Surgical site infections following spine surgery: eliminating the controversies in the diagnosis.
Surgical site infection (SSI) following spine surgery is a dreaded complication with significant morbidity and economic burden. SSIs following spine surgery can be superficial, characterized by obvious wound drainage or deep-seated with a healed wound. Staphylococcus aureus remains the principal causal agent. There are certain pre-operative risk factors that increase the risk of SSI, mainly diabetes, smoking, steroids, and peri-operative transfusions. Additionally, intra-operative risk factors include surgical invasiveness, type of fusion, implant use, and traditional instead of minimally invasive approach. A high level of suspicion is crucial to attaining an early definitive diagnosis and initiating appropriate management. The most common presenting symptom is back pain, usually manifesting 2-4 weeks and up to 3 months after a spinal procedure. Scheduling a follow-up visit between weeks 2 and 4 after surgery is therefore necessary for early detection. Inflammatory markers are important diagnostic tools, and comparing pre-operative with post-operative levels should be done when suspecting SSIs following spine surgery. Particularly, serum amyloid A is a novel inflammatory marker that can expedite the diagnosis of SSIs. Magnetic resonance imaging remains the diagnostic modality of choice when suspecting a SSI following spine surgery. While 18F-fluorodeoxyglucose-positron emission tomography is not widely used, it may be useful in challenging cases. Despite their low yield, blood cultures should be collected before initiating antibiotic therapy. Samples from wound drainage should be sent for Gram stain and cultures. When there is a high clinical suspicion of SSI and in the absence of superficial wound drainage, computed tomography-guided aspiration of paraspinal collections is warranted. Unless the patient is hemodynamically compromised, antibiotics should be deferred until proper specimens for culture are secured.


Biomechanical Evaluation of Plate Versus Lag Screw Only Fixation of Distal Fibula Fractures.
Traditional fixation of unstable Orthopaedic Trauma Association type B/C ankle fractures consists of a lag screw and a lateral or posterolateral neutralization plate. Several studies have demonstrated the clinical success of lag screw only fixation; however, to date no biomechanical comparison of the different constructs has been performed. The purpose of the present study was to evaluate the biomechanical strength of these different constructs. Osteotomies were created in 40 Sawbones(®) distal fibulas and reduced using 1 bicortical 3.5-mm stainless steel lag screw, 2 bicortical 3.5-mm lag screws, 3 bicortical 3.5-mm lag screws, or a single 3.5-mm lag screw coupled with a stainless steel neutralization plate with 3 proximal cortical and 3 distal cancellous screws. The constructs were tested to determine the stiffness in lateral bending and rotation and failure torque. No significant differences in lateral bending or rotational stiffness were detected between the osteotomies fixed with 3 lag screws and a plate. Constructs fixed with 1 lag screw were weaker for both lateral bending and rotational stiffness. Osteotomies fixed with 2 lag screws were weaker in lateral bending only. No significant differences were found in the failure torque. Compared with lag screw only fixation, plate fixation requires larger incisions and increased costs and is more likely to require follow-up surgery. Despite the published clinical success of treating simple Orthopaedic Trauma Association B/C fractures with lag screw only fixation, many surgeons still have concerns about stability. For noncomminuted, long oblique distal fibula fractures, lag screw only fixation techniques offer construct stiffness similar to that of traditional plate and lag screw fixation.


[A case of Merkel cell carcinoma of the eyelid].
An 84-year-old man with Merkel cell carcinoma in the right upper-eyelid is reported. The patient presented with a rapidly growing, reddish-purple, solid tumor with a relatively well-defined margin in the skin of the lid. Increased neuron specific enolase content in the blood returned to normal several months after resection of the tumor and 70 Gy postoperative cobalt radiation. Histopathologic examination of the resected specimen revealed that the tumor was limited by intact epidermis and occupied by moderate-sized, round malignant cells with marked mitoses and scant cytoplasm. The neoplastic cells were positively stained by labeled antibodies for neuron specific enolase, keratin and epithelial membrane antigen. Electron microscopic examination showed abundant perinuclear microfilaments and dense core granules.


Relationships of Ferroptosis and Pyroptosis-Related Genes with Clinical Prognosis and Tumor Immune Microenvironment in Head and Neck Squamous Cell Carcinoma.
Ferroptosis and pyroptosis are two new programmed cell death (PCD) modes discovered in recent years. However, the potential value of ferroptosis and pyroptosis-related genes (FPRGs) in prognosis prediction and the tumor immune microenvironment of head and neck squamous cell carcinoma (HNSCC) is still unclear. We obtained 21 significant FPRGs based on the training dataset (TCGA- HNSC) using the univariate Cox and differential expression analysis. The TCGA- HNSC (n = 502) dataset was clustered into two group (clusters A and B) based on the 21 significant FPRGs. 1467 differentially expressed genes (DEGs) between cluster A and B were put into univariate Cox and Least absolute shrinkage and selection operator (LASSO) analysis to build a risk model. The predictive capability of the risk model was successfully confirmed by internal validation, external validation, and clinical sample validation. To improve the clinical applicability, a nomogram model combined risk score and clinical information were constructed. Moreover, the patients with lower risk score were characterized by increased immune response and tumor mutation burden (TMB), while the patients with higher risk score were characterized by increased TP53 mutation rate. In conclusion, our comprehensive analysis of the FPRGs revealed their significant role in prognosis prediction and the tumor immune microenvironment. The risk model containing 9 FPRGs could be a potential prognostic markers and effective immunotherapy targets for HNSCC.


[Synergistic effect of Epimedii Folium fried with suet oil for warming kidney and enhancing yang in dosage form of self-assembled micelles].
The fried method with suet oil, which can strengthen the effect of Epimedii Folium in warming kidney and enhancing yang, has been widely used in the processing of Epimedii Folium in traditional Chinese medicine. In this paper, we adopted hydrocortisone-induced kidney-yang deficiency rat models, and took physical signs, serum testosterone, corticosterone levels and histopathological examination of rats as indictors to systematically study the synergistic effect of suet oil in warming kidney and enhancing yang of fried Epimedii Folium in the dosage form of self-assembled micelles. Drugs were given orally, and compared with model group, indicating normal physical signs and biochemical indicators, and significant alleviation in disorder of hypothalamic-pituitary-adrenal-thymus (HPAT) axis suppression. All these experimental results indicated that both Epimedium flavonoids and its self-assembled micelles, especially the processed self-assembled micelles of Epimedii Folium, showed the significant effects in warming kidney and enhancing yang, which might be correlated with the regulation of the disorder of HPAT axis suppression and the improvement of major pathological conditions of testicular gonadal tissues. This discovery can further reveal the synergistic effect and mechanism of processing material suet oil on Epimedii Folium.


Perception of physical attractiveness when consuming and not consuming alcohol: a meta-analysis.
Elucidating why people drink and why drinking can lead to negative psychosocial consequences remains a crucial task for alcohol researchers. Because drinking occurs typically in social settings, broader investigation of the associations between alcohol and social experience is needed to advance understanding of both the rewarding and hazardous effects of alcohol use. This review aimed to (a) estimate alcohol's relation to the perception of others' physical attractiveness and (b) suggest theoretical and methodological considerations that may advance the study of this topic. Systematic review of Scopus and PsycInfo databases was conducted to identify experimental and quasi-experimental studies, with either between- or within-subjects designs, that assessed attractiveness ratings provided by individuals who had and had not consumed alcohol (k = 16 studies, n = 1811). A meta-analysis was conducted to evaluate alcohol's aggregate association with physical attractiveness perceptions. Separate a priori secondary analyses examined alcohol's associations with perception of opposite-sex (k = 12 studies) and same-sex (k = 7 studies) attractiveness. The primary analysis indicated that alcohol was related significantly to enhanced attractiveness perceptions [d = 0.19, 95% confidence interval (CI) = 0.05-0.32, P = 0.01; I2 = 5.28, 95% CI = 0.00-39.32]. Analysis of alcohol's association with perception of opposite-sex attractiveness similarly yielded a small, significant positive association (d = 0.30, 95% CI = 0.16-0.44, P < 0.01; I2 = 17.49, 95% CI = 0.00-57.75). Alcohol's relation to perception of same-sex attractiveness was not significant (d = 0.04, 95% CI = -0.18 to 0.26, P = 0.71; I2 = 54.08, 95% CI = 0.00-81.66). Experimental and quasi-experimental studies suggest that consuming alcohol may have a small effect of increasing perceived attractiveness of people of the opposite sex.


The portion of goods that falleth to me: Parental rights, children's rights, and medical decisions after COVID-19.
The advent and perpetuation of the COVID-19 pandemic has served to highlight issues in American law that have long gone unaddressed. Prominent among them are the issues involving parents, the government, and the medical decisions of children. This article examines the current state of American law involving parental rights, children's rights, and the government's role in medical decisions of children and proposes a uniform act as a solution to the discrepancy and unpredictability in this area of American law.


Low-power upconversion in dye-doped polymer nanoparticles.
Examples of nanoscale low-power upconverting systems are rapidly increasing because of their potential application in numerous areas such as bioimaging or drug delivery. The fabrication of dye-doped cross-linked rubbery nanoparticles that exhibit upconversion even at relatively low power densities is reported here. The nanoparticles were prepared by surfactant-free emulsion polymerization of n-butylacrylate with divinylbenzene as a cross-linker, followed by dyeing of the resulting particles with a two-chromophore system composed of a palladium porphyrin sensitizer, and diphenylanthracene. Blue emission (≈440 nm) of these systems was observed upon excitation at 532 nm. In addition to their optical properties, the particles were characterized by electron microscopy and dynamic light scattering.


Congestive heart failure: training for a better life.
Congestive heart failure (CHF) patients who exercise regularly can increase exercise tolerance, decrease dyspnea and fatigue, reduce the risk of arrhythmias, and improve quality of life. Initial stress testing is important for assessing a patient's physiologic response to exercise and for establishing a target heart rate for an individualized exercise program. Patients may need to begin aerobic exercise with interval training and progress slowly. Strength exercise is also useful. Exercise used along with the customarily prescribed CHF medications improves symptoms more than either modality alone.


Zeolite-entrapped organized molecular assemblies. New evidence for highly efficient adjacent cage dyad formation and constrained rotational mobility of tris-ligated polypyridine complexes.
The primary objectives of the present work are to investigate the extent to which an entrapped, tris-ligated polypyridine complex of divalent ruthenium is restricted from rotating within the supercage of Y-zeolite and to provide additional evidence for the high efficiency of synthetic procedures developed for the preparation of adjacent cage dyads entrapped within the Y-zeolite framework. Specifically, the Y-zeolite entrapped complex, Z-[Ru(bpy)(2)(pypz)(2+) ] (where the prefix, Z, indicated a zeolite entrapped complex, bpy = 2,2'-bipyridine and pypz = 2-2-pyridylpyrazine), which contains only one reactive peripheral nitrogen atom, is shown to react with the reagent, (H(2)O)Ru(NH(3))(5)(2+), to yield the entrapped Z-[Ru(bpy)(2)(pypz)-Ru(NH(3))(5)](4+) complex. Treatment with a large excess of bpy, according to previously documented procedures, leads to the formation of the entrapped adjacent cage dyad, Z-[Ru(bpy)(2)(pypz)(2+)/Ru(bpy)(3)(2+)], wherein the two-component complexes are entrapped in adjacent supercages. Spectroscopic measurements confirm the integrity of the component complexes and document a strong interaction between them. Most importantly, it is shown that a second treatment of this material with a large excess of the[(H(2)O)Ru(NH(3))(5)](2+) reagent does not lead to formation of significant amounts of Z-[Ru(bpy)(2)(pypz)-Ru(NH(3))(5)](4+); i.e., the presence of the Ru(bpy)(3)(2+) in the cage adjacent to the primary complex shields the latter from further reaction with the ruthenium pentammine reagent. This result demonstrates that, during the formation of the Ru(bpy)(3)(2+) secondary complex, the detached Ru(NH(3))(5)(2+) fragment does not drift into remote supercages, thereby providing unequivocal evidence for the high efficiency of the synthetic procedure for adjacent cage dyad formation. Furthermore, this result also makes it clear that rotation of the tris-ligated primary complex is restricted by the confinement of the Y-zeolite supercage to the extent that the single reactive peripheral nitrogen cannot be repositioned to a different window of the surrounding supercage.


Towards gene therapy for EBV-associated posttransplant lymphoma with genetically modified EBV-specific cytotoxic T cells.
Epstein-Barr virus (EBV)-associated posttransplant lymphoma (PTLD) is a major cause of morbidity/mortality after hematopoietic stem cell (SCT) or solid organ (SOT) transplant. Adoptive immunotherapy with EBV-specific cytotoxic lymphocytes (CTLs), although effective in SCT, is less successful after SOT where lifelong immunosuppression therapy is necessary. We have genetically engineered EBV-CTLs to render them resistant to calcineurin (CN) inhibitor FK506 through retroviral transfer of a calcineurin A mutant (CNA12). Here we examined whether or not FK506-resistant EBV-CTLs control EBV-driven tumor progression in the presence of immunosuppression in a xenogeneic mouse model. NOD/SCID/IL2rγ(null) mice bearing human B-cell lymphoma were injected with autologous CTLs transduced with either CNA12 or eGFP in the presence/absence of FK506. Adoptive transfer of autologous CNA12-CTLs induced dramatic lymphoma regression despite the presence of FK506, whereas eGFP-CTLs did not. CNA12-CTLs persisted longer, homed to the tumor, and expanded more than eGFP-CTLs in mice treated with FK506. Mice receiving CNA12-CTLs and treated with FK506 survived significantly longer than control-treated animals. Our results demonstrate that CNA12-CTL induce regression of EBV-associated tumors in vivo despite ongoing immunosuppression. Clinical application of this novel approach may enhance the efficacy of adoptive transfer of EBV-CTL in SOT patients developing PTLD without the need for reduction in immunosuppressive therapy.


Discontinuation of total parenteral nutrition in a patient with acquired immunodeficiency syndrome: a Canadian perspective.
Provision of nourishment to terminally ill patients has been a controversial topic in clinical medicine. Determination of the limits of palliative care requires an understanding of the disease process, as well as the boundaries of patient self-determination. With the advent of living wills, the determination of the patient to limit care, including nutrition support, has become socially acceptable. Difficulties arise when there are differences of opinion between the caregiver and the patient. The solutions to these conflicts are often decided in the courtroom, as demonstrated by the Cruzan and Quinlan cases. Living wills are often written to prevent unnecessary financial burdens in hopeless situations. As well, financial considerations influence the decisions made by caregivers in providing care to terminally ill patients. The following case report illustrates the conflict between patient self-determination and limitation of care for financial reasons. The use of substituted judgment within the Canadian health care system and the role of team meetings to resolve ethical decisions are discussed.


Binding of prolactin by fetal rhesus cell membrane fractions.
Interest in possible physiologic roles of prolactin in the developing fetus led to the present study of affinity of human prolactin to fetal rhesus cell membrane fractions. The fractions were prepared by ultracentrifugation and their composition confirmed by electron microscopy. The cell membrane preparations were derived from the fetal placenta, liver, lung, myocardium and brain. Kinetic studies showed apparent binding affinity constants for 125I-labeled human prolactin (hPRL) of the order of 10(9)M-1 and capacities of from 3 ng to over a microgram per organ in late pregnancy for all of these tissues except brain. The calculated binding capacities, although probably underestimated, were found sufficiently high to insure that a portion of maternal and fetal prolactin exists in bound form to fetal tissues, consistent with possible roles in the regulation of fetal tissue cellular function, and provided they have access to circulating PRL.


[Multiplanar imaging of the temporal bone. Initial results].
In the head and neck area CT imaging (particularly the HR-technique) is a well-established diagnostic procedure. Besides other locations it has been successfully used in the preoperative evaluation of the temporal bone. Nevertheless, the sophisticated anatomy of this special area is hard to interpret in certain cases. In the present study we report on our preliminary results in producing a multiplanar reconstruction of the area mentioned above. Temporal bones were used that had been excised during autopsy. The specimen were examined under a CT imager of the 3rd generation with a high-resolution mode. Sections of 1 mm thickness were obtained. For the evaluation a surface model was used; the segmentation was carried out mainly automatically. The surface was calculated using a triangulation algorithm. The obtained data enabled us to receive three-dimensional aspects of the temporal bone; these reconstructions could be examined from any desired perspective. Our results indicate that the multiplanar reconstruction might be of great importance for the diagnostic evaluation of temporal bone diseases in the future. In the meantime several technical problems have to be solved to guarantee a sufficient quality of the reconstructed specimen.


Scedosporium endophthalmitis: two fatal disseminated cases of Scedosporium infection presenting with endophthalmitis.
The incidence of disseminated infection with Scedosporium species is increasing in patients with haematological malignancy. Two fatal cases are reported of patients with acute myeloid leukaemia and neutropenia who presented with Scedosporium endophthalmitis. Diagnosis of fungal infection was delayed as blood and vitreous cultures were positive only after 3 days in patient 1 and blood culture was positive at 7 days in patient 2. Despite antifungal therapy with amphotericin B and additional fluconazole in patient 2, both patients died of overwhelming fungal septicaemia. Post-mortem examination of the right globe in patient 1 showed haemorrhagic necrotizing chorioretinitis with numerous fungal hyphae in choroidal vessels, choroid, retina and vitreous. Scedosporium species are often resistant to conventional antifungal therapy including amphotericin B. Diagnosis is difficult and mortality in disseminated infection is high.


3-Mercaptopyruvate sulfurtransferase: an enzyme at the crossroads of sulfane sulfur trafficking.
3-Mercaptopyruvate sulfurtransferase (MPST) catalyzes the desulfuration of 3-mercaptopyruvate to generate an enzyme-bound hydropersulfide. Subsequently, MPST transfers the persulfide's outer sulfur atom to proteins or small molecule acceptors. MPST activity is known to be involved in hydrogen sulfide generation, tRNA thiolation, protein urmylation and cyanide detoxification. Tissue-specific changes in MPST expression correlate with ageing and the development of metabolic disease. Deletion and overexpression experiments suggest that MPST contributes to oxidative stress resistance, mitochondrial respiratory function and the regulation of fatty acid metabolism. However, the role and regulation of MPST in the larger physiological context remain to be understood.


Combined effects of laser-ICG photothermotherapy and doxorubicin chemotherapy on ovarian cancer cells.
Doxorubicin (DOX) is an anthracycline antibiotic widely used in cancer chemotherapy. Its use is limited by cardiac toxicity and drug resistance. Hyperthermia can aid the functionality of DOX, but current hyperthermia delivery methods are hard to apply selectively and locally. The slow temperature increase associated with the external heating may lead to thermal tolerance in cancer cells. The FDA approved dye indocynine green (ICG) has been demonstrated to absorb near-infrared (NIR) light at 808 nm (ideal for tissue penetration) and emit the energy as heat, making it an ideal agent for localized hyperthermia with a rapid rate of temperature increase. The purpose of this study was to investigate the in vitro cytotoxic effect of combined chemotherapy and hyperthermia to a DOX resistant ovarian cancer cell line (SKOV-3). The effect of two different heating methods, ICG induced rapid rate heating and an incubator induced slow rate heating, were compared. All the experiments were conducted in 96-well plates. Cells were subjected to different concentrations of DOX and 60 min 43 degrees C incubation or 5 microM of ICG with 1 min 808 nm NIR laser. SRB assay was used to measure cell proliferation. ICG itself without laser irradiation was not toxic to SKOV-3 cells. The two types of hyperthermia individually produced similar cytotoxicity. DOX by itself was toxic with an IC(50) value of about 5 microM. Hyperthermia in combination with DOX achieved significantly greater cell killing/growth inhibition at all DOX concentrations compared to DOX alone. A subadditive cytotoxic effect was observed by combining DOX and 60 min 43 degrees C incubation which lead to a lowered DOX IC(50) value of about 1 microM. This value was even lower with 1 min laser-ICG photothermotherapy (0.1 microM) and, though not statistically significant, a synergistic effect may exist between DOX and laser-ICG photothermotherapy. The rate of heating may have an effect on chemotherapy-hyperthermia interaction. In conclusion, the combination of photothermal therapy and chemotherapy may provide a valuable tool for cancer treatment with minimized side effect.


Metabolic syndrome and robustness tradeoffs.
The metabolic syndrome is a highly complex breakdown of normal physiology characterized by obesity, insulin resistance, hyperlipidemia, and hypertension. Type 2 diabetes is a major manifestation of this syndrome, although increased risk for cardiovascular disease (CVD) often precedes the onset of frank clinical diabetes. Prevention and cure for this disease constellation is of major importance to world health. Because the metabolic syndrome affects multiple interacting organ systems (i.e., it is a systemic disease), a systems-level analysis of disease evolution is essential for both complete elucidation of its pathophysiology and improved approaches to therapy. The goal of this review is to provide a perspective on systems-level approaches to metabolic syndrome, with particular emphasis on type 2 diabetes. We consider that metabolic syndromes take over inherent dynamics of our body that ensure robustness against unstable food supply and pathogenic infections, and lead to chronic inflammation that ultimately results in CVD. This exemplifies how trade-offs between robustness against common perturbations (unstable food and infections) and fragility against unusual perturbations (high-energy content foods and low-energy utilization lifestyle) is exploited to form chronic diseases. Possible therapeutic approaches that target fragility of emergent robustness of the disease state have been discussed. A detailed molecular interaction map for adipocyte, hepatocyte, skeletal muscle cell, and pancreatic beta-cell cross-talk in the metabolic syndrome can be viewed at http://www.systems-biology.org/001/003.html.


Detection of the YMDD motif mutation of P gene of hepatitis B virus using polymerase chain reaction-restriction fragment length polymorphism.
OBJECTIVE: To establish a convenient approach to implement polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for detecting of gene mutation. METHODS: Serum samples were collected from l0 patients with chronic hepatitis B who had received oral lamivudine for at least l year, and 3 methods including mismatched PCR-RFLP, direct sequence analysis of the PCR product and cloning prior to secondary sequence analysis were employed respectively to examine the YMDD motif mutation of P gene of hepatitis B virus (HBV). RESULTS: PCR-RFLP revealed wild-type HBV infection in 7 cases mixed infection in 1 case and HBV mutant infection in 2 cases. With direct sequence analysis of the PCR product, 9 cases were found with Wild-type HBV infection and 1 with HBV mutant infection. However, 2 non-wild-type HBVV-infected cases as approved by PCR-RFLP, opposite to the results by direct sequence analysis, were both shown by sequence analysis after cloning to suffer mixed infection. CONCLUSION: Sequence analysis following cloning is the best way to detect YMDD motif mutation in HBV, but in terms of economy and practicability, mismatched PCR-RFLP is of greater significance in mass screening of YMDD motif mutant HBV than the other 2 approaches.


Approach to recurrent respiratory infections.
Rational approach to diagnosis and management of recurrent respiratory infections is needed, or else the child is subjected to unnecessary investigations and multiple drugs. Repeated respiratory symptoms do not mean a respiratory infection. A diagnosis of viral infection does not justify prescription of an antibiotic. Recurrent viral infections are part of the growing up process of any child. Giving antibiotics at every episode to cover "so-called superadded bacterial infections" will lead to "recurrent antibiotics" and adverse effects on growth. Systematic approach should be used to find the underlying cause. An otoscopic examination of a child should form part of a pediatric examination in all cases of respiratory infections. Antibiotics should be judiciously chosen depending on age, socioeconomic status, severity of infection and the type of organism expected and always given in adequate doses and proper duration. Treatment should be specific and symptomatic. Adequate drainage of the sinuses is an important adjuvant therapy. Use of cough syrups with various combinations should be avoided. Efforts should be made to diagnose and treat manifestations of hyperactive airway or allergy, role of CEA (cough equivalent asthma) and WLRI (Wheeze associated lower respiratory infections). Investigations are needed in recent lower respiratory infections and adverse effect on growth, school performance, abnormal physical findings. CBC, CRP, ESR, nasal smear, appropriate cultures, tests for TB, X-Rays, barium studies, milk scan, ultra sound, CT, MRI, bronchoscopy in selected cases.


Functional characterization of cytochrome P450 2A6 allelic variants CYP2A6*15, CYP2A6*16, CYP2A6*21, and CYP2A6*22.
Variation in CYP2A6 levels and activity can be attributed to genetic polymorphism and, thus, functional characterization of allelic variants is necessary to define the importance of CYP2A6 polymorphism in humans. The aim of the present study was to investigate the reported alleles CYP2A6*15, CYP2A6*16, CYP2A6*21, and CYP2A6*22, in terms of the functional consequences of their mutations on the enzyme catalytic activity. With use of the wild-type CYP2A6 cDNA as template, site-directed mutagenesis was performed to introduce nucleotide changes encoding K194E substitution in CYP2A6*15, R203S substitution in CYP2A6*16, K476R substitution in CYP2A6*21, and concurrent D158E and L160I substitutions in CYP2A6*22. Upon sequence verification, the CYP2A6 wild-type and mutant constructs were individually coexpressed with NADPH-cytochrome P450 reductase in Escherichia coli. A kinetic study using a coumarin 7-hydroxylase assay indicated that CYP2A6*15 exhibited higher V(max) than the wild type, whereas all mutant constructs, except for variant CYP2A6*16, exhibited higher K(m) values. Analysis of the V(max)/K(m) ratio revealed that all mutants demonstrated 0.85- to 1.05-fold differences from the wild type, with the exception of variant CYP2A6*22, which only portrayed 39% of the wild-type intrinsic clearance. These data suggested that individuals carrying the CYP2A6*22 allele are likely to have lower metabolism of CYP2A6 substrate than individuals expressing CYP2A6*15, CYP2A6*16, CYP2A6*21, and the wild type.


Elbow US: Anatomy, Variants, and Scanning Technique.
As with other musculoskeletal joints, elbow ultrasonography (US) depends on the examination technique. Deep knowledge of the relevant anatomy, such as the bone surface anatomy, tendon orientation, nerves, and vessels, is crucial for diagnosis. It is important to be aware of the primary imaging pitfalls related to US technique (anisotropy) in the evaluation of deep tendons such as the distal biceps and peripheral nerves. In this article, US scanning technique for the elbow as well as the related anatomy, primary variants, and scanning pitfalls are described. In addition, an online video tutorial of elbow US describes a possible approach to elbow evaluation. Online supplemental material is available for this article.


Synthesis and structure-activity relationships of a novel antifungal agent, azoxybacilin.
A new antifungal substance, azoxybacilin (an unusual amino acid with an azoxy moiety) and its derivatives have been synthesized from Boc-L-Asp-OtBu utilizing the Moss procedure for the preparation of the azoxy moiety. The ester derivative, Ro 09-1824, showed more potent antifungal activity and a broader antifungal spectrum than azoxybacilin did.


Binary Black Hole Mergers from Planet-like Migrations.
If supermassive black holes (BHs) are generically present in galaxy centers, and if galaxies are built up through hierarchical merging, BH binaries are at least temporary features of most galactic bulges. Observations suggest, however, that binary BHs are rare, pointing toward a binary lifetime far shorter than the Hubble time. We show that, almost regardless of the detailed mechanism, all stellar dynamical processes are too slow in reducing the orbital separation once orbital velocities in the binary exceed the virial velocity of the system. We propose that a massive gas disk surrounding a BH binary can effect its merger rapidly, in a scenario analogous to the orbital decay of super-Jovian planets due to a proto-planetary disk. As in the case of planets, gas accretion onto the secondary (here a supermassive BH) is integrally connected with its inward migration. Such accretion would give rise to quasar activity. BH binary mergers could therefore be responsible for many or most quasars.


Intermittent Energy Restriction Is a Feasible, Effective, and Acceptable Intervention to Treat Adolescents with Obesity.
Intermittent energy restriction (IER) is an effective obesity management strategy in adults. The aim of this study was to investigate the feasibility, effectiveness, and acceptability of IER in adolescents (aged 12-17 y) with obesity [adult equivalent body mass index (BMI; kg/m2) ≥30]. During weeks 1-12 participants followed an IER dietary plan consisting of a very-low-energy diet (VLED) 3 d/wk (500-600 kcal/d) and an eating plan consistent with national dietary guidelines 4 d/wk. For weeks 13-26 participants chose to continue with 1-3 VLED d/wk or follow a prescriptive eating plan. Primary outcomes were feasibility and change in BMI expressed as a percentage of the 95th percentile (BMI %95th percentile) at 12 wk. Secondary outcomes were diet acceptability, body composition, cardiometabolic risk, vascular structure and function, quality of life (Pediatric Quality of Life Inventory), and eating behaviors [Dutch Eating Behavior Questionnaire (DEBQ-C)]. Linear mixed models were used to assess change in outcome measures. Of 45 adolescents invited to participate, 30 adolescents (mean ± SD age: 14.5 ± 1.4 y, female n = 25) with a median BMI of 34.9 (range: 27.7-52.4) were recruited. At 12 wk, 23 participants chose to continue with the VLED 2-3 d/wk, and 21 completed the study, indicating the feasibility of IER. Consistent with intention-to-treat analysis, BMI %95th percentile was reduced at 12 wk (difference in estimated marginal means ± SEMs: -5.6 ± 1.1, P < 0.001) and 26 wk (-5.1 ± 1.9, P = 0.013) compared with baseline. Plasma triglycerides were reduced at 26 wk from baseline (-0.33 ± 0.12 mmol/L, P = 0.03). Body fat percentage reduced between 12 and 26 wk (-1.57% ± 0.76%, P = 0.05). Carotid intima-media thickness (CIMT) (-0.06 ± 0.01 mm, P < 0.001) and flow-mediated dilation (absolute increase 0.44% ± 0.11%, P = 0.001) improved between baseline and 12 wk, with reduced CIMT maintained at 26 wk (P < 0.001). DEBQ-C and Pediatric Quality of Life Inventory scores improved throughout the intervention. Nineteen adolescents completed an acceptability interview, rating IER as easy and pleasant to follow (mean ± SD: +2.1 ± 1.2; +1.9 ± 1.2, respectively) on a Likert scale from -4 to +4. IER is a feasible, effective, and acceptable intervention in adolescents with obesity achieving reductions in BMI and cardiovascular disease risk. This trial was registered at www.anzctr.org.au as ACTRN12618000200280.


Complete Genome Sequence of Pseudomonas aeruginosa Strain 8380, Isolated from the Human Gut.
Pseudomonas aeruginosa shows multidrug resistance, which is mainly attributable to its expression of xenobiotic efflux pumps. However, it is unclear how silent pumps are expressed in clinical isolates. Here, we sequenced the complete genome of P. aeruginosa strain 8380, which was isolated from a human gut.


Combined Left Central Retinal Artery Occlusion and Bilateral Anterior Ischemic Optic Neuritis: A Rare Presentation of Giant Cell Arteritis.
Giant cell arteritis, a large vessel vasculitis is characterized by headache, visual impairment, constitutional symptoms, and increased inflammatory markers. Visual involvement in giant cell arteritis ranges from amaurosis fugax to permanent visual loss, and extensive bilateral visual impairment is a rare presentation. We hereby report a case of combined left central retinal artery occlusion and bilateral anterior ischemic optic neuritis in a patient who poorly responded to standard corticosteroid therapy.


Fiber Mach-Zehnder interferometer based on microcavities for high-temperature sensing with high sensitivity.
A high-temperature sensor based on a Mach-Zehnder interferometer (MZI) in a conventional single-mode optical fiber is proposed and fabricated by concatenating two microcavities separated by a middle section. A femtosecond laser is used to fabricate a microhole on the center of a fiber end. Then a micro-air-cavity is formed by splicing the microholed fiber end with a normal fiber end. The interferometer is applied for high-temperature sensing, in the range of 500-1200 °C, with a sensitivity of 109 pm/°C that, to the best of our knowledge, is highest in silica fiber temperature sensors. Also, the interferometer is insensitive to external refractive index (RI), which is desirable for temperature sensors.


Precision Oncology in Pancreatic Cancer. From Surgery- to Genetic-Based Chemotherapy.
Pancreatic ductal adenocarcinoma is one of the most lethal forms of solid tumors. These tumors arise from the exocrine component of the pancreas, probably from acinar stem cells1-3.


Boryl Radicals Enabled a Three-Step Sequence to Assemble All-Carbon Quaternary Centers from Activated Trichloromethyl Groups.
The construction of diversely substituted all-carbon quaternary centers has been a longstanding challenge in organic synthesis. Methods that add three alkyl substituents to a simple C(sp3) atom rely heavily on lengthy multiple processes, which usually involve several preactivation steps. Here, we describe a straightforward three-step sequence that uses a range of readily accessible activated trichloromethyl groups as the carbon source, the three C-Cl bonds of which are selectively functionalized to introduce three alkyl chains. In each step, only a single C-Cl bond was cleaved with the choice of an appropriate Lewis base-boryl radical as the promoter. A vast range of diversely substituted all-carbon quaternary centers could be accessed directly from these activated CCl3 trichloromethyl groups or by simple derivatizations. The use of different alkene traps in each of the three steps enabled facile collections of a large library of products. The utility of this strategy was demonstrated by the synthesis of variants of two drug molecules, whose structures could be easily modulated by varying the alkene partner in each step. The results of kinetic and computational studies enabled the design of the three-step reaction and provided insights into the reaction mechanisms.


Functional, Sensorial, Mobility and Communication Difficulties in the Portuguese Oldest Old (80+).
The ageing of populations is evident in most developed countries, and the oldest old group is one of the segments with the fastest growing. The aim of this paper is to examine sociodemographic and health related characteristics of the portuguese oldest old, using a census-based approach. A descriptive study considering all residents aged 80 years and older at the time of the 2011 Census (n = 532 219) was conducted. Information on sociodemographic characteristics, sensory functions (seeing, hearing), functional status (walking/climbing stairs, bathing/dressing alone), cognition (memory/concentration), and communication (understanding others/being understood) as assessed by the Portuguese census official questionnaires were analyzed. Findings revealed that most of the oldest old are women (64.5%), widowed (53.9%), illiterate (46.1%) and live in private households (88.8%). Walking/climbing stairs (57.1%), vision (39.1%) and hearing (35.1%) were the dimensions where the oldest old presented major constrains. In parallel, understanding others/being understood (25.9%) and memory/concentration (34.4%) were the dimensions with lower percentages of difficulties. Significant differences were found between octogenarians/nonagenarians and centenarians for vision, walk/climb stairs, and bathing/dressing alone, with centenarians presenting a higher percentage of difficulties. Portuguese oldest old showed significant difficulties in activities of daily living, nevertheless cognitive and communication capacities seem to be commonly maintained. Taken together, these findings suggest the need for functional assistance, which can be ultimately managed by the older person him/herself. Based on the observed differences between centenarians and younger oldest old, specific interventions should be equated to better respond to their potentially distinctive needs.


A real-world study of Afatinib plus ramucirumab in treatment-naïve, EGFR-mutated, non-small cell lung cancer.
Recent reports suggested combining ramucirumab with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to overcome EGFR resistance in non-small cell lung cancer (NSCLC). Nonetheless, evidence supporting the activity of afatinib and ramucirumab is lacking. This study investigated the survival benefits and safety profile of afatinib plus ramucirumab in patients with treatment-naïve, EGFR-mutated, metastatic NSCLC. The medical records of patients with EGFR-mutated NSCLC were retrospectively retrieved. Patients who received first-line sequential afatinib followed by ramucirumab and the first-line combination of afatinib plus ramucirumab were included. The Kaplan-Meier was used to estimate the progression-free survival (PFS) of all included patients, patients on sequential afatinib followed by ramucirumab (PFS1), and patients on the up-front combination of afatinib and ramucirumab (PFS2). Thirty-three patients were included (25 women; median age: 63 [45-82] years). The median follow-up of the included patients was 17 months (range 6-89 months). the median PFS for the whole cohort was 71 months (95% CI 67.2-74.8) with eight events during the follow-up. The median PFS1 and PFS2 were 71 months (95 CI not defined) and 26 months (95% CI 18.6-33.4), respectively. In terms of OS, the median OS for all patients and patients on sequential treatment was not defined, while the median OS for patients on upfront combination was 30 months (95% CI 20.9-39.1). There was no significant association between EGFR mutation type and PFS1 or PFS2. Afatinib plus ramucirumab could improve the PFS of patients with EGFR-positive NSCLC at a predictable safety profile. Our data also suggest a survival benefit of adding ramucirumab to afatinib in patients with uncommon mutations, which should be investigated further.


The Relationship between Mold Exposure and Allergic Response in Post-Katrina New Orleans.
Objectives. The study's objective was to examine the relation between mold/dampness exposure and mold sensitization among residents of Greater New Orleans following Hurricane Katrina. Methods. Patients were recruited from the Allergy Clinic of a major medical facility. Any patient receiving a skin prick test for one of 24 molds between December 1, 2005 and December 31, 2008 was eligible for the study. Exposure was assessed using standardized questionnaires. Positive mold reactivity was defined as a wheal diameter >3 mm to any mold genera. Results. Approximately 57% of participants tested positive to any indoor allergen, 10% to any mold. Over half of respondents had significant home damage, 34% reported dampness/mold in their home, half engaged in renovation, and one-third lived in a home undergoing renovation. Despite extensive exposure, and multiple measures of exposure, we found no relationship between mold/dampness exposure and sensitivity to mold allergens. Conclusions. These results along with results of earlier research indicate no excess risk of adverse respiratory effects for residents living in New Orleans after the devastation of Hurricane Katrina.


Etiology of acute lower respiratory tract infection in children from Alabang, Metro Manila.
The etiology of acute lower respiratory tract infection (ALRI) was identified in 235 (43.8%) of 537 hospitalized children less than 5 years of age. Clinical evidence of measles was found in 258 (48.0%) patients, of whom 59 had a second viral infection. A viral agent was identified in an additional 121 patients, so that a total of 379 (70.6%) had viral infections. After measles, respiratory syncytial virus was the most common respiratory virus. Bacteremia was noted in 72 children (13.4%), occurring as frequently in children with measles (14.8%) as in those without (12.1%); Haemophilus influenzae and Salmonella typhi were predominant in the former, and H. influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were prominent in the latter. The presence of bacterial antigen in urine was not helpful in identifying bacterial infection. Extrapulmonary and intrapleural complications, concomitant measles, complicated ALRI, female gender, and malnutrition were associated with increased mortality among children with ALRI. The importance of measles immunization, vitamin A supplementation for alleviation of defects associated with malnutrition, and timely antimicrobial therapy is emphasized.


Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials.
To determine whether hypoalbuminemia is an independent risk factor for poor outcome in the acutely ill, and to assess the potential of exogenous albumin administration for improving outcomes in hypoalbuminemic patients. Hypoalbuminemia is associated with poor outcomes in acutely ill patients, but whether this association is causal has remained unclear. Trials investigating albumin therapy to correct hypoalbuminemia have proven inconclusive. A meta-analysis was conducted of 90 cohort studies with 291,433 total patients evaluating hypoalbuminemia as an outcome predictor by multivariate analysis and, separately, of nine prospective controlled trials with 535 total patients on correcting hypoalbuminemia. Hypoalbuminemia was a potent, dose-dependent independent predictor of poor outcome. Each 10-g/L decline in serum albumin concentration significantly raised the odds of mortality by 137%, morbidity by 89%, prolonged intensive care unit and hospital stay respectively by 28% and 71%, and increased resource utilization by 66%. The association between hypoalbuminemia and poor outcome appeared to be independent of both nutritional status and inflammation. Analysis of dose-dependency in controlled trials of albumin therapy suggested that complication rates may be reduced when the serum albumin level attained during albumin administration exceeds 30 g/L. Hypoalbuminemia is strongly associated with poor clinical outcomes. Further well-designed trials are needed to characterize the effects of albumin therapy in hypoalbuminemic patients. In the interim, there is no compelling basis to withhold albumin therapy if it is judged clinically appropriate.


Multiple solubility maxima of oxolinic acid in mixed solvents and a new extension of Hildebrand solubility approach.
A new extension of the Hildebrand solubility approach which describes drug solubility in solvent mixtures showing multiple solubility peaks, the chameleonic effect, is proposed. The experimental solubilities of oxolinic acid were measured at 25 degrees C in solvent mixtures of ethanol-water and ethanol-ethyl acetate. A plot of the mole fraction of the drug against the solubility parameter (delta) of the solvent mixtures displays two peaks at delta = 30.78 MPa1/2 (80% v/v of ethanol in water) and at delta = 20.90 MPa1/2 (30% v/v of ethanol in ethyl acetate). The new extension proposed reproduces two solubility peaks. The thermograms of the solid phase before and after equilibration with the solvent mixtures did not show significant changes. The new extension was also tested with experimental data previously reported for drugs showing two solubility peaks of different height. The accuracy of other published models for describing two solubility maxima is also compared.


Trifluorothymidine exhibits potent antitumor activity via the induction of DNA double-strand breaks.
TAS-102 is an oral anticancer drug composed of trifluorothymidine (TFT) and TPI (an inhibitor of thymidine phosphorylase that strongly inhibits the biodegradation of TFT). Similar to 5-fluorouracil (5FU) and 5-fluoro-2'-deoxyuridine (FdUrd), TFT also inhibits thymidylate synthase (TS), a rate-limiting enzyme of DNA biosynthesis, and is incorporated into DNA. TFT exhibits an anticancer effect on colorectal cancer cells that have acquired 5FU and/or FdUrd resistance as a result of the overexpression of TS. Therefore, we examined the mode of action of TFT-induced DNA damage after its incorporation into DNA. When HeLa cells were treated with TFT, the number of ring-open aldehyde forms at apurinic/apyrimidinic sites increased in a dose-dependent manner, although we previously reported that no detectable excisions of TFT paired to adenine were observed using uracil DNA glycosylases, thymine DNA glycosylase or methyl-CpG binding domain 4 and HeLa whole cell extracts. To investigate the functional mechanism of TFT-induced DNA damage, we measured the phosphorylation of ATR, ATM, BRCA2, chk1 and chk2 in nuclear extracts of HeLa cells after 0, 24, 48 or 72 h of exposure to an IC(50) concentration of TFT, FdUrd or 5FU using Western blot analysis or an enzyme-linked immunosorbent assay (ELISA). Unlike FdUrd and 5FU, TFT resulted in an earlier phosphorylation of ATR and chk1 proteins after only 24 h of exposure, while phosphorylated ATM, BRCA2 and chk2 proteins were detected after more than 48 h of exposure to TFT. These results suggest that TFT causes single-strand breaks followed by double-strand breaks in the DNA of TFT-treated cells. TFT (as TAS-102) showed a more potent antitumor activity than oral 5FU on CO-3 colon cancer xenografts in mice, and such antitumor potency was supported by the increased number of double-strand breaks occurring after single-strand breaks in the DNA of the TFT-treated tumors. These results suggest that TFT causes single-strand breaks after its incorporation into DNA followed by double-strand breaks, resulting in DNA damage. This effect of TFT on DNA may explain its potent anticancer activity in cancer therapy.


Perceptions about prenatal care: views of urban vulnerable groups.
In the United States, infant mortality rates remain more than twice as high for African Americans as compared to other racial groups. Lack of adherence to prenatal care schedules in vulnerable, hard to reach, urban, poor women is associated with high infant mortality, particularly for women who abuse substances, are homeless, or live in communities having high poverty and high infant mortality. This issue is of concern to the women, their partners, and members of their communities. Because they are not part of the system, these womens' views are often not included in other studies. This qualitative study used focus groups with four distinct categories of people, to collect observations about prenatal care from various perspectives. The 169 subjects included homeless women; women with current or history of substance abuse; significant others of homeless women; and residents of a community with high infant mortality and poverty indices, and low incidence of adequate prenatal care. A process of coding and recoding using Ethnograph and counting ensured reliability and validity of the process of theme identification. Barriers and motivators to prenatal care were identified in focus groups. Pervasive issues identified were drug lifestyle, negative attitudes of health care providers and staff, and non-inclusion of male partners in the prenatal experience. Designing prenatal care relevant to vulnerable women in urban communities takes creativity, thoughtfulness, and sensitivity. System changes recommended include increased attention to substance abuse treatment/prenatal care interaction, focus on provider/staff attitudes, and commitment to inclusion of male partners.


Estrogen deprivation aggravates cardiac hypertrophy in nonobese Type 2 diabetic Goto-Kakizaki (GK) rats.
Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto-Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) (n = 6/subgroup). Four months after the operation, the rats were killed, and the heart was excised rapidly. Metabolic parameters, cardiomyocytes hypertrophy, cardiac fibrosis, and biochemical parameters were determined. GK rats had hyperglycemia with hypoinsulinemia, and estrogen deprivation did not increase the severity of T2DM. Cardiac hypertrophy, cardiac oxidative stress, and phosphor-antinuclear factor κB were higher in WTO and GKS rats than WTS rats, and they markedly increased in GKO rats compared with GKS rats. Furthermore, cardiac fibrosis, transforming growth factor-β, Bax, phosphor-p38, and peroxisome proliferator- activated receptor γ coactivator-1α expression were increased in GKS and GKO rats compared with the lean rats. However, mitochondrial dynamics proteins including dynamin-related protein 1 and mitofusin-2 were not altered by T2DM and estrogen deprivation. Although estrogen deprivation did not aggravate T2DM in GK rats, it increased the severity of cardiac hypertrophy by provoking cardiac inflammation and oxidative stress in nonobese GK rats.


[Vaccinia virus as a vector for transduction of dendritic cells].
Dendritic cells (DC) are very heterogenous population of professional antigen-presenting cells. Precursor cells migrate from bone marrow to peripheral tissues, where immature DC ingest pathogenic microorganisms and then migrate to secondary lymphoid organs. DC differentiate into mature cells that are capable to prime naive T lymphocytes. DC can be used for immunotherapy of cancer and infectious diseases. Transduction of DC by recombinant viral vectors expressing tumor associated antigens (TAA) can result in efficient antigen presentation to T lymphocytes. DC transduced with recombinant vaccinia virus expressing E7 oncoprotein of human papilloma virus 16 are able to protect mice against the growth of syngeneic papillomavirus transformed tumor cells TC1. Antitumor effect was observed also with nonreplicating viruses.


Electrophile-induced ether transfer: a new approach to polyketide structural units.
[Structure: see text] A strategically novel approach to the formation of syn-1,3-diol mono- and diethers through electrophilic activation of homoallylic alkoxymethyl ethers has been developed. The resulting polyketide-like synthetic fragments are generated in good yield and with excellent stereocontrol. A chairlike transition state is proposed to account for the high stereoselectivity. Varying the conditions of the reaction workup results in the efficient generation of mono- and diether containing structural units common to polyketide natural products.


Interaction of an intense few-cycle infrared laser pulse with an ultrathin transparent liquid sheet.
We experimentally study the interaction between intense infrared few-cycle laser pulses and an ultrathin (∼2 µm) flat liquid sheet of isopropanol running in vacuum. We observe a rapid decline in transmission above a critical peak intensity of 50 TW/cm2 of the initially transparent liquid sheet, and the emission of a plume of material. We find both events are due to the creation of a surface plasma and are similar to processes observed in dielectric solids. After calculating the electron density for different laser peak intensities, we find an electron scattering rate of 0.3 fs-1 in liquid isopropanol to be consistent with our data. We study the dynamics of the plasma plume to find the expansion velocity of the plume front.


Identification and characterization of doublesex in Bemisia tabaci.
Bemisia tabaci (Gennadius) is an important agricultural pest with a worldwide distribution. Although B. tabaci is known to have a unique haplodiploid reproductive strategy, its sex determination mechanism is largely unknown. In this study, we cloned the full-length sequence of B. tabaci doublesex (Btdsx) and found that Btdsx has 28 splicing isoforms. We found two new splicing isoforms of transformer 2 (Bttra2), which encode two proteins. We also confirmed that both genes lack sex-specific splicing isoforms. Real-time quantitative PCR analysis showed that the expression of Btdsx and Bttra2 is higher in males than in females. RNA interference of Bttra2 affected the expression of Btdsx and vice versa. Furthermore, silencing of Bttra2 or Btdsx caused malformation of the male genitalia (anal style). It did not affect the female phenotype, but reduced the expression of vitellogenin gene in females. These results indicate that Btdsx is associated with sex determination in B. tabaci and that Btdsx and Bttra2 affect each other and are important for male genitalia formation. In addition to increasing our understanding of the roles of dsx and tra2 in the sex determination of B. tabaci, the results will be useful for studies of sex determination in other haplodiploid species.


How to manage complications in CAS?
The different types of complications which might occur during CAS are described. Recommendations are given how to avoid and how to handle complications.


Expression of selected proteins of the extrinsic and intrinsic pathways of apoptosis in human leukocytes exposed to N-nitrosodimethylamine.
N-nitrosodimethylamine (NDMA) is a xenobiotic widespread in human environment capable of regulating the lifespan of immune cells. In this study, we examined the roles of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/death receptor 5 (DR5) complex and the Fas molecule in the induction of the extrinsic apoptosis pathway in human neutrophils (polymorphonuclear neutrophils (PMNs)) and peripheral blood mononuclear cells (PBMCs) exposed to NDMA. Also we assessed these proteins ability to trigger the intrinsic apoptosis pathway in those cells. For this purpose, we examined the expression of Fas-associated protein with death domain, truncated Bid (tBid) proteins, and apoptogenic factors such as apoptosis-inducing factor, Smac/Diablo, Omi/HtrA2, and caspase-3 as an indication of accomplished apoptosis phenomenon. PMNs and PBMCs were isolated from whole blood by density gradient centrifugation using Polymorphrep. Apoptotic cells were assessed with flow cytometry using a ready-made kit. The expression of proapoptotic molecules was investigated by Western blot analysis of PMNs and PBMCs treated with NDMA and/or rhTRAIL. The obtained results confirm the proapoptotic effects of NDMA on the examined human leukocytes and indicate an active participation of the TRAIL/DR5 complex and Fas protein in the process of apoptosis. Moreover, the research revealed distinct mechanisms of intrinsic apoptosis pathway activation between PMNs and PBMCs exposed to NDMA, as confirmed by the different levels of tBid, Smac/Diablo, Omi/HtrA2, and caspase-3 expression in those cells.


Upregulated Expression of IL2RB Causes Disorder of Immune Microenvironment in Patients with Kawasaki Disease.
The clinical diagnosis of Kawasaki disease (KD) is not easy because of many atypical manifestations. This study is aimed at finding potential diagnostic markers and therapeutic targets for KD and analysing their correlation with immune cell infiltrations. First, we downloaded the KD dataset from the Gene Expression Omnibus (GEO) database and used R software to identify differentially expressed genes (DEGs) and perform functional correlation analysis. Then, CIBERSORT algorithm was used to evaluate immune cell infiltrations in samples. Coexpression analysis between DEGs and infiltrating immune cells was performed to screen the main infiltrating immune cells. Subsequently, the least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to screen the core genes related to KD. Finally, correlation analysis between the core genes and the main infiltrating immune cells was performed. 327 DEGs were screened out in this study. Among them, 72 shared genes were the category of genes most likely to be disease-causing for they did not change before and after treatment. After analysis, it was found that expression level of IL2RB in KD tissues was significantly upregulated, the number of resting CD4+ memory T cells was decreased, and the decrease was significantly negatively correlated with the upregulated expression of IL2RB. Therefore, it was speculated that the upregulated expression of IL2RB disrupted Th1/Th2 cell differentiation balance, which led to a decrease of resting CD4+ memory T cells and finally caused disorder of immune microenvironment in patients with KD. Upregulated expression of IL2RB leads to disorder of immune microenvironment in patients with KD and eventually causes the occurrence and development of KD. Therefore, IL2RB may serve as a diagnostic marker and potential therapeutic target for KD.


Potential pathological understaging of pT3 rectal cancer with less than 26 lymph nodes recovered: a prospective study based on a resampling of 50 rectal specimens.
The aim of the paper was to establish if the 12 lymph nodes recommended by tumor-node-metastasis (TNM) system are sufficient for a correct staging of rectal cancer. For this purpose, we first compared the mean number of lymph nodes recovered in the same surgical specimen at the routine sampling and at a resampling performed by a second expert gastrointestinal pathologist. The study was performed on 50 cases of pT2N0 and pT3N0 rectal cancers, with a minimum number of 12 lymph nodes recovered at first sampling, histologically negative for metastases. Resampling retrieved a variable number (1 to 24) of nodes missed at first sampling. The final pN0 status was maintained in pT2 patients, whereas in 18.7% of pT3 patients, metastatic lymph nodes were detected if the mean number of lymph nodes increased from 17.8 to 26.8 after the second sampling. Interestingly, all pN1 patients had only a single metastatic lymph node measuring less than 4.9 mm. As we have shown that most (five out of six) missed metastatic lymph nodes were detected in specimens in which a maximum number of 19 lymph nodes had been originally recovered, we strongly suggest a resampling of pT3N0 rectal specimens if less than 20 lymph nodes have been recovered.


Potentiation of insulin and tolbutamide of the effect of indomethacin on carrageenan paw edema in the rat.
The influence of insulin, tolbutamide and buformin on the effect of indomethacin as measured in the carrageenan paw edema assay in Sprague-Dawley rats has been studied. Small doses of these agents, having no influence on edema formation when given by themselves, were tested in combination with indomethacin. Insulin and tolbutamide potentiated the effect of indomethacin in the early phase of carrageenan paw swelling (2 hr), while they did not significantly alter the late phase (5 hr). Buformin was ineffective at any time. Insulin and tolbutamide in the doses applied moderately lowered blood sugar level, whereas buformin did not, thus tolbutamide-induced potentiation may be due to insulin release. No change in blood pressure of rats was observed under treatment. The possible mechanism of the supra-additive effect of insulin and indomethacin on the edema formation induced by carrageenan is discussed.


Paclobutrazol Improves the Quality of Tomato Seedlings to Be Resistant to Alternaria solani Blight Disease: Biochemical and Histological Perspectives.
The production and quality of tomato seedlings needs many growth factors and production requirements besides controlling the phytopathogens. Paclobutrazol (PBZ) has benefit applications in improving crop productivity under biotic stress (Alternaria solani, the causal agent of early blight disease in tomatoes). In the current study, the foliar application of PBZ, at rates of 25, 50, and 100 mg L-1, was evaluated against early blight disease in tomatoes under greenhouse conditions. The roles of PBZ to extend tomato seedling lives and handling in nurseries were also investigated by measuring different the biochemical (leaf enzymes, including catalase and peroxidase) and histological attributes of tomato seedlings. Disease assessment confirmed that PBZ enhanced the quality of tomato seedlings and induced resistance to early blight disease post inoculation, at 7, 14, and 21 days. Higher values in chlorophyll content, enzyme activities, and anatomical features of stem (cuticle thickness) and stomata (numbers and thickness) were recorded, due to applied PBZ. This may support the delay of the transplanting of tomato seedlings without damage. The reason for this extending tomato seedling life may be due to the role of PBZ treatment in producing seedlings to be greener, more compact, and have a better root system. The most obvious finding to emerge from this study is that PBZ has a distinguished impact in ameliorating biotic stress, especially of the early blight disease under greenhouse conditions. Further studies, which consider molecular variables, will be conducted to explore the role of PBZ in more detail.


Antioxidant, Antimicrobial, and Insecticidal Properties of a Chemically Characterized Essential Oil from the Leaves of Dittrichia viscosa L.
Since some synthetic insecticides cause damage to human health, compounds in plants can be viable alternatives to conventional synthetic pesticides. Dittrichia viscosa L. is a perennial Mediterranean plant known to possess biological activities, including insecticidal properties. The chemical composition of an essential oil (EOD) from D. viscosa, as well as its antioxidant, antimicrobial, and insecticidal effects on the cowpea weevil (Callosobruchus maculatus) were determined. Forty-one volatile compounds were identified in EOD, which accounted for 97.5% of its constituents. Bornyl acetate (41%) was a major compound, followed by borneol (9.3%), α-amorphene (6.6%), and caryophyllene oxide (5.7%). EOD exhibited significant antioxidant activity in all tests performed, with an IC50 of 1.30 ± 0.05 mg/mL in the DPPH test and an EC50 equal to 36.0 ± 2.5 mg/mL in the FRAP assay. In the phosphor-molybdenum test, EOD results ranged from 39.81 ± 0.7 to 192.1 ± 0.8 mg AAE/g E. EOD was active on E. coli (9.5 ± 0.5 mm), S. aureus (31.0 ± 1.5 mm), C. albicans (20.4 ± 0.5 mm), and S. cerevisiae (28.0 ± 1.0 mm), with MICs ranging from 0.1 mg/mL to 3.3 mg/mL. We found that 1 µL of EOD caused 97.5 ± 5.0% insect mortality after 96 h in the inhalation test and 60.0 ± 8.3% in the ingestion assay. The median lethal concentration (LC50) was 7.8 ± 0.3 μL EO/L, while the effective concentration in the ingestion test (LC50) was 15.0 ± 2.1 μL EO/L. We found that 20 µL of EOD caused a reduction of more than 91% of C. maculatus laid eggs.


[Factor structure of the H.S.C.L. in a sample of French anxious-depressed patients].
The 58 items version of the Hopkins Symptom Check List (Derogatis et al.) was scored on 85 depressed outpatients treated by general practitioners. The data were obtained before any anti-depressant treatment. A principal component factorial analysis with Varimax rotation was used. 41 of the 58 items of the check list were assigned to seven independent factors: interpersonal sensitivity, somatisation (pain), retardation, digestive disorders, autonomic symptoms, sleep and obsessive disorders, depressive mood. Our results are compared to those published by Derogatis.


Traceless and site-specific ubiquitination of recombinant proteins.
Protein ubiquitination is a post-translational modification that regulates almost all aspects of eukaryotic biology. Here we discover the first routes for the efficient site-specific incorporation of δ-thiol-L-lysine (7) and δ-hydroxy-L-lysine (8) into recombinant proteins, via evolution of a pyrrolysyl-tRNA synthetase/tRNA(CUA) pair. We combine the genetically directed incorporation of 7 with native chemical ligation and desulfurization to yield an entirely native isopeptide bond between substrate proteins and ubiquitin. We exemplify this approach by demonstrating the synthesis of a ubiquitin dimer and the first synthesis of ubiquitinated SUMO.


Experiential learning through Program Evaluation: Assessing external barriers to Bridgehaven attendance.
This cross-sectional study was conducted as an experiential project in a graduate Program Evaluation class. We worked together as a team to solve difficulties that occurred when evaluating a program for the first time, including overcoming initial fears and identifying the appropriate focus. The goal of this study was to identify the most common barriers to attendance at Bridgehaven Mental Health Services, a community-based outpatient program tailored to aid in the transition from hospitals to community living. External barriers to attendance were examined by an adapted version of the Structural Barriers to Clinic Attendance Scale (SCBA) and a researcher-created qualitative measure. Between-group t-tests and non-parametric analyses indicated that a far walk from the bus stop and negative perceptions of staff behavior were significant external barriers to Bridgehaven attendance among 42 adult members with severe mental illness. Additionally, themes from the qualitative data revealed that 74.7% of members viewed other obligations and appointments as barriers to their attendance. About half of the members surveyed indicated the positive impact of groups on attendance. Overall findings revealed the importance of considering external barriers, particularly issues related to transportation, scheduling, and social perceptions when identifying solutions to declining attendance rates. Through the process of conducting this study, we learned invaluable skills (e.g., problem-solving, teamwork, collaboration, and flexibility) that will carry with us as we evaluate programs in the future.


Are vasodilators still indicated in the treatment of severe aortic regurgitation?
Aortic regurgitation (AR) is a valve disease that causes severe complications and reduces life expectancy. Surgical correction is required in the late stages of the disease. In less advanced forms, treatment with vasodilators is a consideration. The available evidence suggests that this type of treatment has a favorable effect on the consequences of AR, particularly left ventricular remodeling. However, the impact of vasodilators on clinical endpoints complicating the course of AR remains in doubt. The limited evidence supporting or opposing the utilization of vasodilators in AR hinders drawing firm conclusions and emphasizes the process of individualized interpretation of the clinical presentation of patients with the disease.


Development and validation of RP-HPLC-fluorescence method for quantitative determination of quinidine, a probe substrate for P-glycoprotein inhibition assay using Caco-2 cell monolayer.
A simple, sensitive and specific reverse-phase high-performance liquid chromatographic (RP-HPLC) method with fluorescence detection was developed for quantitation of quinidine from HBSS buffer. The method was applicable in the bi-directional transport assay for evaluation of the inhibitory effect of test compounds on P-glycoprotein-mediated quinidine transport; quinidine was used as a probe P-glycoprotein substrate. The calibration curve was linear (correlation coefficient >/=99) in the range 0.30-100.00 nm. The method was validated and is specific and sensitive with limit of quantitation of 300 pm for quinidine. The method was found to be accurate and precise in the working calibration range. Stability studies were carried out at different storage conditions where the analyte was found to be stable. The applicability and reliability of the analytical method was evaluated by successful demonstration of efflux ratio (P(app)B --> A/P(app)A --> B) in the Caco-2 cell monolayer efflux assay. The efflux ratio for quinidine (100 nm) alone was 10.8, which reduced to less than 2 in the presence of the classical P-gp inhibitors verapamil and ketoconazole (100 mum each).


Characterizing dynamics with covariant Lyapunov vectors.
A general method to determine covariant Lyapunov vectors in both discrete- and continuous-time dynamical systems is introduced. This allows us to address fundamental questions such as the degree of hyperbolicity, which can be quantified in terms of the transversality of these intrinsic vectors. For spatially extended systems, the covariant Lyapunov vectors have localization properties and spatial Fourier spectra qualitatively different from those composing the orthonormalized basis obtained in the standard procedure used to calculate the Lyapunov exponents.


Latest Advances in the Management of Pediatric Gastrointestinal Stromal Tumors.
Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs biologically from adult-type diseases presenting mutations of KIT and PDGFR genes. In this population, more frequent is the wild-type GIST possessing SDH, TRK, RAS, NF1 mutations, among others. Both tumor types require individualized treatment with kinase inhibitors that are still being tested in the pediatric population due to the different neoplasm biology. We review the latest updates to the management of pediatric gastrointestinal tumors with a particular focus on the advances in molecular biology of the disease that enables the definition of possible resistance. Emerging treatment with kinase inhibitors that could serve as targeted therapy is discussed, especially with multikinase inhibitors of higher generation, the effectiveness of which has already been confirmed in the adult population.


Reliability of a tool for measuring theory of planned behaviour constructs for use in evaluating research use in policymaking.
Although measures of knowledge translation and exchange (KTE) effectiveness based on the theory of planned behavior (TPB) have been used among patients and providers, no measure has been developed for use among health system policymakers and stakeholders. A tool that measures the intention to use research evidence in policymaking could assist researchers in evaluating the effectiveness of KTE strategies that aim to support evidence-informed health system decision-making. Therefore, we developed a 15-item tool to measure four TPB constructs (intention, attitude, subjective norm and perceived control) and assessed its face validity through key informant interviews. We carried out a reliability study to assess the tool's internal consistency and test-retest reliability. Our study sample consisted of 62 policymakers and stakeholders that participated in deliberative dialogues. We assessed internal consistency using Cronbach's alpha and generalizability (G) coefficients, and we assessed test-retest reliability by calculating Pearson correlation coefficients (r) and G coefficients for each construct and the tool overall. The internal consistency of items within each construct was good with alpha ranging from 0.68 to alpha = 0.89. G-coefficients were lower for a single administration (G = 0.34 to G = 0.73) than for the average of two administrations (G = 0.79 to G = 0.89). Test-retest reliability coefficients for the constructs ranged from r = 0.26 to r = 0.77 and from G = 0.31 to G = 0.62 for a single administration, and from G = 0.47 to G = 0.86 for the average of two administrations. Test-retest reliability of the tool using G theory was moderate (G = 0.5) when we generalized across a single observation, but became strong (G = 0.9) when we averaged across both administrations. This study provides preliminary evidence for the reliability of a tool that can be used to measure TPB constructs in relation to research use in policymaking. Our findings suggest that the tool should be administered on more than one occasion when the intervention promotes an initial 'spike' in enthusiasm for using research evidence (as it seemed to do in this case with deliberative dialogues). The findings from this study will be used to modify the tool and inform further psychometric testing following different KTE interventions.


Dysthyroid optic neuropathy: atypical initial presentation and persistent visual loss.
Dysthyroid Optic Neuropathy (DON) can lead to irreversible visual loss. We report risk features correlated with poor visual recovery despite an intensive treatment in a series of patients with DON. Retrospective analysis of a non-comparative interventional series. Between 1997 and 2007, 300 consecutive patients with Graves' orbitopathy were seen at the Rothschild Foundation (Paris). Medical records of all consecutive patients who developed a DON were reviewed. Demographic, clinical features and visual function were collected at the time of the first onset, one month follow-up after medical and sometime surgical treatment and at the last examination. Statistical analysis (reflected as p values) gathered the significant observations into detrimental visual recovery prognostic factors for DON. Fifty-six eyes of 29 patients developed a DON. Sixteen eyes (28%) did not improve vision despite usual treatment (intravenous steroids and surgical decompression when necessary). An inferior altitudinal visual field defect (AVF, p=0.0004) and/or a lack of response to intravenous steroids boluses (p= 0.011) were related to a poor recovery. DON prognosis is highly variable. Our results suggest that a non-inflammatory element, probably vascular could be involved in atypical DONs. An earlier recognition could prompt to rapid surgical treatment for these patients.


Robust consensus clustering for identification of expressed genes linked to malignancy of human colorectal carcinoma.
Previous studies have been conducted in gene expression profiling to identify groups of genes that characterize the colorectal carcinoma disease. Despite the success of previous attempts to identify groups of genes in the progression of the colorectal carcinoma disease, their methods either require subjective interpretation of the number of clusters, or lack stability during different runs of the algorithms. All of which limits the usefulness of these methods. In this study, we propose an enhanced algorithm that provides stability and robustness in identifying differentially expressed genes in an expression profile analysis. Our proposed algorithm uses multiple clustering algorithms under the consensus clustering framework. The results of the experiment show that the robustness of our method provides a consistent structure of clusters, similar to the structure found in the previous study. Furthermore, our algorithm outperforms any single clustering algorithms in terms of the cluster quality score.


Evolution and maintenance of phenotypic plasticity.
We introduce a novel framework for exploring the evolutionary consequences of phenotypic plasticity (adaptive and non-adaptive) integrating both genic and epigenetic effects on phenotype via stochastic differential equations and in-silico selection. In accordance with the most significant results derived from prior models, we demonstrate how plasticity is differentially favored when subjected to small vs large environmental shifts, how plasticity is transiently favorable while accommodating a new environment, and how plasticity decreases during epochs where the environment remains stable (canalization). In contrast to these models, however, by allowing the same phenotypic value to be produced via two different paths, i.e. deterministic, genic, vs stochastic, epigenetic mechanisms, we demonstrate when genic contributions alone cannot produce an optimal phenotype, plastic, epigenetic contributions will instead fully accommodate new environments, allowing for both adaptive and non-adaptive plasticity to evolve. Furthermore, we show that while rates of phenotypic accommodation are relatively constant under a wide range of selective conditions, selection will favor the most efficient route to adaptation: deterministic, genic response, or stochastic, plastic response. As a result, plasticity may evolve or canalization may occur within a given epoch depending on the relative mutation rate of genic and epigenetic contributions to phenotype, highlighting the importance of genetic conflict on the evolution of plasticity.


Inferior alveolar nerve injury related to surgery for an erupted third molar.
Removal of third molars is one of the most common operations performed in oral surgery. A well recognized serious complication of mandibular third molar extraction is injury to the inferior alveolar nerve (IAN). We describe a case of an unusual nerve passage discovered after the extraction of a completely erupted third molar. The likelihood of direct damage to the IAN can be predicted with more specific information obtained by the use of a preoperative computerized tomography scan when conventional radiography does not clearly show the nerve canal.


Audit of acute pancreatitis management: a tale of two hospitals.
A case note audit of existing practices in the management of acute pancreatitis (AP) at a district general hospital (DGH) and a teaching hospital was undertaken to determine if practices were in accordance with published UK guidelines. Casenotes of all adults admitted with AP over a period of one year at the two hospitals were reviewed. Ninety-five patients were treated for AP at the teaching hospital and 52 at the DGH. The age, sex and aetiological distributions at the two hospitals were similar. Fifteen (15.8%) patients at the teaching hospital and eight (15.3%) at the DGH had severe AP. Four patients died at each hospital. Prognostic Glasgow criteria tests (excluding LDH) were completed within 48 hours in 43% patients at the teaching hospital and 48% at the DGH. Five of the twenty-five cholecystectomies at the teaching hospital and 4/18 at the DGH were performed within four weeks after admission with AP. Audit of current practice has highlighted deficiencies at many levels compared with current evidence-based guidelines, although this has not resulted in unexpected mortality. It remains to be seen whether new measures to aid compliance with guidelines will result in improvement in morbidity and mortality.


Multivariate classification of systemic vascular resistance using photoplethysmography.
Systemic vascular resistance (SVR) classification is useful for the diagnosis and prognosis of critical pathophysiological conditions, with the ability to identify patients with abnormally high or low SVR of immense clinical value. In this study, a supervised classifier, based on Bayes' rule, is employed to classify a heterogeneous group of intensive care unit patients (N = 48) as being below (SVR < 900 dyn s cm(-5)), within (900 ⩽ SVR ⩽ 1200 dyn s cm(-5)) or above (SVR > 1200 dyn s cm(-5)) the clinically accepted range for normal SVR. Features derived from the finger photoplethysmogram (PPG) waveform and other routine cardiovascular measurements (heart rate and mean arterial pressure) were used as inputs to the classifier. In the construction of the classifier model, two techniques were used to approximate the class conditional probability densities--a single Gaussian distribution model (also known as discriminant analysis) and a non-parametric model using the Parzen window kernel density estimation method. An exhaustive feature search was performed to select a feature subset that maximized the performance indicator, Cohen's kappa coefficient (κ). The Gaussian model with multiple features achieved the best overall kappa coefficient (κ = 0.57), although the results from the non-parametric model were comparable (κ = 0.51). The optimum subset in the Gaussian model consisted of PPG waveform variability features, including the low-frequency to high-frequency ratio (LF/HF) and the normalized mid-frequency power (MF(NU)), in addition to the PPG pulse wave features, such as pulse width, peak-to-notch time, reflection index, and notch time ratio. The classifier performed particularly well in discriminating low SVR, with a sensitivity of 85%, specificity of 86%, positive predictive value of 88% and a negative predictive value of 82%. The results highlight the feasibility of deploying a multivariate statistical approach of SVR classification in the clinical setting, simply using a non-invasive and easy-to-measure PPG waveform signal.


Characterizing the "fungal shunt": Parasitic fungi on diatoms affect carbon flow and bacterial communities in aquatic microbial food webs.
Microbial interactions in aquatic environments profoundly affect global biogeochemical cycles, but the role of microparasites has been largely overlooked. Using a model pathosystem, we studied hitherto cryptic interactions between microparasitic fungi (chytrid Rhizophydiales), their diatom host Asterionella, and cell-associated and free-living bacteria. We analyzed the effect of fungal infections on microbial abundances, bacterial taxonomy, cell-to-cell carbon transfer, and cell-specific nitrate-based growth using microscopy (e.g., fluorescence in situ hybridization), 16S rRNA gene amplicon sequencing, and secondary ion mass spectrometry. Bacterial abundances were 2 to 4 times higher on individual fungal-infected diatoms compared to healthy diatoms, particularly involving Burkholderiales. Furthermore, taxonomic compositions of both diatom-associated and free-living bacteria were significantly different between noninfected and fungal-infected cocultures. The fungal microparasite, including diatom-associated sporangia and free-swimming zoospores, derived ∼100% of their carbon content from the diatom. By comparison, transfer efficiencies of photosynthetic carbon were lower to diatom-associated bacteria (67 to 98%), with a high cell-to-cell variability, and even lower to free-living bacteria (32%). Likewise, nitrate-based growth for the diatom and fungi was synchronized and faster than for diatom-associated and free-living bacteria. In a natural lacustrine system, where infection prevalence reached 54%, we calculated that 20% of the total diatom-derived photosynthetic carbon was shunted to the parasitic fungi, which can be grazed by zooplankton, thereby accelerating carbon transfer to higher trophic levels and bypassing the microbial loop. The herein termed "fungal shunt" can thus significantly modify the fate of photosynthetic carbon and the nature of phytoplankton-bacteria interactions, with implications for diverse pelagic food webs and global biogeochemical cycles.


High effectiveness of pandemic influenza A (H1N1) vaccination in healthcare workers from a Portuguese hospital.
Vaccination of healthcare workers (HCWs) was made a high priority during the phase six pandemic of the novel influenza A H1N1 (pH1N1) virus. We surveyed adherence to pH1N1 vaccination and the incidence of pH1N1 infection between vaccinated and unvaccinated HCWs. Employees at the S. João Hospital in Porto, Portugal, were offered pH1N1 vaccinations free of charge. Pandemrix(®) was the vaccine administered. As part of the pandemic plan, employees with influenza-like symptoms (ILS) were called upon to take an RT-PCR H1N1 test. If the test results were positive, they had to stay off work for at least 7 days. Sociodemographic data, vaccination status, contact with infectious patients, ILS and pH1N1 test results were documented in a standardised manner. The survey population comprised 5,592 employees. The vaccination rate was 30.8% (n = 1,720) for pH1N1 and 50.4% (n = 2,819) for the 2009/2010 seasonal trivalent inactivated influenza vaccine (TIV). One mild anaphylactic reaction occurred after pH1N1 vaccination. Minor local side effects occurred more often after pH1N1 vaccination than after 2009/2010 seasonal TIV (38.0% vs. 12.3%). Pandemic H1N1 infection was diagnosed in 97 HCWs (1.7%). Compared to employees with no regular patient contact, nurses (2.8%) had the highest risk of pH1N1 infection (adjusted OR 3.8; 95% CI 1.2-6.8). Vaccination reduced the pH1N1 infection risk (OR 0.12; 95% CI 0.05-0.29). Vaccine effectiveness was 90.4% (95% CI 73.5-97.3%). Vaccination reduced the pH1N1 infection risk considerably. The pandemic plan to contain the pH1N1 infection was successful. Nurses had the highest risk of pH1N1 infection and are therefore a target group for vaccination measures.


Changes in Medical Cannabis Use After Recreational Cannabis Legalization in Canada.
Background: As part of its recreational cannabis legalization in October 2018, Canada imposed an excise tax of 10% (or $1 a gram, whichever is higher) on both recreational and medical cannabis. There is little evidence to inform the ongoing debate on whether the legalization had adverse impacts on medical cannabis use. Methods: We used an interrupted time series design and data on medical cannabis shipments (i.e., mail-order deliveries of cannabis from a licensed producer to a patient authorized to obtain medical cannabis) in Canada between quarter 1 of 2014 and quarter 1 of 2020. We examined changes in medical cannabis shipments after Canada's recreational cannabis legalization both across Canada and for each province. As this study used publicly available, province-level aggregate data, ethics approval was not required. Results: Recreational cannabis legalization was associated with significant reductions in medical cannabis use in 7 out of 10 Canadian provinces. Compared with the counterfactual estimated from prelegalization trends, the reduction in quarter 1 of 2020 varied from 500 shipments per 100,000 population (95% CI=312-688 shipments per 100,000 population) or 32% (95% CI=22-43%) in Newfoundland and Labrador to 3,778 shipments per 100,000 population (95% CI=2,972-4,585 shipments per 100,000 population) or 74% (95% CI=68-79%) in Alberta. At the national level, the number of medical cannabis shipments decreased by 823 per 100,000 population (95% CI=725-921 shipments per 100,000 population) or 48% (95% CI=45-52%). Conclusions: Recreational cannabis legalization was associated with reductions in medical cannabis use. Our findings call for policy attention to address possible adverse impacts of recreational cannabis legalization on medical cannabis users.


Surfactant-assisted hydrothermal synthesis of Eu(3+)-doped white light hydroxyl sodium yttrium tungstate microspheres and their conversion to NaY(WO(4))(2).
In this work, large-scale three-dimensional "flake-ball" microarchitectures of Eu(3+) doped white light hydroxyl sodium yttrium tungstate were prepared by the well-known hydrothermal approach at 180 degrees C for 48 h in the presence of triblock-copolymer poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123). NaY(WO(4))(2):Eu(3+) phosphor was formed by annealing the hydrothermal product at approximately 630 degrees C for 2 h. A time-dependent microstructure evolution study was performed under hydrothermal reaction. The evolution process is the self-assembly process of P123, and the effects of other reaction parameters, such as influence of the concentration of P123 on morphology, and the influence of temperature on PL. The mechanism by which the "flake-ball" particles are formed is discussed in detail. The PL spectra of Eu(3+)-doped hydroxyl sodium yttrium tungstate phosphor contain two parts: the broad blue-green band and the (5)D(0)-->(7)F(J) (J = 1, and 2) characteristic transition of Eu(3+). This approach provides a facile route for the production of high-quality hydroxyl sodium yttrium tungstate microstructures with an interesting optical property.


Crossover from superdiffusive to diffusive mixing in plastically deformed solids.
We derive expressions for the effective diffusion coefficient of Richardson's pairs in plastically strained solids as a function of the pair separation distance R. We predict that a crossover from superdiffusive to diffusive mixing takes place when R becomes comparable to the coherence length of the shearing events underlying the plastic deformation. Molecular dynamics simulations on nanocrystalline and amorphous systems support this analysis, which thus provides new insight on deformation mechanisms in these systems. Superdiffusive mixing is experimentally observable by monitoring the rate of dissolution of precipitates as a function of their initial size.


Mucopolysaccharidosis-Plus Syndrome: Report on a Polish Patient with a Novel VPS33A Variant with Comparison with Other Described Patients.
Eleven patients from Yakutia with a new lysosomal disease assumed then as mucopolysaccharidosis-plus syndrome (MPS-PS) were reported by Gurinova et al. in 2014. Up to now, a total number of 39 patients have been reported; in all of them, the c.1492C>T (p.Arg498Trp) variant of the VPS33A gene was detected. Here, we describe the first Polish MPS-PS patient with a novel homozygous c.599G>C (p.Arg200Pro) VPS33A variant presenting over 12 years of follow-up with some novel clinical features, including fetal ascites (resolved spontaneously), recurrent joint effusion and peripheral edemas, normal growth, and visceral obesity. Functional analyses revealed a slight presence of chondroitin sulphate (only) in urine glycosaminoglycan electrophoresis, presence of sialooligosaccharides in urine by thin-layer chromatography, and normal results of lysosomal enzymes activity and lysosphingolipids concentration in dried blood spot. The comparison with other MPS-PS described cases was also provided. The presented description of the natural history of MPS-PS in our patient may broaden the spectrum of phenotypes in this disease.


Anthelmintic effect of Indigofera tinctoria L on Haemonchus contortus obtained from sheep in Indonesia.
Hemonchosis has resulted in huge economic losses for sheep farmers worldwide. Secondary metabolite compounds from Indigofera tinctoria L. can be used as anthelmintics. This study aimed to evaluate the in vitro and in vivo effects of I. tinctoria L. aqueous extract (IAE) as an anthelmintic against adult Haemonchus contortus isolated from sheep. Ten active adult worms were placed in each Petri dish containing 25 mL of IAE, each having a different concentration of IAE (at concentrations 100, 120, 140, 160, 180, 200, and 220 mg/mL). Each experiment was repeated. The positive control used 1% albendazole, and the negative control used 0.62% saline water. The number of immobile worms and the time of mortality were recorded after 2, 4, 6, and 8 h. The dead worms were subsequently tested using scanning electron microscopy (SEM) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the in vivo study, 15 sheep with an average fecal egg count (FEC) of 1000 eggs per gram were treated with IAE for 9 days: Group A (negative control, saline water 0.62%), Group B (21 mg/mL), Group C (41 mg/mL), Group D (62 mg/mL), and Group E (positive control, albendazole 100 mg/mL). Measurements of the body weight, FEC reduction test, and hematology testing were performed on days 0, 7, and 14. SEM was performed using worms found from the abomasum of slaughtered sheep. The leaves of I. tinctoria L. contained a number of secondary metabolites, including total tannins, saponins, flavonoids, and alkaloids. The most effective concentration that killed the adult H. contortus worms was 220 mg/mL (93.33% mortality) after 8 h of treatment. The electrophoresis results showed that the protein band at a dose of 22% was less than that of the control. The highest FECR value of the treatment group on the 14th day after treatment was at a dose of 62 mg/mL. The highest weight gain as well as the highest increased hemoglobin (Hb), packed cell volume (PCV), and total erythrocyte count (TEC) values on the 14th day after treatment were at a dose of 41 mg/mL. The SEM results showed that IAE treatment caused the worms' anterior parts to become wrinkled with thick creases and cuticle abrasion (in vitro) and the anterior part to shrink along with the presence of aggregates in the worm cuticle (in vivo). The aqueous extract of I. tinctoria contains tannins, saponins, flavonoids, and alkaloids and has an anthelmintic effect with decreased FEC, increased weight gain, Hb, PCV, and TEC, causing damage to the worms' body and reducing the protein profile of adult H. contortus worms.


Acoustical cavity excitation.
A tutorial exposition is given of cavity excitations and it is shown that relatively simple analytical solutions for the excitation of acoustic fields in cavities with lossy walls can be obtained for a broad class of such cavities. The standard analytic procedure whereby one expresses the acoustic field as a sum over the eigenmodes of the cavity is reviewed and its limitations are pointed out. An alternate procedure is to seek to make use of Green's functions depending on a single coordinate and to not express such Green's functions as sums over eigenfunctions. Instead, one expresses the Green's function as a closed form function that has a discontinuous slope at the value of the coordinate corresponding to the source location. Although the class of cavities for which this approach is possible is limited, it is sufficiently broad to be of intrinsic interest and the results may be helpful to those seeking benchmark solutions and analytic insight. Displayed examples are for cavities whose shapes are spheres and cylinders, with interior monopole, dipole, line, and distributed sources. The formulation yields simple expressions for the total power absorbed by the cavity walls.


Use of multiple primers in RAPD analysis of clonal organisms provides limited improvement in discrimination.
Randomly amplified polymorphic DNA (RAPD) analysis using two or more primers has been reported to provide additional discriminatory ability over one primer used individually. This may be of particular application in epidemiological typing of clonal organisms, such as Shiga toxin-producing E. coli O157, where strain differentiation can be difficult. Using four arbitrary primers individually, and in all possible permutations, E. coli O157 isolates and other arbitrarily chosen E. coli strains were typed using RAPD analysis. For most nonclonal strains, the use of two primers resulted in increased differentiation between isolates; however, more than two primers did not increase further the discriminatory capacity. E. coli O157 isolates that produced virtually identical profiles using one primer did not show increased differentiation when using two or more primers, demonstrating that in some cases, where strains of an organism are highly related, there is limited advantage to using more than one primer in RAPD analysis.


Performance characteristics of single point diamond machined metal mirrors for infrared laser applications.
Single point diamond knives have been used to machine to microinch tolerances. This micromachining can also produce optics of high quality. Optical micromachining capabilities in terms of materials, shapes, and optical figure are discussed. Comparisons are made between micromachined mirrors and superpolished surfaces including reflectivity, absorption, scatter, roughness, autocorrelation length, and Nomarski microscopy. 10.6-microm pulsed damage data and preliminary 10.6-microm cw damage investigations are also reported. Micromachined well with superpolished samples.