Five new deep-sea species of nudibranchs (Gastropoda: Heterobranchia: Cladobranchia) from the Northeast Pacific.
Increased exploration of northeastern Pacific deep-sea habitats has revealed a diverse and often poorly-known invertebrate community, including a number of undescribed species of nudibranchs studied herein. We used morphology to distinguish several new species from their congeners, and generated data where possible for mitochondrial (COI, 16S) and nuclear markers (H3) to place them in a phylogenetic context. We described here Tritonia nigritigris sp. nov., Dendronotus claguei sp. nov., Ziminella vrijenhoeki sp. nov., Cuthona methana sp. nov., Aeolidia libitinaria sp. nov. and redescribed Zeusia herculea (Bergh, 1894). Another species of Tritonia is described but not named due to the absence of reproductive system information. Although there are difficulties in collection from deep-sea habitats, only two of our new species are known from single specimens. As with many other deep-sea regions, we expect the number of new species from this region to increase with further exploration. Because the deep regions of the northeast Pacific are particularly vulnerable to the effects of decreasing oxygenation due to climate change, we consider that documenting this fauna has some level of urgency.


Failure to find a distance effect in pigeon choice.
Primates take longer to choose between alternatives with smaller differences in value. This effect-a particular instance of the distance effect in symbolic comparisons-has not been replicated in birds. Instead, birds appear to respond independently to each alternative, such that the latency to choose depends primarily on the alternative of highest value. Three experiments tested for the distance effect in pigeons under conditions not previously considered. Experiment 1 presented pigeons with forced- and binary free-choice trials, where each alternative was one of three possible delays to reinforcement (4, 8, and 16 s). Pigeons were exposed to the choice stimuli for different amounts of time and with different sample response requirements prior to the choice response. Experiment 2 added a fourth (0-s delay) alternative. Experiment 3 substituted the 16-s delay with a second 4-s delay. In all experiments, pigeons systematically chose the shortest delay to reinforcement. Latency to choose the 4-s delay did not vary when choosing against the 8-s or 16-s delay, regardless of whether choice stimuli were exposed for the duration of nine pecks (Experiment 1), or whether a 0-s delay alternative was sometimes present (Experiment 2). Latency to choose the preferred of two identical alternatives (4-s vs. 4-s) was shorter than the latency to choose between different alternatives (4-s vs. 8-s; Experiment 3); this is the opposite of a distance effect. These results show no evidence of a distance effect in pigeon choice, consistent with the hypothesis that pigeons respond independently to each choice alternative.


Detection of Reactive Oxygen and Nitrogen Species by Electron Paramagnetic Resonance (EPR) Technique.
During the last decade there has been growing interest in physical-chemical oxidation processes and the behavior of free radicals in living systems. Radicals are known as intermediate species in a variety of biochemical reactions. Numerous techniques, assays and biomarkers have been used to measure reactive oxygen and nitrogen species (ROS and RNS), and to examine oxidative stress. However, many of these assays are not entirely satisfactory or are used inappropriately. The purpose of this chapter is to review current EPR (Electron Paramagnetic Resonance) spectroscopy methods for measuring ROS, RNS, and their secondary products, and to discuss the strengths and limitations of specific methodological approaches.


MicroRNA-181 Variants Regulate T Cell Phenotype in the Context of Autoimmune Neuroinflammation.
Recent studies have revealed that multiple sclerosis (MS) lesions have distinct microRNA (miRNA) expression profiles. miR-181 family members show altered expression in MS tissues although their participation in MS pathogenesis remains uncertain. Herein, we investigated the involvement of miR-181a and miR-181b in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). miR-181a and -b levels were measured in the central nervous system (CNS) of patients with MS and mice with EAE as well as relevant leukocyte cultures by real-time RT-PCR. To examine the role of the miRNAs in leukocyte differentiation and function, miR-181a and -b mimic sequences were transfected into cultured primary macrophages and purified CD4+ T cells which were then analyzed by RT-PCR and flow cytometry. Luciferase reporter assays were performed to investigate the interaction of miR-181a and -b with the 3'-UTR of potential target transcripts, and the expression of target genes was measured in the CNS of EAE mice, activated lymphocytes, and macrophages. Expression analyses revealed a significant decrease in miR-181a and -b levels in brain white matter from MS patients as well as in spinal cords of EAE mice during the acute and chronic phases of disease. Suppression of miR-181a was observed following antigen-specific or polyclonal activation of lymphocytes as well as in macrophages following LPS treatment. Overexpression of miR-181a and -b mimic sequences reduced proinflammatory gene expression in macrophages and polarization toward M1 phenotype. miR-181a and -b mimic sequences inhibited Th1 generation in CD4+ T cells and miR-181a mimic sequences also promoted Treg differentiation. Luciferase assays revealed Suppressor of mothers against decapentaplegic 7 (Smad7), as a direct target of miR-181a and -b. Our data highlight the anti-inflammatory actions of miR-181a and -b in the context of autoimmune neuroinflammation. miR-181a and -b influence differentiation of T helper cell and activation of macrophages, providing potential therapeutic options for controlling inflammation in MS.


[Need for social psychiatric services--a management model in scientific evaluation].
Social-psychiatric services have for a long time been a focus in the controversial discussion about the further development of outpatient mental health care. Presented is the Baden-Württemberg Social Psychiatric Services model, which is oriented towards outpatient social welfare provision of persons with chronic mental illness, complementing the medical-psychiatric treatment provided by office-practice psychiatrists. Evaluation of the Social Psychiatric Service for its first year of full operation, 1984, has shown that this type of service delivery organization is capable, above all, of reaching persons with "recently" chronic mental illness, who are serviced in the framework of community mental health care systems mainly on an outpatient basis. Provision of care, i.e. of social welfare and counselling measures, may in this group constitute an efficient contribution towards their social rehabilitation. Effective functioning of this organizational model presupposes sufficiently well-established cooperation with other facilities and services involved in service provision, which, as the Baden-Württemberg trial has shown, can in actual fact be ensured.


Blood transfusion in major emergency abdominal surgery.
Major emergency abdominal surgery is associated with excess mortality. Transfusion is known to be associated with increased morbidity and emergency surgery is an independent risk factor for perioperative transfusion. The primary objectives of this study were to identify risk factors for transfusion, and secondarily to investigate the influence of transfusion on clinical outcomes after major emergency abdominal surgery. This study combined retrospective observational data including intraoperative, postoperative, and transfusion data in patients undergoing major emergency abdominal surgery from January 2010 to October 2016 at a Danish university hospital. The primary outcome was a transfusion of any kind from initiation of surgery to postoperative day 7. Secondary outcomes included 7-, 30-, 90-day and long-term mortality (median follow-up = 34.6 months, IQR = 13.0-58.3), lengths of stay, and surgical complication rate (Clavien-Dindo score ≥ 3a). A total of 1288 patients were included and 391 (30%) received a transfusion of any kind. Multivariate logistic regression identified age, hepatic comorbidity, cardiac comorbidity, post-surgical anemia, ADP-receptor inhibitors, acetylsalicylic acid, anticoagulants, and operation type as risk factors for postoperative transfusion. 60.1% of the transfused patients experienced a serious surgical complication within 30 days of surgery compared with 28.1% of the non-transfused patients (p < 0.001). Among patients receiving a postoperative transfusion, unadjusted long-term mortality was increased with a hazard ratio of 3.8 (95% CI 2.9-5.0), p < 0.01. Transfused patients had significantly higher mortality at 7-, 30-, 90- and long-term, as well as a longer hospital stay but in the multivariate analyses, transfusion was not associated with mortality. Peri- and postoperative transfusion in relation to major emergency abdominal surgery was associated with an increased risk of postoperative complications. The potential benefits and harms of blood transfusion and clinical significance of pre- and postoperative anemia after major emergency abdominal surgery should be further studied in clinical prospective studies.


Effect of electrical energy on the efficacy of biofilm treatment using the bioelectric effect.
The use of electric fields in combination with small doses of antibiotics for enhanced treatment of biofilms is termed the 'bioelectric effect' (BE). Different mechanisms of action for the AC and DC fields have been reported in the literature over the last two decades. In this work, we conduct the first study on the correlation between the electrical energy and the treatment efficacy of the bioelectric effect on Escherichia coli K-12 W3110 biofilms. A thorough study was performed through the application of alternating (AC), direct (DC) and superimposed (SP) potentials of different amplitudes on mature E. coli biofilms. The electric fields were applied in combination with the antibiotic gentamicin (10 μg/ml) over a course of 24 h, after the biofilms had matured for 24 h. The biofilms were analysed using the crystal violet assay, the colony-forming unit method and fluorescence microscopy. Results show that there is no statistical difference in treatment efficacy between the DC-, AC- and SP-based BE treatment of equivalent energies (analysis of variance (ANOVA) P>0.05) for voltages <1 V. We also demonstrate that the efficacy of the BE treatment as measured by the crystal violet staining method and colony-forming unit assay is proportional to the electrical energy applied (ANOVA P<0.05). We further verify that the treatment efficacy varies linearly with the energy of the BE treatment (r2 =0.984). Our results thus suggest that the energy of the electrical signal is the primary factor in determining the efficacy of the BE treatment, at potentials less than the media electrolysis voltage. Our results demonstrate that the energy of the electrical signal, and not the type of electrical signal (AC or DC or SP), is the key to determine the efficacy of the BE treatment. We anticipate that this observation will pave the way for further understanding of the mechanism of action of the BE treatment method and may open new doors to the use of electric fields in the treatment of bacterial biofilms.


Experience with neovaginal construction using the full-thickness skin graft in vaginal agenesis.
The correction of vaginal agenesis requires the creation of a neovaginal cavity that is dissected between the bladder and the rectum. To protect the length of the cavity, it is necessary to ensure the complete epithelialization of the apex of the neovaginal cavity. The author prefers to tailor 2 pieces of full-thickness skin grafts longitudinally on a vaginal stent that is molded into bullet shape. Six girls with vaginal agenesis underwent neovaginal construction using this method. The apex of the neovaginal cavity was perfectly epithelialized using this vaginal stent. The length of the neovaginal cavity that is dissected during the operation was protected. The follow-up period ranged from 24 to 93 months (median, 57.2 months). Postoperative stricture or contracture of the neovagina did not occur in all patients. As a result, full-thickness skin graft is an efficient method for vaginal construction in patients with vaginal agenesis.


Understanding older women's health care concerns: a qualitative study.
Older women often have different physical and psychological health priorities compared to men, and health systems must strive to extend and improve health care delivery to meet older women's specific health care needs. The goal of this study was to obtain information from older women on how to improve health care services to best support their efforts to age successfully and receive optimal quality health care in later life. Focus groups were conducted among women aged 65 or older recruited from the community in the Montreal, Quebec area. A total of 36 women participated. The focus group sessions were audiotaped, and the transcripts of each session were analyzed for issues and themes emerging from the text. Content analysis using the framework approach was used to explore and understand the experience of the focus group participants. The data from the text were then coded according to the relevant and emergent ideas and concepts. Participants felt that their physical health care needs were being met, but that a number of issues relating to psychological health were inadequately addressed by health care professionals. The importance of feeling validated as active participants in a health care relationship, recognition of fears and anxieties associated with aging, and the need for information-sharing and education were all viewed as important health care priorities for older women. Time and accessibility were identified as the most significant barriers towards receiving optimal health care in later life. The current health care system does not meet the global health care needs of older women. Health care leaders must recognize that success in program development and delivery for older women will require designing clinical programs that address both the physiological and psychosocial requirements of women. Only when women feel that they are being cared for in a comprehensive manner, one that includes attention to physical, psychological and emotional health, are we likely to be delivering health care that optimally promotes successful aging.


[Hemorrhagic shock and encephalopathy. Its possible relation with heat stroke].
A comparative study of two patients, one affected by haemorrhagic shock and encephalopathy (HSE) and the other by heatstroke is reported. Both presented shock, disseminated intravascular coagulation, neurological damage and hepatopathy. A lowered alpha 1-antitrypsin concentration as well as a slightly increased circulating immune complexes and complement consumption were observed in the HSE patient but not in the heatstroke one. In both, cultures for bacteria were negative, the viral serology was non-specific and hepatitis A and B studies were negative. HSE patient died. A possible relationship between HSE, heatstroke, malignant hyperthermia and halothane hepatitis is postulated. Fever, potentially hepatotoxic drugs or unknown agents (HSE) might trigger this clinical picture.


Nasal Carriage Rate, Antimicrobial Susceptibility Pattern, and Associated Factors of Staphylococcus aureus with Special Emphasis on MRSA among Urban and Rural Elementary School Children in Gondar, Northwest Ethiopia: A Comparative Cross-Sectional Study.
Staphylococcus aureus is a Gram-positive, catalase-positive, and coagulase-positive bacterial species commonly found on the skin and in the nose of most healthy individuals. The anterior nares of nose are the most frequent carriage sites for S. aureus in both adults and children. Methicillin resistance among S. aureus isolates has steadily increased worldwide. The main objective of this study was to determine nasal carriage rate, antimicrobial susceptibility pattern, and associated risk factors of Staphylococcus aureus with special emphasis on MRSA among urban and rural elementary school children in Gondar, Northwest Ethiopia. A community based comparative cross-sectional study was conducted on 622 urban and rural elementary school children in Gondar from January 1st to March 30th, 2018. Data was collected using a questionnaire and nasal swab samples were collected by sterile cotton tip swab moistened with sterile normal saline. Collected samples were inoculated on mannitol salt agar and incubated aerobically at 37°C for 24 hrs. S. aureus was confirmed by observing colony characteristics and biochemical tests. MRSA was detected using cefoxitin disc by Modified Kirby-Bauer disk diffusion technique. Finally data was entered, cleared, and checked using Epi-info version 7 and exported to SPSS version 20 for analysis. Odds ratio and logistic regression were used for statistical association. P-value ≤ 0.05 at 95% CI was considered for statistical association. Of the 622 school children, the overall prevalence of S. aureus was 143/622 (23%). Of them, 14/143 (9.79%) were MRSA. The carriage rate in urban schools was 83/622 (13.3%) whereas it was 60/622 (9.6%) in rural schools. The prevalence of MRSA among urban schools, 9.1%, was higher than their urban counterparts, 0.7%. Gentamycin, clindamycin, and ciprofloxacin were the most effective whereas penicillin and tetracycline were resistant. Children's fathers' educational status and number of children in class room were significantly associated with S. aureus but only living in urban of children significantly associated with MRSA. This study showed high prevalence of S. aureus and MRSA, 143/622 (23%) and 14/143 (9.79%), respectively. So, decolonization of nasal carriers of MRSA and reducing the number of students per classroom should be addressed. Moreover, regular large scale survey should be conducted to assess the burden and intervene accordingly.


Phosphorylation state of the native high-molecular-weight neurofilament subunit protein from cervical spinal cord in sporadic amyotrophic lateral sclerosis.
The intraneuronal aggregation of phosphorylated high-molecular-weight neurofilament protein (NFH) in spinal cord motor neurons is considered to be a key pathological marker of amyotrophic lateral sclerosis (ALS). In order to determine whether this observation is due to the aberrant or hyper-phosphorylation of NFH, we have purified and characterized NFH from the cervical spinal cords of ALS patients and controls. We observed no differences between ALS and normal controls in the physicochemical properties of NFH in Triton X-100 insoluble protein fractions, with respect to migration patterns on 2D-iso electrofocusing (IEF) gels, the rate of Escherichia coli alkaline phosphatase mediated dephosphorylation, or the rate of calpain-mediated proteolysis. The rate of calpain-mediated proteolysis was unaffected by either exhaustive NFH dephosphorylation or by the addition of calmodulin to the reaction. Phosphopeptides and the phosphorylated motifs characterized by liquid chromatography tandem mass spectroscopy (LC/MS/MS) analysis demonstrated that all the phosphorylated residues found in ALS NFH were also found to be phosphorylated in normal human NFH samples. Hence, we have observed no difference in the physicochemical properties of normal and ALS NFH extracted from cervical spinal cords, suggesting that the perikaryal aggregation of highly phosphorylated NF in ALS neurons reflects the aberrant somatotopic localization of normally phosphorylated NFH.


Why reject a sensory imagery theory of control consciousness?
Mandik (2010) defends a motor theory of control consciousness according to which nonsensory states, like motor commands, directly contribute to the awareness we have of ourselves as being in control of our actions. Along the way, he argues that his theory is to be preferred over Prinz's (2007) sensory imagery theory, which denies that nonsensory states play any direct role in the generation of control consciousness. I argue that Mandik's criticisms of Prinz's theory fall short, but that nonetheless there are reasons to favor a motor theory of control consciousness over a sensory imagery theory.


Complete wavefront and polarization control for ultrashort-pulse laser microprocessing.
We report on new developments in wavefront and polarization control for ultrashort-pulse laser microprocessing. We use two Spatial Light Modulators in combination to structure the optical fields of a picosecond-pulse laser beam, producing vortex wavefronts and radial or azimuthal polarization states. We also carry out the first demonstration of multiple first-order beams with vortex wavefronts and radial or azimuthal polarization states, produced using Computer Generated Holograms. The beams produced are used to nano-structure a highly polished metal surface. Laser Induced Periodic Surface Structures are observed and used to directly verify the state of polarization in the focal plane and help to characterize the optical properties of the setup.


Utility of Adrenocorticotropic Hormone in Assessing the Response to Transsphenoidal Surgery for Cushing's Disease.
To compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics in subjects with Cushing's disease (CD) following transsphenoidal surgery (TSS) and to determine the value of early postoperative ACTH levels in predicting subsequent hypocortisolemia. Following TSS for CD, serum cortisol and plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid coverage. A total of 26 subjects (25 female) underwent 28 operations. Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who achieved hypocortisolemia had significantly lower ACTH levels by 19 hours postoperatively (P = .007). Plasma ACTH fell to <30 pg/mL in 86% and <20 pg/mL in 82% of subjects who subsequently achieved hypocortisolemia. Plasma ACTH declined to <30 pg/mL by a mean of 10 hours and to <20 pg/mL by 13 hours prior to hypocortisolemia. Follow-up data were available on 25 patients for a median of 23 months. Three subjects who achieved initial surgical remission had disease recurrence at 19, 24, and 36 months; all of these subjects had a postoperative nadir serum cortisol levels <3 μg/dL and plasma ACTH <20 pg/mL. Following TSS for CD, plasma ACTH declined prior to achievement of hypocortisolemia in most subjects. In the majority, the ACTH level reached a nadir of <20 pg/mL. Low early postoperative ACTH levels predict early hypocortisolemia but may not accurately predict long-term remission.


A dispersed-ozone flotation (DOF) separator for tertiary wastewater treatment.
A dispersed-ozone flotation (DOF) separator was devised for a pilot study of tertiary wastewater treatment for re-use purposes. As a compact device combining coagulation, ozonation and flotation in an integrated unit, the DOF separator achieved a very high removal of SS, TOC, UV254 and colour, as well as effective inactivation of coliform and total bacteria within a short hydraulic retention time of 30 min. The finished water quality is comparable to or better than that by a conventional tertiary treatment process using coagulation, sedimentation, filtration and chlorine disinfection, and meets the quality standards for non-drinkable domestic reuse.


Complex Frontal Pneumosinus Dilatans Associated with Meningioma: A Report of Two Cases and Associated Literature Review.
Introduction Pneumosinus dilatans (PSD) is a rare phenomenon involving the expansion of the paranasal sinuses, without bony destruction or a mass. Previously documented cases have demonstrated simple expansion of a solitary air cell. We present two unique cases of PSD in the presence of meningioma, in which complex new cells developed within the frontal sinus. One of the two patients developed associated sinus disease. Case 1 A 28-year-old man presented with facial pain. A computed tomography scan showed an abnormally enlarged, septated right frontal sinus, not present on childhood scans. He underwent a modified endoscopic Lothrop approach to divide the septations, and his symptoms resolved. Case 2 A 72-year-old woman presented with a 3-month history of headaches. Scans revealed a left frontal meningioma and multiple enlarged, dilated left frontal air cells. She had no clinical sinusitis and therefore was managed conservatively. Conclusions PSD has been widely documented in association with fibrous dysplasia and meningioma. The most prevalent theory of the mechanism of PSD is of obstruction of the sinus ostium causing sinus expansion through a "ball-valve" effect. Our cases, which demonstrate septated PSD, suggest a more complex process involving local mediators and highlight the need to consider underlying meningioma in pneumosinus dilatans.


Recovering missing mesothelioma deaths in death certificates using hospital records.
In Brazil, underreporting of mesothelioma and cancer of the pleura (MCP) is suspected to be high. Records from death certificates (SIM) and hospital registers (SIH-SUS) can be combined to recover missing data but only anonymous databases are available. This study shows how common data can be used for linkage and as an assessment of accuracy. Mesothelioma (all sites, ICD-10 codes C45.0-C45.9) and cancer of the pleura (C38.4) were retrieved from both information systems and combined using a linkage algorithm. Accuracy was examined with non-anonymous databases, limited to the state of São Paulo. We found 775 cases in death certificates and 283 in hospital registers. The linkage matched 57 cases, all accurately paired. Three cases, 0.4% in SIM and 1.3% in SIH-SUS, could not be matched because of data inconsistencies. A computer linkage can recover MCP cases from hospital records not found in death certificates in Brazil.


The Par3 polarity protein is an exocyst receptor essential for mammary cell survival.
The exocyst is an essential component of the secretory pathway required for delivery of basolateral proteins to the plasma membranes of epithelial cells. Delivery occurs adjacent to tight junctions (TJ), suggesting that it recognizes a receptor at this location. However, no such receptor has been identified. The Par3 polarity protein associates with TJs but has no known function in membrane traffic. We now show that, unexpectedly, Par3 is essential for mammary cell survival. Par3 silencing causes apoptosis, triggered by phosphoinositide trisphosphate depletion and decreased Akt phosphorylation, resulting from failure of the exocyst to deliver basolateral proteins to the cortex. A small region of PAR3 binds directly to Exo70 and is sufficient for exocyst docking, membrane-protein delivery and cell survival. PAR3 lacking this domain can associate with the cortex but cannot support exocyst function. We conclude that Par3 is the long-sought exocyst receptor required for targeted membrane-protein delivery.


Invasive Pneumococcal Disease in Patients With Sickle Cell Disease.
Patients with sickle cell disease (SCD) are at risk of fatal sepsis with encapsulated bacteria, such as Streptococcus pneumoniae, because of the inherent autosplenectomy that occurs in SCD. This risk is thwarted with oral penicillin prophylaxis during the first 5 years of life, and with stringent vaccination against S. pneumoniae alongside routine childhood immunization. But compared with the general African American pediatric population, the rate of invasive pneumococcal disease (IPD) in patients with SCD still remains high, resulting in hospitalization and fatality. Patients with SCD who developed IPD from 2004 up to 2013 were identified using microbiology records. Descriptive analysis of presence of risk factors for IPD, type of SCD, pneumococcal vaccination and prophylaxis status, clinical presentation, microbiological data, and the outcome of IPD was performed. Eight patients with SCD developed IPD (7 bacteremia and 1 respiratory tract infection). Three of the 8 isolates underwent serotype analysis (15 C in 2 and 15A in 1), none covered with the current vaccination program. One patient had fatal outcome (15A). Breakthrough cases of IPD may involve nonvaccine isolates, and seem to occur after 5 years of age when oral penicillin prophylaxis has been terminated.


Using the theory of planned behavior to examine pharmacists' intention to utilize a prescription drug monitoring program database.
Prescription drug monitoring programs (PDMPs) are state-operated electronic databases that contain patients' controlled drug histories. Most states provide these data to pharmacists via online web portals to combat prescription drug abuse and diversion. The objectives of this study were to: 1) explore the theory of planned behavior's (TPB) utility in predicting Texas pharmacists' intention to utilize an online accessible PDMP; 2) to determine the contribution of each construct, attitude (A), subjective norm (SN) and perceived behavioral control (PBC) in predicting pharmacists' intention; and 3) test whether the addition of perceived obligation (PO) is significantly related to pharmacists' intention. A cross-sectional, 36-item questionnaire was developed from focus groups and literature of pharmacists' views regarding prescription drug abuse. A total of 998 practicing Texas community pharmacists were surveyed to collect data on their intention to utilize a PDMP database. Descriptive statistics, multivariate and hierarchical logistic regression analyses were used to address the study objectives. The response rate was 26.2% (261/998). TPB constructs were significant predictors of pharmacists' high intention to utilize the PDMP. Pharmacists with positive attitudes were almost twice as likely to have high intention (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.2-2.8). SN was the strongest predictor of pharmacists' high intention (OR = 2.2, 95% CI = 1.4-3.3). Pharmacists with high PBC were also twice as likely to have high intention (OR = 1.9, 95% CI = 1.2-3.0). Additionally, pharmacists' PO contributed to the prediction of high intention (OR = 1.8, 95% CI = 1.0-3.1) above that explained by the TPB model constructs (X(2) = 4.14, P < 0.05). TPB with the addition of PO was useful in predicting pharmacists' high intention to utilize a PDMP database. Interventions that address pharmacists' A, SN, PBC, and PO may be valuable to increase pharmacists' high intention. Pharmacists' utilization of PDMPs may lead to a decrease in the morbidity and mortality associated with prescription drug abuse. Future studies that assess whether intention to use PDMPs translates to actual usage are needed to strengthen these findings.


Goodpasture's disease in pregnancy: case report and review of the literature.
Goodpasture's disease is a rare phenomenon in pregnancy. It is characterized by antiglomerular basement membrane antibodies resulting in glomerulonephritis and pulmonary hemorrhage. We present a case of a patient with a preconceptional diagnosis of Goodpasture's disease and chronic hypertension. Multidisciplinary antepartum care included close monitoring and treatment of blood pressure, renal function, and fetal status. Our patient ultimately was delivered at 33 weeks for superimposed preeclampsia but recovered without incident. Her infant also did well after 36 days in the neonatal intensive care unit, requiring only supportive care. This case demonstrates that successful pregnancy outcomes can be achieved in patients with Goodpasture's disease with a careful multidisciplinary approach involving maternal fetal medicine and nephrology.


Multisensory integration and ADHD-like traits: Evidence for an abnormal temporal integration window in ADHD.
Abnormalities in multimodal processing have been found in many developmental disorders such as autism and dyslexia. However, surprisingly little empirical work has been conducted to test the integrity of multisensory integration in Attention Deficit Hyperactivity Disorder (ADHD). The main aim of the present study was to examine links between symptoms of ADHD (as measured using a self-report scale in a healthy adult population) and the temporal aspects of multisensory processing. More specifically, a Simultaneity Judgement (SJ) and a Temporal Order Judgement (TOJ) task were used in participants with low and high levels of ADHD-like traits to measure the temporal integration window and Just-Noticeable Difference (JND) (respectively) between the timing of an auditory beep and a visual pattern presented over a broad range of stimulus onset asynchronies. The Point of Subjective Similarity (PSS) was also measured in both cases. In the SJ task, participants with high levels of ADHD-like traits considered significantly fewer stimuli to be simultaneous than participants with high levels of ADHD-like traits, and the former were found to have significantly smaller temporal windows of integration (although no difference was found in the PSS in the SJ or TOJ tasks, or the JND in the latter). This is the first study to identify an abnormal temporal integration window in individuals with ADHD-like traits. Perceived temporal misalignment of two or more modalities can lead to distractibility (e.g., when the stimulus components from different modalities occur separated by too large of a temporal gap). Hence, an abnormality in the perception of simultaneity could lead to the increased distractibility seen in ADHD.


Elimination of the field-dependent aberrations of the JWST-like space telescopes in the multi-field fine-phasing process.
This paper investigates the alignment strategies for eliminating the field-dependent aberrations of the class of large three-mirror anastigmatic (TMA) space telescopes with a segmented primary mirror (PM) like the James Webb Space Telescope (JWST) in the multi-field fine-phasing process based on the framework of nodal aberration theory. During the single-field (on-axis field) fine-phasing process, the individual segment tip, tilt, and piston errors, as well as the de-space of the secondary mirror, are well corrected, and the PM is also adjusted to compensate for those aberrations induced by the misalignments of other mirrors at the center of the science field of view. However, interrogating off-axis field points can reveal the presence of large wavefront errors due to mirror misalignments. Eliminating these field-dependent aberrations is the main goal of the multi-field fine-phasing process. This paper first presents an analytic study on an established alignment strategy used for eliminating the field-dependent aberrations. While it is demonstrated that this alignment strategy has the ability to reduce the field dependency of the wavefront errors, it will, however, also be revealed that this strategy still exhibits some problems, and its alignment efficiency is low. Then, a new alignment strategy with higher alignment efficiency is further proposed. Detailed simulations with a TMA telescope that has similar parameters with the JWST are performed to illustrate the efficiency and rationality of the proposed strategy. This work can not only contribute to an in-depth understanding of the multi-field fine-phasing process, but also present a possibility to improve the efficiency of this process.


Nocardiopsis kunsanensis sp. nov., a moderately halophilic actinomycete isolated from a saltern.
A moderately halophilic actinomycete, designated HA-9T, was isolated from a saltern in Kunsan, Republic of Korea, and was the subject of polyphasic identification. Analysis of 16S rDNA indicated that the isolate belonged to the genus Nocardiopsis, but differed genetically from other Nocardiopsis species. Strain HA-9T contained meso-diaminopimelic acid, no diagnostic sugars, hexa- or octa-hydrogenated menaquinones with 10 isoprene units, straight-chain saturated or monounsaturated, iso-, anteiso-, 10-methyl branched fatty acids with 13-18 carbons and type III phospholipids. All of these characters consistently assign the isolate to the genus Nocardiopsis. All of the validly described Nocardiopsis species, including moderately halophilic Nocardiopsis halophila, can be differentiated from the saltern isolate using morphological and physiological traits. On the basis of polyphasic evidence, the name Nocardiopsis kunsanensis sp. nov. is proposed for strain HA-9T (= KCTC 9831T), which is designated the type strain.


Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen.
Tamoxifen is an anti-estrogen used in the treatment of breast cancer and to reduce the incidence of breast cancer in high risk women. Although the brain is an estrogen target organ and several studies have found a beneficial effect of estrogen on cognitive function, the effect of tamoxifen on cognition has not been reported. Therefore, we initiated a follow-up study of women who had participated in a study of breast cancer to assess the effect of tamoxifen treatment on cognitive function. We recruited previously interviewed patients who were cases in a population-based case-control study of 2,653 women with primary breast cancer diagnosed between 1987 and 1996 at ages 55-72 years in Los Angeles County, California, USA. In November 1997, each case was mailed a follow-up questionnaire. Cognitive function was assessed by (1) clock drawing. (2) copying a box drawing, and (3) narrative writing to describe a pictured scene. Women reporting treatment with tamoxifen were categorized as standard-term users (4-5 years), short-term users (< 4 years) or long-term users (6 + years) and compared to never users. Tamoxifen users were also classified as past or current users. Differences in the mean cognitive test scores were tested after adjusting for age, age at diagnosis, stage of disease, radiation therapy, chemotherapy, race, education, marital status, previous use of oral contraceptives, type of menopause, age at last menstrual period, previous use of hormone replacement therapy, and depressive symptoms using analysis of covariance. All p-values for differences in the proportion of women who had errors on the tests are 2-sided and adjusted for age, stage of disease at diagnosis, and chemotherapy. Information from 1,163 women aged 57-75 years of age was analyzed; 710 had taken tamoxifen. There was little difference between women who had used tamoxifen for the standard five years and never users on the three cognitive tests. However, more women who had used tamoxifen for the standard term reported seeing their physician for memory problems than non-users (3.8% vs 1.5%, p = 0.04). This was especially true for current users of standard-term (8.0%, p = 0.003). Current users also had a significantly lower mean complexity score (p = 0.03) on the narrative writing task. No differences were seen between past users and non-users. Our study suggests that current use of tamoxifen may adversely effect cognition. Further study of tamoxifen and cognition is needed so that healthy women considering tamoxifen for the primary prevention of breast cancer have comprehensive information about the side effects of the treatment.


Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.
Long-term estrogen therapy can reduce the risk of osteoporotic fracture and cardiovascular disease in postmenopausal women. At present, however, these beneficial effects are not separable from undesirable stimulation of breast and endometrial tissues. We studied the effect of raloxifene, a nonsteroidal benzothiophene, on bone mineral density, serum lipid concentrations, and endometrial thickness in 601 postmenopausal women. The women were randomly assigned to receive 30, 60, or 150 mg of raloxifene or placebo daily for 24 months. The women receiving each dose of raloxifene had significant increases from base-line values in bone mineral density of the lumbar spine, hip, and total body, whereas those receiving placebo had decreases in bone mineral density. For example, at 24 months, the mean (+/-SE) difference in the change in bone mineral density between the women receiving 60 mg of raloxifene per day and those receiving placebo was 2.4+/-0.4 percent for the lumbar spine, 2.4+/-0.4 percent for the total hip, and 2.0+/-0.4 percent for the total body (P<0.001 for all comparisons). Serum concentrations of total cholesterol and low-density lipoprotein cholesterol decreased in all the raloxifene groups, whereas serum concentrations of high-density lipoprotein cholesterol and triglycerides did not change. Endometrial thickness was similar in the raloxifene and placebo groups at all times during the study. The proportion of women receiving raloxifene who reported hot flashes or vaginal bleeding was not different from that of the women receiving placebo. Daily therapy with raloxifene increases bone mineral density, lowers serum concentrations of total and low-density lipoprotein cholesterol, and does not stimulate the endometrium.


Patient Awareness and Expectations of Pharmacist Services During Hospital Stay.
There are insufficient data in the United States regarding patient awareness and expectations of hospital pharmacist availability and services. The objective of this research is to assess patient awareness and expectations of hospital pharmacist services and to determine whether a marketing campaign for pharmacist services increases patient awareness and expectations. Eligible inpatients were surveyed before and after implementation of a hospital-wide pharmacist services marketing campaign (12 items; Likert scale of 1 [strongly disagree] to 4 [strongly agree]; maximum total score of 48) regarding awareness of pharmacist services. The primary outcome was the change in median total survey scores from baseline. Other outcomes included the frequency of patient requests for pharmacists. Similar numbers of patients completed the survey before and after the campaign (intervention, n = 140, vs control, n = 147). Awareness of pharmacist availability and services was increased (41 [interquartile ranges, IQRs: 36-46] vs 37 [IQR 31-43]; P < .001). Patients were 7 times more likely to request a pharmacist following the marketing campaign implementation. Awareness among inpatients of pharmacist services is low. Marketing pharmacist availability and services to patients in the hospital improves awareness and expectations for pharmacist-provided care and increases the frequency of patient-initiated interaction between pharmacists and patients. This could improve patient outcomes as pharmacists become more integrally involved in direct patient care.


Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet.
Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons.


Meat Value Chain Losses in Iran.
To stop hunger, reducing food losses is a potential movement towards saving food. A large portion of these losses could be avoided and reduced through the improved food chain in many countries. Raising awareness on how and where food losses occur will help recovering foods such as meat by identifying solutions and convincing people to implement those solutions. This, in turn, will lead to private and public efforts to recover meat that might be otherwise wasted. After highlighting the importance of food saving benefits and relevant statistics, this paper explains the possible ways to reduce meat loss and waste in abattoirs and presents a framework for prevention according to the estimates of meat losses in Iran meat supply. The current article answers the questions of where do we have the meat loss in Iran and what approaches are most successful in reducing losses in the meat industry. The national average loss and waste in meat production are about 300,000 metric tonnes (about 15%). Many segments and players are involved with this huge amount of losses in the meat value chain, a large portion of these losses could be avoided and reduced by about 25% through using by-products with the mechanization of design and manufacturing. The production amount of mechanically deboned meat (MDM) is 105,091,000 kg, concluding the major waste (88.33%) of total poultry losses. Ensuring appropriate actions by exploiting the full potential of engaged Iranian associations and institutes is considered to reduce the losses.


Polarized Secretion of Matrix Metalloproteinases and Their Inhibitors by Retinal Pigment Epithelium Derived from Induced Pluripotent Stem Cells During Wound Healing.
To characterize the secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) by induced pluripotent stem cell-derived retinal pigment epithelium (iPS-RPE) during wound healing. We hypothesize that iPS-RPE secretes mediators of tissue remodeling such as MMPs and TIMPs to promote migration and proliferation of cells during wound healing. iPS-RPE was grown on transwells until fully confluent and pigmented. The monolayers were scratched to induce a wound. Conditioned media were collected from the apical and basolateral sides of the transwells every 72 h for 12 days. The media were analyzed by multiplex ELISA assays to detect secreted MMPs and TIMPs. Activity assays were performed to detect the active form of MMP-2 in conditioned media. MMP-2 and TIMP-1, -2, -3, and -4 were detected in conditioned media from iPS-RPE. The proteins were found to be secreted in a polarized manner. The apical secretion and activation of MMP-2 was elevated from days 3 to 12 after wounding. TIMP-1, -2, -3, and -4 were detected in conditioned media from both the apical and basolateral sides of wounded cells. Apical secretion of all 4 TIMPs increased within 3 days after wounding. These results indicate that iPS-RPE secretes MMP-2 and all 4 TIMPs in a polarized manner. After wounding, apical secretion of MMP-2 was higher compared to control. Apical secretion of all 4 TIMPs increased compared to control, while only TIMP-1 showed increased basolateral secretion compared to control.


Role-play for medical students learning about communication: guidelines for maximising benefits.
Role-play is widely used as an educational method for learning about communication in medical education. Although educational theory provides a sound rationale for using this form of simulation, there is little published evidence for its effectiveness. Students' prior experiences of role-play may influence the way in which they engage in this method. This paper explores students' experiences with the aim of producing guidelines for maximising the benefits of role-play within this learning context. First-year undergraduate medical students participated in a role-play session as part of their communication programme. Before and after the session, students completed questionnaires. In the pre-session questionnaire, students were asked about their experiences of role-play and asked to identify helpful and unhelpful elements. Immediately after the session, students answered similar questions in relation to the role-play activity they had just completed. Descriptive statistics were used to analyse quantitative data and qualitative data was thematically analysed. 284 students completed evaluation forms. Although 63 (22.2%) had prior unhelpful experiences, most students (n = 274; 96.5%) found this experience helpful. Summary findings were that students reported the key aspects of helpful role-play were opportunities for observation, rehearsal and discussion, realistic roles and alignment of roles with other aspects of the curriculum. Unhelpful aspects were those that evoked strong negative emotional responses and factors that contributed to a lack of realism. Role-play was valued by students in the acquisition of communication skills even though some had prior unhelpful experiences. Guidelines for effective role-play include adequate preparation, alignment of roles and tasks with level of practice, structured feedback guidelines and acknowledgment of the importance of social interactions for learning.


Human-tiger conflict: a review and call for comprehensive plans.
Human-tiger (Panthera tigris Linnaeus, 1758) conflicts (HTC), manifested primarily as attacks on people and domestic animals, exacerbate at least 2 major threats to tigers: (i) conflicts often result in mortality or removal of tigers from the wild; and (ii) they result in negative attitudes towards tigers by local people, thereby reducing support for tiger conservation. Although HTC has decreased over the past century, it will likely increase if current and proposed conservation initiatives to double tiger populations are successful. Increased HTC could undermine successful conservation initiatives if proactive steps are not taken to reduce HTC. The present paper provides a review of the impacts of HTC and the measures taken to reduce it in ways that reduce negative impacts on both humans and tigers, and stresses the need for development and implementation of comprehensive plans to reduce HTC.


A Novel Inherited Mutation of SCN8A in a Korean Family with Benign Familial Infantile Epilepsy Using Diagnostic Exome Sequencing.
Mutations in SCN8A, which codes for the voltage-gated sodium channel NaV1.6, have been described in relation to infantile onset epilepsy with developmental delay and cognitive impairment. Here, we report the case of an infant and her father with early onset benign familial infantile epilepsy, but without cognitive or neurological impairment. In this patient, diagnostic exome sequencing (DES) identified a heterozygous mutation (c.4427G>A; p.Gly1476Asp) in the SCN8A gene. This mutation, confirmed by Sanger sequencing, effects a highly conserved amino acid. In-silico analysis predicts that this mutation may be pathogenic. To our knowledge, this is the first clinical report on Korean benign familial infantile epilepsy with a SCN8A mutation. We were able to achieve good seizure control in our patients with sodium channel blockers. This result suggests the application of DES will be valuable for the diagnosis of patients with infantile epilepsy but no cognitive impairment.


Characterization and analysis of frog photoreceptor membranes.
Frog photoreceptor membranes contain 54,000 g of protein per mole of visual pigment chromophore, virtually all of it insoluble membrane protein. Acrylamide gel electrophoresis indicates one major polypeptide class, most likely the visual pigment apoprotein. Suspensions of these photoreceptor membranes accumulate calcium ions when ATP is present, a characteristic that may play a part in visual excitation.


Effects of advanced traffic signal status warning systems on vehicle emission reductions at signalized intersections.
Signalized intersections have been identified as vehicle emission hotspots, where drivers decelerate, idle, and accelerate their vehicles in response to signal changes. Advanced traffic signal status warning systems (ATSSWSs) can be applied to reduce traffic emissions at intersections by mitigating unnecessary braking and acceleration. In this study, two types of ATSSWSs, variable message sign (VMS) based and vehicle-to-infrastructure (V2I) based, were designed, and their environmental effectiveness was evaluated through driving simulator-based experiments. Three scenarios were designed and tested: (1) baseline without an ATSSWS, (2) with the VMS-based ATSSWS, and (3) with the V2I-based ATSSWS. The Motor Vehicle Emission Simulator model was used to evaluate and compare the environmental effectiveness of these two types of ATSSWSs. The results indicate that the proposed ATSSWSs can reduce traffic emissions at signalized intersections. In particular, the V2I-based ATSSWS can substantially reduce CO2, NOx, CO, and HC emissions. The results will help transportation practitioners with implementing advanced driver information systems and decision making on emission reduction policies. Implications: Signalized intersection has been identified as one of hottest spots for vehicle emissions where signal control causes vehicles to frequently decelerate, idle, and accelerate. Advanced Traffic Signal Status Warning Systems (ATSSWS) can be applied to reduce traffic emission at intersections by decreasing vehicles' unnecessary brakes and accelerations. The results of this study will assist transportation practitioners in implementing advanced driver information systems and making decisions on emission reduction policies.


Correlation between synthesis variation of 2-alkylquinolones and the antifungal activity of a Burkholderia cepacia strain collection.
Twenty epiphytic and rhizospheric bacterial strains harbouring strong antifungal activities were isolated from the Tunisian environment. This group of bacteria was identified as Burkholderia cepacia genomovar I using 16S rDNA and recA fragment gene sequence analyses for two selected strains and RFLP technique for the eighteen other ones. This identification did not show variability between isolates despite the significant differences in the antifungal activities of their culture supernatant and the organic crude extract against Aspergillus niger and other phytopathogenic fungi. Chromatographic and mass spectrometric analyses of these extracts allowed us to confirm the difference between strains of the group. Their metabolic production showed differences in term of contents and quantities of secreted molecules, particularly those which were identified to be involved in the antifungal activities. Two metabolites, named Bc-255 and Bc-257 secreted by the entire group at different amounts, have been purified and tested separately against A. niger. Bc-255 showed an activity twice as high as those shown by Bc-257. The structural characterization of these two compounds by mass spectrometry and nuclear magnetic resonance spectroscopy allowed their identification as two analogous 2-alkylquinolones with only one difference at the alkyl chain.


Modeling the impact of rescinding Michigan's primary and secondary seat belt laws on death and injury from passenger vehicle crashes.
Seat belts are the most effective method of decreasing fatal and nonfatal motor vehicle crash injury. Advocacy groups have recently been successful in enacting repeals of mandatory motorcycle helmet laws in several states. In some states, this has prompted renewed efforts aimed at repealing mandatory seat belt laws. To evaluate and quantify the potential impact of rescinding seat belt laws on annual crash-related fatalities, nonfatal injuries, and associated economic costs, using Michigan as a model, to inform the national debate. Proportional injury rates were calculated utilizing police-reported statewide passenger vehicle crash data from 1999 and 2002, where belt use rates approximate estimates associated with repeal of primary and secondary seat belt laws. Proportional rates were applied to the most recent year of crash data (2011) to estimate changes in statewide fatalities and nonfatal injuries. National cost estimates were applied to injury data to calculate associated economic costs. Full repeal of the seat belt law is estimated to result in an additional 163 fatalities, 13,722 nonfatal injuries, and an associated societal cost of $1.6 billion annually. Repeal of the primary seat belt law only is estimated to result in an additional 95 fatalities, 9156 nonfatal injuries, and an associated societal cost of $1.0 billion annually. This analysis suggests that repealing the either the primary or full seat belt law would have a substantial and negative impact on public health, increasing motor vehicle crash related fatality, nonfatal injury, and associated economic costs.


Forest and surface water as predictors of Borrelia burgdorferi and its vector Ixodes scapularis (Acari: Ixodidae) in Indiana.
The objective of this study was to assess whether the distribution of Borrelia burgdorferi, the causative agent of Lyme disease, and its vector tick Ixodes scapularis Say (Acari: Ixodidae) across Indiana is influenced by large-scale landscape features, specifically the proportion of forest within the surrounding landscape and the distance to water features such as lakes and major streams. Hunter-killed deer were checked for ticks in designated check-stations in the opening firearm hunting season between 2005 and 2007. Hunting locations for approximately 3,600 deer were used in ArcGIS (ESRI, Redlands, CA) to examine the influence of forest and water features in the surrounding area on the occurrence of the tick and bacteria. In total, 82 of the 92 (89%) Indiana counties were sampled from 2005 to 2007. The proportion of tick-infested deer was 13.6, 15.8, and 25.5% in these years, respectively. There was a significant nonlinear response for I. scapularis to forest cover in 1 yr that indicated a greater probability of this tick presence at intermediate levels of forest area. Infested does were harvested in significantly more forested areas than bucks. No significant correlation was found neither between levels of forest area and B. burgdorferi nor between water bodies and both organisms.


Functional analysis of the VirSR phosphorelay from Clostridium perfringens.
Toxin production in Clostridium perfringens is controlled by the VirSR two-component signal transduction system, which comprises the VirS sensor histidine kinase and the VirR response regulator. Other studies have concentrated on the elucidation of the genes controlled by this network; there is little information regarding the phosphorelay cascade that is the hallmark of such regulatory systems. In this study, we have examined each step in this cascade, beginning with autophosphorylation of VirS, followed by phosphotransfer from VirS to VirR. We also have studied the effects of gene dosage and phosphorylation in vivo. We have used random and site-directed mutagenesis to identify residues in VirS that are important for its function and have identified a region in the putative sensory domain of VirS that appeared to be essential for function. In vitro phosphorylation studies showed that VirSc, a truncated VirS protein that lacked the N-terminal sensory domain, was capable of autophosphorylation and could subsequently act as a phosphodonor for its cognate response regulator, VirR. Conserved residues of both VirS and VirR, including the D57 residue of VirR, were shown to be essential for this process. By use of Targetron technology, we were able to introduce a single copy of virR or virR(D57N) onto the chromosome of a virR mutant of C. perfringens. The results showed that in vivo, when virR was present in single copy, the production of wild-type levels of perfringolysin O was dependent on the presence of virS and an unaltered D57 residue in VirR. These results provide good evidence that phosphorylation is critical for VirR function.


Is the WMS-IV verbal paired associates as effective as other memory tasks in discriminating amnestic mild cognitive impairment from normal aging?
Paired associate learning tasks are reportedly particularly sensitive to preclinical Alzheimer's disease. We aimed to determine the effectiveness of the recently updated Wechsler Memory Scale verbal paired associates (VPA) in distinguishing the earliest stages of memory impairment (amnestic mild cognitive impairment, aMCI), and the clinical application at the case level, compared with other episodic memory tasks. Participants were 77 people with aMCI and 77 matched healthy older adults (HOA). VPA performance distinguished aMCI from HOA at the group level with large effect sizes, of similar size to the other tasks at immediate recall, but smaller than the CVLT-II list-learning task at delayed recall. Similarly, receiver operating characteristic (ROC) analysis demonstrated good discrimination, similar to other tasks, but again with CVLT-II more accurate at delayed recall. Although group differences remained for normative data, on a case basis using existing normative data the VPA failed to identify 70% of aMCI as impaired. The findings suggest further examination of the normative data is required before the VPA is useful in clinical practice, and highlight the importance of comprehensive neuropsychological assessment in detecting mild memory changes in older adults.


Catechol-O-Methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics: importance in pathophysiology and pathogenesis.
The metabolic O-methylation of endogenous catecholamines and other catechols catalyzed by catechol-O-methyltransferase (COMT; EC 184.108.40.206) was first described by Dr. Julix Axelrod and his colleagues almost half a century ago. In the past several years, research interest in this catechol-metabolizing system has been renewed because of its potential pathophysiological and pathogenic significance in estrogen-induced hormonal cancers, in the development of degenerative brain disorders, as well as in the development of cardiovascular diseases. In this review paper, I provide a brief overview of the COMT metabolic system, with particular attentions being paid to the following three areas: (i) the regulation of this catechol-metabolizing system by endogenous regulatory factors (mainly S-adenosyl-L-homocysteine and homocysteine) as well as by exogenous factors such as dietary phytochemicals; (ii) decreased metabolic O-methylation of endogenous catecholamines as an important risk factor for the development of neurodegenerative disorders such as Parkinson's and Alzheimer's diseases in the elderly and also as a risk factor for the development of a variety of cardiovascular diseases; and (iii) the relative importance of the COMT-catalyzed O-methylation metabolism of endogenous catechol estrogens in the causation and prevention of estrogen-induced hormonal cancers. Some unifying hypotheses are also discussed in this paper with the hope that they may provide useful mechanistic insights into our understanding of the biological functions that are associated with this important metabolic system.


Resistance to change, of behavior and of theory.
The persistence of operant behavior when disrupted tends to be positively related to how often reinforcers were delivered in the past. Behavioral momentum theory describes this finding as the outcome of Pavlovian processes. That is, the relation between discriminative stimuli and reinforcers that were delivered in their presence strengthens behavior, thereby making it more likely to persist. If only the story were that simple. A growing number of findings challenge the basic tenets of behavioral momentum theory. Some even call into question whether Pavlovian relations contribute to persistence in the first place. In this paper, I will review behavioral momentum theory and some of the data that have been problematic for the theory. I will argue that despite these very real challenges, the theory provides important utility not only to basic analyses of response persistence but also to clinical interventions directed at long-term reductions in problem behavior. It, for example, has set the stage for the development of alternative conceptual analyses of resistance to change, two of which will be highlighted for readers. Moreover, behavioral momentum theory may tell us something important about the reasons it continues to have an influence on the field, despite the challenging data that deter it.


Client satisfaction with substance abuse treatment.
A survey of 15 publicly-funded treatment agencies in Iowa was conducted to identify correlates of satisfaction with substance abuse treatment for voluntary clients. We used stratified least-squares regression analysis to identify program characteristics that were associated with greater satisfaction levels. In order to investigate satisfaction among voluntary clients, we stratified the data using three measures of client choice. These were self-reports of the extent to which the respondent felt pressured by the threat of jail, legal action, or family demands. Women tended to be more satisfied than men. Satisfaction scores for clients who indicated they were in treatment by choice were correlated with judgements about program characteristics. Phone availability, time with counselor, counselor skill, and sensitivity were associated with greater levels of satisfaction in all three models. Parking, privacy and cleanliness were significant in two out of three models.


Methyl-beta-cyclodextrin suppresses hyaluronan synthesis by down-regulation of hyaluronan synthase 2 through inhibition of Akt.
Hyaluronan synthases (HAS1-3) are integral plasma membrane proteins that synthesize hyaluronan, a cell surface and extracellular matrix polysaccharide necessary for many biological processes. It has been shown that HAS is partly localized in cholesterol-rich lipid rafts of MCF-7 cells, and cholesterol depletion with methyl-beta-cyclodextrin (MbetaCD) suppresses hyaluronan secretion in smooth muscle cells. However, the mechanism by which cholesterol depletion inhibits hyaluronan production has remained unknown. We found that cholesterol depletion from MCF-7 cells by MbetaCD inhibits synthesis but does not decrease the molecular mass of hyaluronan, suggesting no major influence on HAS stability in the membrane. The inhibition of hyaluronan synthesis was not due to the availability of HAS substrates UDP-GlcUA and UDP-GlcNAc. Instead, MbetaCD specifically down-regulated the expression of HAS2 but not HAS1 or HAS3. Screening of signaling proteins after MbetaCD treatment revealed that phosphorylation of Akt and its downstream target p70S6 kinase, both members of phosphoinositide 3-kinase-Akt pathway, were inhibited. Inhibitors of this pathway suppressed hyaluronan synthesis and HAS2 expression in MCF-7 cells, suggesting that the reduced hyaluronan synthesis by MbetaCD is due to down-regulation of HAS2, mediated by the phosphoinositide 3-kinase-Akt-mTOR-p70S6K pathway.


Oriented and sustained protein expression on biomimicking electrospun fibers for evaluating functionality of cells.
A proper protein orientation is often required in order to achieve specific protein-receptor interaction to elicit a desired biological response. Here, we present a Protein A-based biomimicking platform that is capable of efficiently orienting proteins for evaluating cellular behaviour. By absorbing Protein A onto aligned bio-mimicking polycaprolactone (PCL) fibers, we demonstrate that protein binding could be retained on these fibers for at least 7 days under physiologically relevant conditions. We further show that Protein A served as a molecular orientor to arrange the recombinant proteins in similar orientations. Such protein-orienting scaffolds were further verified to be biologically functional by using sensitive primary rat cortical neurons (CNs) and oligodendrocyte progenitor cells (OPCs), as model neural cells for a stringent proof of concept. Specifically, CNs that were seeded on fibers coated with Protein A and a known enhancer of neurite growth (L1 Cell Adhesion Molecular L1CAM) displayed the longest total neurite length (462.77 ± 100.79 μm, p < 0.001) as compared to the controls. Besides that, OPCs seeded on fibers coated with Protein A and Neuregulin-1 Type III (Nrg1 type III) (myelin enhancer) produced the longest myelin ensheathment length (19.8 ± 11.69 μm). These results demonstrate the efficacy of this platform for protein screening applications.


Genome Sequencing Reveals a Mixed Picture of SARS-CoV-2 Variant of Concern Circulation in Eastern Uttar Pradesh, India.
Uttar Pradesh is the densely populated state of India and is the sixth highest COVID-19 affected state with 22,904 deaths recorded on November 12, 2021. Whole-genome sequencing (WGS) is being used as a potential approach to investigate genomic evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In this study, a total of 87 SARS-CoV-2 genomes-49 genomes from the first wave (March 2020 to February 2021) and 38 genomes from the second wave (March 2021 to July 2021) from Eastern Uttar Pradesh (E-UP) were sequenced and analyzed to understand its evolutionary pattern and variants against publicaly available sequences. The complete genome analysis of SARS-CoV-2 during the first wave in E-UP largely reported transmission of G, GR, and GH clades with specific mutations. In contrast, variants of concerns (VOCs) such as Delta (71.0%) followed by Delta AY.1 (21.05%) and Kappa (7.9%) lineages belong to G clade with prominent signature amino acids were introduced in the second wave. Signature substitution at positions S:L452R, S:P681R, and S:D614G were commonly detected in the Delta, Delta AY.1, and Kappa variants whereas S:T19R and S:T478K were confined to Delta and Delta AY.1 variants only. Vaccine breakthrough infections showed unique mutational changes at position S:D574Y in the case of the Delta variant, whereas position S:T95 was conserved among Kappa variants compared to the Wuhan isolate. During the transition from the first to second waves, a shift in the predominant clade from GH to G clade was observed. The identified spike protein mutations in the SARS-CoV-2 genome could be used as the potential target for vaccine and drug development to combat the effects of the COVID-19 disease.


[Channel-forming proteins. III. Colicins].
A brief review is devoted to the results of the study of molecular mechanism interaction between membrane-active colicins and membranes in model systems. The data on physical-chemical properties of colicins most studied, the relationship between the structure and the properties of ion channels formed by them in membranes are given. The characteristics of such channels, the dependence of their functioning on the composition of aqueous medium and on transmembrane potential are discussed in detail. The hypotheses on the structure of colicin channels and experimental data concerning the size of their water pore ane considered.


Mediation of oviposition responses in the malaria mosquito Anopheles stephensi Liston by certain fatty acid esters.
The chemical factors involved in oviposition site selection by mosquitoes have become the focus of interest in recent years, and considerable attention is paid to the chemical cues influencing mosquito oviposition. Studies on synthetic oviposition attractants/repellents of long-chain fatty acid esters against Anopheles stephensi are limited. Screening and identification of chemicals which potentially attract/repel the gravid females to/or from oviposition site could be exploited for eco-friendly mosquito management strategies. The ester compounds demonstrated their ability to repel and attract the gravid A. stephensi females in the treated substrates. Significant level of concentration-dependent negative oviposition response of mosquitoes to octadecyl propanoate, heptadecyl butanoate, hexadecyl pentanoate, and tetradecyl heptanoate were observed. In contrast, decyl undecanoate, nonyl dodecanoate, pentyl hexadecanoate, and propyl octadecanoate elicited concentration-dependent positive oviposition responses from the gravid mosquitoes. Forcing a female to retain her eggs due to unavailability of a suitable oviposition site and attracting them to lay the eggs in a baited ovitraps shall ensure effective control of mosquito breeding and population buildup because the oviposition bioassay target the most susceptible stage of an insect life cycle. Treating relatively smaller natural breeding sites with an effective repellent and placing ovitraps containing an attractant in combination with insect-growth regulator (IGR)/insecticide would be a promising method of mosquito management.


Continuing education needs of hospital librarians.
The Hospital Library Section (HLS) of MLA conducted a survey of its members to determine their continuing education needs and preferences. A questionnaire mailed with the HLS Newsletter gathered information in four general areas: preferred modes of continuing education, subjects viewed as most important, motivators and deterrents, and topics for presentation at the 1985 MLA annual meeting. Additional data were collected on the type and bed size of the member's institution. Of the 560 questionnaires mailed, 257 (46%) were returned. Overall, for continuing education, members favored one-day courses dealing with automated systems, planning and marketing; for annual meeting topics, they were additionally interested in health care finance.


Cutis laxa. Ultrastructural and biochemical studies.
Specimens from one case each of acquired and congenital cutis laxa were examined by electron microscopy. Elastic flbers of the dermis and subcutaneous arteries and veins were found to have similar changes. Elastin was diminished and microfilaments were visible throughout the entire fiber. Electron-dense, amorphous or granular layers that alternate with relatively electron-light layers were deficient. This electron-dense substance was unevenly aggregated within or in the vicinity of elastic fiber. In the congenital case, the aggregation and deposition fo the electron-dense substance was often pronounced. In the vein, deficient deposition of elastin and admixture of microfilaments and amorphous substance were also found. Such admixture was often encircled by fibroblasts or smooth muscle cells. In the artery, multiplication of basal lamina was seen. Collagen fibers and anchoring fibrils of the skin were normal.


Percutaneous tracheostomy: to bronch or not to bronch--that is the question.
Percutaneous tracheostomy is a routine procedure in the intensive care unit (ICU). Some surgeons perform percutaneous tracheostomies using bronchoscopy believing that it increases safety. The purpose of this study was to evaluate percutaneous tracheostomy in the trauma population and to determine whether the use of a bronchoscope decreases the complication rate and improves safety. A retrospective review was completed from January 2007 to November 2010. Inclusion criteria were trauma patients undergoing percutaneous tracheostomy. Data collected included age, Abbreviated Injury Score by region, Injury Severity Score, ventilator days, and outcomes. Complications were classified as early (occurring within <24 hours) or late (>24 hours after the procedure). During the study period, 9,663 trauma patients were admitted, with 1,587 undergoing intubation and admission to the ICU. Tracheostomies were performed in 266 patients and 243 of these were percutaneous; 78 (32%) were performed with the bronchoscope (Bronch) and 168 (68%) without bronchoscope (No Bronch). There were no differences between the groups in Abbreviated Injury Score by region, Injury Severity Score, probability of survival, ventilator days, and length of ICU or overall hospital stay. There were 16 complications, 5 (Bronch) and 11 (No Bronch). Early complications were primarily bleeding (Bronch 3% vs. No Bronch 4%, not statistically significant). Late complications included tracheomalacia, tracheal granulation tissue, bleeding, and stenosis; Bronch 4% versus No Bronch 3%, (not statistically significant). One major complication occurred, with loss of airway and cardiac arrest, in the bronchoscopy group. Percutaneous tracheostomy was safely and effectively performed by an experienced surgical team both with and without bronchoscopic guidance with no difference in the complication rates. This study suggests that the use of bronchoscopic guidance during tracheostomy is not routinely required but may be used as an important adjunct in selected patients, such as those with HALO cervical fixation, obesity, or difficult anatomy.


Plasticity between neuronal pairs in layer 4 of visual cortex varies with synapse state.
In neocortex, the induction and expression of long-term potentiation (LTP) and long-term depression (LTD) vary depending on cortical area and laminae of presynaptic and postsynaptic neurons. Layer 4 (L4) is the initial site of sensory afference in barrel cortex and primary visual cortex (V1) in which excitatory inputs from thalamus, L6, and neighboring L4 cells are integrated. However, little is known about plasticity within L4. We studied plasticity at excitatory synaptic connections between pairs and triplets of interconnected L4 neurons in guinea pig V1 using a fixed delay pairing protocol. Plasticity outcomes were heterogeneous, with some connections undergoing LTP (n = 7 of 42), some LTD (n = 19 of 42), and some not changing (n = 16 of 42). Although quantal analysis revealed both presynaptic and postsynaptic plasticity expression components, reduction in quantal size (a postsynaptic property) contributing to LTD was ubiquitous, whereas in some cell pairs, this change was overridden by an increase in the probability of neurotransmitter release (a presynaptic property) resulting in LTP. These changes depended on the initial reliability of the connections: highly reliable connections depressed with contributions from presynaptic and postsynaptic effects, and unreliable connections potentiated as a result of the predominance of presynaptic enhancement. Interestingly, very strong, reliable pairs of connected cells showed little plasticity. Pairs of connected cells with a common presynaptic or postsynaptic L4 cell behaved independently, undergoing plasticity of different or opposite signs. Release probability of a connection with initial 100% failure rate was enhanced after pairing, potentially avoiding silencing of the presynaptic terminal and maintaining L4-L4 synapses in a broader dynamic range.


Exact solution for scalar diffraction between tilted and translated planes using impulse functions over a surface.
The diffraction relation between a plane and another plane that is both tilted and translated with respect to the first one is revisited. The derivation of the result becomes easier when the impulse function over a surface is used as a tool. Such an approach converts the original 2D problem to an intermediate 3D problem and thus allows utilization of easy-to-interpret Fourier transform properties due to rotation and translation. An exact solution for the scalar monochromatic propagating waves case when the propagation direction is restricted to be in the forward direction is presented.


Systemic Levels of Interleukin-6 Correlate With Progression Rate of Geographic Atrophy Secondary to Age-Related Macular Degeneration.
Geographic atrophy (GA) is a clinical phenotype of late age-related macular degeneration (AMD) with no current treatment available. In this study, we investigated markers of chronic inflammation in plasma of patients with GA and how these relate to progression rate. We prospectively included 42 patients with GA, 41 patients with neovascular AMD, and 27 healthy controls. We quantified levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF) receptor 2, and C-reactive protein (CRP). We adapted an inflammation summary score to cluster conceptually related markers of chronic inflammation. Enlargement rate of the atrophic lesion was measured from fundus autofluorescence images performed at baseline and after 1 year. Patients with GA showed an increase in proinflammatory markers of IL-6 (P = 0.009), TNF receptor 2 (P = 0.013), and CRP (P = 0.017) compared to healthy controls. We found that IL-8 levels were markedly higher in patients with GA when compared to patients with neovascular AMD (P = 0.013). The inflammation summary score was high in patients with neovascular AMD (P = 0.024), but even higher in patients with GA (<0.001), when compared to healthy controls. GA enlargement was measured in 36 patients, who completed follow-up. Plasma levels of IL-6 had a moderate but significant correlation with GA enlargement rate (R2 = 0.23, P = 0.0035). Markers of chronic inflammation strongly associates with presence of GA secondary to AMD. Plasma IL-6 possesses predictive ability of progression and constitutes the first known plasma biomarker of disease activity in GA. These findings shed light into a poorly understood clinical phenotype of AMD and highlights the important role of chronic inflammation in GA.


Up-regulation of emotional responses to reward-predicting stimuli: an ERP study.
Altered reward processing is a hallmark symptom of many psychiatric disorders. It has recently been shown that people are capable of down-regulating reward processing. Here, we examined whether people are capable of up-regulating emotional responses to reward-predicting stimuli. Participants passively viewed colored squares that predicted a reward or no reward, and up- or down-regulated their emotional responses to these reward-predicting stimuli by focusing on the reward meaning or the color of the squares respectively. The amplitude of the late positive potential (LPP) was taken as an objective index of regulation success. The LPP in response to reward-predicting squares was enhanced by up-regulation, suggesting that up-regulation of emotional responses to reward-predicting stimuli using a cognitive strategy is feasible. These results are highly relevant for the treatment of disorders characterized by diminished motivation, and for reward-based decision making in daily life.


U.S.S.R. and U.S. nutrient intake, plasma lipids, and lipoproteins in men ages 40-59 sampled from Lipid Research Clinics populations.
Correlates of high-density lipoprotein (HDL) cholesterol and other lipids and lipoproteins were studied in white men ages 40-59 who were part of the 15% random sample recalled to Visit 2 of the Lipid Research Clinics Program Prevalence Study. Standardized examinations were conducted by two U.S.S.R. and nine U.S. clinics. Mean plasma lipid and lipoprotein cholesterol levels differed significantly between the two countries, with the U.S.S.R. subpopulations having higher mean total plasma and HDL cholesterol levels and HDL/total cholesterol ratios and lower mean triglyceride levels and low-density lipoprotein (LDL)/HDL cholesterol ratios than the U.S. subpopulations. Small, but statistically significant, differences were found in some dietary components. The U.S.S.R. sample had a significantly higher intake of saturated fatty acids, carbohydrates, complex carbohydrates, and kilocalories/kilogram body weight and a significantly lower intake of total fat, polyunsaturated fatty acids, protein, and polyunsaturated/saturated fat ratio. The multiple regression models tested were not major predictors for total plasma cholesterol or LDL cholesterol. Characteristics associated with higher HDL cholesterol levels in both countries were lean body mass, ethanol consumption, abstinence from cigarette smoking, and lower dietary consumption of carbohydrates.


Metabolic reprogramming of host cells upon bacterial infection: Why shift to a Warburg-like metabolism?
The finding that the Warburg effect observed in proliferating cancer cells is also observed during immune responses renewed the interest in the study of metabolic reprogramming of immune cells, a field of investigation called immunometabolism. However, the specific mechanisms and processes underlying metabolic changes of host cells upon bacterial infection remain poorly understood. Several recent reports have reported that mammalian cells infected with intracellular bacteria have an altered metabolism that resembles the Warburg effect seen in cancer cells. In this Review, we will summarize current knowledge on metabolic reprogramming and discuss putative causes underlying the preferential remodelling of host cells to Warburg-like metabolic programs during infection by intracellular bacteria.


Anticonvulsant effects of methyl ethyl ketone and diethyl ketone in several types of mouse seizure models.
The anticonvulsant effects of acetone have been reported in various animal models of epilepsy. We recently demonstrated that other ketone bodies, methyl ethyl ketone (MEK) and diethyl ketone (DEK), suppressed status epilepticus that was induced by lithium-pilocarpine in rat. In the present study, the anticonvulsant effects of MEK and DEK were evaluated by using four different types of mouse seizure models, which were induced by pentylenetetrazole, kainic acid, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), and electroshock. The effects of clonazepam, a typical anticonvulsant, and acetone were also evaluated and compared with MEK and DEK. In this study, MEK (5 and 10 mmol/kg, i.p.) and DEK (2.5 and 5 mmol/kg, i.p.) produced anticonvulsant activity against all types of seizure models. Furthermore, MEK and DEK showed almost the same potencies against four different seizure models used, while clonazepam showed significant higher ED(50) values against kainic acid-induced and electroshock-induced seizure models as compared with the pentylenetetrazole- or DMCM-induced seizure model. In each study, the highest doses of clonazepam (1 or 3mg/kg) did not show clear anticonvulsant effects against the kainic acid- or electroshock-induced seizures. In conclusion, MEK and DEK showed broad-spectra anticonvulsant effects in both chemically- and electroshock-induced experimental seizure models.


A highly accurate, low cost test for BRCA1 mutations.
The hereditary breast and ovarian cancer syndrome is associated with a high frequency of BRCA1 mutations. However, the widespread use of BRCA1 testing has been limited to date by three principal concerns: the fear of loss of health and life insurance, the uncertain clinical value of a positive test result, and the current lack of an inexpensive and sensitive screening test for BRCA1 mutations. We have developed an inexpensive system for gene mutational scanning, based on a combination of extensive multiplex PCR amplification and two dimensional electrophoresis. The efficiency of this system, as a screening test for BRCA1 mutations, was evaluated in a panel of 60 samples from high risk women, 14 of which contained a previously identified mutation in BRCA1. All 14 mutations were identified, as well as an additional five that had previously escaped detection. In addition to the 19 mutations, a total of 15 different polymorphic variants were scored, most of which were recurring. All were confirmed by nucleotide sequencing. The cost of screening per sample was calculated to be approximately US$70 for the manual technique used in this study, and may be reduced to approximately US$10 with the introduction of commercially available PCR robotics and fluorescent imaging. Implementation of this method of mutation screening in the research and clinical setting should permit rapid accrual of quantitative data on genotype-phenotype associations for the evaluation of diagnostic testing.


Identification of material parameters based on Mohr-Coulomb failure criterion for bisphosphonate treated canine vertebral cancellous bone.
Nanoindentation has been widely used to study bone tissue mechanical properties. The common method and equations for analyzing nanoindentation, developed by Oliver and Pharr, are based on the assumption that the material is linearly elastic. In the present study, we adjusted the constraint of linearly elastic behavior and use nonlinear finite element analysis to determine the change in cancellous bone material properties caused by bisphosphonate treatment, based on an isotropic form of the Mohr-Coulomb failure model. Thirty-three canine lumbar vertebrae were used in this study. The dogs were treated daily for 1 year with oral doses of alendronate, risedronate, or saline vehicle at doses consistent, on a mg/kg basis, to those used clinically for the treatment of post-menopausal osteoporosis. Two sets of elastic modulus and hardness values were calculated for each specimen using the Continuous Stiffness Measurement (CSM) method (E(CSM) and H(CSM)) from the loading segment and the Oliver-Pharr method (E(O-P) and H(O-P)) from the unloading segment, respectively. Young's modulus (E(FE)), cohesion (c), and friction angle (phi) were identified using a finite element model for each nanoindentation. The bone material properties were compared among groups and between methods for property identification. Bisphosphonate treatment had a significant effect on several of the material parameters. In particular, Oliver-Pharr hardness was larger for both the risedronate- and alendronate-treated groups compared to vehicle and the Mohr-Coulomb cohesion was larger for the risedronate-treated compared to vehicle. This result suggests that bisphosphonate treatment increases the hardness and shear strength of bone tissue. Shear strength was linearly predicted by modulus and hardness measured by the Oliver-Pharr method (r(2)=0.99). These results show that bisphosphonate-induced changes in Mohr-Coulomb material properties, including tissue shear cohesive strength, can be accurately calculated from Oliver-Pharr measurements of Young's modulus and hardness.


A ctenophore (comb jelly) employs vortex rebound dynamics and outperforms other gelatinous swimmers.
Gelatinous zooplankton exhibit a wide range of propulsive swimming modes. One of the most energetically efficient is the rowing behaviour exhibited by many species of schyphomedusae, which employ vortex interactions to achieve this result. Ctenophores (comb jellies) typically use a slow swimming, cilia-based mode of propulsion. However, species within the genus Ocyropsis have developed an additional propulsive strategy of rowing the lobes, which are normally used for feeding, in order to rapidly escape from predators. In this study, we used high-speed digital particle image velocimetry to examine the kinematics and fluid dynamics of this rarely studied propulsive mechanism. This mechanism allows Ocyropsis to achieve size-adjusted speeds that are nearly double those of other large gelatinous swimmers. The investigation of the fluid dynamic basis of this escape mode reveals novel vortex interactions that have not previously been described for other biological propulsion systems. The arrangement of vortices during escape swimming produces a similar configuration and impact as that of the well-studied 'vortex rebound' phenomenon which occurs when a vortex ring approaches a solid wall. These results extend our understanding of how animals use vortex-vortex interactions and provide important insights that can inform the bioinspired engineering of propulsion systems.


Skeletal mastocytosis.
To characterise the condition of skeletal mastocytosis, an uncommon cause of apparently "idiopathic" osteoporosis. Transiliac crest biopsy specimens submitted over a period of five years were examined for nodular accumulation of mast cells. The cases were reviewed histologically and clinical follow up was obtained from hospital notes. Six cases of mastocytosis occurring in bone biopsy specimens submitted to our department were identified. Four patients presented initially with vertebral collapse and the other two were known to have extraskeletal mast cell disease at presentation. On clinical review of the four patients with vertebral collapse, one was found to have urticaria pigmentosa. This patient died from his mastocytosis, whereas the three patients without evidence of extraskeletal disease remain alive and well. Histological examination showed that patients with the poorer clinical outcome had severe peritrabecular fibrosis as well as mast cell nodules; those with prolonged disease-free survival had nodules without peritrabecular fibrosis. There is a form of mastocytosis which presents clinically as "idiopathic" osteoporosis. Clinically it does not have the same prognostic implications as skeletal disease in "malignant mastocytosis", running a much more benign course.


Escherichia coli O-Antigen Gene Clusters of Serogroups O62, O68, O131, O140, O142, and O163: DNA Sequences and Similarity between O62 and O68, and PCR-Based Serogrouping.
The DNA sequence of the O-antigen gene clusters of Escherichia coli serogroups O62, O68, O131, O140, O142, and O163 was determined, and primers based on the wzx (O-antigen flippase) and/or wzy (O-antigen polymerase) genes within the O-antigen gene clusters were designed and used in PCR assays to identify each serogroup. Specificity was tested with E. coli reference strains, field isolates belonging to the target serogroups, and non-E. coli bacteria. The PCR assays were highly specific for the respective serogroups; however, the PCR assay targeting the O62 wzx gene reacted positively with strains belonging to E. coli O68, which was determined by serotyping. Analysis of the O-antigen gene cluster sequences of serogroups O62 and O68 reference strains showed that they were 94% identical at the nucleotide level, although O62 contained an insertion sequence (IS) element located between the rmlA and rmlC genes within the O-antigen gene cluster. A PCR assay targeting the rmlA and rmlC genes flanking the IS element was used to differentiate O62 and O68 serogroups. The PCR assays developed in this study can be used for the detection and identification of E. coli O62/O68, O131, O140, O142, and O163 strains isolated from different sources.


[Effect of Baicalin on Pyroptosis of Diffuse Large B-Cell Lymphoma Cell Lines DB and Its Mechanism].
To investigate the effect of Baicalin on the proliferation and pyroptosis of diffuse large B-cell lymphoma cell line DB and its mechanism. DB cells were treated with baicalin at different concentrations (0, 5, 10, 20, 40 μmol/L). Cell proliferation was detected by CCK-8 assay and half maximal inhibitory concentration (IC50) was calculated. The morphology of pyroptosis was observed under an inverted microscope, the integrity of the cell membrane was verified by LDH content release assay, and the expressions of pyroptosis-related mRNA and protein (NLRP3, GSDMD, GSDME, N-GSDMD, N-GSDME) were detected by real-time fluorescence quantitative PCR and Western blot. In order to further clarify the relationship between baicalin-induced pyroptosis and ROS production in DB cells, DB cells were divided into control group, baicalin group, NAC group and NAC combined with baicalin group. DB cells in the NAC group were pretreated with ROS inhibitor N-acetylcysteine (NAC) 2 mmol/L for 2 h. Baicalin was added to the combined treatment group after pretreatment, and the content of reactive oxygen species (ROS) in the cells was detected by DCFH-DA method after 48 hours of culture. Baicalin inhibited the proliferation of DB cells in a dose-dependent manner (r=-0.99), and the IC50 was 20.56 μmol/L at 48 h. The morphological changes of pyroptosis in DB cells were observed under inverted microscope. Compared with the control group, the release of LDH in the baicalin group was significantly increased (P<0.01), indicating the loss of cell membrane integrity. Baicalin dose-dependently increased the expression levels of NLRP3, N-GSDMD, and N-GSDME mRNA and protein in the pyroptosis pathway (P<0.05). Compared with the control group, the level of ROS in the baicalin group was significantly increased (P<0.05), and the content of ROS in the NAC group was significantly decreased (P<0.05). Compared with the NAC group, the content of ROS in the NAC + baicalin group was increased. Baicalin significantly attenuated the inhibitory effect of NAC on ROS production (P<0.05). Similarly, Western blot results showed that compared with the control group, the expression levels of pyroptosis-related proteins was increased in the baicalin group (P<0.05). NAC inhibited the expression of NLRP3 and reduced the cleavage of N-GSDMD and N-GSDME (P<0.05). Compared with the NAC group, the NAC + baicalin group had significantly increased expression of pyroptosis-related proteins. These results indicate that baicalin can effectively induce pyroptosis in DB cells and reverse the inhibitory effect of NAC on ROS production. Baicalin can inhibit the proliferation of DLBCL cell line DB, and its mechanism may be through regulating ROS production to affect the pyroptosis pathway.


Defining the research agenda to measure and reduce tuberculosis stigmas.
Crucial to finding and treating the 4 million tuberculosis (TB) patients currently missed by national TB programmes, TB stigma is receiving well-deserved and long-delayed attention at the global level. However, the ability to measure and evaluate the success of TB stigma-reduction efforts is limited by the need for additional tools. At a 2016 TB stigma-measurement meeting held in The Hague, The Netherlands, stigma experts discussed and proposed a research agenda around four themes: 1) drivers: what are the main drivers and domains of TB stigma(s)?; 2) consequences: how consequential are TB stigmas and how are negative impacts most felt?; 3) burden: what is the global prevalence and distribution of TB stigma(s) and what explains any variation? 4): intervention: what can be done to reduce the extent and impact of TB stigma(s)? Each theme was further subdivided into research topics to be addressed to move the agenda forward. These include greater clarity on what causes TB stigmas to emerge and thrive, the difficulty of measuring the complexity of stigma, and the improbability of a universal stigma 'cure'. Nevertheless, these challenges should not hinder investments in the measurement and reduction of TB stigma. We believe it is time to focus on how, and not whether, the global community should measure and reduce TB stigma.