Correspondence between hospital admission and the pneumonia severity index (PSI), CURB-65 criteria and comparison of their predictive value in mortality and hospital stay.
Pneumonia severity assessment systems, such as the pneumonia severity index (PSI) and CURB-65, were designed to guide physicians to admit the patients involved to appropriate wards of hospitals. This study evaluated concordance rate of decisions leading to patients' hospitalization in accordance with PSI and CURB-65 criteria and comparison of the two systems' P-values in evaluating mortality and the hospitalization period of the patients in question. A total of 134 hospitalized patients with community-acquired pneumonia (CAP) were evaluated. Patients were classified on the basis of risk factors implicated in the PSI and CURB-65 systems. Prognostic P-values and indication measures of hospitalization for the two systems were then compared. Eighty-seven males (64.9%) and 47 females (35.1%) with a mean age of 64.23±19.82 (15-103) years were enrolled in the study. Based on the results of both systems, hospitalization was indicated in 112 cases (83.6%) and there was total agreement between the two systems in 61 cases (45.5%). There was no significant association between hospitalization duration in the two systems. However, both systems significantly predicted mortality within the hospitalization period with rather equal accuracies. Patients expired more frequently in the group with indication of hospitalization based on the PSI classes. However, there was no significant difference in the mortality between the two groups with and without admission indication according to the CURB-65 system. A considerable portion of our hospitalizations met the related criteria of the PSI/CURB-65. The two evaluation systems have near equal sensitivity and specificity for predicting mortality among hospitalized patients with CAP when the PSI class IV-V and CURB-65 score ≥ 2.


Orbital reorientation in MnV2O4 observed by V NMR.
The simultaneous occurrence of the structural and magnetic phase transitions observed in MnV2O4 is one clear example of strong interplay among the spin, orbital and lattice degrees of freedom. The structure of MnV2O4 is switched by the magnetic field and the linear magnetostriction is very high. The orbital order mediates the interaction between the spin and the lattice generating these phenomena. In this work, we present experimental evidence of an orbital order in MnV2O4 and its reorientation under a rotating magnetic field as obtained by nuclear magnetic resonance(NMR). The shift in the resonance frequency of the V NMR spectrum is symmetrical with respect to 45° as an external magnetic field of 7 T rotates from the c-axis to the b-axis, indicating that the initial easy axis flips to the orthogonal direction most parallel to the field direction. The spectrum of V3+ ions splits into four peaks with a maximum shift of 40 MHz. Our analysis revealed that this is the combined effect of the anisotropic hyperfine field due to an ordered orbital and the dipolar hyperfine field. Reorientation of the orbital order in response to an external magnetic field accompanies the macroscopically observed magnetostriction in MnV2O4.


G-Quadruplexes Involving Both Strands of Genomic DNA Are Highly Abundant and Colocalize with Functional Sites in the Human Genome.
The G-quadruplex is a non-canonical DNA structure biologically significant in DNA replication, transcription and telomere stability. To date, only G4s with all guanines originating from the same strand of DNA have been considered in the context of the human nuclear genome. Here, I discuss interstrand topological configurations of G-quadruplex DNA, consisting of guanines from both strands of genomic DNA; an algorithm is presented for predicting such structures. I have identified over 550,000 non-overlapping interstrand G-quadruplex forming sequences in the human genome--significantly more than intrastrand configurations. Functional analysis of interstrand G-quadruplex sites shows strong association with transcription initiation, the results are consistent with the XPB and XPD transcriptional helicases binding only to G-quadruplex DNA with interstrand topology. Interstrand quadruplexes are also enriched in origin of replication sites. Several topology classes of interstrand quadruplex-forming sequences are possible, and different topologies are enriched in different types of structural elements. The list of interstrand quadruplex forming sequences, and the computer program used for their prediction are available at the web address http://moment.utmb.edu/allquads.


[The interferon-induced and antiviral activities of dipeptides].
Five phosphodipeptides were synthesized; two of them (H-Lys-Ala(P) and H-Pro-Ala(P) had interferon-induced activity. These dipeptides at millimolar concentrations (10(-4)) and 10(-5) M) induced the synthesis of late (40-hour) interferon in human peripheral blood lymphocytes. The dipeptides H-Lys-Ala(P) and H-Pro-Ala(P) showed a protective antiviral activity in in vivo studies when singly intraperitoneally administered to mice 2 hours before inoculation with murine encephalomyocarditis virus.


Factors That Influence Intraoperative Decision-Making among Pediatric Neurosurgeons: A Grounded Theory Study.
Pediatric neurosurgery is a subspecialty of medicine that is responsible for diagnosing, managing, and treating neurological disease in children with the use of surgery. Good intraoperative decision-making is critical to ensuring patient safety, yet almost nothing is known about what factors play a role in intraoperative decisions. As such, the purpose of this paper was to explore the factors that influence intraoperative decisions when pediatric neurosurgeons encounter something unexpected or uncertain during surgery. The study utilized the grounded theory method of data collection and analysis. Twenty-six pediatric neurosurgeons from 12 countries around the world were interviewed between June and October 2020 about the factors that go into making intraoperative decisions. Data were analyzed line by line and constant comparison was used to examine relationships within and across codes and categories. Pediatric neurosurgeons reflected on 6 factors while operating in order to come to a decision about how to proceed when they encountered an uncertainty or complication. The study findings resulted in a conceptual model that describes how concrete data including biological and technological factors and contextual data including emotional/relational factors, surgeon factors, and cultural factors influence risk assessment when making an intraoperative decision during surgery. The findings from this research can be used for training and educating surgeons about intraoperative decision-making processes. Pedagogical modules can be developed that include training sessions on factors that may implicitly and explicitly influence thinking processes during an operation. Surgeons may also benefit from having open discussions with surgical colleagues about the rich, emotional, intellectual scope of the work that they do with all the challenges that these relationships can bring into decision-making in the operating room.


Human lung mast cells mediate pneumococcal cell death in response to activation by pneumolysin.
Mast cells are emerging as contributors to innate immunity. Mouse mast cells have a pivotal role in protection against bacterial infection, and human cord blood-derived mast cells reduce bacterial viability in culture. The objectives of this study were to determine whether human lung mast cells (HLMCs) might be protective against pneumococcal lung infection through direct antimicrobial activity. Tissue-derived HLMCs and the human mast cell lines HMC-1 and LAD2 were cocultured with wild-type and mutant pneumococci, and viability and functional assays were performed. Mast cells were also stimulated with purified pneumolysin. HLMCs killed wild-type serotype-2 (D39) pneumococci in coculture but had no effect on an isogenic pneumolysin-deficient (PLN-A) pneumococcus. D39 wild-type, but not PLN-A pneumococci, induced the release of leukotriene C4 from human mast cells in a dose-dependent manner, which was not accompanied by histamine release. Stimulation of mast cells with sublytic concentrations of purified pneumolysin replicated this effect. Furthermore, pneumolysin induced the release of the cathelicidin LL-37 from HLMCs, purified LL-37 reduced pneumococcal viability, and neutralizing Ab to LL-37 attenuated mast cell-dependent pneumococcal killing. In addition, at high concentrations, all pneumococcal strains tested reduced HLMC viability through a combination of pneumolysin and H2O2-dependent mechanisms. HLMCs exhibit direct antimicrobial activity to pneumococci through their activation by pneumolysin. This antimicrobial activity is mediated, in part, by the release of LL-37 from HLMCs. This suggests that mast cells provide an early warning system and potentially limit pneumococcal dissemination early in the course of invasive pulmonary pneumococcal disease.


Six-year cumulative treatment effect and treatment efficacy of a dual focus myopia control contact lens.
Accumulated axial growth observed during a 6-year clinical trial of a dual focus myopia control contact lens was used to explore different approaches to assess treatment efficacy. Axial length measurements from 170 eyes in a 6-year clinical trial of a dual focus myopia control lens (MiSight 1 day, CooperVision) were analysed. Treatment groups comprised one having undergone 6 years of treatment and the other (the initial control group) having 3 years of treatment after 3 years of wearing a single vision control lens. Efficacy was assessed by comparing accumulated ocular growth during treatment to that expected of untreated myopic and emmetropic eyes. The impact of treatment on delaying axial growth was quantified by comparing the increased time required to reach criterion growths for treated eyes and survivor analysis approaches. When compared to the predicted accumulated growth of untreated eyes, 6 years of treatment reduced growth by 0.52 mm, while 3 years of treatment initiated 3 years later reduced growth by 0.19 mm. Accumulated differences between the growth of treated and untreated myopic eyes ranged between 67% and 52% of the untreated myopic growth, and between 112% and 86% of the predicted difference in growth between untreated myopic and age-matched emmetropic eyes. Treated eyes took almost 4 years longer to reach their final accumulated growth than untreated eyes. Treatment increased the time to reach criterion growths by 2.3-2.7 times. Estimated growth of age-matched emmetropic and untreated myopic eyes provided evidence of an accumulated slowing in axial elongation of 0.52 mm over 6 years, and the treated growth remained close to that expected of emmetropic eyes. Six years of dual focus myopia control delayed the time to reach the final growth level by almost 4 years.


Factors associated with physical function capacity in an urban cohort of people living with the human immunodeficiency virus in South Africa.
Effective disease management for people living with human immunodeficiency virus (PLWH) includes the encouragement of physical activity. Physical function capacity in PLWH may be influenced by a variety of factors. This study describes the physical function capacity as assessed with the 6-minute walk test (6MWT) of an urban cohort of PLWH and determined whether a history of pulmonary tuberculosis (PTB), anthropometric measures, age and gender predicted distance walked. Secondary data collected from 84 PLWH on antiretroviral therapy were analysed. Information included 6MWT distance, anthropometric measurements and demographic profiles. Descriptive and inferential statistics were undertaken on the data. A regression analysis determined predictive factors for 6MWT distance achieved. Significance was set at a p-value of ≤ 0.05. The study consisted of 66 (78.6%) women and 18 (21.4%) men with a mean age of 39.1 (± 9.2) years. The 6MWT distance of the cohort was 544.3 (± 64.4) m with men walking further (602.8 [± 58.6] m) than women (528.3 [± 56.4] m); however, women experienced greater effort. The majority of the sample did not report a history of PTB (n = 67; 79.8%). Age, gender and anthropometric measures were associated with 6MWT distance, but of low to moderate strength. The regression equation generated included age and gender. This model was statistically significant (p < 0.00) and accounted for 34% of the total variance observed. Age and gender were predictive factors of physical function capacity and women experienced greater effort. This study provides information on the physical function capacity of PLWH and a suggested 6MWT reference equation for PLWH in South Africa.


Clonal analysis of nestin(-) vimentin(+) multipotent fibroblasts isolated from human dermis.
Although several studies have shown that dermal fibroblasts possess adipogenic, osteogenic or chondrogenic differentiation potential, no study has characterized this cell population in detail, and there is as yet no evidence that a single dermal fibroblast can differentiate into all these types of cells. In this study, dermal fibroblasts were isolated from human foreskin using a regular dermal fibroblast culture system. These cells could be expended in adherent culture for over 40 cell doublings. In addition, dermal fibroblasts exhibited adipogenic, osteogenic and chondrogenic phenotypes when they were cultured in the presence of certain inducers. Importantly, clonal analysis showed that 6.4% (3/47) of the single-cell-derived clones were tripotent, 19.1% (9/47) of the clones were bipotent, and 10.6% (5/47) of the clones were unipotent. Furthermore, one of the three tested tripotent clones exhibited neurogenic and hepatogenic differentiation potential. Phenotypic analyses showed that the tripotent fibroblasts were nestin(-) vimentin(+), which is different from the dermis-derived stem cells reported by others. These results indicate that dermal fibroblasts are a heterogeneous population containing progenitors with various levels of differentiation potential, and the nestin(-) vimentin(+) fibroblasts may represent a novel type of multipotent adult stem cells in human dermis.


Use of naltrexone in the treatment of alcoholism nationally in the Department of Veterans Affairs.
Naltrexone is one of only two medications currently approved by the Food and Drug Administration for the treatment of alcoholism. We attempted to determine the proportion of patients with a diagnosis of alcoholism who were prescribed naltrexone in the Department of Veterans Affairs health-care system during a 6-month period and the sociodemographic and clinical characteristics that distinguished them from veterans who were not prescribed naltrexone. By using Veterans Affairs workload databases, all outpatients diagnosed with alcoholism (International Classification of Diseases, 9th revision, codes 303.xx or 305.00) during a 6-month period (October 2000 to March 2001) were selected (n = 194,001). Patients in this group who were prescribed naltrexone during this period were identified. Logistic regression was used to compare those who were prescribed naltrexone with other alcoholics. In this sample, only 3,705 patients (1.9%) of the 194,001 veterans with an alcohol use disorder were prescribed naltrexone. Logistic regression analysis showed that naltrexone use was associated with comorbid disorders (bipolar disorder, dysthymia, major depressive disorder, posttraumatic stress disorder, and drug abuse) and recent psychiatric hospitalization. African Americans and veterans with organic brain syndromes were less likely to be prescribed naltrexone. These results suggest that prescribers have not embraced reports of naltrexone's efficacy in alcohol dependence, perhaps due to a general disinclination to use medications rather than a specific attitude toward naltrexone, especially in uncomplicated alcoholism.


Prediction of Alzheimer's Disease in Amnestic Mild Cognitive Impairment Subtypes: Stratification Based on Imaging Biomarkers.
Prediction of progression to Alzheimer's disease (AD) in amnestic mild cognitive impairment (MCI) is challenging because of its heterogeneity. To evaluate a stratification method on different cohorts and to investigate whether stratification in amnestic MCI could improve prediction accuracy. We identified 80 and 79 patients with amnestic MCI from different cohorts, respectively. They underwent baseline magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. We performed hierarchical clustering with three imaging biomarkers: Brain volume on MRI, left hippocampus grey matter loss on MRI, and left inferior temporal gyrus glucose hypometabolism on FDG-PET. Regions-of-interest for biomarkers were defined by the Automated Anatomical Labeling atlas. We performed voxel-wise statistical parametric mapping to explore differences between clusters in patterns of grey matter loss and glucose hypometabolism. We compared time to progression using an interval-censored parametric model. We evaluated predictive performance using logistic regression. Similar clusters were found in different cohorts. MCI1 had the healthiest biomarker profile of cognitive performance and imaging biomarkers. MCI2 had cognitive performance and MRI measures intermediate between those of nonconverters and converters. MCI3 showed the severest reduction in brain volume and left hippocampal atrophy. MCI4 showed remarkable glucose hypometabolism in the left inferior temporal gyrus, and also demonstrated significant decreases in most cognitive scores, including non-memory functions. MCI4 showed the highest risk for progression. The prediction of progression of MCI2 especially benefited from the stratification. Stratification with imaging biomarkers in amnestic MCI can be a good approach for improving predictive performance.


Expression of a repeating phosphorylated disaccharide lipophosphoglycan epitope on the surface of macrophages infected with Leishmania donovani.
Murine peritoneal macrophages were infected with living, virulent Leishmania donovani promastigotes. At intervals after infection, the macrophage surfaces were probed for the expression of lipophosphoglycan (LPG) epitopes by immunofluorescence with anti-LPG monoclonal antibodies. A repeating phosphorylated disaccharide epitope of LPG was detected as early as 5 to 10 min postinfection and was initially localized to the immediate area of internalization of the promastigote into the macrophage. The epitopes were evenly distributed over the entire macrophage surface by 25 min postinfection. Treatments which inhibited macrophage phagolysosomal degradation processes had no effect on epitope expression, whereas reagents that affected macrophage membrane flow and, thus, phagocytosis drastically reduced or abolished expression. Purified LPG or phosphoglycan, the delipidated form of the LPG molecule, was also shown to bind to a variety of different cell types in a temperature-independent manner. Since LPG has been implicated as having an immunoprotective role in leishmaniasis, these results suggest a further mechanism(s) by which Leishmania LPG might be involved in parasite pathogenicity and virulence.


Compatibility and stability of ondansetron hydrochloride, dexamethasone, and lorazepam in injectable solutions.
The stability of ondansetron hydrochloride, dexamethasone sodium phosphate, and lorazepam in 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) minibags and glass bottles was studied. Triplicate solutions of 8 or 32 mg of ondansetron (as the hydrochloride salt) mixed with 20 mg of dexamethasone phosphate (as the sodium salt) with or without 2 mg of lorazepam were compounded in 50-mL PVC minibags and glass bottles containing either 5% dextrose injection or 0.9% sodium chloride injection and stored at 23-25 degrees C. Duplicate measurements were performed when drugs were added and at 1, 2, 4, 8, and 24 hours after addition. Samples of the 32-mg ondansetron admixtures were collected under aseptic conditions to inspect for precipitation and to count particles with a laser particle analyzer. Samples of all admixtures were evaluated for chemical stability by stability-indicating high-performance liquid chromatography. Ondansetron hydrochloride and dexamethasone were physically compatible and chemically stable for up to 24 hours under the study conditions. The concentration of lorazepam in PVC containers dropped below 90% of the original concentration within four hours. In addition, particle counts in lorazepam-containing solutions were higher when 0.9% sodium chloride injection was the diluent than when 5% dextrose injection was the diluent. In admixtures containing all drugs, ondansetron hydrochloride and dexamethasone sodium phosphate in 5% dextrose injection or 0.9% sodium chloride injection were stable for up to 24 hours when stored in PVC bags or glass bottles.(ABSTRACT TRUNCATED AT 250 WORDS)


Regulation of CTL by ecto-nictinamide adenine dinucleotide (NAD) involves ADP-ribosylation of a p56lck-associated protein.
Receptor-mediated activation of T lymphocytes involves protein phosphorylation by several protein tyrosine kinases, among those the src-related enzymes p56lck and p59fyn. Accumulating evidence supports the notion that these enzymes are regulated by tyrosine phosphorylation and dephosphorylation, but much is yet to be learned about regulation of their activity. Here we demonstrate that p56lck but not p59fyn exists as a complex with a 40-kDa protein, which in its ADP-ribosylated form inhibits p56lck kinase activity. ADP-ribosylation of this protein is mediated by an arginine-specific mono-ADP-ribosyltransferase, which makes use of extracellular nicotinamide adenine dinucleotide (NAD). This enzyme is a glycosyl-phosphatidylinositol-anchored protein releasable from the surface of cytotoxic T cells by glycosyl-phosphatidylinositol-specific phospholipase C. Release of arginine-specific mono-ADP-ribosyltransferase results in failure of extracellular NAD to downmodulate p56lck kinase activity. Concomitant to suppression of the kinase by NAD, CD8 mediated transmembrane signaling and p56lck kinase activation are inhibited.


Drug Policy in Estonia.
The aim of this article was to present a general overview of the health care system as well as pricing and reimbursement environment in Estonia. In Estonia the main stakeholders in the pharmaceutical sector are the Ministry of Social Affairs, the State Agency of Medicine, and the Estonian Health Insurance Fund. The national health insurance scheme is public, and approximately 95% of the population is covered by it. It is a social insurance, and universal and equal access to health care based on national health insurance is granted. The Estonian Health Insurance Fund is financed from social taxes and state budget and is responsible for the reimbursement of pharmaceuticals in the hospital setting. It acts as an advisory body to the Ministry of Social Affairs on the process of reimbursement regarding cost effectiveness. Pharmaceutical products' reimbursement dossiers submission and decisions are dealt with on the state level. Health technology assessment analyses are required by the authorities and the Baltic Guidelines for Economic Evaluations of Pharmaceuticals have to be followed. The reimbursement lists are positive lists only, and the criteria upon which reimbursement decisions are based are officially defined. Revisions of reimbursement are performed depending on the need and they are based on the prices of reference countries.


Nicotine Withdrawal Induces Neural Deficits in Reward Processing.
Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p < .001). Exploratory analyses indicated withdrawal increased time to initiate the next trial following unexpected punishment trials (p < .001) and response time on reward trials during withdrawal was positively related to nicotine dependence (p < .001). Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and unpleasant stimuli may be particularly effective for alleviating nicotine withdrawal.


Homeobox genes and models for patterning the hindbrain and branchial arches.
Antennapedia class homeobox genes, which in insects are involved in regional specification of the segmented central regions of the body, have been implicated in a similar role in the vertebrate hindbrain. The development of the hindbrain involves the establishment of compartments which are subsequently made distinct from each other by Hox gene expression, implying that the lineage of neural cells may be an important factor in their development. The hindbrain produces the neural crest that gives rise to the cartilages of the branchial skeleton. Lineage also seems to be important in the neural crest, as experiments have shown that the crest will form cartilages appropriate to its level of origin when grafted to a heterotopic location. We show how the Hox genes could also be involved in patterning the mesenchymal structures of the branchial skeleton. Recently it has been proposed that the rhombomere-restricted expression pattern of Hox 2 genes is the result of a tight spatially localised induction from underlying head mesoderm, in which a prepattern of Hox expression is visible. We find no evidence for this model, our data being consistent with the idea that the spatially localised expression pattern is a result of segmentation processes whose final stages are intrinsic to the neural plate. We suggest the following model for patterning in the branchial region. At first a segment-restricted code of Hox gene expression becomes established in the neuro-epithelium and adjacent presumptive neural crest. This expression is then maintained in the neural crest during migration, resulting in a Hox code in the cranial ganglia and branchial mesenchyme that reflects the crest's rhombomere of origin. The final stage is the establishment of Hox 2 expression in the surface ectoderm which is brought into contact with neural crest-derived branchial mesenchyme. The Hox code of the branchial ectoderm is established later in development than that of the neural plate and crest, and involves the same combination of genes as the underlying crest. Experimental observations suggest the idea of an instructive interaction between branchial crest and its overlying ectoderm, which would be consistent with our observations. The distribution of clusters of Antennapedia class genes within the animal kingdom suggests that the primitive chordates ancestral to vertebrates had at least one Hox cluster. The origin of the vertebrates is thought to have been intimately linked to the appearance of the neural crest, initially in the branchial region.(ABSTRACT TRUNCATED AT 400 WORDS)


Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.
Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed as a valid adjunct in many procedures in oral and dental surgery. However, further RCTs are required to support this evidence.


Evaluation of factors reported by veterinarians who chose not to enter clinical academic veterinary medicine.
To identify factors that may have influenced veterinarians' decisions to not pursue careers in clinical academic veterinary medicine. 363 board-certified veterinarians. An online survey, open from July 7 to July 21, 2015, was used to gather data from board-certified veterinarians who were members of ≥ 1 of the 22 specialty organizations recognized by the American Board of Veterinary Specialties of the AVMA. Responses from those who reported never to have held an academic appointment were included in the study. Results were compiled and analyzed by gender and clinical discipline. Approximately 10,000 board-certified veterinarians were solicited to participate in the survey, and 1,314 (13.1%) responded. Among those, 363 (27.6%) reported never having held an academic position. Females more commonly reported no interest in teaching (44/185 [23.8%]) and disagreement with the statement that compensation in academic medicine was too low (39/164 [23.8%]), compared with responses by males (24/158 [15.2%] and 22/148 [14.9%], respectively). The strongest magnitude of interrater agreement was for the paired survey statements regarding too much bureaucracy and excessive expectation for committee and administrative work (weighted κ, 0.569). Many factors contribute to veterinarians' decisions about whether to pursue careers in academic medicine, and results indicated that some factors may vary depending on gender or clinical discipline. Recognition of these factors may help guide academic leaders in devising strategies and programs to enhance veterinarians' interest in clinical academic medicine careers.


Peptide-mediated broad-spectrum plant resistance to tospoviruses.
Plant viruses have a significant impact on agronomic losses worldwide. A new strategy for engineering virus-resistant plants by transgenic expression of a dominant interfering peptide is presented here. This peptide of 29 aa strongly interacts with the nucleocapsid proteins (N) of different tospoviruses. Transgenic Nicotiana benthamiana lines expressing the peptide fused to a carrier protein were challenged with five different tospoviruses that have a nucleocapsid protein interacting with the peptide. In the transgenic plants, strong resistance to tomato spotted wilt virus, tomato chlorotic spot virus, groundnut ring spot virus, and chrysanthemum stem necrosis virus was observed. This therefore demonstrates the feasibility of using peptide "aptamers" as an in vivo tool to control viral infection in higher plants.


Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect.
The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people. Current therapy relies upon a combination of pegylated interferon-alpha and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus. The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC(50)) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log(10) reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors.


Effect of acute beta-adrenergic blockade on lactate-induced panic.
Many clinical and theoretic attempts have been made to link anxiety disorders and the beta-adrenergic nervous system. Six patients with panic disorder, who had panic attacks produced by sodium lactate infusions, were given repeated lactate infusions that were immediately preceded by intravenous administration of propranolol hydrochloride. In all cases, propranolol pretreatment infusion failed to prevent panic attacks, anxiety, tachycardia, and increased systolic BP during the lactate infusion.


Anti-stress, Glial- and Neuro-differentiation Potential of Resveratrol: Characterization by Cellular, Biochemical and Imaging Assays.
Environmental stress, exhaustive industrialization and the use of chemicals in our daily lives contribute to increasing incidence of cancer and other pathologies. Although the cancer treatment has revolutionized in last 2-3 decades, shortcomings such as (i) extremely high cost of treatment, (ii) poor availability of drugs, (iii) severe side effects and (iv) emergence of drug resistance have prioritized the need of developing alternate natural, economic and welfare (NEW) therapeutics reagents. Identification and characterization of such anti-stress NEW drugs that not only limit the growth of cancer cells but also reprogram them to perform their specific functions are highly desired. We recruited rat glioma- and human neuroblastoma-based assays to explore such activities of resveratrol, a naturally occurring stilbenoid. We demonstrate that nontoxic doses of resveratrol protect cells against a variety of stresses that are largely involved in age-related brain pathologies. These included oxidative, DNA damage, metal toxicity, heat, hypoxia, and protein aggregation stresses. Furthermore, it caused differentiation of cells to functional astrocytes and neurons as characterized by the upregulation of their specific protein markers. These findings endorse multiple bioactivities of resveratrol and encourage them to be tested for their benefits in animal models and humans.


[Neutron-photon radiotherapy of brain tumors].
The data on combined photon-neutron radiation therapy of brain tumors (23 patients) are presented. Total focal dose (NSD) of photon radiation was 48-60 isoGy; neutron radiation--2.4 Gy (OBE equivalent to gamma radiation of 14.4 Gy). Out of 23 patients, 15 (65.2%) had suffered from tumor disease for a long time which continued after surgery or combined treatment, while 8 (34.8%) were followed up after treatment for primary brain tumor. First symptoms were evaluated. Dehydration therapy was given to 16 (69.6%). Photon- neutron radiation therapy follow-up was up 12 months. Immediate results were assessed every week. The number of complaints went down by approximately 12-15%; improvement was reported in 13 (56.5%), stabilization--9 (39.2%), deterioration--1 (4.8%). According to CT examination of the brain one month later, condition at focal site was unchanged in 17 (73.9%), 10% regression of tumor--6(26.1%). General aggravation of symptoms without roentgenological signs of tumor progression was registered in one case 3 months later. Brain tumor relapsed in still another patient 4 months later. All patients survived 12 months. These indices were 1.5-2 times higher than those for treatment of similar pathology using photon component alone.


Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study.
Multiple islet autoimmunity increases risk of diabetes, but not all individuals positive for two or more islet autoantibodies progress to disease within a decade. Major islet autoantibodies recognise insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A). Here we describe the baseline characteristics of a unique cohort of 'slow progressors' (n = 132) who were positive for multiple islet autoantibodies (IAA, GADA, IA-2A or ZnT8A) but did not progress to diabetes within 10 years. Individuals were identified from five studies (BABYDIAB, Germany; Diabetes Autoimmunity Study in the Young [DAISY], USA; All Babies in Southeast Sweden [ABIS], Sweden; Bart's Oxford Family Study [BOX], UK and the Pittsburgh Family Study, USA). Multiple islet autoantibody characteristics were determined using harmonised assays where possible. HLA class II risk was compared between slow progressors and rapid progressors (n = 348 diagnosed <5 years old from BOX) using the χ2 test. In the first available samples with detectable multiple antibodies, the most frequent autoantibodies were GADA (92%), followed by ZnT8A (62%), IAA (59%) and IA-2A (41%). High risk HLA class II genotypes were less frequent in slow (28%) than rapid progressors (42%, p = 0.011), but only two slow progressors carried the protective HLA DQ6 allele. No distinguishing characteristics of slow progressors at first detection of multiple antibodies have yet been identified. Continued investigation of these individuals may provide insights into slow progression that will inform future efforts to slow or prevent progression to clinical diabetes.


Relating vision status to academic achievement among year-2 school children in Malaysia.
Vision affects daily activities, but of particular importance is the impact upon the learning process. Many studies have been conducted to establish the relationship between vision problems and academic performance. The results are varied, however, and suggest additional research is needed with particular care given to study design. This study included 1,103 year-2 school children enrolled in 7 public schools in the Klang Valley region of Malaysia. There were an equal proportion of males (50.6%) and females (49.4%). The testing battery was designed to assess visual acuity, ocular muscle balance, visual analysis skills, visual-spatial skills, and visual-motor integration skills. Children with average and above-average achievement showed a different visual performance profile from those children with low academic achievement. They had a statistically significant better pass rate in physical aspects (visual acuity), physiological aspects (ocular motor balance), and perceptual aspects (visual-motor integration/visual-spatial and visual-analysis skills). Children with low academic achievement are more likely to exhibit problems in visual acuity, ocular motor balance, visual-motor integration and most all components of visual analysis skills. This finding supports the concept that visual performance is key to learning and therefore of chief concern as to school achievement.


The ethical challenges of field research: A personal narrative.
One of the biggest components of the disciplines, Sociology and Social Anthropology is fieldwork. Despite the significance of fieldwork as a method, there is limited scholarship on the myriad experiences of the fieldworker. This commentary emphasises the need to document field narratives of researchers, while using the personal field experience of the author as a prototype. The author encountered these experiences in 2016 as part of an independent and self-funded study (Understanding aging in old age homes of Delhi, India) that she had conducted in Delhi post the submission of her PhD thesis titled: Three essays in aging: Social capital, family dynamics and transnational arrangements. The said thesis was completed at the Indian Institute of Technology Gandhinagar, (pp: 1-169) from the year 2013-2018. In particular, the commentary sheds light on the ethical challenges faced during fieldwork. Specifically, this commentary, against the backdrop of the author's encounters in an old age home, analyses the importance of primary themes such as the subjective-objective approach, passionate detachment, rapport building, critical reflexivity and the insider-outsider perspective while conducting fieldwork.


Injury to skeletal muscle fibers of mice following lengthening contractions.
We tested the hypothesis that lengthening contractions result in greater injury to skeletal muscle fibers than isometric or shortening contractions. Mice were anesthetized with pentobarbital sodium and secured to a platform maintained at 37 degrees C. The distal tendon of the extensor digitorum longus muscle was attached to a servomotor. A protocol consisting of isometric, shortening, or lengthening contractions was performed. After the contraction protocol the distal tendon was reattached, incisions were closed, and the mice were allowed to recover. The muscles were removed after 1-30 days, and maximum isometric force (Po) was measured in vitro at 37 degrees C. Three days after isometric and shortening contractions and sham operations, histological appearance was not different from control and Po was 80% of the control value. Three days after lengthening contractions, histological sections showed that 37 +/- 4% of muscle fibers degenerated and Po was 22 +/- 3% of the control value. Muscle regeneration, first seen at 4 days, was nearly complete by 30 days, when Po was 84 +/- 3% of the control value. We conclude that, with the protocol used, lengthening, but not isometric or shortening contractions, caused significant injury to muscle fibers.


Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10.
We describe the cloning and expression of HSPDE4A10, a novel long form splice variant of the human cAMP phosphodiesterase PDE4A gene. The 825 amino acid HSPDE4A10 contains a unique N terminus of 46 amino acids encoded by a unique 5' exon. Exon-1(4A10) lies approximately 11 kilobase pairs (kb) downstream of exon-1(4A4) and approximately 13.5 kb upstream of the PDE4A common exon 2. We identify a rat PDE4A10 ortholog and reveal a murine ortholog by nucleotide sequence database searching. PDE4A10 transcripts were detected in various human cell lines and tissues. The 5' sequence flanking exon-1(4A10) exhibited promoter activity with the minimal functional promoter region being highly conserved in the corresponding mouse genomic sequence. Transient expression of the engineered human PDE4A10 open reading frame in COS7 cells allowed detection of a 121-kDa protein in both soluble and particulate fractions. PDE4A10 was localized primarily to the perinuclear region of COS7 cells. Soluble and particulate forms exhibited similar K(m) values for cAMP hydrolysis (3-4 microM) and IC(50) values for inhibition by rolipram (50 nM) but the V(max) value of the soluble form was approximately 3-fold greater than that of the particulate form. At 55 degrees C, soluble HSPDE4A10 was more thermostable (T(0.5) = 11 min) than the particulate enzyme (T(0.5) = 5 min). HSPDE4A10 and HSPDE4A4B are shown here to be similar in size and exhibit similar maximal activities but differ with respect to sensitivity to inhibition by rolipram, thermostability, interaction with the SRC homology 3 domain of LYN, an SRC family tyrosyl kinase, and subcellular localization. We suggest that the unique N-terminal regions of PDE4A isoforms confer distinct properties upon them.


Vitrectomy for epiretinal membrane in adult-onset Coats' disease.
Coats' disease is characterized by retinal vascular telangiectasia and subretinal and intraretinal exudation. A relatively benign form of the disease that occurs in adults is referred to as adult-onset Coats' disease. Involvement of macula in the form of macular edema and exudation are the common presenting features in both forms of the disease. We describe a rare case of adult-onset Coats' disease that presented with epiretinal membrane (ERM). Laser photocoagulation of retinal vascular telangiectasia resulted in worsening of patient's symptoms and ERM. Early pars plana vitrectomy resulted in resolution of the patient's symptoms. Utility of ultra-wide-field imaging and rationale of early vitrectomy in such cases are discussed.


Psychometric properties of the Screening Inventory of Psychosocial Problems (SIPP) in Dutch cancer patients treated with radiotherapy.
The Screening Inventory of Psychosocial Problems (SIPP) was developed to assess psychosocial distress in Dutch cancer patients. It is short, easily completed by patients and quickly interpreted by medical staff. In this study, we investigated the psychometric properties of the SIPP in 289 Dutch cancer patients treated with radiotherapy. The SIPP was administered alongside the Hospital Anxiety and Depression Scale and the Mental Adjustment to Cancer scale. In-depth structured clinical interviews were also conducted with 76 patients. Results indicate that the psychometric properties of the SIPP are promising with respect to its reliability, construct validity as evaluated with confirmatory factor analysis, and convergent and divergent validity. Receiver operating characteristics analysis showed that the SIPP successfully differentiates between patients known to have symptoms of distress and those who do not. The SIPP is therefore a reliable and valid instrument for identifying distress in cancer patients. It differs from previously developed instruments in that it measures different domains of distress in only a few minutes, and provides opportunity for patients to indicate whether they would like to discuss identified problem areas. Due to its convenient format, the SIPP may easily be used to assess psychosocial distress in cancer patients as a routine part of the clinical consultation.


Bacteriology and beta-lactamase activity in acute and chronic maxillary sinusitis.
To assess the bacteriology and beta-lactamase enzyme activity in aspirates of 10 acutely and 13 chronically inflamed maxillary sinuses. The predominant organisms isolated in acute sinusitis were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, and those found in chronic sinusitis were Prevotella species, Fusobacterium species, and Peptostreptococcus species. Four beta-lactamase-producing organisms (BLPOs) were isolated in four specimens (40%) obtained from acutely inflamed sinuses, and 14 BLPOs were recovered from 10 chronically inflamed sinuses (77%). The predominant BLPOs in acute sinusitis were H influenzae, and M catarrhalis; those in chronic sinusitis were Staphylococcus aureus, Prevotella species, Fusobacterium species, and Bacteroides fragilis. Beta-lactamase activity was detected in 12 (three in acute and nine in chronic sinusitis) of the 14 aspirates that contained BLPOs. The detection of beta-lactamase activity in sinus aspirates provides support for the role of BLPOs in the failure of penicillin therapy in sinusitis.


The essential role of bursicon during Drosophila development.
The protective external cuticle of insects does not accommodate growth during development. To compensate for this, the insect life cycle is punctuated by a series of molts. During the molt, a new and larger cuticle is produced underneath the old cuticle. Replacement of the smaller, old cuticle culminates with ecdysis, a stereotyped sequence of shedding behaviors. Following each ecdysis, the new cuticle must expand and harden. Studies from a variety of insect species indicate that this cuticle hardening is regulated by the neuropeptide bursicon. However, genetic evidence from Drosophila melanogaster only supports such a role for bursicon after the final ecdysis, when the adult fly emerges. The research presented here investigates the role that bursicon has at stages of Drosophila development which precede adult ecdysis. We addressed the mechanism and timing of hormonal release from bursicon-positive motor neurons at the larval neuromuscular junction. Our findings indicate that vesicle membrane proteins which are required for classical neurotransmitter release are also expressed at these peptidergic motor neuron terminals; and that these terminals secrete hormones including bursicon at the neuromuscular junction, coinciding with larval ecdysis. This release surprisingly occurs in two waves, indicating bursicon secretion preceding and following the ecdysis sequence. Next, we addressed the functional significance of bursicon signaling during development, by disrupting the expression of its receptor, rickets, in different target tissues. We determined that rickets is developmentally required in the epidermis and imaginal discs for proper formation of the prepupa. It is also required to harden the pharate adult cuticle before eclosion. Significantly, we have also found that the available rickets mutants are not genetic nulls as previously believed, which necessitated the use of targeted RNA interference to disrupt rickets expression. Our results are consistent with the view that bursicon is the insect tanning hormone. However, this is the first study to rigorously demonstrate both its release and function during development. Importantly, we provide new evidence that bursicon release can precede the initiation of larval ecdysis, and that bursicon tans the puparium. Our results firmly establish bursicon signaling as essential to insect growth and development.


Symbiodinium thermophilum sp. nov., a thermotolerant symbiotic alga prevalent in corals of the world's hottest sea, the Persian/Arabian Gulf.
Coral reefs are in rapid decline on a global scale due to human activities and a changing climate. Shallow water reefs depend on the obligatory symbiosis between the habitat forming coral host and its algal symbiont from the genus Symbiodinium (zooxanthellae). This association is highly sensitive to thermal perturbations and temperatures as little as 1°C above the average summer maxima can cause the breakdown of this symbiosis, termed coral bleaching. Predicting the capacity of corals to survive the expected increase in seawater temperatures depends strongly on our understanding of the thermal tolerance of the symbiotic algae. Here we use molecular phylogenetic analysis of four genetic markers to describe Symbiodinium thermophilum, sp. nov. from the Persian/Arabian Gulf, a thermally tolerant coral symbiont. Phylogenetic inference using the non-coding region of the chloroplast psbA gene resolves S. thermophilum as a monophyletic lineage with large genetic distances from any other ITS2 C3 type found outside the Gulf. Through the characterisation of Symbiodinium associations of 6 species (5 genera) of Gulf corals, we demonstrate that S. thermophilum is the prevalent symbiont all year round in the world's hottest sea, the southern Persian/Arabian Gulf.


Follicular lymphoma prognostic factors in the modern era: what is clinically meaningful?
Follicular lymphomas (FL) account for 30% of non-Hodgkin's lymphomas (NHL). Their evolution is heterogeneous. Some patients present with indolent forms undergoing several relapses while in other patients the disease evolves abruptly toward aggressive NHL. This is why accurate prognostic indices are required so that treatment strategies may be optimized for each patient and so that trials may be conducted in groups of patients that are as homogeneous as possible. The Follicular Lymphoma International Prognostic Index (FLIPI) has been designed to separate patients into 3 groups with significantly different hazard ratios for death. Its accuracy has been confirmed in several studies. The FLIPI2 was designed more recently to separate patients with significantly different hazard ratios for progression/relapse in the era of anti-CD20 monoclonal antibody treatments. Gene profile studies have shown that the prognosis of FL is mainly related to the type, number, and activation of immune cells in the microenvironment of lymphomatous follicles. Immunohistochemical studies suggest that macrophages, CD4+ T cells and among them T-regulatory cells (T-regs) and programed death-1 cells (PD-1 cells) play a major role in the outcome of FLs. However, additional confirmatory studies are required due to discrepancies in results. Up to now, these biological study results are more useful for approaching the pathophysiology of FL rather than to be used as prognostic tools in clinical practice.


Impact of the role of senior dual disability coordinator on the perceived self-efficacy and job satisfaction of mental health clinicians.
This study aimed to evaluate a new service role in mental health services, namely, the senior dual disability coordinator role (SDDC) for its impact on the perceived self-efficacy of mental health clinicians in managing clients with dual disability (mental illness and acquired brain injury and/or intellectual disability) and their job satisfaction. Mental health clinicians from a health service district in Queensland, Australia who contacted the SDDC for clinical consultation and liaison between July 2011 and July 2013 were asked to complete a questionnaire assessing perceived self-efficacy in working with clients with dual disability as well as their job satisfaction, prior to (T1) and following (T2) their contact with the SDDC. Twenty-five clinicians completed and returned pre- and post-measure questionnaires. Self-reported knowledge of dual disability, clinical skills in dual disability, service knowledge in dual disability as well as perceived self-efficacy, and job satisfaction increased significantly from T1 to T2. There were no significant differences across professional discipline or years of service. The delivery of a clinical consultation liaison service as part of the role of SDDC may assist mental health clinicians with self-efficacy and job satisfaction, regardless of the number of years they have worked in the service or their professional discipline. Mental health clinicians with improved self-efficacy for working with clients with dual disability may be more likely to consider the client suitable for services through mental health and follow-up with treatment and linking the client with other identified suitable services. Implications for Rehabilitation Dual disability (mental illness and acquired brain injury and/or intellectual disability) presents specific challenges for mental health services Specific strategies are needed to build capacity among mental health practitioners in order to meet the needs of people with dual disability and provide appropriate services. Introducing dual disability coordinators as a specific position within a health service district may assist to improve self-efficacy and job satisfaction of mental health practitioners assisting people with dual disability.


Docosahexaenoic acid and eicosapentaenoic acid suppress adhesion molecule expression in human aortic endothelial cells via differential mechanisms.
Dietary PUFAs modulate the progression of cardiovascular disease, but the underlying mechanisms within vascular cells remain unclear. The aim of this study was to investigate the biological function and regulatory mechanisms of PUFAs in LPS-activated human aortic endothelial cells (HAECs). To simulate the in vivo conditions of atherosclerosis, we have established an in vitro model in which THP-1 monocytes adhere to HAECs. Our results showed that n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) remarkably attenuated the adhesion of THP-1 cells to HAECs, probably through inhibiting the expression of VCAM-1 and ICAM-1. Using lipid raft isolation and confocal microscopy, we found that DHA and EPA suppressed the translocation of TLR4 into lipid rafts. Furthermore, DHA and EPA inhibited the ubiquitination and translocation of TRAF6, and the phosphorylation of TAK1, p38, and IκBα. We demonstrated that DHA reduced the phosphorylation of PKR, but EPA increased the expression of A20. Additionally, silencing of A20 reversed the inhibitory effect of EPA on the expression of adhesion molecules. Our study revealed differential signaling pathways modulated by n-3 PUFAs in LPS-stimulated HAECs. These signaling pathways are potential targets for the prevention of atherosclerotic progression.


Association between phenotypic characteristics of Escherichia coli and UTI recurrence in immunocompromised patients: A case-control study.
Urinary tract infection (UTI) recurrence is important in immunocompromised patients. There is a trend to study genotypically and phenotypically the role of certain virulence factors of Escherichia coli in the diagnosis of recurrent UTI. The main objective of this study was to determine if there is an association between phenotypic characteristics of E coli and UTI recurrence in immunocompromised patients. A case-control study was performed on immunocompromised patients from Hospital Regional de Alta Especialidad del Bajío, Mexico. E coli strains isolated from these patients were identificated and antimicrobial susceptibility test were performed. Strains with filamented cell morphology, mucoid colonial phenotype, or biofilm production were considered cases. Strains without the characteristics were considered controls. UTI recurrence was identified based on clinical records. The odds ratio (OR) was calculated to quantify the magnitude of the association. An association between filamented cell morphology and UTI recurrence was found (OR = 2.19 95% CI 1.06-4.51; P = .031). No association was found between mucoid colony morphology (P>.05) or biofilm production (P>.05) and UTI recurrence. An association between mucoid colony morphology and extended-spectrum β-lactamase production was found (OR = 3.09 95% 1.59-5.99; P<.001). Filamented cell morphology and mucoid colonial phenotype may have a possible diagnostic value for the detection of UTI recurrence and antimicrobial resistance. Further diagnostic test studies are needed to fully assess their clinical utility.


[The reaction of the immune system to insulinlike growth factor-1 in postmenopausal women with breast cancer].
Taking into account the information about the role of insulin-like growth factor -1 (IGF-1) in breast cancer the main aim of the present study was to investigate the cellular immune response to IGF-1. There were examined 58 patients with breast cancer (61 +/- 1 years, BMI 31,2 +/- 0,9 kg/m2, all postmenopausal) and 10 with benign tumors of the breast (56 +/- 2 years, BMI 30,8 +/- 0,7 kg/m2 all menopausal) as well as 17 patients suffering from cancer of different sites. Sensibilization of lymphocytes to IGF-1 was measured in the reaction of blast transformation of peripheral blood lymphocytes. The majority of breast cancer patients (47/58) revealed the sensibilization of peripheral blood lymphocytes to IGF-1. Thus in a part of patients (29 /47) this reaction was suppressed and revealed after suppression of cyclooxygenase and/or blocking of the histamine H2-receptors by corresponding pharmaceutics drugs in vitro.


Secretion of glycated insulin from pancreatic beta-cells in diabetes represents a novel aspect of beta-cell dysfunction and glucose toxicity.
Hyperglycaemia, a significant pathophysiological state in diabetes mellitus, may contribute to defective pancreatic beta-cell function, secretion and action of insulin through glycation of important regulatory proteins. This paper highlights recent data supporting the concept that pancreatic beta-cell dysfunction is associated with increased glycation of functional proteins. The pancreatic beta-cell provides a highly favourable environment for the intracellular glycation of insulin which is a relatively rapid, glucose-dependent process. Using a novel radioimmunoassay and immunocytochemical techniques, glycated insulin has been shown to be stored and secreted from pancreatic beta-cells in both human and animal models of diabetes. Glycated insulin represents a significant proportion of total circulating insulin in type 2 diabetes and may have impaired metabolic clearance compared with native insulin. Since glycation of insulin disturbs normal cellular function and results in decreased biological activity, it may play a significant contributory role in the insulin resistance and glucose intolerance of type 2 diabetes. Further studies are necessary to evaluate the possible significance of glycated insulin in both the pathophysiology of diabetes and future therapeutic approaches.


Metabolic Profiling of Chloroacetanilide Herbicides in Earthworm Coelomic Fluid Using 1H NMR and GC-MS.
Earthworms ( Eisenia fetida) are vital members of the soil environment. Because of their sensitivity to many contaminants, monitoring earthworm metabolism may be a useful indicator of environmental stressors. Here, metabolic profiles of exposure to five chloroacetanilide herbicides and one enantiomer (acetochlor, alachlor, butachlor, racemic metolachlor, S-metolachlor, and propachlor) are observed in earthworm coelomic fluid using proton nuclear magnetic resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS). Multiblocked-orthogonal partial least-squares-discriminant analysis (MB-OPLS-DA) and univariate analysis were used to identify metabolic perturbations in carnitine biosynthesis, carbohydrate metabolism, lipid metabolism, nitrogen metabolism, and the tricarboxylic acid cycle. Intriguingly, stereospecific metabolic responses were observed between racemic metolachlor and S-metolachlor exposed worms. These findings support the utility of coelomic fluid in monitoring metabolic perturbations induced by chloroacetanilide herbicides in nontarget organisms and reveal specificity in the metabolic impacts of herbicide analogues in earthworms.


A computational analysis of the antigenic properties of haemagglutinin in influenza A H3N2.
Modelling antigenic shift in influenza A H3N2 can help to predict the efficiency of vaccines. The virus is known to exhibit sudden jumps in antigenic distance, and prediction of such novel strains from amino acid sequence differences remains a challenge. From analysis of 6624 amino acid sequences of wild-type H3, we propose updates to the frequently referenced list of 131 amino acids located at or near the five identified antibody binding regions in haemagglutinin (HA). We introduce a class of predictive models based on the analysis of amino acid changes in these binding regions, and extend the principle to changes in HA1 as a whole by dividing the molecule into regional bands. Our results show that a range of simple models based on banded changes give better predictive performance than models based on the established five canonical regions and can identify a higher proportion of vaccine escape candidates among novel strains than a current state-of-the-art model.


The platform transfer splint: 2 case reports of a mobility aide for persons with arm injuries or conditions.
Limited or impaired mobility is a major obstacle to maximizing length of stay efficiency for inpatient rehabilitation. Trauma patients and others with multiple limb impairments present a mobility challenge to all rehabilitation centers. Of particular concern are patients with forearm fractures who are nonambulatory. With shorter inpatient stays, patients are being discharged home or to other settings with continued weight-bearing restrictions. These patients put great demands on their caregivers as a result of their limited mobility. The Platform Transfer Splint (PTS) has been developed to overcome limitations seen in this patient population. It is an upper extremity splint that allows weight bearing through the humerus for patients with impairments of the forearm or hand. With use of the PTS, patients can become independent in transfers and wheelchair propulsion. Two case studies are presented to show the impact of the PTS on patient mobility and discharge disposition. Fabrication of the splint is also discussed.


Modifier effects in autism at the MAO-A and DBH loci.
Autism is one of a group of pervasive developmental disorders (PDD) characterized by qualitative impairments in reciprocal social communication and by a preference for repetitive, stereotyped activities, interests, and behaviors. The disorder is caused in large part by genetic mechanisms, though no disease genes have yet been identified. The objective of this study was to investigate three markers, two in the DBH gene and one in the MAO-A gene, for maternal or fetal modifier effects on level of functioning (IQ). At the same time, the possibility of maternal or fetal susceptibility effects was also examined. We assembled 67 affected sibpairs and 45 singletons and determined allele frequencies at the three markers among the affected children and first degree relatives. Sizeable and significant modifier effects were found at the MAO locus and, to a lesser extent, at the DBH locus. Susceptibility effects were also found but not without qualification. We conclude that maternal genotypes at the MAO-A locus, and possibly at the DBH one, may modify IQ in children with autism through the intrauterine environment.


LOCAL TRANSLATION. Response to Comment on "Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling".
Reid and Nicchitta propose that most cellular translation is carried out by a noncycling pool of endoplasmic reticulum (ER)-associated ribosomes. However, proximity-specific ribosome profiling data place an upper bound of about 7 to 16% on the fraction of cytosolic protein translation carried out by ribosomes accessible to ER-tethered biotin ligases. Moreover, yeast pulse-labeling experiments argue against there being a static population of ER-associated ribosomes.


Spinal processing: anatomy and physiology of spinal nociceptive mechanisms.
The processing of nociceptive input that occurs at the spinal level represents the first stage of effective control over its access to higher regions of the central nervous system. Recent developments in both the anatomy and physiology of nociceptive processing pathways at this level are beginning to yield an integrated understanding of structure and function. Most small afferent axons terminate in the more superficial laminae of dorsal horn, but technical difficulties have, until recently, prevented analysis of the functional properties of identified small fibres. A direct input of nociceptive afferents on to particular dorsal horn neurons is difficult to establish in view of the slow impulse conduction in these fibres and the small size of target neurons in the substantia gelatinosa. The small cells themselves are being analysed for relations between structure and function, using physiological, intracellular staining and immunocytochemical techniques to characterize their properties. They appear to be a highly heterogeneous population with many sub-classes, whether typed according to the transmitter they contain, e.g. enkephalin, to their physiological responses: whether excitatory or inhibitory to nociceptive and other inputs, or to both. The multireceptive neurons that project out of the dorsal horn toward supraspinal regions are, in general, located in deeper laminae and are likely to receive nociceptive information through polysynaptic pathways. The nocireceptive neurons in lamina I, which receive exclusively nociceptive inputs from myelinated and non-myelinated afferents project, at least in part, to thalamic and brain stem regions. Polysynaptic nociceptive pathways in dorsal horn may be subject to different controls from neurons in laminae I and II. Tonic descending inhibition is operative on the former and it is becoming clearly established that descending systems such as those containing noradrenaline, can regulate the access of nociceptive information to higher levels. The mechanisms of such descending controls and the importance of their interaction with segmental control systems, such as those involving the dynorphin opioids, are just beginning to be understood. Many somatosensory neurons in dorsal horn, both the large cells, some of which project supraspinally, and the small cells of superficial laminae, receive convergent nociceptive and non-nociceptive inputs. Although solely nociresponsive neurons are clearly likely to fill a role in the processing and signalling of pain in the conscious central nervous system, the way in which such useful specificity could be conveyed by multireceptive neurons is difficult to appreciate.(ABSTRACT TRUNCATED AT 400 WORDS)


Liposome-assisted selective polycondensation of alpha-amino acids and peptides.
The main question of this paper is whether and to what extend lipid bilayers can aid in the polycondensation of amino acids and peptides. This means in particular how such bilayers can favor the selection of certain sequences out of a large number of theoretical possible ones. In a first series of experiments we started from a library of Trp-containing dipeptides of the type Trp-X where X is an amino acid residue; and we could show that, when adding this mixture to the POPC liposomes containing a hydrophobic quinoline condensing agent (EEDQ), only the hydrophobic Trp-Trp dipeptide is selected out by the liposomes and transformed into a longer oligomer. Trp-oligomers up to 29 monomers long (water insoluble) could be obtained by using the matrix support of liposomes. Mixed POPC/DDAB liposomes (positive charge) were used to produce co-oligopeptides that contain Trp and Glu residues in the same sequence. Arg/Trp and His/Trp containing sequences were obtained in presence of negatively charged liposomes (mixed POPC/DOPA-liposomes). The polycondensation of racemic NCA-amino acids has been studied to clarify if homochiral sequences are produced preferentially in presence or absence of liposomes. LC-MS and isotope labeling of the L-amino acid, participating in the polymerization reaction achieved this on the level of a direct product analysis. So the individual stereoisomer distribution up to a polymerization degree of 10 (in the case of Trp) could be determined. The data for Trp and other amino acids (Leu, Ile) and amino acid mixtures (Trp/Leu, Trp/Ile, Leu/Ile and Trp/Leu/Ile) show that homochiral sequences are produced preferentially if compared with a random (Bernoulli) distribution.


A self-adapting system for the automated detection of inter-ictal epileptiform discharges.
Scalp EEG remains the standard clinical procedure for the diagnosis of epilepsy. Manual detection of inter-ictal epileptiform discharges (IEDs) is slow and cumbersome, and few automated methods are used to assist in practice. This is mostly due to low sensitivities, high false positive rates, or a lack of trust in the automated method. In this study we aim to find a solution that will make computer assisted detection more efficient than conventional methods, while preserving the detection certainty of a manual search. Our solution consists of two phases. First, a detection phase finds all events similar to epileptiform activity by using a large database of template waveforms. Individual template detections are combined to form "IED nominations", each with a corresponding certainty value based on the reliability of their contributing templates. The second phase uses the ten nominations with highest certainty and presents them to the reviewer one by one for confirmation. Confirmations are used to update certainty values of the remaining nominations, and another iteration is performed where ten nominations with the highest certainty are presented. This continues until the reviewer is satisfied with what has been seen. Reviewer feedback is also used to update template accuracies globally and improve future detections. Using the described method and fifteen evaluation EEGs (241 IEDs), one third of all inter-ictal events were shown after one iteration, half after two iterations, and 74%, 90%, and 95% after 5, 10 and 15 iterations respectively. Reviewing fifteen iterations for the 20-30 min recordings 1 took approximately 5 min. The proposed method shows a practical approach for combining automated detection with visual searching for inter-ictal epileptiform activity. Further evaluation is needed to verify its clinical feasibility and measure the added value it presents.


[Dynamics of cortical evoked activity during human learning to discriminate microintervals of time using feedback].
The dynamics of the cortical evoked activity in the process of learning of time microintervals (10, 60 and 180 ms) discrimination was studied in healthy adults. Feedback stimulus visually informing of the real correlations of the differentiated pauses facilitates the discrimination. The factor of the visual field does not affect the estimation of brief time intervals. At correct identifications, the P300 wave is recorded with a higher amplitude, than at errors. In the trial following the "nonconfirming" feedback stimulus, the standard and test stimuli evoke in the left hemisphere a greater P300 wave, than in the trial after the "confirming" stimulus. Feedback influence is retained in the long-term memory.


[Perineo-scrotal gangrene (Fournier's gangrene)].
Four cases of perineoscrotal gangrene are reported herein. All were immune-suppressed and three were diabetics. Its primary focus was in the GU tract or intestine. Culture was positive for Gram-negative aerobes and anaerobes. Early aggressive surgery and adjuvant antibiotic therapy achieved an excellent survival rate.


Tuberculous pleural effusions. Evidence for selective presence of PPD-specific T-lymphocytes at site of inflammation in the early phase of the infection.
Patients with tuberculous pleural effusions may show cutaneous anergy to tuberculin purified-protein derivative (PPD). This phenomenon has been attributed either to preferential sequestration of antigen-specific T-lymphocytes to the pleural space or to the presence of suppressor monocytes in the blood. In 2 patients with primary tuberculous infection involving the pleura and with skin anergy to PPD, the in vitro proliferation of pleural and peripheral blood T-cells to PPD was evaluated. Although peripheral blood T-cells were not reactive, pleural T-cells showed a marked proliferative response to PPD. At least in the first patient, the lack of proliferation of circulating T-cells could not be related to the presence of suppressor monocytes. Interestingly, after 4 to 8 wk of specific chemotherapy, PPD skin test became positive and the blood T-lymphocytes responded in vitro to the same antigen. Pleural T-lymphocytes were used to generate long-term, PPD-specific T-cell lines and could be maintained in vitro for more than 3 months with repeated cycles of stimulation. The pleural and the blood T-lymphocytes and the T-cell lines were also characterized phenotypically: although the majority of the T-lymphocytes present in the pleural space after Mycobacterium tuberculosis infection were Leu-3-positive (helper T-cells), T-cell lines proliferating in response to PPD included high numbers of Leu-2-positive cells (suppressor/cytotoxic T-cells). These data suggest that early skin anergy in tuberculous pleurisy may be associated with sequestration of PPD-reactive T-lymphocytes in the pleural spaces involving both Leu-2-and Leu-3-positive T-cells.


Wrinkling and failure behavior of single-layer MoS2 sheets under in-plane shear.
In this paper, the wrinkling and failure behavior of single layer MoS2 (SLMoS2) sheets under in-plane shear is investigated using molecular simulations and the nonlocal model. Wrinkling and failure features, such as the stress-strain relation, the amplitude and the half-wavelength, are comprehensively explored. The effects of size, temperature and pre-existing cracks on the wrinkling and failure behavior are then taken into consideration. It is found that the whole process can be divided into three stages, i.e., the pre-buckling stage, the buckling stage and the failure stage. The classical continuum model is found to be limited in quantitatively analyzing the wrinkling behavior due to the lack of size effect. The nonlocal parameter, a key parameter to characterize the size effect, is first reported. What is more, compared with edge cracks, SLMoS2 sheets are more sensitive to pre-existing centre cracks. This work can provide a better understanding of the wrinkling and failure properties of SLMoS2 sheets under shear loads, and should be helpful for developing various flexible electronic devices.


The relative amounts of plasma transthyretin forms in familial transthyretin amyloidosis: a quantitative analysis by Fourier transform ion-cyclotron resonance mass spectrometry.
Familial transthyretin amyloidosis (ATTR) is a fatal autosomal dominant disease characterized by the formation of amyloid fibers, mainly composed of transthyretin (TTR). Protein aggregation and amyloid fiber formation are considered concentration dependent processes and since most ATTR patients are heterozygous it is crucial to determine the ratio between mutant and non-mutant TTR forms in human plasma. Using a high resolution mass spectrometry based approach we determined the ratio of TTR forms in ATTR patients, V30M mutation carriers, symptomatic and asymptomatic ones, as well as ATTR patients that received a wild type cadaveric liver transplant. Domino transplanted patients that received a liver from an ATTR patient were also investigated. We found that although wild type TTR is diminished in the plasma of non-transplanted ATTR patients comparatively to healthy subjects, the relationship with the V30M variant does not change with illness progression. Those who received a wild type liver showed no mutant protein while domino transplanted patients presented the same relative amount of V30M as found in asymptomatic and symptomatic individuals. The V30M to wild type TTR ratio in plasma is the same for all ATTR patients studied, showing no variation with disease clinical progression. Our results point to the involvement of additional non-genetic factors on the pathogenesis of this disease.


Analysis of Clinical and Laboratory Alterations Related to Dengue Case Severity: Comparison between Serotypes 2 and 4 in Brazil.
The increase in severe dengue (SD) cases has caused great impact on public health and has concerned authorities of countries where the disease is endemic and epidemics reach high proportions. The recognition of progression signs of this severe disease during the initial febrile phase can be difficult, since the symptoms are often indistinguishable from other febrile diseases. The aim of this study was to evaluate the clinical manifestations and laboratory findings in patients from two dengue outbreaks and their association with the disease. The study was conducted in patients (n = 153) with signs and symptoms consistent with dengue occurred during two distinct epidemics, 2010 and 2013, in the city of Campos dos Goytacazes, Rio de Janeiro, Brazil. According to the 2009 World Health Organization criteria, patients were classified as dengue without warning signs ([DwoWS] 60.6%, 57/94), dengue with warning signs ([DwWS] 30.9%, 29/94), and SD (4.25%, 4/94). Patients with DwWS/SD presented lower platelet and leukocyte counts and higher transaminase levels when compared with the DwoWS ones. Interestingly, patients from the epidemic of 2010 caused by dengue virus 2 (DENV-2) had lower platelet counts than patients of the 2013 epidemic caused by DENV-4. Furthermore, plasma leakage, gastrointestinal bleeding, and pleural effusion, hallmarks for a more severe disease, were also more frequently observed in those cases. Although previous studies may have extensively reported the wide range of the clinical aspects of dengue, the characterization of DENV-4 is desirable considering the burden of the disease during epidemics, especially for the health units and hospitals performing patient's management.


Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies?
We found that congenital uterine anomalies have a negative impact on reproductive outcome in recurrent-miscarriage couples, being associated with further miscarriage with a normal embryonic karyotype. There has been no study comparing live birth rates between patients with and without surgery. We conducted a prospective study to prove that surgery for a bicornuate or septate uterus might improve the live birth rate. A total of 170 patients with congenital uterine anomalies suffering two or more miscarriages were examined. The live birth rate after ascertainment of anomalies, cumulative live birth rate and infertility rate, were compared between patients with and without surgery. In patients with a septate uterus, the live birth rate (81.3%) at the first pregnancy after ascertainment of anomalies with surgery tended to be higher than that (61.5%) in those without surgery. The infertility rates were similar in both groups, while the cumulative live birth rate (76.1%) tended to be higher than without surgery (60.0%). Surgery showed no benefit in patients with a bicornuate uterus for having a baby, but tended to decrease the preterm birth rate and the low birth weight. The possibility that surgery has benefits for having a baby in patients with a septate uterus suffering recurrent miscarriage could not be excluded.


Induction of thioredoxin and thioredoxin reductase gene expression in lungs of newborn primates by oxygen.
Thioredoxin (TRX) is a potent protein disulfide oxidoreductase important in antioxidant defense and regulation of cell growth and signal transduction processes, among them the production of nitric oxide. We report that lung TRX and its reductase, TR, are specifically upregulated at birth by O2. Throughout the third trimester, mRNAs for TRX and TR were expressed constitutively at low levels in fetal baboon lungs. However, after premature birth (125 or 140 of 185 days gestation), lung TRX and TR mRNAs increased rapidly with the onset of O2 or air breathing. Lung TRX mRNA also increased in lungs of term newborns with air breathing. Premature animals (140 days) breathing 100% O2 develop chronic lung disease within 7-14 days. These animals had greater TRX and TR mRNAs after 1, 6, or 10 days of life than fetal control animals. In 140-day animals given lesser O2 concentrations (as needed) who do not develop chronic lung disease, lung TRX and TR mRNAs were also increased on days 1 and 6 but not significantly on day 10. In fetal distal lung explant culture, mRNAs for TRX and TR were elevated within 4 h in 95% O2 relative to 1% O2, and the response was similar at various gestations. In contrast, TRX protein did not increase in lung explants from premature animals (125 or 140 days) but did in those from near-term (175-day) fetal baboons after exposure to hyperoxia. However, lung TRX protein and activity, as well as TR activity, eventually did increase in vivo in response to hyperoxia (6 days). Increases in TRX and TR mRNAs in response to 95% O2 also were observed in adult baboon lung explants. When TRX redox status was determined, increased O2 tension shifted TRX to its oxidized form. Treatment of lung explants with actinomycin D inhibited TRX and TR mRNA increases in 95% O2, indicating transcriptional regulation by O2. The acute increase in gene expression for both TRX and TR in response to O2 suggests an important role for these proteins during the transition from relatively anaerobic fetal life to O2 breathing at birth.


Duchenne muscular dystrophy: quality of life among 95 patients evaluated using the Life Satisfaction Index for Adolescents.
The purpose of this study was to evaluate the quality of life (QoL) of patients with Duchenne muscular dystrophy (DMD) in different stages of the disease, by means of the Life Satisfaction Index for Adolescents (LSI-A). The practicality of this scale was also verified. The LSI-A was applied four times to 95 patients with DMD who were undergoing steroid therapy, at three-month intervals. The patients were divided into four groups according to age. The results from the four applications and the inter and intra-examiner concordance were treated statistically. Comparing the different age groups, patients with DMD did not lose QoL, even with disease progression. We concluded that, in spite of the progressive course of the disease, the QoL in patients with DMD does not get worse. The use of a scale that embraces a great diversity of circumstances in patients' lives, without considering clinical aspects excessively, is a good alternative for assessing the QoL of these patients.


AAEM case report 16. Botulism. American Association of Electrodiagnostic Medicine.
Early diagnosis of botulism is essential for effective treatment. Electrophysiologic testing can be of major help to establish a prompt diagnosis, but the classic electrodiagnostic features of botulism are often elusive. Decrement or increment of compound muscle action potential (CMAP) amplitudes to slow or fast rates of nerve stimulation are often unimpressive or totally absent. Reduction of CMAP amplitudes, denervation activity, or myopathic-like motor unit potentials in affected muscles are found more frequently but they are less specific. In general, the electrophysiologic findings taken together suggest involvement of the motor nerve terminal, which should raise the possibility of botulism. The case reported here illustrates a common clinical presentation of botulism. This study emphasizes realistic expectations of the electrodiagnostic testing, the differential diagnosis, and the potential pitfalls often encountered in the interpretation of the electrophysiologic data.


Pterostilbene, a natural dimethylated analog of resveratrol, inhibits rat aortic vascular smooth muscle cell proliferation by blocking Akt-dependent pathway.
Vascular smooth muscle cells (VSMCs) are the main cellular component in the arterial wall, and abnormal proliferation of VSMCs plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty, and possibly in the development of hypertension. Pterostilbene, a natural dimethylated analog of resveratrol, is known to have diverse pharmacological activities including anti-cancer, anti-inflammation and anti-oxidant activities. The present study was designed to investigate the effects of pterostilbene on platelet-derived growth factor (PDGF)-BB-induced VSMCs proliferation as well as the molecular mechanisms of the antiproliferative effects. The cell growth of VSMCs was determined by cell counting and [(3)H]thymidine incorporation assays. Pterostilbene significantly inhibited the DNA synthesis and proliferation of PDGF-BB-stimulated VSMCs in a concentration-dependent manner. The inhibition percentages of pterostilbene at 1, 3 and 5microM to VSMCs proliferation were 68.5, 80.7 and 94.6%, respectively. The DNA synthesis of pterostilbene at 1, 3 and 5microM in VSMCs was inhibited by 47.4, 76.7 and 100%, respectively. Pterostilbene inhibited the PDGF-BB-stimulated phosphorylation of Akt kinase. However, pterostilbene did not change the expression of extracellular signal-related kinase (ERK) 1/2, PLCgamma1, phosphatidylinositol (PI)3 kinase and PDGF-Rbeta phosphorylation. In addition, pterostilbene down-regulated the cell cycle-related proteins including the expression of cyclin-dependent kinase (CDK) 2, cyclin E, CDK4, cyclin D1, retinoblastoma (Rb) proteins and proliferative cell nuclear antigen (PCNA). These findings suggest that the inhibition of pterostilbene to the cell proliferation and DNA synthesis of PDGF-BB-stimulated VSMCs may be mediated by the suppression of Akt kinase. Furthermore, pterostilbene may be a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.


Bacterial Tubulins A and B Exhibit Polarized Growth, Mixed-Polarity Bundling, and Destabilization by GTP Hydrolysis.
Bacteria of the genus Prosthecobacter express homologs of eukaryotic α- and β-tubulin, called BtubA and BtubB (BtubA/B), that have been observed to assemble into filaments in the presence of GTP. BtubA/B polymers are proposed to be composed in vitro by two to six protofilaments in contrast to that in vivo, where they have been reported to form 5-protofilament tubes named bacterial microtubules (bMTs). The btubAB genes likely entered the Prosthecobacter lineage via horizontal gene transfer and may be derived from an early ancestor of the modern eukaryotic microtubule (MT). Previous biochemical studies revealed that BtubA/B polymerization is reversible and that BtubA/B folding does not require chaperones. To better understand BtubA/B filament behavior and gain insight into the evolution of microtubule dynamics, we characterized in vitro BtubA/B assembly using a combination of polymerization kinetics assays and microscopy. Like eukaryotic microtubules, BtubA/B filaments exhibit polarized growth with different assembly rates at each end. GTP hydrolysis stimulated by BtubA/B polymerization drives a stochastic mechanism of filament disassembly that occurs via polymer breakage and/or fast continuous depolymerization. We also observed treadmilling (continuous addition and loss of subunits at opposite ends) of BtubA/B filament fragments. Unlike MTs, polymerization of BtubA/B requires KCl, which reduces the critical concentration for BtubA/B assembly and induces it to form stable mixed-orientation bundles in the absence of any additional BtubA/B-binding proteins. The complex dynamics that we observe in stabilized and unstabilized BtubA/B filaments may reflect common properties of an ancestral eukaryotic tubulin polymer.IMPORTANCE Microtubules are polymers within all eukaryotic cells that perform critical functions; they segregate chromosomes, organize intracellular transport, and support the flagella. These functions rely on the remarkable range of tunable dynamic behaviors of microtubules. Bacterial tubulin A and B (BtubA/B) are evolutionarily related proteins that form polymers. They are proposed to be evolved from the ancestral eukaryotic tubulin, a missing link in microtubule evolution. Using microscopy and biochemical approaches to characterize BtubA/B assembly in vitro, we observed that they exhibit complex and structurally polarized dynamic behavior like eukaryotic microtubules but differ in how they self-associate into bundles and how this bundling affects their stability. Our results demonstrate the diversity of mechanisms through which tubulin homologs promote filament dynamics and monomer turnover.


Extraosseous osteosarcoma of the penis.
Osteosarcomas have been reported as arising in a number of extraosseous primary sites, most commonly in the retroperitoneum and the muscles of the thighs and limb girdles, but also in a variety of other organs. We present a case arising in the penis, which we believe to be only the fifth reported in the literature and the only documented long-term survivor. Careful histopathological analysis and surgical management remain of key importance in the management of all sarcomas arising in soft tissue.


Interactions and hybrid complex formation of anionic algal polysaccharides with a cationic glycine betaine-derived surfactant.
The interaction between anionic algal polysaccharides ((κ)-, (ι)-, (λ)-carrageenans, alginate and ulvan) and a cationic glycine betaine (GB) amide surfactant possessing a C18:1 alkyl chain has been studied using isothermal titration calorimetry (ITC), zeta-potential measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM), atomic force microscopy (AFM), and surface tension measurements. It was observed that this cationic surfactant derived from renewable raw materials induced cooperative binding with the anionic polymers at critical aggregation concentration (CAC) and the CAC values are significantly lower than the corresponding critical micelle concentration (CMC) for the surfactant. The CMC of cationic GB surfactant was obtained at higher surfactant concentration in polysaccharide solution than in pure water. More interestingly, the presence of original polysaccharide/surfactant hybrid complexes formed above the CMC value was evidenced from (κ)-carrageenan by microscopy (TEM and AFM). Preliminary investigations of the structure of these complexes revealed the existence of surfactant nanoparticles surrounded with polysaccharide matrix, probably resulting from electrostatic attraction. In addition, ITC measurements clearly showed that the interactions of the κ-carrageenan was stronger than for other polysaccharides ((ι)-, (λ)-carrageenans, alginate and ulvan). These results may have important impact on the use of the GB amide surfactant in formulations based on algal polysaccharides for several applications such as in food, cosmetics, and detergency fields.


Global economic trade-offs between wild nature and tropical agriculture.
Global demands for agricultural and forestry products provide economic incentives for deforestation across the tropics. Much of this deforestation occurs with a lack of information on the spatial distribution of benefits and costs of deforestation. To inform global sustainable land-use policies, we combine geographic information systems (GIS) with a meta-analysis of ecosystem services (ES) studies to perform a spatially explicit analysis of the trade-offs between agricultural benefits, carbon emissions, and losses of multiple ecosystem services because of tropical deforestation from 2000 to 2012. Even though the value of ecosystem services presents large inherent uncertainties, we find a pattern supporting the argument that the externalities of destroying tropical forests are greater than the current direct economic benefits derived from agriculture in all cases bar one: when yield and rent potentials of high-value crops could be realized in the future. Our analysis identifies the Atlantic Forest, areas around the Gulf of Guinea, and Thailand as areas where agricultural conversion appears economically efficient, indicating a major impediment to the long-term financial sustainability of Reducing Emissions from Deforestation and forest Degradation (REDD+) schemes in those countries. By contrast, Latin America, insular Southeast Asia, and Madagascar present areas with low agricultural rents (ARs) and high values in carbon stocks and ES, suggesting that they are economically viable conservation targets. Our study helps identify optimal areas for conservation and agriculture together with their associated uncertainties, which could enhance the efficiency and sustainability of pantropical land-use policies and help direct future research efforts.


miR-18a Inhibitor Suppresses Leukemia Cell Proliferation by Upregulation of PTEN Expression.
BACKGROUND Leukemia is common in aging adults and has very high mortality worldwide. The present study was designed to investigate the therapeutic efficacy of miR-18a inhibitor against WEHI-3 and THP-1 leukemia cells. MATERIAL AND METHODS The changes in miR-18a inhibitor-transfected WEHI-3 and THP-1 cell proliferative potential was measured by use of the Cell Counting Kit-8 assay. Apoptotic changes were analyzed by electron microscopy, and evaluation of PI3K, AKT, mTOR, and PTEN expression was assessed by RT-qPCR assay. RESULTS Transfection of miR-18a inhibitor significantly (P<0.05) suppressed the proliferative potential of WEHI-3 and THP-1 cells. The WEHI-3 cells showed the presence of characteristic apoptotic bodies on transfection with miR-18a inhibitor at 48 h. Flow cytometry showed that miR-18a inhibitor transfection significantly (P<0.05) increased the WEHI-3 cell percentage in G1 phase. The transfection of miR-18a inhibitor significantly (P<0.05) promoted apoptosis in WEHI-3 cells. In WEHI-3 cells, miR-18a inhibitor transfection markedly suppressed the expression of PI3K, AKT, and mTOR mRNA. The expression of PTEN mRNA was significantly (P<0.05) upregulated by miR-18a inhibitor transfection in WEHI-3 cells. CONCLUSIONS The present study investigated the therapeutic efficacy of miR-18a inhibitor against WEHI-3 and THP1 leukemia cells. The study demonstrated that miR-18a inhibitor suppressed the proliferative potential of WEHI-3 and THP1 cells and activated apoptotic process through upregulation of PTEN mRNA expression. Therefore, miR-18a inhibitor can be of therapeutic importance for the treatment of leukemia.