminogen activator antigen (tPAag), von Willebrand factor and thrombomodulin for evaluation of the haemostatic function. In the total study population there were significantly reduced levels after 1 year treatment in ICAM-1 (P<0.001), E-selectin (P=0.022) and P-selectin (P<0.001), whereas a significant increase was observed in VCAM-1 (P=0.003). Almost the same pattern was seen within both groups although the increase in VCAM-1 was only seen in the simvastatin group (P=0.017). An overall reduction in tPAag was further observed (P=0.048). The reduction in proinflammatory and to some extent haemostatic markers of endothelial function after 1 year treatment with either simvastatin or atorvastatin may be indicative of a less activated state of the endothelium which possibly may contribute to modulation of the progression of atherosclerosis.


Autoantibodies against RNA polymerase I in scleroderma and Sjögren's syndrome sera.
Anti-RNA polymerase I antibodies were detected by radioimmunoassay in the sera of 8 out of 9 Sjögren's syndrome patients, 11 out of 19 individuals with scleroderma, and 19 out of 19 systemic lupus erythematosus patients. The results of the radioimmunoassay were confirmed by demonstrating the ability of the patients' IgG to inhibit RNA polymerase I activity in vitro. Sera from four patients in each category were also tested for reaction with individual subunits of RNA polymerase I. All 4 SLE sera, 3 out of 4 scleroderma sera and 1 out of 4 Sjögren's syndrome sera contained antibodies against the 65 kDa (S3) subunit of RNA polymerase I in addition to antibodies against one other subunit. Sera from the remaining scleroderma and Sjögren's syndrome patients tested in this assay contained only anti-S3 antibodies. These results demonstrate that anti-RNA polymerase I antibodies are characteristic of a variety of rheumatic autoimmune sera.


Fibroblast growth factor-23 and renin-angiotensin system levels in vitamin-D-dependent rickets type I.
As 1,25(OH)2D3 vitamin D3 induces fibroblast growth factor-23 (FGF-23) production and suppresses the renin-angiotensin-aldosterone system (RAAS), its absence in vitamin-D-dependent rickets type I (VDDR-I) may have adverse health consequences. An infant presented at age 8 months with hypocalcemia and rickets and very low 1,25(OH)2D3 levels. Genetic analysis confirmed VDRR-I, and calcitriol therapy was initiated. During periods of nonadherence to therapy, chemical measurements revealed detectable FGF-23 levels, with undetectable 1,25(OH)2D3, hypophosphatemia, low tubular reabsorption of phosphate, hypocalcemia, and very elevated parathyroid hormone (PTH) levels. These changes, in addition to elevated RAAS levels, normalized during calcitriol therapy despite elevated FGF-23 levels. At age 12 years, all rachitic manifestations were absent, and bone mineral density (BMD) and the echocardiogram were normal. Whereas 1,25(OH)2D3 is not indispensable for FGF-23 production, PTH in the absence of vitamin D may maintain FGF-23 secretion despite hypocalcemia. Normalization of urinary phosphate losses despite elevated FGF-23 during calcitriol-mediated suppression of secondary hyperparathyroidism points to a cardinal role of PTH as a cause of the phosphaturia in VDRR-I. Normalization of RAAS by calcitriol may conceivably prevent adverse cardiovascular outcomes.


The relationship of lateral releases to patella viability in total knee arthroplasty.
A prospective clinical and radionuclide study was done to ascertain the effect of a lateral release on patella vascularity in total knee arthroplasty. Although the basic surgical procedure was the same in all 36 knees, postoperative technetium bone scans revealed a higher incidence (9 of 16, 56.4%) of vascular compromise in knees with a lateral release than in those without a lateral release (3 of 20, 15%). Although only one clinical complication (fractured patella not requiring secondary surgery) occurred, the lateral release itself appears to have a causal relationship with patella viability. It does not seem to be the sole determinant, however, because the development of a "cold" patella in three knees that did not have a lateral release implicates other factors, such as thermal necrosis and anatomic variation of the blood supply.


One-step screen-printed electrode modified in its bulk with HRP based on direct electron transfer for hydrogen peroxide detection in flow injection mode.
The preparation and performances of screen-printed carbon electrodes modified in their bulk with HRP (HRP-SPCE) is reported. The resulting modified HRP-SPCE was prepared in a one-step procedure, and then was optimised as an amperometric biosensor operating at [0-100] mV versus Ag/AgCl in flow injection mode for hydrogen peroxide. The amperometric response was due to direct electron transfer (DET) between HRP and SPCE surface. Factors such as chemical modification of the enzyme or the nature and rate of the binder were investigated regards to their influence on the sensitivity, linear range and operational stability. The best performing HRP-SPCE in terms of sensitivity and operational stability was obtained when graphite powder was modified with HRP previously oxidised by periodate ion (IO(4)(-)).


Peptide inhibition of morphine-induced dopaminergic supersensitivity.
Injection of the peptide cyclo(Leu-Gly) into rats prior to chronic exposure to morphine, inhibits: 1) the development of analgesic tolerance; 2) some signs of physical dependence; and, 3) morphine-induced increases in behavioral responses to dopamine agonists. Although there was no change in the total number of high affinity striatal dopamine receptors, chronic morphine treatment did increase the affinity of the ligand at the receptor. The peptide blocked not only the affinity change, but the increased behavioral response to apomorphine as well. These behavioral changes correlate significantly with the neurochemical changes in dopamine receptors following chronic morphine treatment. Therefore, some of the pharmacological efforts of morphine may be mediated by changes in CNS dopamine receptors and that the peptides may act by inhibiting these neurochemical changes.


Double Fence Porphyrins that are Compatible with Cobalt(II/III) Electrolyte for High-Efficiency Dye-Sensitized Solar Cells.
A series of new double fence porphyrin dyes bJS1-bJS3, with eight long alkoxyl chains attached to four β-phenyl groups, have been designed and synthesized. The single fence meso-substituted counterparts mJS1-mJS3 were also prepared as reference dyes. Dyes bJS1-bJS3 and mJS1-mJS3 exhibit power conversion efficiencies of 8.03-10.69 % and 2.33-6.69 %, respectively. Based on photovoltaic studies, the remarkable cell performance of double fence porphyrin sensitizers can be attributed to reduced dye aggregation and a decreased charge-recombination rate. Notably, porphyrins bJS2 and bJS3 exhibit better efficiency than the benchmark YD2-o-C8 (9.83 % in this work), demonstrating that the double fence structure is a promising design strategy for efficient porphyrin sensitizers in high-performance DSSCs.


Parental-reported snoring from the first month of life and cognitive development at 12 months of age.
The aim of the present study was to evaluate the effect of persistent snoring in the first year of life on developmental outcomes. As part of a longitudinal study of snoring and sleep in infancy, we identified 13 children (10 males) who commenced snoring shortly after birth and continued to snore frequently (≥ 3 nights/week) at 6 and 12 months of age and 78 controls (31 males) who were reported by parents to never snore in the absence of a cold. Infants were assessed with the Bayley Scales of Infant and Toddler Development Edition III and parents completed demographic and sleep questionnaires. Infants reported to snore frequently from the first month of life and who continued to snore frequently until 12 months of age had significantly lower cognitive development scores (mean=94.2; SD=3.9) compared to controls (mean=100.6; SD=3.7) (F (1, 96)=40 6, p<0.001; η(p)(2)=0.32). Persistent frequent snoring from the first month of life was associated with lower cognitive development scores at 12 months of age. It is possible that this deficit will become worse with age.


Telocytes in the esophageal wall of chickens: a tale of subepithelial telocytes.
The esophagus is a tubular organ which act as a passage for food from oral cavity to stomach. Telocytes (TCs) are a unique type of interstitial cell whose existence in many organs of various species still remains unknown. In the present study, we used transmission electron microscopy (TEM) and immunohistochemistry (CD34, Vimentin, PDGFR-α) to identify subepithelial TCs in the esophageal wall of chickens. TEM micrographs confirmed the presence of TCs in the lamina propria, tunica submucosa, and tunica muscularis muscular layer of the esophageal wall. A large population of TCs were observed just beneath the epithelial layer of the esophageal wall, and the TCs demonstrated structural heterogenicity, featuring various cell body shapes of cell bodies and telopodes (Tps) with podoms, podomeres, and dichotomous branching. Furthermore, a large number of extracellular vesicles were found to be associated with TCs/Tps. Cellular extensions from TCs were observed in close proximity to blood vessels, immune cells, and mucosal glands. In the submucosa, Tps and immune cells were in very close contact. Immunohistochemical results showed that there were CD34+ cells, vimentin+ cells, and PDGFR-α+ cells in the subepithelium, lamina propria, and mucosal glands of the chicken esophageal wall, which was consistent with the TEM results. Overall, our data confirmed the existence of TCs in the chicken esophagus and suggested that TCs might contribute to epithelial regeneration and tissue homeostasis.


Pediatric foreign body ingestion in Makkah, Saudi Arabia: A retrospective epidemiological study.
To improve the local data and demographics of foreign body (FB) ingestion in the Makkah, Saudi Arabia and to provide basic statistics for future studies in the local community. We carried out a record-based retrospective epidemiological study of 153 pediatric patients with FB ingestion who presented to our center in Makkah, Saudi Arabia, between December 2014 and December 2019. Adult age, impacted FB at other sites, and chemical ingestion were excluded. Descriptive statistical analyses were performed. There has been an alarming increase in the number of children admitted to hospitals following FB ingestion. Approximately 41.8% of these patients were under the age of 4 years, with boys (63.4%) accounting for the majority. Most of the ingested FB were coins (60.8%), and 96.7% of the patients remained under 24 hours of observation at the hospital. The results showed a highly statistically significant relationship between the FB type, age, length of hospital stay, and esophagoscopic findings. A large number of children presented with ingested FB, especially those younger than 4 years of age, whose clinical presentation varied from asymptomatic to severe complications, and urgent endoscopic intervention might have decreased serious complications. Further preventive measures are necessary within homes in addition to increasing caregivers' awareness of the different circumstances of FB ingestion and the time required for urgent admission.


Efficient production of α-monoglucosyl hesperidin by cyclodextrin glucanotransferase from Bacillus subtilis.
α-Monoglucosyl hesperidin is a promising food additive with various activities. However, there are a few reports about the production of α-monoglucosyl hesperidin. Here, to develop a practical and safe process for α-monoglucosyl hesperidin synthesis, we used nonpathogenic Bacillus subtilis as a host to express cyclodextrin glucanotransferase (CGTase) from Bacillus sp. A2-5a. The promoters and signal peptides were screened to optimize the transcription and secretion of CGTase in B. subtilis. The results of optimization showed that the best signal peptide and promoter were YdjM and PaprE, respectively. Finally, the enzyme activity increased to 46.5 U mL-1, 8.7 times that of the enzyme expressed from the strain containing pPHpaII-LipA, and the highest yield of α-monoglucosyl hesperidin was 2.70 g L-1 by enzymatic synthesis using the supernatant of the recombinant B. subtilis WB800 harboring the plasmid pPaprE-YdjM. This is the highest α-monoglucosyl hesperidin production level using recombinant CGTase to date. This work provides a generally applicable method for the scaled-up production of α-monoglucosyl hesperidin. KEY POINTS: • A three-step procedure was created for high throughput signal peptide screening. • YdjM and PaprE were screened from 173 signal peptides and 13 promoters. • α-Monoglucosyl hesperidin was synthesized by CGTase with a yield of 2.70 g L-1.


Hoechst fluorescence pattern of heterochromatin in three closely related members of Drosophila.
Heterochromatin distribution in metaphase chromosomes of three morphologically and karyologically similar members of Drosophila, D. s.sulfurigaster, D. s.bilimbata and D. pallidifrons was studied by the Hoechst 33258 staining method. Comparison showed remarkable uniformity of H-heterochromatin among the three members except for in their Y-chromosomes. On the basis of these observations phylogenetic relationships are discussed.


Influence of sesamoid position after scarf osteotomy for hallux valgus on patient-reported outcome. A prospective cohor study.
The objective was to evaluate the influence of the postoperative sesamoid position as measured with conventional radiographs on the patient-reported outcome after scarf osteotomy. The hypothesis was that incomplete reduction of the sesamoid would result in a decreased functional outcome. Eighty-two patients who underwent scarf osteotomy for hallux valgus were prospectively assessed for up to two postoperative years. The Self-Reported Foot and Ankle Score (SEFAS) was used to assess the quality of life, and the American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal-Interphalangeal Scale (AOFAS) for the functional outcome. A visual analogue scale (VAS) assessed pain, and Likert scale for patient satisfaction. Radiologically, hallux valgus angle (HVA), first-second intermetatarsal angle (IMA), and sesamoid position were analyzed. According to the final sesamoid position, patients were classified as normal position (48 patients) and outlier position (34 patients). A power analysis, conventional and logistic regression statistical analysis were performed. At the final follow-up, significant improvements in all clinical scores were observed for both groups (p = 0.001) with no significant difference in AOFAS score (p = 0.413), but SEFAS score (p = 0.023), VAS-pain (p = 0.006), and satisfaction (p = 0.014) were significantly better in the normal group than in the outlier group. There were significant differences between groups in final HVA (p = 0.042) and IMA (p = 0.040). In multivariate analysis, only lower VAS-pain score (OR 0.4, 95% CI 0.2-0.6; p = 0.039) and normal sesamoid position (OR 2.4, 95% CI 1.6-3.2; p = 0.012) were significant predictor of patient satisfaction. At two postoperative years, normal sesamoid position as measured on weight-bearing radiographs was associated with lower pain and better patient satisfaction in patients underwent scarf osteotomy for moderate to severe hallux valgus.


Medical management of gallstones: a cost-effectiveness analysis.
Ursodeoxycholic acid (ursodiol) is an oral dissolution agent recently approved by the Food and Drug Administration for treatment of cholelithiasis. The authors conducted a cost-effectiveness analysis comparing ursodiol with elective cholecystectomy and expectant management for men and women of ages 50 and 70 with typical chronic biliary symptoms. Using published literature and national cost data, the authors performed a decision analysis in which the outcome measures were life expectancy, quality-adjusted life expectancy, and expected lifetime treatment cost. The analysis applies to patients with symptoms of biliary colic, noncalcified gallstones less than 20 mm in diameter, and functioning oral cholecystograms, who are candidates for elective cholecystectomy. Excluded were patients with acute cholecystitis or known or suspected common bile duct stones. Ursodiol is both clinically advantageous and less expensive than surgery for symptomatic men aged 64 or more, and for symptomatic women aged 69 or more. At ages younger than these, the clinical advantage of surgery is small and could be nullified if ursodiol were targeted at patients for whom dissolution is most likely to be effective, based on evidence of stone size and composition. Expected lifetime costs of ursodiol range from $300-400 more than surgery for 50-year-olds to $700-1,000 less than surgery for 70-year-olds. Ursodiol is the preferred choice for patients throughout this age range who are at significantly elevated risk of operative mortality. Ursodiol is a clinically advantageous and cost-effective alternative to elective cholecystectomy, especially for older and high-risk patients.


Bromoperoxidase activity and vanadium level of the brown alga Ascophyllum nodosum.
Vanadium-dependent peroxidase activity in extracts of Ascophyllum nodosum growing in the intertidal region close to Roscoff/France, and algal vanadium levels, followed approximately similar seasonal variation, as deduced from a study lasting from April 2005 to March 2006. High peroxidase (PO) activity was found in extracts obtained from algae collected in between midwinter to spring [approximately 100-190 U per g dry mass (dm), triiodide assay] with a maximum in April. Periods of reduced PO activity lasted from summer to early winter (approximately 50-90 U per g dm). High vanadium levels (1.5-2.2 mg kg(-1)dm) were found in algae collected from midwinter to spring, whereas reduced levels (0.6-1.4 mg kg(-1)dm) were found in summer to early winter.


Bruegel and the Cost of the Bended Knee.
In Pieter Bruegel's painting, "The Seven Acts of Charity" he portrays 2 subjects with flexed knees. One of them cannot walk while the other can walk but does so with excessive energy expenditure.


The effect of inadequate access to peri-implant hygiene on marginal bone level. A 4-year cohort prospective study.
The objective of this four-year cohort prospective study was to evaluate the effect of inadequate access to peri-implant hygiene on marginal bone level (MBL). Forty-one partially edentulous patients (16 males and 25 females, aged 49.8 ± 11.9 years) who had implants with at least one year in function were selected. Patients were clinically and radiographically evaluated at three different times: baseline (T0), 2-year (T1), and 4-year (T2) follow-up intervals. At baseline, implants were classified and allocated into two groups: those presenting adequate access (ACC) and inadequate access (no-ACC) to peri-implant hygiene. A linear mixed-effects model for clustered longitudinal data was used to analyze MBL, probing depth (PD), plaque index (PI), and bleeding on probing (BoP). Of 131 implants, 74 were considered as having ACC, and 57 as having no-ACC at T0. Implants in the no-ACC group presented a statistically greater mean MBL measurement at T2 than implants in the ACC group (p = .011). In the no-ACC group, a significant reduction in PD from T0 to T1 (p = .019) and from T0 to T2 (p = .010) was observed. Regardless of the group, PI significantly increased at both T1 (p = .00001) and T2 (p = .00004). Regardless of time, the prevalence of BoP was significantly higher in the no-ACC group than in the ACC group (p = .012). Inadequate access to peri-implant hygiene frequently resulted in more peri-implant inflammation and MBL over time. Proper accessibility to peri-implant hygiene should be carefully considered during planning of implant restoration, and patients properly motivated into maintenance care.


Calcium-dependent protein kinase 21 phosphorylates 14-3-3 proteins in response to ABA signaling and salt stress in rice.
The calcium-dependent protein kinases (CDPKs) are a class of plant-specific kinase that directly bind Ca2+ and mediate the calcium-signaling pathways to play important physiological roles in growth and development. The rice genome contains 31 CDPK genes, one of which, OsCPK21, is known to modulate the abscisic acid (ABA) and salt stress responses in this crop; however, the molecular mechanisms underlying this regulation are largely unknown. In the present study, we performed yeast two-hybrid screening, glutathione S-transferase pull-down, co-immunoprecipitation, and bimolecular fluorescence complementation assays to confirm the interaction between OsCPK21 and one of its putative targets, Os14-3-3 (OsGF14e). We used an in vitro kinase assay and site-directed mutagenesis to verify that OsCPK21 phosphorylates OsGF14e at Tyr-138. We used real-time PCR to reveal that several ABA and salt inducible genes were more highly expressed in the OsCPK21-OE and OsGF14e WT-OE plants than in the mutant OsGF14e Y138A-OE and wild-type plants. These results suggest that OsCPK21 phosphorylates OsGF14e to facilitate the response to ABA and salt stress.


Satisfaction of Iranian Medical Universities' faculty members towards holding Shahid Motahari Annual Educational Festival.
Shahid Motahari Annual Educational Festival aims to improve the quality of medical education in the Islamic Republic of Iran, and has held since 2008. The present study was performed to determine the satisfaction level of Iranian medical universities' faculty members about holding Shahid Motahari Annual Educational Festival during the past six years, from 2008 to 2014. This cross-sectional study was conducted on 473 faculty members (FMs) including deputies and educational administrators, managers, and faculty members of medical education development centers, members of scientific committees, and faculty members who participated in Shahid Motahari Festival from 42 medical sciences universities in Iran. Data collection instruments were two reliable and valid questionnaires on the background and also participants' satisfaction towards Shahid Motahari Educational Festival. Data were analyzed using SPSS Software, version 14. Among all participants, 30 FMs (6.3%) were educational deputies, 36 FMs (7.6%) managers of medical education development centers, 226 FMs (56.2%) members of scientific committees, 29 FMs (6.1%) members of the national committees, 343 FMs (27.5%) attendees, and 264 FMs (55.8%) had participated for retraining. The total satisfaction level of the participants was 73.3% which shows a good satisfaction level. The results identified the main important strength points such as "proposals' review process at the country level" and weakness points such as "organizing the festival".


Genetic diversity of the Metarhizium anisopliae complex in Colima, Mexico, using microsatellites.
Metarhizium anisopliae is a complex of cryptic species with wide geographical distribution and versatile lifestyles. In this study, 45 isolates of the Metarhizium genus harbored in the "Colección de Hongos Entomopatógenos" of the "Centro Nacional de Referencia de Control Biológico" from different substrates, insect-host, and localities from Colima, Mexico, were phylogenetically identified using the 5'end of translation elongation factor 1-α (5'TEF) and intergenic nuclear region MzFG543igs. Seven species were recognized, M. acridum (n = 26), M. pemphigi (n = 1), and within the PARB and MGT clades: M. anisopliae (N = 7; sensu stricto: n = 2; sensu lato: n = 5), M. brunneum (n = 2), M. guizhouense (n = 2), M. pingshaense (n = 2), and M. robertsii (n = 5). Twenty-nine SSR markers were developed for M. acridum; according to the analysis of 12 polymorphic SSR loci, M. acridum showed low genetic diversity, revealing five genotypes with a dominant one (n = 21). Based on the analysis of 13 specific SSR loci, 14 genotypes were identified within the PARB and MGT clades. This study contributes to generating valuable information about the community structure and genotypic diversity of Metharhizum species in the state of Colima, Mexico.


General practitioners' perceptions of pharmacists' new services in New Zealand.
In recent years, the pharmacy profession has moved towards more patient-oriented services. Some examples are medication review, screening and monitoring for disease, and prescribing. The new services are intended to be in close collaboration with general practitioners (GPs) yet little is known of how GPs in New Zealand perceive these new services. Objective To examine GPs' perceptions of pharmacists' new services. Study was undertaken at GPs' practices in two localities in New Zealand. Qualitative, face to face, semi-structured interviews were undertaken of 18 GPs. The cohort included GPs with less/more than 20 years of practice, and GPs who had experience of working in localities where some patients had undergone a medication review (Medicines Use Review, MUR) by community pharmacists. GPs were asked to share their perceptions about pharmacists providing some new services. Data were thematically analysed with constant comparison using NVivo 8 software. Using a business strategic planning approach, themes were further analysed and interpreted as the services' potential Strengths, Weaknesses, Opportunities and Threats (SWOTs). GPs' perceptions of pharmacists' new services. GPs were more supportive of pharmacists' playing active roles in medication review and less supportive of pharmacists practising screening-monitoring and prescribing. Discussions Pharmacists' knowledge and skills in medication use and the perceived benefits of the services to patients were considered the potential strengths of the services. Weaknesses centred around potential patient confusion and harm, conflict and irritation to GPs' practice, and the potential to fragment patient-care. Opportunities were the possibilities of improving communication, and having a close collaboration and integration with GPs' practice. Apparent threats were the GPs' perceptions of a related, and not renumerated, increase in their workloads, and the perception of limited benefit to patients. Pharmacists should exploit their own strengths and the potential opportunities for these services, and reduce any weaknesses and threats. A possible strategic plan should include increased effective communication, piloting services, and the integration of some services into medical practices.


Fibrosis and adipose tissue dysfunction.
Fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1α that in turn leads to a potent profibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an equally important role on systemic metabolic alterations as fibrotic conditions play in the liver, heart, and kidney. Here, we discuss recent advances in our understanding of the genesis, modulation, and systemic impact of excessive extracellular matrix (ECM) accumulation in adipose tissue of both rodents and humans and the ensuing impact on metabolic dysfunction.


Influence of experience on performance of individual surgeons in thyroid surgery: prospective cross sectional multicentre study.
To determine the association between surgeons' experience and postoperative complications in thyroid surgery. Prospective cross sectional multicentre study. High volume referral centres in five academic hospitals in France. All patients who underwent a thyroidectomy undertaken by every surgeon in these hospitals from 1 April 2008 to 31 December 2009. Presence of two permanent major complications (recurrent laryngeal nerve palsy or hypoparathyroidism), six months after thyroid surgery. We used mixed effects logistic regression to determine the association between length of experience and postoperative complications. 28 surgeons completed 3574 thyroid procedures during a one year period. Overall rates of recurrent laryngeal nerve palsy and hypoparathyroidism were 2.08% (95% confidence interval 1.53% to 2.67%) and 2.69% (2.10% to 3.31%), respectively. In a multivariate analysis, 20 years or more of practice was associated with increased probability of both recurrent laryngeal nerve palsy (odds ratio 3.06 (1.07 to 8.80), P=0.04) and hypoparathyroidism (7.56 (1.79 to 31.99), P=0.01). Surgeons' performance had a concave association with their length of experience (P=0.036) and age (P=0.035); surgeons aged 35 to 50 years had better outcomes than their younger and older colleagues. Optimum individual performance in thyroid surgery cannot be passively achieved or maintained by accumulating experience. Factors contributing to poor performance in very experienced surgeons should be explored further.


Anti-inflammatory effects of sodium-glucose co-transporter 2 inhibitors on atherosclerosis.
Atherosclerosis is a very common macrovascular complication in type 2 diabetes mellitus, and cardiovascular disease is the primary cause of death in diabetes patients. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are a newly identified class of drugs targeting the renal proximal tubules to increase glucose excretion. Large-scale clinical trials have confirmed the cardiovascular protective effects of SGLT inhibitors in patients with diabetes diagnosed with or at a higher risk of atherosclerotic cardiovascular disease. In addition to its direct effect on glycemic control, the function of SGLT-2i in the alleviation of volume load, renal protection, and reduction of inflammation plays an essential role in its therapeutic effect on atherosclerosis. SGLT-2i are known to decrease the levels of inflammatory factors in circulation and in arteries in situ, inhibit foam cell formation and macrophage infiltration, and sustain plaque stability, ultimately blocking the development and progression of atherosclerosis.


Evaluation of PCA3 and multiparametric MRI's: collective benefits before deciding initial prostate biopsy for patients with PSA level between 3-10ng/mL.
To analyze the contribution of multiparametric MRI and PCA3 assay, predecision of initial biopsy in PSA level between 3-10 ng/mL patients with normal digital rectal examination(DRE). PSA level 3-10 ng/mL, patients, with normal DRE results and no previous prostate biopsy history, were included in this study. Each patient underwent multiparametric MRI one week before biopsy. Urine sample taking for PCA3 examination preceded the biopsy. Systematic and targeted biopsies were conducted. Patients with high PSA levels were seperated into two groups as: high PCA3 scored and low PCA3 scored. Then each group was divided into two sub-groups as: MRI lesion positive and negative. Tumor incidence, positive predictive values(PPV) and negative predictive values(NPV) were calculated. 53 patients were included between February 2013 and March 2014. Mean age 61.22 ± 1.06. Mean PSA value 5.13 ± 0.19 ng / mL. Mean PCA3 score 98.01 ± 23.13 and mean prostate size was 48.96 ± 2.67 grams. Fourty nine patients had both PCA3 score and multiparametric MRI. The PCA3's PPV value was 58.33%. If multiparametric MRI lesions are added to high PCA3 scores , the PPV appears to elevate to 91.66%. NPV of PCA3 was 96%. NPV was 95% when there was no lesion in the multiparametric MRI with low PCA3 scores. Sensitivity was 91.66% , specificity was 95% respectively. Adding multimetric MRI can also support biopsy decision for patients with high PCA3 value. When PCA3 value is low, patients can be survailled without any need to take a MRI.


Clinical Outcomes of Anticoagulated Patients With Atrial Fibrillation After Falls or Head Injury: Insights From RE-LY.
Falls are always a concern regarding the balance of risk/benefit in patients with atrial fibrillation treated with anticoagulants. In this analysis, we aimed to evaluate the outcomes of patients that had a fall/head injury reported in the RE-LY clinical trial (Randomized Evaluation of Long-Term Anticoagulation Therapy) and to explore the safety of dabigatran (a nonvitamin K antagonist oral anticoagulant). We performed a post hoc retrospective analysis of intracranial hemorrhage and major bleeding outcomes in the RE-LY trial with 18 113 individuals with atrial fibrillation, according to the status occurrence of falls (or head injury) reported as adverse events. Multivariate Cox regression models were used to provide adjusted hazard ratio (HR) and 95% CI. In the study, 974 falls or head injury events were reported among 716 patients (4%). These patients were older and had more frequently comorbidities such as diabetes, previous stroke, or coronary artery disease. Patients with fall had a higher risk of major bleeding (HR, 2.41 [95% CI, 1.90-3.05]), intracranial hemorrhage (HR, 1.69 [95% CI, 1.35-2.13]), and mortality (HR, 3.91 [95% CI, 2.51-6.10]) compared to those who did not have reported falls or head injury. Among patients who had falls, those allocated to dabigatran showed a lower intracranial hemorrhage risk (HR, 0.42 [95% CI, 0.18-0.98]) compared with warfarin. In this population, the risk of falls is important and confers a worse prognosis, increasing intracranial hemorrhage, and major bleeding. Patients who fell and were under dabigatran was associated with lower intracranial hemorrhage risk than those anticoagulated with warfarin, but the analysis was merely exploratory.


Marijuana use among American Indian adolescents: a growth curve analysis from ages 14 through 20 years.
To describe the developmental course of marijuana use among a group of American Indian adolescents, aged 14 through 20 years. A group of 1,766 American Indian adolescents from 3 culture groups provided repeated measures of 30-day marijuana use twice a year across a 3-year period. Linking 5 age cohorts, hierarchical linear modeling was used to model a curvilinear trajectory of marijuana use. Gender and community differences were examined as well. Support was found for a "maturational" model of marijuana use across time: Use increased in middle adolescence, peaked in later adolescence, and began to decrease in early adulthood. Both gender and community differences in trajectories were significant as well. Marijuana use among American Indian adolescents follows a clear developmental trajectory. Growth curve analysis can provide an additional tool for studying the effects of interventions that may not be apparent in a traditional evaluation design.


Nutritional Modulation of Innate Immunity: The Fat-Bile-Gut Connection.
Altered nutritional behavior in Western societies has unleashed numerous metabolic disorders, intimately linked to profound disruptions of the immune system. Here we summarize how nutrition modulates innate immunity. We outline recent findings regarding nutrient signaling and we particularly focus on the collateral impact of nutrition on the microbiome and on the bile acid (BA) pool. We discuss how the integration of postprandial signals by the gut microbiota, along with the absorption routes of metabolites, differentially affects immune niches to orchestrate immune responses. Finally, we discuss the potential consequences of these signals in the light of trained immunity. A better understanding of nutrition signaling will permit the optimization of therapeutic and dietary strategies against the arising immune disorders.


Priapism associated with iloperidone: a case report.
Priapism is a known side effect of antipsychotics. The causal mechanism seems to be mediated through α1-adrenergic receptor blockade which many antipsychotics are known to possess. We present the first detailed case of iloperidone-induced priapism in a patient with bipolar disorder with psychotic features. His case highlights some of the important risk factors clinicians should consider when using iloperidone, as it may be the highest-risk antipsychotic for causing priapism given it is a very potent blocker of the alpha-adrenergic receptor.


Molecular cloning and expression of IL2 cDNA from the Tibet pig.
Interleukin-2 is a vital cytokine secreted by activated T lymphocytes, and plays important role in the regulation of cellular and humoral immunity of animals. In our experiment, IL2 cDNA of the Tibet Pig was first cloned by RT-PCR from ConA-stimulated lymphocytes in the blood and subcloned into pMD-18 T vector, which then was identified with endonuclease restriction. The sequencing result showed that Tibet pig IL-2 (TPIL-2) cDNA was 503 bp long (ORF was 465 bp) (Genbank accession number: AY 294018). The recombinant prokaryotic and eukaryotic expression plasmids of the cDNA were then constructed to analyse the ability to stimulate the proliferation of porcine lymphocytes in vitro. The recombinant porcine IL-2 expressed in the prokaryotic cells was found to be of 43 kDa molecular mass, which was consistent with a 17.4 kDa protein deduced from the IL-2 cDNA sequence (glutathione S-transferase molecular mass is 26 kDa); the recombinant protein in eukaryotic cells was confirmed by use of specific rabbit anti-porcine IL-2 serum in an ELISA. The bioactivity of TPIL-2 was detected through MTT colorimetry by stimulating the proliferation of pig ConA-stimulated blasts in vitro. The results indicate that the TPIL-2 significantly promoted the proliferation of ConA-stimulated blasts of pig. This confirms that IL-2 cDNA of the Tibet pig was successfully cloned and expressed in prokaryotic and eukaryotic cells, which lays the foundation for the the preparation of specific recombinant IL-2 protein and development of novel immune adjuvants to raise the immunity of pigs against various infectious pathogens and increase the immunoprotective efficacy of vaccines.


Blood sample collection in lizards.
Blood sample collection in lizards is an important technique. This column describes techniques for sample collection from the ventral coccygeal vein and the ventral abdominal vein.


Working Conditions and Long-Term Sickness Absence Due to Mental Disorders: A Prospective Record Linkage Cohort Study Among 19- to 39-Year-Old Female Municipal Employees.
We examined associations between working conditions and long-term sickness absence due to mental disorders (LTSA-MD) among younger female public sector employees from different employment sectors. Survey data collected in 2017 (n = 3048) among 19- to 39-year-old female employees of the City of Helsinki, Finland, were used to examine job demands, job control, physical workload, computer work, and covariates. Register data on LTSA-MD were used over 1-year follow-up. Negative binomial regression models were applied. Adverse psychosocial and physical working conditions were associated with higher LTSA-MD during the follow-up. Health and social care workers had the highest number of days of LTSA-MD. Working conditions are important factors when aiming to prevent LTSA-MD among younger employees, in the health and social care sector in particular.


The treatment of sleep-related painful erections.
As specialists in male genital problems, urologists and sexologists will most likely to be involved in the treatment of males presenting with sleep-related painful erections (SRPEs). This means that this phenomenon needs to be recognized by urologists and sexologists, and that they should have knowledge of the current diagnostic and therapeutic approaches. Aim. To review the literature on SRPE and to find the best pharmacological treatment. Methods. Four personal clinical observations from two clinics and 29 other cases with SRPE found in PubMed were analyzed, especially regarding the results of pharmacological treatment. The results of pharmacological treatment. Many of the various treatments proved to be ineffective and only a few showed efficacy for a few weeks or months. The only effective drugs in the long term were baclofen, clonazepam, and clozapine. Until now, the phenomenon of SRPE is not well understood. The rarity of the published cases undoubtedly does not reflect the actual occurrence of SRPE. Controlled double-blind pharmacological trials are needed, and long-term follow-up including polysomnography coupled with nocturnal penile tumescence and rigidity monitoring may provide further information about SRPE.


Enterobacteriaceae in food safety with an emphasis on raw milk and meat.
There has been a growing interest in traditional dairy (such as raw milk cheeses) and meat products, in recent years. However, these products are suitable and nutrient medium and may be easily contaminated by microorganisms such as Enterobacteriaceae. Enterobacteriaceae are considered to be the indicator bacteria for microbiological quality of food and hygiene status of a production process. Additionally, the food contaminated by Enterobacteriaceae poses a microbiological risk for consumers. In fact, the contamination of raw milk and meat by Enterobacteriaceae amid manufacturing may easily occur from various environmental sources, and this group of bacteria is frequently detected in dairy and meat products. Therefore, monitoring the microbiological quality of the used raw material and maintaining high standards of hygiene in the production process are mandatory for a high quality of traditional products and the safety of the potential consumers. The goal of this review is to present the most recent survey on Enterobacteriaceae growth, number, and distribution in raw milk cheeses and meat, as well as to discuss the sources of contamination and methods of control. KEY POINTS: • Enterobacteriaceae: role and importance in milk and meat products, EU legal regulations • Dynamics, distribution, and survival of Enterobacteriaceae in milk and meat • Mechanisms of control of Enterobacteriaceae in dairy products.


Effects of isosorbide dinitrate on portal hypertension in alcoholic cirrhosis.
It has recently been reported that vasodilators lower portal pressure in patients with cirrhosis. This effect, however, is not definitively proven. The effect of isosorbide dinitrate (5 mg sublingually) on splanchnic and systemic hemodynamics was investigated in 13 patients with alcoholic cirrhosis and portal hypertension. The administration of isosorbide dinitrate reduced hepatic venous pressure gradient by 34% (P less than 0.001), mean arterial pressure by 30% (P less than 0.001), cardiac index by 17% (P less than 0.001) and systemic vascular resistance by 11% (P = 0.05). Hepatic blood flow was not affected by the treatment. Significant correlations were found between the decrease in hepatic venous pressure gradient and that of cardiac index (P less than 0.05) and mean arterial pressure (P less than 0.05). These data indicate that isosorbide dinitrate lowers portal pressure in patients with cirrhosis. Decrease in cardiac output, rise in splanchnic arterial vascular resistance and decrease in porto-hepatic resistance seem to participate in determining the effect.


Nonspecific interstitial pneumonia.
Traditionally, a subset of patients diagnosed as having idiopathic pulmonary fibrosis had positive results on cellular biopsies (prominent lymphoplasmacytic inflammation), bronchoalveolar lavage lymphocytosis, a clinical response to steroids, and a better long-term prognosis. On review of the lung histopathology, the lesion was characterized by varying degrees of inflammation and fibrosis. This entity is now recognized as a distinct entity among idiopathic interstitial pneumonias.


Extraction of an erythrotropin-like factor from bovine serum albumin (Cohn fraction V).
Different batches of commercially available bovine serum albumin (Cohn fraction V) were tested in a serum-free medium for their ability to stimulate thymidine incorporation in erythroid cells of fetal bovine liver. All preparations stimulated thymidine incorporation. Crystallized, charcoal-treated, or fatty acid-free albumin had substantially lower thymidine incorporation-stimulating activities than the crude preparations. The albumin preparations also had a synergistic effect with respect to erythropoietin on erythroid cells from rat liver, a typical property of erythrotropins. One gram of one of the batches of Cohn fraction V was fractionated by reversed-phase high performance liquid chromatography (HPLC). The fraction with thymidine incorporation-stimulating activity had a similar elution position as erythrotropin isolated from fetal bovine serum. Further purification using reversed-phase HPLC in the presence of trifluoroacetic acid and heptafluorobutyric acid and gel permeation HPLC resulted in the isolation of a factor that is very similar to fetal bovine serum erythrotropin. It has practically the same specific activity as the purified fetal peptide in the rat liver bioassay. These results suggest that many of the beneficial effects of the albumin preparations added as supplement of serum-free tissue culture media may be due to the presence of erythrotropin-like factors.


Clinical vicissitudes of adoption.
Many interacting forces shape the unique experience of adoption. The adoptive parents' fantasies, fears, and perceived lack of entitlement to the child can detrimentally influence their parenting abilities. The adopted child's often powerful need to master early abandonment may lead to maladaptive behaviors that feed the adoptive parents' fears and fantasies regarding the child's past and future. The therapist familiar with the challenges of adoption can take an empathic stance with the adoptive parents and the adoptive child that can contain their anxieties and conflicts and pave the way toward a better resolution of their individual and shared experience.


Ecological aspects of ontogenetic shifts in prey size utilization in the bay goby (Pisces: Gobiidae).
Two age classes (0+ to 3+ and 4+ to 7+) of bay gobies (Lepidogobius lepidus Girard) differed in the sizes of whole prey (except polychaetes) recovered from the digestive tract. Although older fish consumed greater amounts of larger prey they did not capture larger individuals of a given prey type for seven of nine prey classes. The remaining two, harpacticoid copepods and ostracods contribute minimally to ontogenetic differences. The switch to larger prey appears to either decrease exposure to predation through a reduction in foraging time or increase energy intake. This is facilitated through older fishes greater size and/or superiority in intraspecific competition. These differences can probably be viewed as adaptations to selective pressures imposed by fluctuating food resources on predation levels in bays and estuaries.