Effect of oil sands process-affected water on toxicity of retene to early life-stages of Japanese medaka (Oryzias latipes).
Toxicity of oil sands process-affected water (OSPW) to aquatic organisms has been studied, but effects of co-exposure to OSPW and polycyclic-aromatic hydrocarbons (PAHs), which are an important class of chemicals in tailings ponds used to store OSPW, has not been investigated. The goal of the current study was to determine if organic compounds extracted from the aqueous phase of relatively fresh OSPW from Base-Mine Lake (BML-OSPW) or aged OSPW from Pond 9 experimental reclamation pond (P9-OSPW) modulated toxic potency of the model alkyl-PAH, retene, to early life-stages of Japanese medaka (Oryzias latipes). Embryos were exposed to retene by use of a partition controlled delivery (PCD) system made of polydimethylsiloxane (PDMS) until day of hatch. Incidences of pericardial edema and expression of CYP1A were not significantly greater in larvae exposed only to dissolved organic compounds from either OSPW but were significantly greater in larvae exposed only to retene. Expression of CYP1A and incidences of pericardial edema were significantly greater in larvae co-exposed to retene and 5×equivalent of dissolved organic compounds from BML-OSPW compared to retene alone. However, there was no effect of co-exposure to retene and either a 1×equivalent of dissolved organic compounds from BML-OSPW or 5×equivalent of dissolved organic compounds from P9-OSPW. While there was evidence that exposure to 5×equivalent of dissolved organic compounds from BML-OSPW caused oxidative stress, there was no evidence of this effect in larvae exposed only to retene or co-exposed to retene and a 5×equivalent of dissolved organic compounds from BML-OSPW. These results suggest that oxidative stress is not a mechanism of pericardial edema in early-life stages of Japanese medaka. Relatively fresh OSPW from Base Mine Lake might influence toxicity of alkylated-PAHs to early life stages of fishes but this effect would not be expected to occur at current concentrations of OSPW and is attenuated by aging of OSPW.


Stability, Aromaticity, and Photophysical Behaviors of Macrocyclic Molecules: A Theoretical Analysis.
The macrocyclic molecules with terthiophene (TTH) isomers unit exhibit intriguing properties in terms of aromaticity, stability, and absorption. In this work, we theoretically designed a series of macrocyclic molecules featured with TTH and dithienothiophene (DTT) π-conjugated building units, which are used to permute pyrrole unit in porphyrin skeleton. Density functional theory and time-dependent DFT methods are used to evaluate the performance of the designed molecules. Our simulations show that molecules 1-3 exhibit excellent optoelectronic performance. Specifically, the molecule with the DTT unit is more stable than the one with TTH unit in terms of aromaticity and aromatic stabilization energy. This is because DTT unit enhances the coplanarity of the molecular material, facilitating electronic communication. Calculation of vertical electronic excitations suggests the absorption feature of these molecules is mainly contributed by the electronic excitations of higher occupied molecular orbital (HOMO) → lowest unoccupied molecular orbital (LUMO)+1 and HOMO-1 → LUMO. Judging from the key parameters determining the overall performance, 3 stands out because of its good planarity, large HOMO-LUMO gap, and strong aromaticity among all molecules. Interestingly, molecule 1 has the current density flow distributes around the outer section of TTH unit; in contrast, molecule 3 with DTT unit has the current density flow located at the inner section of DTT, which is beneficial for stability and aromaticity. Second-order perturbation energies are calculated to rationalize this observation. We expect that these research results can provide valuable insights into the rational design of novel molecular materials for a variety of applications.


Evidence of marine ice-cliff instability in Pine Island Bay from iceberg-keel plough marks.
Marine ice-cliff instability (MICI) processes could accelerate future retreat of the Antarctic Ice Sheet if ice shelves that buttress grounding lines more than 800 metres below sea level are lost. The present-day grounding zones of the Pine Island and Thwaites glaciers in West Antarctica need to retreat only short distances before they reach extensive retrograde slopes. When grounding zones of glaciers retreat onto such slopes, theoretical considerations and modelling results indicate that the retreat becomes unstable (marine ice-sheet instability) and thus accelerates. It is thought that MICI is triggered when this retreat produces ice cliffs above the water line with heights approaching about 90 metres. However, observational evidence confirming the action of MICI has not previously been reported. Here we present observational evidence that rapid deglacial ice-sheet retreat into Pine Island Bay proceeded in a similar manner to that simulated in a recent modelling study, driven by MICI. Iceberg-keel plough marks on the sea-floor provide geological evidence of past and present iceberg morphology, keel depth and drift direction. From the planform shape and cross-sectional morphologies of iceberg-keel plough marks, we find that iceberg calving during the most recent deglaciation was not characterized by small numbers of large, tabular icebergs as is observed today, which would produce wide, flat-based plough marks or toothcomb-like multi-keeled plough marks. Instead, it was characterized by large numbers of smaller icebergs with V-shaped keels. Geological evidence of the form and water-depth distribution of the plough marks indicates calving-margin thicknesses equivalent to the threshold that is predicted to trigger ice-cliff structural collapse as a result of MICI. We infer rapid and sustained ice-sheet retreat driven by MICI, commencing around 12,300 years ago and terminating before about 11,200 years ago, which produced large numbers of icebergs smaller than the typical tabular icebergs produced today. Our findings demonstrate the effective operation of MICI in the past, and highlight its potential contribution to accelerated future retreat of the Antarctic Ice Sheet.


[Clinical research of primary intraspinal hemangiopericytoma].
To investigate the effective means of treatment for primary intraspinal hemangiopericytoma. The clinical presentation, imaging features, treatment and prognosis of 23 cases of intraspinal hemangiopericytoma, 14 males and 9 females, aged 39.1 (14 - 65), were analyzed retrospectively. Subtotal resection was performed on 11 cases, subtotal resection and radiotherapy on 4 cases, total resection on 5 cases, and total resection and radiotherapy on 3 cases. Spinal stabilization was conducted on 2 cases after total resection with severe damage of the vertebral body or pedicle of vertebral arch. Nineteen cases were followed up for 3.8 years (6 months-10 years). The recurrence rate was 68% and the metastasis rate was 21%. Primary intraspinal hemangiopericytoma should be resected en bloc with neighboring dura mater to reduce blood loss and recurrence. Resection of large lesions may be safer after preoperative embolization. The patients undergoing subtotal resection need adjuvant radiotherapy. The patients with evident spinal involvement may benefit from spinal stabilization. Lesions arising from dural mater have better prognosis. Postoperative long-term follow-up is necessary.


Association between Diet Quality Indices and Incidence of Type 2 Diabetes in the Melbourne Collaborative Cohort Study.
Type 2 diabetes mellitus is a common condition whose incidence is increasing worldwide, and for which obesity and diet are important risk factors. The aim of this study was to assess the association of three diet quality scores with diabetes risk and how much of the association was mediated through body size. The Melbourne Collaborative Cohort Study recruited 41,513 men and women aged 40-69 years during 1990-1994. At baseline, data were collected on lifestyle and diet, anthropometric measures were performed. Incident diabetes was assessed by self-report at follow-up surveys in 1994-1998 and 2003-2007. The associations between the dietary inflammatory index (DII®), Mediterranean Diet Score (MDS) and the Alternative Healthy Eating Index-2010 and incident diabetes were assessed using Poisson regression, adjusting for age, sex, physical activity, smoking, alcohol consumption, socio-economic status (area based) and family history of diabetes. Data from 39,185 participants were included in the analysis and 1989 cases of diabetes were identified. Both DII and AHEI-2010 were associated with diabetes incidence, but MDS was not. In the top quintile of DII (most pro-inflammatory) vs. the least inflammatory quintile IRR was 1.49 95% CI (1.30, 1.72), p trend across quintiles <0.001. For AHEI-2010 the IRR was 0.67 (0.58, 0.78), p trend <0.001 for the healthiest vs. the least healthy quintile. Mediation analysis indicated that body size (body mass index/waist to hip ratio) mediated 35-48% of the association with incident diabetes for the AHEI and DII. Healthier diets may reduce risk of diabetes both by reducing weight gain and other mechanisms such as reducing inflammation.


[A case of pulmonary amebiasis].
A 57-year-old man was admitted to our hospital because of dyspnea and right abdominal pain. Chest X-ray radiogram showed right massive pleural effusion. Ultrasonic echogram of abdomen showed a unilocular liver cyst. He was treated with intravenous infusion of meropenem, and percutaneous pleural and liver drainage were performed. At the time of drainage, we injected contrast medium into the liver cyst and confirmed a fistula connecting to the right pleural space. Initially we made a diagnosis of bacterial empyema and liver abscess, yet there was no response to the initial treatment. Cultures of pleural effusion and liver abscess were confirmed to be negative. A few days after admission, the patient stated that he was a homosexual. Liver amebiasis and its perforation became the most likely diagnosis, and metronidazole was administered. On admission day 21, tests for anti-amebic antibody were positive. Finally he fully recovered. We must be aware of the rare pulmonary manifestation of amebiasis. We report this case and review the literature.


A psychoanalytic study of Edward de Vere's The Tempest.
There is now abundant evidence that Freud was correct in believing Edward de Vere (1550-1604) wrote under the pseudonym "William Shakespeare." One common reaction is "What difference does it make?" I address that question by examining many significant connections between de Vere's life and The Tempest. Such studies promise to bring our understanding of Shakespeare's works back into line with our usual psychoanalytic approach to literature, which examines how a great writer's imagination weaves a new creation out of the threads of his or her life experiences. One source of the intense controversy about de Vere's authorship is our idealization of the traditional author, about whom we know so little that, as Freud noted, we can imagine his personality was as fine as his works.


Efficacy of combined gemcitabine, oxaliplatin and pegaspargase (P-gemox regimen) in patients with newly diagnosed advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma.
Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive neoplasm with a poor outcome. Asparaginase-based regimens are recommended for patients with advanced-stage or relapsed/refractory ENKTL. We retrospectively investigated the efficacy and toxicity of combined gemcitabine, oxaliplatin, and pegaspargase (P-gemox) in these patients. A total of 35 patients with newly diagnosed stage III-IV, relapsed or refractory ENKTL were treated with 2 to 8 cycles of P-gemox: gemcitabine (1250 mg/m2) and oxaliplatin (85 mg/m2) injected intravenously and pegaspargase (2500 IU/m2) injected intramuscularly on day 1 and repeated every 2 weeks. Upon completion of treatment, the overall response rate was 80.0%, with a complete response in 51.4% of patients. The 1-, 2- and 3- year progression-free survival rates were 45.0%, 38.6% and 38.6%, and overall survival rates were 76.8%, 64.7% and 64.7%, respectively. Patients who attained a complete response showed better progression-free survival than those without a complete response (p = 0.01). The major adverse effects were hematologic toxicity and liver dysfunction. Grade 3/4 leucopenia and neutropenia occurred in 40.0% of patients. No treatment-related deaths occurred. These results indicate the P-gemox regimen is a safe and effective treatment for patients with newly diagnosed advanced-stage or relapsed/refractory ENKTL. We anticipate future prospective trials will confirm the efficacy.


Emergency Department Observation Units: Has the Time Come?
Background: Economic pressures for efficiency in health care have led to the need for new strategies for the care of patients with acute chest pain. Methods: Chest pain observation units have been developed in many hospitals and are widely considered to have the potential to provide rapid and safe evaluations for low-risk patients with acute chest pain. Critical pathways are also an increasingly used strategy for the management of this patient population. Results: Available data suggest that chest pain observation units can decrease 6 month resource utilization compared with patients admitted to traditional sites of care. However, the potential exists for these units to increase resource utilization by encouraging admissions to the hospital of patients who otherwise would have been discharged directly home. Conclusions: Chest pain observation units appear to be an important innovation for the care of patients with a low risk for acute myocardial infarction. Use of guidelines for the se units may permit true increases in efficiency without compromising quality.


Understanding Spatial and Contextual Factors Influencing Intraregional Differences in Child Vaccination Coverage in Bangladesh.
In Bangladesh, policy discourse has mostly focused on regional inequities in health, including child immunization coverage. Knowledge of local geographical and contextual factors within regions, however, becomes pertinent in efforts to address these inequities. We used the Bangladesh Demographic and Health Survey 2011 to examine factors that influence intraregional differences in vaccination coverage using a multilevel analysis. We found that in spite of the provision of health facilities at each level of administrative governance, only distance to the Upazilla Health Complex was a consistent predictor for each dose of vaccine, highlighting the remote locations of the communities that remain underserved. Our analysis demonstrates the value of subregional analyses that identify the characteristics of communities that are vulnerable to incomplete immunization coverage. Unless specific policy actions are taken to increase coverage in these remote areas, geographic inequities are likely to persist within regions, and desired targets will not be achieved.


A Survey of Turkish Nurses' Knowledge of Incontinence-Associated Dermatitis.
The purpose of this study was to determine the knowledge of incontinence-associated dermatitis (IAD) among nurses working in intensive care units. Descriptive study. The study was conducted in 6 intensive care units of a 550-bed academic research hospital in Turkey. Licensed practical and registered nurses with a minimum of a Bachelor of Science in Nursing degree employed full-time on these units were invited to participate. The survey consisted of statements that examined the demographic characteristics (14 questions) and knowledge levels (59 statements) of the nurses. For each statement, nurses were required to mark only one of the following options: "correct," "incorrect," or "no knowledge." Data were collected from July to September 2016. The Shapiro-Wilk test, Mann-Whitney U test, Kruskal-Wallis H test, post hoc multiple comparison test, and Spearman's correlation coefficient were used to analyze the data. Of the 126 RNs who participated in the study, 46.83% (n = 59) had an undergraduate degree in nursing. The majority (29.37%) practiced in gastroenterology surgery and urology intensive care units. The mean knowledge score was 33.05 ± 10.16 (min = 0, max = 59). The most correctly answered statement (94.44%; n = 119) was "The pH of the skin plays a role in skin barrier function." The statement with the most incorrect or "no knowledge" answers (96.03%; n = 120) was "The natural moisturizing factor found in the structure of corneocytes helps the skin to maintain its oil levels." Based on correctly answered statements, we found knowledge levels of the prevention and treatment of IAD were higher among nurses with a master of science degree in nursing (40.67 ± 4.32) and lower among licensed practical nursing (29.12 ± 10.08) (P < .05). In this study, knowledge of the nurses on identification, prevention, and treatment of IAD was low. Comprehensive basic nursing education and in-service training programs on IAD are recommended.


Diet and colorectal cancer: an investigation of the lectin/galactose hypothesis.
Mucosal expression of terminal unsubstituted galactose is increased in colon cancer and precancer and allows interaction with mitogenic galactose-binding lectins of dietary or microbial origin. This study tests the hypothesis that galactose, which is variably plentiful in fruit and vegetable but not cereal fibers, might prevent cancer by binding and inhibiting such lectins. Colorectal cancer cases (512) and controls (512) were matched for age, sex, primary care practitioner, and postal code. A 160-item food-frequency questionnaire was used to estimate their usual pre-illness (6 months previous) diet, aspirin intake, and exercise. Neither cereal fiber nor fruit and vegetable fiber were protective when assessed by univariate analysis, whereas dietary fiber galactose content showed a dose-related protective effect (odds ratio [OR] highest quartile/lowest quartile, 0.67; confidence interval [CI], 0.47-0.95) that remained protective when adjusted for energy, red meat, alcohol, calcium, protein and fat intake, regular aspirin usage, and exercise. Intake of nonlegume green vegetables, assessed because of the high lectin content of legumes, was also protective (OR, 0.54; CI, 0.35-0.81), but this was not independent of galactose. Protective effects of exercise and regular daily aspirin consumption and harmful effects of high energy consumption and high red meat intake were confirmed. The protective effect of fruit and vegetable fibers may be related to their galactose content. This provides further evidence that the association between diet and colon cancer is mediated via specific food components and may explain the discrepant results of studies addressing the protective effects of fiber.


In vivo and in vitro analysis of cardiac troponin I phosphorylation.
Adrenergic stimulation induces positive changes in cardiac contractility and relaxation. Cardiac troponin I is phosphorylated at different sites by protein kinase A and protein kinase C, but the effects of these post-translational modifications on the rate and extent of contractility and relaxation during beta-adrenergic stimulation in the intact animal remain obscure. To investigate the effect(s) of complete and chronic cTnI phosphorylation on cardiac function, we generated transgenic animals in which the five possible phosphorylation sites were replaced with aspartic acid, mimicking a constant state of complete phosphorylation (cTnI-AllP). We hypothesized that chronic and complete phosphorylation of cTnI might result in increased morbidity or mortality, but complete replacement with the transgenic protein was benign with no detectable pathology. To differentiate the effects of the different phosphorylation sites, we generated another mouse model, cTnI-PP, in which only the protein kinase A phosphorylation sites (Ser(23)/Ser(24)) were mutated to aspartic acid. In contrast to the cTnIAllP, the cTnI-PP mice showed enhanced diastolic function under basal conditions. The cTnI-PP animals also showed augmented relaxation and contraction at higher heart rates compared with the nontransgenic controls. Nuclear magnetic resonance amide proton/nitrogen chemical shift analysis of cardiac troponin C showed that, in the presence of cTnI-AllP and cTnI-PP, the N terminus exhibits a more closed conformation, respectively. The data show that protein kinase C phosphorylation of cTnI plays a dominant role in depressing contractility and exerts an antithetic role on the ability of protein kinase A to increase relaxation.


Effects of renal function on pharmacokinetics of recombinant human granulocyte colony-stimulating factor in lung cancer patients.
Animal studies suggest that the kidney is involved in the elimination of recombinant human granulocyte colony-stimulating factor (rhG-CSF), which is used for patients with neutropenia during cancer chemotherapy. Since anticancer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study was designed to evaluate the relationship between the pharmacokinetics of rhG-CSF and renal function in lung cancer patients compared to the absolute neutrophil count (ANC). The pharmacokinetic studies were conducted with 25 lung cancer patients. Following chemotherapy using platinum-based compounds, a bolus 5 microg of rhG-CSF/kg of body weight was intravenously injected from the first day of leukopenia or neutropenia. Pharmacokinetic parameters were estimated by fitting the concentration in serum-time data to a two-compartment model according to the population pharmacokinetics and the Bayesian method. Creatinine clearance (CL(CR)) was predicted by the Cockcroft-Gault formula. rhG-CSF clearance (CL(G-CSF)) correlated significantly with the ANC (r = 0.613; P < 0.001) and CL(CR) (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination of the ANC and CL(CR) accounted for 57.4% of the variation of CL(G-CSF). In patients with an ANC of <1,000/microl, CL(CR) accounted for 72.9% of the variation of CL(G-CSF) (P < 0.001). Our findings suggest that renal function and neutrophil counts correlate with CL(G-CSF) and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.


Cutting the limits of aminobisphosphonates: new strategies for the potentiation of their anti-tumour effects.
Therapy with aminobisphosphonate (N-BPs), and zoledronic acid (ZOL) especially, has become a standard of care for patients with malignant bone disease. In addition, preclinical and preliminary clinical data suggest that N-BPs exert their direct or indirect anti-tumour effects on cancer growth factor release, cancer cell adhesion, invasion and viability, cancer angiogenesis and cancer cell apoptosis. Here, we will discuss the molecular mechanisms of the antitumour effects induced by ZOL. Despite their well-established in vitro anti-tumour effects N-BPs have not clear in vivo anti-tumour activity in humans. The bases of these discrepancies will be discussed in the text with a special focus on the pharmacokinetic limits of N-BPs. Moreover, the following molecular and pharmacological strategies in order to overcome N-BPs limitations will be described: i) development of pharmacological combinations with other biological agents; ii) finding of new molecular targets of N-BPs; iii) development of new pharmacological formulations of N-BPs. Finally, a new scenario of integrated bio-medicine and pharmacology will be depicted in order to drive the optimization of anti-cancer activity of N-BPs.


The influence of age and gender on haematological parameters in Lipizzan horses.
Haematological parameters [red blood cell count (RBC), white blood cell count (WBC), packed cell volume (PCV), haemoglobin concentration, mean cell volume (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC)] in resting Lipizzan horses were determined for 143 stallions, 104 mares and 25 foals. The mean RBC and WBC values in Lipizzans were in the lower part of the normal range for warm-blooded horses. The mean PCV, MCV and MCH values were higher, but the mean haemoglobin concentration and MCHC values were lower than reported for other warm-blooded horses. In foals, the mean RBC, WBC, PCV, haemoglobin concentration and MCHC values were higher, whereas MCV and MCH were lower than in older animals. Results indicating a significant decrease in WBC (P < 0.01) and an increase in MCV, MCH and MCHC (P < 0.05) with increasing age are consistent with some other reports on warm-blooded horses. The age-related variations in RBC and PCV were less marked. Contrary to some reports, RBC (P < 0.01), WBC and haemoglobin concentration (P < 0.001) were higher in Lipizzan stallions than in mares, but differences in MCHC, MCH and MCV were insignificant. The specific haematological values determined in Lipizzans are presumably a result of selection and should be taken into consideration when dealing with this race of horses.


[[Proportional hazards model analysis of women's reproductive career in present-day Japan]].
The 1st section of this paper, using a method to decompose a change in the total marital fertility rate into the quantum and tempo effects, confirmed the major effect of birth timing on the 1970s trends in the total marital fertility rate based on the pooled data of the 8th and 9th Japanese National Fertility Surveys of 1982 and 1987, respectively. In the next section, proportional hazards model analyses of the 1st, 2nd, and 3rd birth functions for the pooled data made it clear that the 1st and 2nd birth intervals among the marriage cohorts since the end of the 1960s were shorter than those in the early 1960s even after having controlled for other variables. Given that 1 conception or more can occur during a birth interval, proportional hazards model analyses were again utilized to examine the effects of various variables on the time elapsed since marriage and the 1st conception, the time between the end of the 1st pregnancy and the 2nd conception, and the time between the end of the 2nd pregnancy and the 3rd conception. The authors found that the 1st-conception probability of the marriage cohorts since the late 1960s was smaller than that of predecessors, while the 2nd-conception probability was not affected by marriage cohort. In the last section, a logistic regression analysis of the probability of induced abortion showed that the probability of aborting a 2nd pregnancy decreased in the 1970s compared with that in the early 1960s. When a proportional hazards model analysis of the 2nd birth function was applied after omitting those cases where the 1st pregnancy did not result in birth and/or the 2nd pregnancy was aborted, the strong effect of marriage cohort on the 2nd birth probability was substantially diluted. These facts suggest that the shortened 2nd birth interval in the 1970s was partly caused by the shrinking probability of aborting a 2nd pregnancy in this period.


Vanillin inhibits translation and induces messenger ribonucleoprotein (mRNP) granule formation in saccharomyces cerevisiae: application and validation of high-content, image-based profiling.
Vanillin, generated by acid hydrolysis of lignocellulose, acts as a potent inhibitor of the growth of the yeast Saccharomyces cerevisiae. Here, we investigated the cellular processes affected by vanillin using high-content, image-based profiling. Among 4,718 non-essential yeast deletion mutants, the morphology of those defective in the large ribosomal subunit showed significant similarity to that of vanillin-treated cells. The defects in these mutants were clustered in three domains of the ribosome: the mRNA tunnel entrance, exit and backbone required for small subunit attachment. To confirm that vanillin inhibited ribosomal function, we assessed polysome and messenger ribonucleoprotein granule formation after treatment with vanillin. Analysis of polysome profiles showed disassembly of the polysomes in the presence of vanillin. Processing bodies and stress granules, which are composed of non-translating mRNAs and various proteins, were formed after treatment with vanillin. These results suggest that vanillin represses translation in yeast cells.


Necrotizing Pneumonia.
Necrotizing pneumonia refers to the development of necrosis, liquefication, and cavitation of the lung parenchyma from an infectious pathogen. Nearly 4% of all community-acquired pneumonias are necrotizing, although studies retrospectively evaluating the incidence have found it to be increasing during the past 20 years. Common presenting symptoms include fever, tachypnea, and cough, and most of those afflicted also develop complications such as parapneumonic effusions, empyemas, or bronchopleural fistulae. When compared to age-matched controls with parapneumonic effusions or severe pneumonias without a necrotizing component, those with necrotizing pneumonia have been shown to have more elevated white blood cell counts and inflammatory markers that take longer to normalize, a longer duration of symptoms despite initiation of therapy, and a longer hospital stay. Despite the high incidence of complications during the acute phase of illness, the overall prognosis of necrotizing pneumonia has been shown to be promising, with nearly all children surviving the illness. [Pediatr Ann. 2017;46(2):e65-e68.].


Mechanisms related to psychological well-being in older women with chronic illnesses: age and disease comparisons.
The influence of type of illness (breast cancer versus osteoarthritis) and age on physical health and functioning, self-system interpretive mechanisms, and women's psychological well-being were examined. Self-system interpretive mechanisms are considered mediators of the effects of physical health on psychological well-being and include social comparisons, social integration, and illness perceptions. Young-old (aged 60-74) and old-old (75 +) women, diagnosed with osteoarthritis (N = 102) or breast cancer (N = 86), who volunteered for the study were interviewed using structured self-report scales. Young-old and old-old women did not differ in terms of health status, interpretive mechanisms, or on three of five indices of psychological well-being. On the other hand, women with arthritis, regardless of age, reported more functional health problems, more symptoms, and perceived their illness as more severe, more chronic, and less controllable than women with breast cancer. Although women with arthritis and breast cancer differed significantly in terms of physical health, they did not differ on multiple measures of psychological well-being. For both groups, women who made more positive social comparisons and who had more extensive social networks had higher levels of psychological well-being, regardless of physical health problems.


A single institution experience with weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease.
The purpose of this study is to report our experience with weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. Treatment was begun at a dose of 40 mg/m2 and escalated weekly by 5-10 mg/m2, depending upon response and tolerance, to a maximum dose of 60 mg/m2. Remission was induced with weekly intramuscular methotrexate alone in 12 (60%) of 20 patients in 2-12 (median 8) weeks. The remaining 7 patients had a complete response to alternate chemotherapy. There were no major toxicities. Although the results of the present study are less favorable in terms of response, the overall published results using weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease indicate that it is comparable in efficacy to other first-line treatments while having the advantages of convenience, low cost, and low toxicity.


Purification and crystallization of a dimeric form of acetylcholinesterase from Torpedo californica subsequent to solubilization with phosphatidylinositol-specific phospholipase C.
A dimeric form of acetylcholinesterase from Torpedo californica was purified to homogeneity by affinity chromatography subsequent to solubilization with a phosphatidylinositol-specific phospholipase C of bacterial origin. Bipyramidal crystals of the enzyme were obtained from solutions in polyethylene glycol 200. The crystals diffract to 2.0 A (1 A = 0.1 nm) resolution. They were found to be orthorhombic, space group P2221, with a = 163.4(+/- 0.2) A, b = 112.1(+/- 0.2) A, c = 81.3(+/- 0.1) A.


Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL.
Immune complexes (IC) prepared with human low density lipoprotein (LDL) and rabbit LDL antibodies induce foam cell transformation of human macrophages and activate the release of proinflammatory mediators by human macrophages and THP-1 cells. Because the affinity of human oxidized LDL (oxLDL) antibodies is lower than that of rabbit antibodies, IC formed with human antibodies could have limited pathogenic potential. Immune complexes prepared with human oxidized LDL (oxLDL) and purified human oxLDL antibodies (predominantly of the IgG1 and IgG3 isotypes) were presented to THP-1 cells using two protocols previously described in studies of the properties of LDL-IC prepared with rabbit antibodies. OxLDL/human oxLDL antibody IC immobilized by adsorption to red blood cells (RBC) induced the release of significantly higher levels of TNF from THP-1 cells (872-313 pg/ml) than oxLDL adsorbed to RBC (461-75.6 pg/ml) and caused a higher degree of cholesterol ester accumulation in the same cells (5.4-0.77 in cells incubated with IC-coated RBC vs 1.99-1.16 in oxLDL-coated RBC). Insoluble IC prepared with oxLDL/human oxLDL antibody were even more effective in promoting intracellular accumulation of cholesterol in THP-1 cells (total cholesterol = 53.8-13.5 and cholesterol esters = 24.0-7.2 mg/l in THP-1 cells incubated with insoluble IC (200 micrograms) vs total cholesterol = 32.4-8.2 and cholesterol esters = 7.7 +/- 2.8 micrograms/l in THP-1 cells incubated with an identical concentration of oxLDL) and also induced the release of TNF. Thus we have demonstrated that IC prepared with human oxLDL and human oxLDL antibodies have the same atherogenic and proinflammatory properties as IC prepared with human LDL and rabbit LDL antibodies. This strongly supports the concept that modified LDL-IC present in circulation and/or tissues play an important pathogenic role in arteriosclerosis.


Pembrolizumab-Induced Sarcoid-Like Reaction: FDG-PET Scan Interpretation in the Era of Immunotherapy.
Immunotherapy has revolutionized the treatment of malignant melanomas. Immunotherapy is associated with multi-system toxicities, which are referred to as immune-related adverse events (irAEs). Positron emission tomography (PET) with fluorodeoxyglucose (FDG) and CT is the preferred imaging modality to monitor disease progression in melanoma. FDG uptake by a sarcoid-like reaction (SLR) can mimic cancer progression, thereby posing a diagnostic and therapeutic dilemma. We present the case of a 39-year-old patient with malignant melanoma on immunotherapy who presented with PET scan findings of adenopathy with increased uptake. This case highlights the challenges in interpreting PET scan in the setting of an SLR.


Predictors of health-related quality of life and costs in adults with epilepsy: a systematic review.
Given the high burden of epilepsy on both health-related quality of life (HRQoL) and costs, identification of factors that are predictive of either reduced HRQoL or increased expenditure is central to the better future targeting and optimization of existing and emerging interventions and management strategies for epilepsy. Searches of Medline, Embase, and Cochrane Library (up to July 2010) to identify studies examining the association between demographic, psychosocial, and condition-related factors and HRQoL, resource utilization or costs in adults with epilepsy. For each study, predictor factor associations were summarized on the basis of statistical significance and direction; the results were then combined across studies. Ninety-three HRQoL and 16 resource utilization/cost studies were included. Increases in seizure frequency, seizure severity, level of depression, and level of anxiety and presence of comorbidity were strongly associated with reduced HRQoL. The majority of studies were cross-sectional in design and had an overall methodologic quality that was judged to be "moderate" for HRQoL studies and "poor" for health care resource or costs studies. In the 53 multivariate studies, age, gender, marital status, type of seizure, age at diagnosis, and duration of epilepsy did not appear to be associated with HRQoL, whereas the predictive influence of educational and employment status, number of antiepileptic drugs (AEDs) and AED side effects was unclear. The association between predictive factors and HRQoL appeared to be consistent across individuals whether refractory or seizures controlled or managed by AEDs. There were insufficient multivariate studies (five) to reliably comment on the predictors of resource utilization or cost in epilepsy. In addition to seizure control, effective epilepsy management requires the early detection of those most at risk of psychological dysfunction and comorbidity, and the targeting of appropriate interventions. There is need for more rigorous studies with appropriate multivariate statistical methods that prospectively investigate the predictors of HRQoL, resource utilization, and costs in epilepsy.


Psychotropic Medication Use among Insured Children with Autism Spectrum Disorder.
This study examined psychotropic medication use among 7901 children aged 1-17 with autism spectrum disorder (ASD) in five health systems, comparing to matched cohorts with no ASD. Nearly half (48.5 %) of children with ASD received psychotropics in the year observed; the most common classes were stimulants, alpha-agonists, or atomoxetine (30.2 %), antipsychotics (20.5 %), and antidepressants (17.8 %). Psychotropic treatment was far more prevalent among children with ASD, as compared to children with no ASD (7.7 % overall), even within strata defined by the presence or absence of other psychiatric diagnoses. The widespread use of psychotropics we observed, particularly given weak evidence supporting the effectiveness of these medications for most children with ASD, highlights challenges in ASD treatment and the need for greater investment in its evaluation.


[Experimental investigations into the effect of Escherichia coli and Clostridium perfringens on the steroid estrone].
Together with the faecal and the urinary discharge of animals and humans natural and synthetic estrogenes are excreted into the environment. About their degradation in the environment only few facts are known. Their reduction is probably of microbial enzymatical nature. For looking into that question it was investigated by in-vitro-attempts whether Escherichia coli or Clostridium perfringens influence the estrone. Therefore estrone was incubated together with the microorganisms tested (experimental groups) and without those (control groups) in nutrient medium for these bacteria over 48 hours with 37 degrees C (aerobic) or 42 degrees C (anaerobic). For the executed procedure an enzyme immunoassay was used. It could be seen that E. coli does not show a provable effect on the estrone concentration under this conditions. Whereas C. perfringens might have a potency for the degradation of the hormone tested. The experiments shows that there exists obviously a difference between estrone and 4-pregnene-20 beta-o1-3-one in the same system of test.


The cardioprotective effects of metformin.
In patients with type 2 diabetes mellitus, treatment with metformin is associated with a lower cardiovascular morbidity and mortality, compared with alternative glucose-lowering drugs. It has been suggested that metformin might exert direct protective effects on the heart. This review appraises recent experimental animal studies on the effect of metformin on myocardial ischaemia-reperfusion injury and remodeling. In murine models of myocardial infarction, the administration of metformin potently limits infarct size. Activation of adenosine monophosphate-activated protein kinase, increased formation of adenosine, and the prevention of opening of the mitochondrial permeability transition pore at reperfusion all contribute to this cardioprotective effect. In addition, metformin therapy attenuates postinfarction cardiac remodeling. There is evidence that activation of adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase, and a reduced collagen expression are crucial for this effect. The finding that metformin limits myocardial infarct size and remodeling in animal models of myocardial infarction suggests that patients suffering from myocardial ischaemia could benefit from treatment with metformin, even when these patients do not have diabetes. Currently, several clinical trials are being performed to test this hypothesis.


Discordance Between Patient and Clinician Experiences and Priorities in Rural Interhospital Transfer: A Mixed Methods Study.
Rural emergency department (ED) patients require interhospital transfer for definitive care at nearly 6 times the national rate, yet transfer decision-making is variable. The goal of this study was to understand patient experiences, preferences, and decision-making in the rural interhospital transfer process, and to measure the concordance between patient opinions and provider perceptions. Ours is a mixed methods study of patients transferred to a 711-bed Midwestern academic medical center and the emergency physicians in community hospitals. Qualitative interviews were conducted by a single research assistant with admitted patients transferred from an ED, and a corresponding survey was distributed to community emergency physicians. Standardized scenarios were posed to both groups to understand transfer priorities. Seventy-nine patients and 40 physicians participated in this study. Patients and physicians cited proximity to home, medical expertise, a personal relationship with a health care provider, health insurance, privacy concerns, and patient choice as the primary factors that influenced patient transfer priorities. Compared with patient respondents, physicians overestimated the patient-perceived importance of proximity to home (P = .015) and being cared for by a personal physician (P = .049), but they underestimated the value of receiving treatment in a comprehensive medical center (P = .002). In standardized scenarios, physicians agreed with patients in transfer preferences for conditions requiring neurosurgical consultation, but they underestimated patients' desire for transfer for pneumonia requiring mechanical ventilation. Patients and physicians recognize similar factors that influence patient preferences in interhospital ED transfer, but physicians may overestimate the value of nonmedical influences on decision-making priorities.


Medical Degree Disparity Among Authors of Original Research in Pediatric Journals.
Research and scholarly output are integral parts of residency training for both residents and faculty. With the transition to a single accreditation system, scholarly activity and output of osteopathic physicians have garnered significant interest. Previous research has shown that osteopathic physicians in emergency medicine and obstetrics and gynecology infrequently publish original research in high impact journals. To determine whether there is a disparity between osteopathic and allopathic physicians among authors who publish original research manuscripts in three high-impact pediatric journals. The medical degree designation of the first and senior author (last author) and any advanced degree either author may have obtained were retrieved from the Journal of Pediatrics (J Pediatr), Pediatrics, and JAMA Pediatrics (JAMA Pediatr) for the years 2000, 2005, 2010 and 2015. Data was analyzed using simple descriptive statistics and linear regression. In total, 2232 manuscripts and 4296 authors were reviewed with 0.58% (25/4296) of all authors being osteopathic physicians. A total of 0.81% (18/2232) of first authors and 0.34% (7/2064) of senior authors were osteopathic physicians. For those with a dual degree, a total of 0.64% (5/777) of first and 0.33% (3/904) of senior authors were osteopathic physicians. No statistical trend could be established for increased first (p=0.24), senior (p=0.16), dual degree first (p=0.08) or dual degree senior (p=0.06) osteopathic physician authorship. Likewise, no statistical trend for increased authorship could be established for any Doctor of Osteopathic Medicine (DO) authorship role in the three journals over the time period studied. Very few osteopathic physicians have served as either the first or senior author in published original research manuscripts for the Journal of Pediatrics, Pediatrics, or JAMA Pediatrics for the years studied. Also, no statistical trend could be established for increased osteopathic physician publication over the same years.


[Significance of p16 and C-myc expression in the laryngeal squamous cell carcinoma].
To study the clinical significance of p16 and C-myc expression in the laryngeal squamous cell carcinoma (LSCC). Immunohisto-chemical detection of p16 proteins and C-myc proteins, in 47 cases of LSCC and 6 cases of normal tissues from the larynx, were conducted in paraffin-embeded sections. No staining was found in 6 cases of normal tissue; The positive expression of p16 and C-myc proteins expression rates did not correlate with sex, age and position of the tumors (P > 0.05); but related to the staging and grade of LSCC (P < 0.05). The expression of C-myc proteins were higher in the case with lymph nodal metastasis than that without lymph nodal metastasis (P < 0.05). The expression of p16 and C-myc protein may play an important role in the development of LSCC, and may be a new indicator to assess the prognosis of LSCC.


Modification of agility running technique in reaction to a defender in rugby union.
Three-dimensional kinematic analysis examined agility running technique during pre-planned and reactive performance conditions specific to attacking ball carries in rugby union. The variation to running technique of 8 highly trained rugby union players was compared between agility conditions (pre-planned and reactive) and also agility performance speeds (fast, moderate and slow). Kinematic measures were used to determine the velocity of the centre of mass (COM) in the anteroposterior (running speed) and mediolateral (lateral movement speed) planes. The position of foot-strike and toe-off was also examined for the step prior to the agility side- step (pre-change of direction phase) and then the side-step (change of direction phase). This study demonstrated that less lateral movement speed towards the intended direction change occurred during reactive compared to pre-planned conditions at pre-change of direction (0.08 ± 0.28 m·s(-1) and 0.42 ± 0.25 m·s(-1), respectively) and change of direction foot-strikes (0.25 ± 0.42 m·s(-1) and 0.69 ± 0.43 m·s(-1), respectively). Less lateral movement speed during reactive conditions was associated with greater lateral foot displacement (44.52 ± 6.10% leg length) at the change of direction step compared to pre-planned conditions (41.35 ± 5.85%). Importantly, the anticipation abilities during reactive conditions provided a means to differentiate between speeds of agility performance, with faster performances displaying greater lateral movement speed at the change of direction foot- strike (0.52 ± 0.34 m·s(-1)) compared to moderate (0.20 ± 0.37 m·s(-1)) and slow (-0.08 ± 0.31 m·s(-1)). The changes to running technique during reactive conditions highlight the need to incorporate decision-making in rugby union agility programs. Key pointsChanges to running technique occur when required to make a decision.Fast agility performers use different stepping strategies in reactive conditions.Decision-making must be incorporated in agility training programs.


Measurements of Proton Pumping in Arum maculatum Mitochondria.
Direct evidence is presented for the lack of a pH change in the medium associated with electron flow along the alternative, cyanide-resistant pathway in Arum maculatum mitochondria. When these mitochondria oxidize succinate via the cytochrome chain, the medium becomes acidified. However, when the main respiratory chain is blocked by cyanide or antimycin A, oxygen consumption continues, but no pH change occurs. This confirms the lack of a charge separation across the membrane, so that phosphorylation cannot be supported during operation of the alternative oxidase.


[Voiding disturbance in elderly males examined by prostate mass screening. Gunma Urological Oncology Study Group].
Information about voiding disturbance was obtained from 34,140 elderly males in Gunma Aged Club Association (Q group) through a questionnaire and from 8,129 males by prostate mass screening for prostate disease (MS group) as to: (1) the characteristics of the subjects examined by the mass screening, (2) the relationship between the voiding disturbance and aging and (3) the frequency of voiding disturbance in the normal elderly males. In MS group, the percentage of young subjects, especially less than 60 years old, who complained voiding disturbance was higher than the expected percentage on the assumption that it increases with aging. The percentage of voiding disturbance in these young subjects was also higher than that of males in the same decade in Q group. In their past and present history, the percentage of benign prostatic hypertrophy (BPH) in these young subjects was higher than the expected percentage on the assumption that the incidence of BPH increases with aging. Judging from these results, it was estimated that they were not satisfied with the medical care by which they were treated or were being treated, and they received this mass screening to obtain consultation for their complains. Loss of the force was related with the prostate size estimated by digital rectal examination but not with aging. However, nocturia was well related with aging but not with the prostate size. Hesitancy, strain and dribbling were not apparently related with either the prostate size or aging. It was demonstrated that frequency of nocturia was 0 to 1 in less than 60 years old normal males, 0 to 2 in 60 to 79 years old ones and 0 to 3 in over 80 years old ones. The other symptoms studied in each decade were also analyzed and discussed.


Evaluating In Vitro DNA Damage Using Comet Assay.
DNA damage is a common phenomenon for each cell during its lifespan, and is defined as an alteration of the chemical structure of genomic DNA. Cancer therapies, such as radio- and chemotherapy, introduce enormous amount of additional DNA damage, leading to cell cycle arrest and apoptosis to limit cancer progression. Quantitative assessment of DNA damage during experimental cancer therapy is a key step to justify the effectiveness of a genotoxic agent. In this study, we focus on a single cell electrophoresis assay, also known as the comet assay, which can quantify single and double-strand DNA breaks in vitro. The comet assay is a DNA damage quantification method that is efficient and easy to perform, and has low time/budget demands and high reproducibility. Here, we highlight the utility of the comet assay for a preclinical study by evaluating the genotoxic effect of olaparib/temozolomide combination therapy to U251 glioma cells.


Home parenteral nutrition for patients with inoperable malignant bowel obstruction.
The use of home parenteral nutrition (HPN) in patients with inoperable malignant bowel obstruction (IMBO) is controversial. The efficacy, safety, and indications for HPN in these patients is uncertain, and its benefit is difficult to demonstrate. The records of 17 patients (9, ovarian cancer; 4, colon cancer; 4, other) with IMBO receiving HPN managed by the Nutrition Support Team (NST) at Yale-New Haven Hospital from 1980 to 1989 were reviewed. Median survival was 53 days and was longest in the two patients with appendiceal carcinomatosis (208 and 159 days), intermediate in patients with colon cancer (median 90 days), and shortest in patients with ovarian cancer (median 39 days). Survival was unrelated to age or sex. All patients died of their underlying disease; 82% of deaths occurred at home. Only one treatment-related complication requiring readmission occurred. Fourteen patients and their families (82%) perceived their therapy as highly beneficial or beneficial. The NST agreed with this assessment in 11 patients but did not share this perception in three patients. These three patients had a short duration of HPN (less than 25 days) or minimal rehabilitation. It is concluded that HPN for patients with IMBO is associated with a low complication rate, may be most beneficial for those patients with gastrointestinal tract primary tumors, and is usually perceived by patients and care providers as beneficial. HPN has palliative benefit and facilitates compassionate home care for carefully selected patients with IMBO.


Assessments of coping after acquired brain injury: a systematic review of instrument conceptualization, feasibility, and psychometric properties.
To identify measures of coping styles used by patients with acquired brain injury; to evaluate the conceptualization, feasibility, and psychometric properties of the instruments; and to provide guidance for researchers and clinicians in the choice of a suitable instrument. Systematic review. The search identified 47 instruments, of which 14 were selected. The instruments focused on dispositional coping, situation-specific coping, or domain-specific coping. Psychometric properties were scarcely investigated. The COPE stood out in terms of psychometric properties but had low feasibility. The brief COPE, Coping Scale for Adults-short form, and Utrecht Coping List stood out in terms of feasibility, and the available psychometric properties of these instruments were good. Only the Coping With Health Injuries and Problems was used as other report. Information on psychometric properties of coping instruments in acquired brain injury is scarcely available and limits the strength of our recommendations. For patients with mild injuries, we cautiously recommend the COPE and for patients with more severe injuries the brief COPE, Coping Scale for Adults-short form, Utrecht Coping List, and Coping With Health Injuries and Problems-other-report. Other instruments may be used to address particular issues such as coping with a specific stressful situation or illness.


The blood-brain barrier disruption to circulating proteins in the early period after fluid percussion brain injury in rats.
Breakdown of the blood-brain barrier (BBB) immediately after traumatic brain injury is not clearly understood. In the present study we focused on the integrity of the BBB to circulating proteins within the first hour after injury. For this purpose, vascular permeability to endogenous albumin and to the exogenous protein tracer horseradish peroxidase (HRP) was examined after a lateral fluid percussion brain injury in rats. Albumin was immunolocalized in brain sections at 3 and 60 min after impact. This distribution was compared with the histochemical localization of HRP given before impact at the same time points. In a separate experiment HRP was given prior to sacrifice to determine the time course for the barrier disruption. Permeability to this protein was assessed at 13, 30, and 60 min after impact. Prominent extravasation of albumin occurred within 3 min of injury and was present in multiple foci within the injured hemisphere. At 60 min the extravasated albumin was present in the same sites, where it was widely distributed. Throughout the related brain parenchyma, little difference was found between the extravascular distribution of albumin and HRP. In the delayed administration paradigm breakdown of the BBB was noted in the impact site, hemorrhagic site in the deep cortical layer, hippocampus, thalamus, and midbrain at 13 min after injury. This injured barrier was restored in most regions by 30 min. However, the impact site and hemorrhagic site remained permeable up to 60 min postinjury. In addition, newly developed barrier disruption to HRP occurred in the parasagittal cortex at 30 and 60 min. In conclusion, widespread breakdown of the BBB to circulating proteins occurred within a few minutes after traumatic brain injury. The time course for this barrier disruption is characterized by three different patterns: (1) transient, (2) prolonged, and (3) delayed opening. This variation in the development of barrier disruption may be related to the secondary barrier failure as well as the primary opening after injury.


HLA-B*0749N: the first HLA-B*07 null allele.
In the present article, we report the identification of the first HLA-B*07 null allele found in a Polish patient awaiting a kidney allograft. A discrepant result obtained between serological typing (HLA-B "blank") and high-resolution molecular typing using PCR-SSP method (HLA-B*070201 allele) suggested the presence of a null allele. Genomic DNA sequencing of the HLA-B*07 allele revealed a single nucleotide substitution at the 3' end of the exon 4 leading to a premature stop codon.


Rhodococcus equiU19 strain harbors a nonmobilizable virulence plasmid.
Rhodococcus equiis the causative agent of pyogenic pneumonia in foals, and a virulence-associated protein A (VapA) encoded on the pVAPA virulence plasmid is important for its pathogenicity. In this study, we analyzed the virulence of R. equi strain U19, originally isolated in the Netherlands in 1997 and the genetic characteristics of the pVAPA_U19 plasmid. U19 expressed VapA that was regulated by temperature and pH and underwent significant intracellular proliferation in macrophages. The restriction fragment length polymorphism of pVAPA_U19 digested with EcoRI was similar to that of pREAT701 (85 kb Type I) harbored by R. equi ATCC33701, although the band pattern at 10-20 kb differed. Whole-genome sequencing showed that pVAPA_U19 was 51,684 bp in length and that the vapA pathogenicity island region and the replication/participation were almost identical to those in pREAT701. By contrast, the open reading frames (ORF26-ORF45) genes of pREAT701 (approximately 29,000 bp) were absent from pVAPA_U19. In this lacking region, mobility (MOB) genes, such as relaxase, which allow conjugative DNA processing, and the mating pair formation (MPF) genes, which are a form of the Type IV secretion system and provide the mating channel, were present. Coculture between U19 and five different recipient strains (two plasmid-cured strains and three cryptic plasmid-harboring strains) demonstrated that pVAPA_U19 could not support conjugation. Therefore, pVAPA_U19 does not differ significantly from the previously reported pVAPA in terms of virulence and plasmid replication and maintenance but is a nonmobilizable plasmid unable to cause conjugation because of the absence of genes related to MOB and MPF.


Gun possession among Massachusetts batterer intervention program enrollees.
Batterers with access to firearms present a serious lethal threat to their partners. The purpose of this exploratory study is to estimate the prevalence of and risk markers for gun possession among Massachusetts men enrolled in batterer intervention programs. The authors found that 1.8% of the men reported having a gun in or around their home. Those most likely to report having a gun were White, earned 25,000 US dollars or more per year, had served in the military, engaged in problem gambling, and had attempted homicide or threatened their partner with a firearm. Recommendations for strengthening relevant gun laws both within and outside of Massachusetts are discussed.


Randomized Comparison of Pazopanib and Doxorubicin as First-Line Treatment in Patients With Metastatic Soft Tissue Sarcoma Age 60 Years or Older: Results of a German Intergroup Study.
Doxorubicin is a standard of care in patients with advanced, inoperable soft tissue sarcoma (STS). We tested whether pazopanib has efficacy comparable to that of doxorubicin in elderly patients with STS and offers superior tolerability for hematologic toxicity. Patients age 60 years or older without previous systemic treatment for progressive advanced or metastatic STS who had Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate organ function were included. Treatment consisted of pazopanib 800 mg once per day or doxorubicin 75 mg/m2 once every 3 weeks (≤ 6 cycles) after being randomly assigned in a 2:1 ratio. Noninferiority was assumed for progression-free survival (PFS), if the upper limit of the 95% CI for the hazard ratio (HR) was less than 1.8. Neutropenia and febrile neutropenia were key secondary end points. The European Organisation for Research and Treatment of Cancer (30-item) Quality of Life Questionnaire and geriatric assessment were used to measure patient-reported outcomes. Cox regression analysis and Kaplan-Meier curves were used for analysis. Pazopanib and doxorubicin were given to 81 and 39 patients, respectively. The median age was 71 years (range, 60-88 years). PFS was noninferior (HR, 1.00; 95% CI, 0.65 to 1.53) and the incidence of grade 4 neutropenia and febrile neutropenia favored pazopanib. Objective response rates for pazopanib and doxorubicin were 12.3% and 15.4%, respectively. Overall survival did not differ significantly between arms (HR, 1.08; 95% CI, 0.68 to 1.72; P = .735). Geriatric assessment revealed 2 or more comorbidities in 15.8% of the patients and impairment of activities of daily living in 28.3% of patients. Pazopanib was noninferior to doxorubicin, rendering pazopanib a putative therapeutic option in the first-line treatment of STS in patients age 60 years or older. The distinct adverse event profile may be used to counsel patients and tailor therapy to individual needs.


Rivaroxaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials.
Rivaroxaban is a newly developed oral medicine that direct inhibits factor Xa for the prevention and treatment of thromboembolic disorders. The objective of this study was to compare the efficacy and safety of rivaroxaban versus enoxaparin, a medicine routinely used for thromboprophylaxis after total hip or knee arthroplasty. We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, and Embase. The primary efficacy outcome for our meta-analysis was total venous thromboembolism (VTE) and all-cause mortality. The primary safety outcome was bleeding events, which were categorized as major, clinically relevant non-major, or minor events. Eight RCTs, involving 15,586 patients, were included in our meta-analysis. Compared to enoxaparin, thromboprophylaxis with rivaroxaban was associated with significantly fewer VTE and all-cause mortality [9,244 patients, risk ratio (RR) 0.56, 95% confidence interval (CI) 0.39-0.80] cases and a similar incidence of bleeding cases (major bleeding events: 13,384 patients, RR 1.65, 95% CI 0.93-2.93; clinically relevant non-major bleeding events: 13,384 patients, RR 1.21, 95% CI 0.98-1.50; total bleeding events, 13,384 patients, RR 1.10, 95% CI 0.97-1.24). The total hip or knee arthroplasty subgroup analysis revealed consistent efficacy and safety findings. Rivaroxaban was more effective than the recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty.


A simplified approach to the diagnosis of elevated intra-abdominal pressure.
Previous methods described to measure bladder pressure require additional setup, making these techniques complex and time consuming. We describe a simple U-tube technique and investigate its accuracy for measuring intra-abdominal pressure (IAP). Warm saline was infused into the peritoneum of five pigs to increase IAP. Indirect methods of measuring IAP included bladder, inferior vena cava (IVC), and gastric pressures. Bladder pressure was measured by both the standard and U-tube technique. IVC pressure was measured via a femoral line and gastric pressure was transduced through an orogastric tube. In addition, 30 patients undergoing laparoscopy were prospectively investigated. Insufflated abdominal pressure readings were obtained and compared with bladder pressures measured by the U-tube technique (n = 20) and standard technique (n = 10). In the animal study, U-tube manometry had the highest degree of correlation (r(2) = 0.98) and the lowest bias (0.51 +/- 1.63 mm Hg). The bladder pressure measured by the U-tube technique was between 0.1 and 0.9 mm Hg less than the directly measured IAP (95% confidence interval). There was a high degree of correlation between IAP and the standard technique for bladder pressure (r(2) = 0.93), IVC pressure (r(2) = 0.93), and gastric pressure (r(2) = 0.90). Strong correlation also existed between the U-tube and standard techniques for measuring bladder pressure (r(2) = 0.96). In humans, a strong correlation between insufflated abdominal pressure and bladder pressure (U-tube technique, r(2) = 0.79; standard technique, r(2) = 0.53) was also encountered. The accuracy of the U-tube manometry technique for measuring intra-abdominal pressure is comparable to previously described techniques. The U-tube technique is simple, does not require additional equipment, and can be performed by any member of the medical team.


Two-step affinity purification of the hepatitis C virus ribonucleoprotein complex.
Positive-strand RNA viruses replicate their RNA genome within a ribonucleoprotein (RNP) complex that is associated with cellular membranes. We used a two-step method of purification to isolate hepatitis C virus (HCV) RNP complexes from human hepatoma cell line Huh7, which stably expresses HCV subgenomic replicons. The procedure involved hybridization of replicon-expressing cellular lysates with oligonucleotides tagged with biotin and digoxigenin at their respective termini complementary to subgenomic replicon RNA followed by avidin-agarose enrichment of the mixture and subsequent immunoprecipitation of biotin-eluted material with anti-digoxigenin antibody. The immunoprecipitates were immunoblotted with antisera against HCV nonstructural (NS) proteins. The analysis revealed the association of all the HCV NS proteins (NS3, NS4a, NS4b, NS5a, and NS5b) that are encoded by the subgenomic replicon RNA. The HCV RNP complex migrated in a native polyacrylamide gel with an approximate molecular mass of 450 kD. The association of these viral proteins in the RNP complex reinforces the widely acknowledged notion that RNA viruses accomplish replication within a membranous RNP complex.


[Cataract surgery. Anterior capsulorrhexis technique].
The cataract surgery is in a continuous dynamic because of the technological progress. The last years the surgical technique for cataract has changed and the most important progresses are the use of small incisions that don't require sutures, the realise of the anterior capsulotomy with smooth margins (continuous circular capsulorrhexis) and the extracapsular extraction of the cataract by phacoemulsification. The authors described the most usual techniques of the anterior capsulotomy with the advantages offered by capsulorrhexis, an important surgical step from the manual extracapsular extraction of the cataract to phacoemulsification.


Successful Treatment of Major Abdominal Trauma in a 9-year-old Male due to Bomb Explosion.
The present case report describes a pediatric patient that sustained and survived major abdominal trauma due to an open-air explosion during the Syrian civil war. A 9-year-old male patient was brought to our hospital's paediatric emergency department after a bomb explosion that occurred 8 hours prior to presentation. The patient had a severe flap-like skin defect that extended from the below the umbilicus to the right femur. The defect was embedded with multiple stones, plastic, and soil fragments of varying size. Debridement of the anterior abdominal wall was performed, followed by exploratory laparotomy. Multiple sites of perforation of the small bowel were resected, and anastomosis was performed. Vacuum-assisted closure (VAC) was applied to the large wound area. The VAC dressing was changed every 3 days. Granulation tissue developed post-operatively after 26 days and the defect was repaired using skin grafts harvested from the patient's left leg. The patient was considered fully recovered and was discharged 34 days post-surgery. The presented case shows that despite the severity of the patient's major abdominal injuries, rapid wound debridement, exploratory laparotomy, VAC therapy and a multidisciplinary approach are crucial in preventing death and achieving a full recovery.


Optical Autocorrelator with Special Application to MTF Measurement.
An optical autocorrelator is described which is based on a modified Sagnac two-mirror interferometer that operates in the zero-fringe mode. The real-time radiant flux output is the square of the autocorrelation of the aperture function. In a particular application, when the aperture function is the pupil function of a lens under test, the autocorrelator output is the MTF of the lens. The system is not limited in focal length; aperature size is limited only by the sizes of the beam splitters and mirrors. Experimental results are given with comparison data for both infinite-conjugate MTF and the autocorrelation of an annular aperture. Methods of adapting the system for measurement of the phase of the transfer function and for finite conjugate testing are also described.


Distribution patterns in generalized vitiligo.
Vitiligo is a common pigmentation disorder affecting approximately 1% of the world population. Nonetheless, its distribution pattern is not well investigated. The aim of this study was to investigate whether the distribution pattern of vitiligo is dependent on the clinical characteristics. A total of 700 generalized vitiligo patients were included in this retrospective observational cohort study. The most important predilection areas were the face (87%), followed by acral areas (76.3%) and extremities (59.7%). In women, joints (P = 0.002) (especially elbows), hips (P < 0.001), trunk (P < 0.001) and body folds (P < 0.001) (especially axillas) were more frequently affected compared to men. In contrast, in men more depigmentations in the beard area and genital area were observed (P < 0.001). Vitiligo at a young age is more prone to be localized at the lower extremities whereas the upper extremities are more susceptible at an older age. In the face, the periocular area is linked to a younger age, in contrast to the perioral area. Acral areas were more frequently affected in patients with autoimmune disorders (in particular thyroid disease) (P = 0.001). These results point to important differences in the distribution pattern according to the clinical characteristics. Although in some of these areas Koebner's phenomenon probably plays a role, other differences may represent a specific characteristic vulnerability related to the age, gender or typical association with autoimmune disease.


Accumulation and Subcellular Localization of alpha-Galactosidase-Hemagglutinin in Developing Soybean Cotyledons.
We have investigated the accumulation and intracellular localization of soybean (Glycine max [L.] Merr. cv Forrest) alpha-galactosidase-hemagglutinin during seed development. Cotyledon tissue was embedded in Lowicryl K4M and immunocytochemical localization was accomplished through treating thin sections with alpha-galactosidase antisera followed by indirect labeling with protein A coupled to colloidal gold. Gold particles were localized on the Golgi apparatus and protein bodies. We interpret this to indicate that alpha-galactosidase-hemagglutinin is transferred to and transported through the Golgi apparatus and finally deposited within the protein body by a Golgi apparatus-mediated process.


Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease.
Analysis of the leukocyte transriptome, in particular the Finkel-Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk factor, the links between smoking status and coronary artery disease (CAD) remains unclear. We aimed to analyze the relationship between smoking status and c-Fos expression in circulating leukocytes of patients with CAD. c-Fos expression was measured by RT-Q-PCR, from blood leukocytes of 239 consecutive patients after acute myocardial infarction (MI). The patients were asked about their smoking status and stratified into 3 groups: current smokers (CS) (N = 85), past smokers (PS) (N = 78) and never smokers (NS) (N = 76). NS had a higher risk profile including hypertension, and CS were younger than PS and NS (-13 years and 17 years respectively). There was only a trend towards lower CRP levels in NS and PS than in CS. The mean c-Fos transcript level was slightly higher in CS than in PS and NS (0.924 vs. 0.908 and 0.861 AU, respectively; p = 0.005). By univariate analysis, neither age, nor sex, nor CRP nor white blood cell count was associated with c-Fos transcript levels. By multivariate analysis, CS (vs. PS + NS) was the strongest predictor of the c-Fos transcript level, (B = 0.042 ± 0.014, p = 0.003), even after adjustment for confounding factors (i.e. hypertension, chronic medication, family history of CAD, and prior MI). Our work suggests that c-Fos transcript level in blood leukocyte could be considered a cumulative biomarker of smoking. As the c-Fos gene has been put forward as a new factor in the progression and severity of atherosclerosis, it could be considered a novel potential pathway of tobacco toxicity in coronary artery disease.


"Fun slipping into the doctor's role"-The relationship between sonoanatomy teaching and professional identity formation before and during the Covid-19 pandemic.
The various psychological dimensions of professional identity formation (PIF) are an important aspect of the study course for undergraduate medical students. Anatomical learning environments have been repeatedly shown to play a critical role in forming such an identity; however, relevance of PIF during sonoanatomical training remains underexplored. At the end of their basic anatomy studies, third-semester medical students took part in a four-day block course on anatomy and imaging. Anatomical content was revised in small groups using peer teaching and imaging methods, including one hour of hands-on sonoanatomy sessions each day. On-site sonoanatomy was identified as an excellent format to support students' transition from the pre-clinical to clinical phase as medical experts-to-be. Students enjoyed practical exercises and the clinical input, which increased their interest in the medical profession and their academic studies. This study further examined the effects of the transition into an online-only format, necessitated by the current Covid-19 pandemic. A comparison was made between the quantitative and qualitative evaluation data, and the written results of examinations of several on-site (n = 1096, mean age = 22.4 years ± 2.18), and online-only cohorts (n = 230, mean age = 22.6 years ± 2.21). The online-only transition led to a reduction of all PIF-related variables measured, losing identity-related variables, increasing students' stress levels, and reducing their long-term academic performance. Together, this study demonstrates presence of PIF in undergraduate sonoanatomy teaching, and cautions against the uncritical online-only substitution of hands-on learning environments.


Bismuth gallate coordination networks inspired by an active pharmaceutical ingredient.
The effect of solvent has been investigated for the synthesis of bismuth gallate compounds, of which the water-based bismuth subgallate has been used as an active pharmaceutical ingredient (API) for over a century. Using methanol as a solvent, two new bismuth gallates were acquired: first a flexible 3-periodic metal-organic framework (MOF) forms, which transforms upon extended synthesis times into a layered 2-periodic coordination polymer of the same bismuth-to-gallate ratio. The structures were determined by three-dimensional electron diffraction. Synthesis in ethanol resulted in the formation of the MOF phase, but not the layered phase. The layered material of the methanol-based synthesis was used as a Lewis acid catalyst due to its higher stability, showing a comparatively quick and regiospecific conversion of styrene oxide to 2-methoxy-2-phenylethanol, indicating the presence of open metal sites in the material. The acquisition of bismuth gallate structures of varying periodicity highlights the prospect of acquiring novel MOFs and coordination polymers from the same components of APIs.


A new family of transcription factors.
CudA, a nuclear protein required for Dictyostelium prespore-specific gene expression, binds in vivo to the promoter of the cotC prespore gene. A 14 nucleotide region of the cotC promoter binds CudA in vitro and ECudA, an Entamoeba CudA homologue, also binds to this site. The CudA and ECudA DNA-binding sites contain a dyad and, consistent with a symmetrical binding site, CudA forms a homodimer in the yeast two-hybrid system. Mutation of CudA binding sites within the cotC promoter reduces expression from cotC in prespore cells. The CudA and ECudA proteins share a 120 amino acid core of homology, and clustered point mutations introduced into two highly conserved motifs within the ECudA core region decrease its specific DNA binding in vitro. This region, the presumptive DNA-binding domain, is similar in sequence to domains in two Arabidopsis proteins and one Oryza protein. Significantly, these are the only proteins in the two plant species that contain an SH2 domain. Such a structure, with a DNA-binding domain located upstream of an SH2 domain, suggests that the plant proteins are orthologous to metazoan STATs. Consistent with this notion, the DNA sequence of the CudA half site, GAA, is identical to metazoan STAT half sites, although the relative positions of the two halves of the dyad are reversed. These results define a hitherto unrecognised class of transcription factors and suggest a model for the evolution of STATs and their DNA-binding sites.


Plasma insulin and blood pressure response to oral glucose tolerance test in young borderline hypertensives.
In order to evaluate whether borderline hypertension might be associated with hyperinsulinaemia, twenty non-obese borderline hypertensives and twenty matched normotensives underwent a standard oral glucose tolerance test and 24-h ambulatory blood pressure monitoring. Blood pressure, plasma glucose and insulin were measured at fasting and 15, 30, 60, 120 and 180 minutes after glucose load. Fasting plasma insulin was significantly higher in borderline hypertensives in comparison to normotensives (16.6 +/- 6.9 vs 12.4 +/- 4.2 mU/l; P < 0.05). Plasma insulin response estimated by the positive incremental area under the curve did not differ significantly between two groups but borderline hypertensives showed a larger interindividual difference. Decrease of systolic blood pressure after glucose load was significantly greater in borderline hypertensive subjects. Furthermore, blood pressure and plasma insulin relationship was different in borderline hypertensives compared to normotensives.


Lipoproteins are an important bacterial component responsible for bone destruction through the induction of osteoclast differentiation and activation.
Bacterial infection can cause inflammatory bone diseases accompanied by the bone destruction resulting from excess generation of osteoclasts. Although lipoproteins are one of the major immunostimulating components of bacteria, little is known about their effects on bone metabolism. In this study, we investigated the role of lipoproteins in bacteria-induced bone destruction using Staphylococcus aureus wild type, its lipoprotein-deficient mutant, and synthetic lipopeptides Pam2CSK4 and Pam3CSK4 known to mimic bacterial lipoproteins. Formaldehyde-inactivated S. aureus or the synthetic lipopeptides induced severe bone loss in the femurs of mice after intraperitoneal administration and in a calvarial bone implantation model, whereas the lipoprotein-deficient S. aureus did not show such effects. Mechanism studies further identified three action mechanisms for the lipopeptide-induced osteoclast differentiation and bone resorption via (i) enhancement of osteoclast differentiation through Toll-like receptor 2 and MyD88-dependent signaling pathways; (ii) induction of pro-inflammatory cytokines, TNF-α and IL-6; and (iii) upregulation of RANKL expression with downregulation of osteoprotegerin expression in osteoblasts. Taken together, these results suggest that lipoprotein might be an important bacterial component responsible for bone destruction during bacterial infections through augmentation of osteoclast differentiation and activation.


Concordance of Chest CT and Nucleic Acid Testing in Diagnosing Coronavirus Disease Outside its District of Origin (Wuhan, China).
This study aimed to determine the concordance between CT and nucleic acid testing in diagnosing coronavirus disease (COVID-19) outside its district of origin (Wuhan, China). Twenty-three consecutive patients with COVID-19, confirmed by nucleic acid testing, were enrolled from two designated hospitals outside the district of disease origin. We collected clinical, laboratory, and CT data and assessed the concordance between CT manifestations and nucleic acid test results by comparing the percentage of patients with and without abnormal CT findings. Furthermore, using Chi-square tests, we analyzed the differences in CT manifestations between patients with and without an exposure history or symptoms. Multiple ground-glass opacities (GGOs), with or without consolidation, were observed on the initial CT scans of 19 patients (82.6%), whereas the remaining 4 (17.4%) showed no CT abnormalities, indicating that the initial chest CT findings were not entirely concordant with the nucleic acid test results in diagnosing COVID-19. Among the latter 4 patients, we observed multiple GGOs with and without consolidation in 2 patients on the follow-up chest CT scans taken on days 7 and 14 after admission, respectively. The remaining 2 patients showed no abnormalities on the follow-up CT scans. Furthermore, abnormal CT findings were found more frequently in patients who had been exposed to COVID-19 in its district of origin than in those who had not been exposed and in symptomatic patients than in asymptomatic patients (all p<0.05). Patients with positive results on nucleic acid testing may or may not have the abnormal CT manifestations that are frequently found in symptomatic patients with a history of exposure to the district of COVID-19 origin.


A review of quantitative studies of benzene metabolism.
Benzene is a ubiquitous, highly flammable, colorless liquid that is a known hematotoxin, myelotoxin, and human leukemogen. Benzene-induced toxicity in animals is clearly mediated by its metabolism. The mechanisms of acute hemato- and myelotoxicity in humans are almost certainly the same as in animals, and there is compelling evidence that metabolism is requisite for the induction of leukemia in humans. A very large number of experimental investigations of benzene metabolism have been conducted with animals, both in vivo and in vitro. There have also been many investigations of benzene metabolism in humans and with human tissues, Although the blood or tissue concentrations of benzene metabolites in humans resulting from benzene exposure have never been measured. Further, a number of mathematical models of benzene metabolism and dosimetry have been developed. In this article, we consider results from both experimental and mathematical modeling research, with particular emphasis on the last decade, and discuss the factors that are likely to be most influential in the metabolism of benzene.


Fate of Costochondral Grafts for Micrognathia: 3D Analysis of Postoperative Length, Position, and Graft Take.
Costochondral grafting is performed in the reconstruction of severe micrognathia. In this study, we report our experience with graft take, as well as unique findings that have not been focused on in the past literature such as postoperative position and changes in the shape of the graft and thinning of the skull base in contact with the graft. Between 2002 and 2019, costochondral grafting was performed on 15 sides of 10 patients with micrognathia. Graft take and other detailed findings such as growth, position, and changes in the shape of the grafts and skull base in contact with the grafts were evaluated using computed tomography images. Graft take was obtained in all cases, and subsequent distraction could be performed in 8 of 10 graft sites as planned. Six of 15 grafts were displaced anterior to the preoperative planned position. However, there were no cases with complications due to deviation such as trismus. Concave deformity of the skull base in contact with the graft was observed in 9 graft sites. The thinning and bending deformation were observed in 2 grafts. Costochondral grafting was considered a reasonable method for first-line treatment of severe micrognathia. Several unique findings that have not been focused on in the past literature were observed. These should be kept in mind when performing costochondral grafting. Several modifications to the present protocol are suggested to improve the quality of graft take.


Resection of a lateral supratentorial endodermal cyst complicated by postoperative seizures: A case report.
Endodermal cysts are uncommon cystic lesions usually located at the ventral aspects of the spine. A lateral supratentorial location of such cysts is extremely rare. A unique case of a lateral supratentorial endodermal cyst that required surgical intervention due to uncal herniation, complicated with postoperative seizures, is presented. A 48-year-old man presented with transient motor aphasia and diplopia. Magnetic resonance imaging showed a cystic lesion occupying the left frontal and temporal convexity with midline shift and uncal herniation. Cyst resection was performed, and cyst contents with mucous-like components were aspirated. Histopathological examination showed an endodermal cyst. The patient showed no neurological deficits immediately after surgery but developed tonic-clonic seizures 9 h after surgery. Sedation and intubation were required to control the seizures. After administering multiple antiepileptic drugs, he was extubated on the 5th day after surgery. He was discharged home in a month with mild impairment in dexterity of his right hand. Surgical intervention for endodermal cysts can be complicated by postoperative seizures caused by chemical irritation of brain cortex due to spillage of cyst contents. It is important to irrigate the cyst wall very well intraoperatively and pay attention not to spill the cyst fluid to unaffected locations. Preoperative administration of antiepileptic drugs should also be considered if endodermal cysts, not simple arachnoid cysts, are suspected preoperatively.


Enhanced photocurrent from organic polymers-based photodiodes by blending PbS colloidal quantum dots.
Enhanced photocurrent from organic polymer-based photodiodes by blending PbS colloidal quantum dots (CQDs) are presented. The absorption spectra of nanocomposites of PbS CQDs and organic polymers, Poly[2-methoxy-5-(2'-ethylhexyloxy-pphenylenevinylene)] (MEH-PPV) and [6,6]-phenyl-C61-butyric acid methylester (PCBM), are the superposition of those of pristine constituents, indicating the absorption of the PbS CQDs contributes to the effective near-infrared light absorption for the photodiodes. The enhanced photocurrent for photodiodes made of MEH-PPV:PCBM:PbS is attributed to the excitons dissociation at the interfaces of PbS/MEH-PPV and PbS/PCBM, as well as charge transport in MEH-PPV and PCBM.


Enzymatic deprotection of the cephalosporin 3'-acetoxy group using Candida antarctica lipase B.
Cephalosporins remain one of the most important classes of antibiotics. A useful site for derivatization involves generation of and chemistry at the 3'-hydroxymethyl position. While 3'-acetoxymethyl-substituted cephalosporins are readily available, deacetylation to access the free 3'-hydroxymethyl group is problematic when the carboxylic acid is protected as an ester. Herein we report that this important transformation has been efficiently accomplished using Candida antarctica lipase B. Although this transformation is difficult to carry out using chemical methods, the enzymatic deacetylation has been successful on gram scale, when the cephalosporin is protected as either the benzhydryl or tert-butyl esters and on the corresponding sulfoxide and sulfone of the tert-butyl ester.


Tactile spatial acuity at the human fingertip and lip: bilateral symmetry and interdigit variability.
We used the spatial threshold for discrimination of grating orientation to assess tactile spatial acuity at the lower lip and each fingertip, bilaterally, in seven normal human subjects. We confirmed previous findings that: (1) this test is highly reliable, and (2) acuity at the lip is substantially higher than at the fingertips. In addition, we showed that: (1) acuity does not differ significantly between right and left sides, and (2) among fingertips, acuity is lowest at the fifth digit and comparable on the other digits.


Rockpool gobies change colour for camouflage.
Camouflage is found in a wide range of species living in numerous habitat types, offering protection from visually guided predators. This includes many species from the intertidal zone, which must cope with background types diverse in appearance and with multiple predator groups foraging at high and low tide. Many animals are capable of either relatively slow (hours, days, weeks) or rapid (seconds and minutes) colour change in order to better resemble the background against which they are found, but most work has been restricted to a few species or taxa. It is often suggested that many small intertidal fish are capable of colour change for camouflage, yet little experimental work has addressed this. Here, we test rock gobies (Gobius paganellus) for colour change abilities, and whether they can tune their appearance to match the background. In two experiments, we place gobies on backgrounds of different brightness (black or white), and of different colours (red and blue) and use digital image analysis and modelling of predator (avian) vision to quantify colour and luminance (perceived lightness) changes and camouflage. We find that gobies are capable of rapid colour change (occurring within one minute), and that they can change their luminance on lighter or darker backgrounds. When presented on backgrounds of different colours, gobies also change their colour (hue and saturation) while keeping luminance the same. These changes lead to predicted improvements in camouflage match to the background. Our study shows that small rockpool fish are capable of rapid visual change for concealment, and that this may be an important mechanism in many species to avoid predation, especially in complex heterogeneous environments.


Phenotypic and functional characteristics of highly differentiated CD57+NKG2C+ NK cells in HIV-1-infected individuals.
Natural killer (NK) cells are important anti-viral effector cells. The function and phenotype of the NK cells that constitute an individual's NK cell repertoire can be influenced by ongoing or previous viral infections. Indeed, infection with human cytomegalovirus (HCMV) drives the expansion of a highly differentiated NK cell population characterized by expression of CD57 and the activating NKG2C receptor. This NK cell population has also been noted to occur in HIV-1-infected individuals. We evaluated the NK cells of HIV-1-infected and HIV-1-uninfected individuals to determine the relative frequency of highly differentiated CD57+NKG2C+ NK cells and characterize these cells for their receptor expression and responsiveness to diverse stimuli. Highly differentiated CD57+NKG2C+ NK cells occurred at higher frequencies in HCMV-infected donors relative to HCMV-uninfected donors and were dramatically expanded in HIV-1/HCMV co-infected donors. The expanded CD57+NKG2C+ NK cell population in HIV-1-infected donors remained stable following antiretroviral therapy. CD57+NKG2C+ NK cells derived from HIV-1-infected individuals were robustly activated by antibody-dependent stimuli that contained anti-HIV-1 antibodies or therapeutic anti-CD20 antibody, and these NK cells mediated cytolysis through NKG2C. Lastly, CD57+NKG2C+ NK cells from HIV-1-infected donors were characterized by reduced expression of the inhibitory NKG2A receptor. The abundance of highly functional CD57+NKG2C+ NK cells in HIV-1-infected individuals raises the possibility that these NK cells could play a role in HIV-1 pathogenesis or serve as effector cells for therapeutic/cure strategies.


Mutation of the inducible ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE2 alters lignin composition and improves saccharification.
ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE1 (ATR1) and ATR2 provide electrons from NADPH to a large number of CYTOCHROME P450 (CYP450) enzymes in Arabidopsis (Arabidopsis thaliana). Whereas ATR1 is constitutively expressed, the expression of ATR2 appears to be induced during lignin biosynthesis and upon stresses. Therefore, ATR2 was hypothesized to be preferentially involved in providing electrons to the three CYP450s involved in lignin biosynthesis: CINNAMATE 4-HYDROXYLASE (C4H), p-COUMARATE 3-HYDROXYLASE1 (C3H1), and FERULATE 5-HYDROXYLASE1 (F5H1). Here, we show that the atr2 mutation resulted in a 6% reduction in total lignin amount in the main inflorescence stem and a compositional shift of the remaining lignin to a 10-fold higher fraction of p-hydroxyphenyl units at the expense of syringyl units. Phenolic profiling revealed shifts in lignin-related phenolic metabolites, in particular with the substrates of C4H, C3H1 and F5H1 accumulating in atr2 mutants. Glucosinolate and flavonol glycoside biosynthesis, both of which also rely on CYP450 activities, appeared less affected. The cellulose in the atr2 inflorescence stems was more susceptible to enzymatic hydrolysis after alkaline pretreatment, making ATR2 a potential target for engineering plant cell walls for biofuel production.


Inhibition of ion channels by hirsutine in rat pheochromocytoma cells.
Effects of hirsutine, an alkaloid that produces a potent ganglion blocking effect, were investigated using rat pheochromocytoma PC12 cells. Hirsutine (1 to 10 microM) suppressed dopamine-release evoked by 100 microM nicotine. In voltage-clamped cells, hirsutine (1 to 10 microM) inhibited the inward current activated by 100 microM nicotine. Hirsutine was equipotent to hexamethonium in blocking the nicotine-activated current. The voltage-dependency of the nicotine activated current was not modified by hirsutine. Effects of hirustine on other ion channels were tested to determine its selectivity. Inward currents mediated through ATP-activated channels were scarcely affected by hirsutine (up to 100 microM). However, hirustine (10 microM) inhibited Ba currents passing through Ca channels and K currents activated by depolarizing voltage steps. The results suggest that hirsutine potently blocks nicotinic receptor-channels, but hirsutine also inhibits voltage-gated Ca and K channels. Roles of the inhibition of these channels in the pharmacological effects of hirsutine were discussed.


Caloric restriction and intervention in pancreatic carcinogenesis in the rat.
In two experiments, the effects of caloric restriction during the postinitiation phase of pancreatic carcinogenesis were evaluated. Male Lewis rats were given injections of azaserine at 14 days of age and weaned to the postinitiation test protocols at 21 days of age. In the first experiment, the caloric content of the diets was restricted by 10, 15, 20, and 30% of the intakes of the ad libitum-fed rats. A sixth group was fed diet ad libitum for only 5-6 h/day; i.e., they were "meal-fed". The development of putative preneoplastic lesions (henceforth termed foci) was evaluated by quantitative stereological (morphometric) analysis of the pancreas. Caloric restriction during the 4-month postinitiation phase resulted in a significant reduction in focal development beginning at 10% caloric restriction and increasing with more severe restriction. The caloric intake of the meal-fed group closely matched the caloric intake of the 10 or 15% caloric restriction groups and the focal response of the meal-fed rats was similar to the groups restricted in calories by 15 to 20%. In the second experiment, rats were initiated with azaserine and weaned to one of four groups: ad libitum; meal-fed; meal-fed for 2 months and ad libitum thereafter; or ad libitum for 2 months and meal-fed thereafter. Foci were evaluated at 2 and 4 months; neoplasm incidence and multiplicity were determined at 14 months postinitiation. Compared to the ad libitum group, the meal-fed group had significantly fewer foci at all times of evaluation and significantly fewer neoplasms. When rats were meal fed for 2 months and then switched to ad libitum feeding for the remainder of the experiment, the focal outcome at 4 months was similar to the group meal fed for all 4 months; and at 14 months the neoplastic outcome was intermediate between the ad libitum and the meal-fed group. Intervention in the ad libitum feeding regimen at 2 months by meal feeding for the remainder of the experiment resulted in a significant decrease in the focal and neoplastic development, as compared to the group fed ad libitum continuously. These two intervention groups were intermediate in response between the meal-fed and ad libitum-fed groups. These results indicate that the postinitiation phase of pancreatic carcinogenesis can be modulated by relatively simple dietary interventions such as moderate caloric restriction.