Perioperative, Spatiotemporally Coordinated Activation of T and NK Cells Prevents Recurrence of Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating cancer resistant to therapy, including checkpoint immunotherapies, and early tumor resection and (neo)adjuvant chemotherapy fails to improve a poor prognosis. In a transgenic mouse model of resectable PDAC, we investigated the coordinated activation of T and natural killier (NK) cells in addition to gemcitabine chemotherapy to prevent tumor recurrence. Only neoadjuvant, but not adjuvant treatment with a PD-1 antagonist effectively supported chemotherapy and suppressed local tumor recurrence and improved survival involving both NK and T cells. Local T-cell activation was confirmed by increased tumor infiltration with CD103+CD8+ T cells and neoantigen-specific CD8 T lymphocytes against the marker neoepitope LAMA4-G1254V. To achieve effective prevention of distant metastases in a complementary approach, we blocked the NK-cell checkpoint CD96, an inhibitory NK-cell receptor that binds CD155, which was abundantly expressed in primary PDAC and metastases of human patients. In gemcitabine-treated mice, neoadjuvant PD-1 blockade followed by adjuvant inhibition of CD96 significantly prevented relapse of PDAC, allowing for long-term survival. In summary, our results show in an aggressively growing transgenic mouse model of PDAC that the coordinated activation of both innate and adaptive immunity can effectively reduce the risk of tumor recurrence after surgery, facilitating long-term remission of this lethal disease.Significance: Coordinated neoadjuvant and adjuvant immunotherapies reduce the risk of disease relapse after resection of murine PDAC, suggesting this concept for future clinical trials. Cancer Res; 78(2); 475-88. ©2017 AACR.


Treatment Outcomes and Adverse Drug Effects of Ethambutol, Cycloserine, and Terizidone for the Treatment of Multidrug-Resistant Tuberculosis in South Africa.
Treatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.


Trends in Physician Reimbursement for Spinal Procedures Since 2010.
Retrospective cohort study. To identify trends in spinal procedure reimbursement in our practice since 2010. In an uncertain healthcare climate with continuous reform, trends in physician reimbursement are unclear. Market forces of supply and demand, legislation imposing penalties for quality measures, local competition, and geographic location have the potential to affect reimbursement. An emphasis on quality-of-care and cost reduction is placed on providers and insurers. In a high-cost area such as spine surgery, it is unknown what the reimbursement trends have been over the last 7 years of major healthcare reforms. We collected payments received data for the 20 most commonly billed Current Procedural Terminology (CPT) codes for spinal surgery from January 2010 to December 2016. Payments were adjusted for inflation using the Consumer Price Index for Medical Care in the Northeastern United States. Insurers were separated into four groups: Medicare, Medicaid, Private Insurance, and Workers Compensation and No Fault (WC/NF). Using a weighted average to adjust for variation in procedures performed, average payments were trended over time. Average payments were trended by insurance group averaged by CPT code. After adjusting for inflation, average overall payments for spinal claims from 2010 to 2016 increased 13.6%. Average reimbursement declined 1.9% from 2010 to 2013 and rose 16.8% from 2014 to 2016. Average Medicaid payments increased 150.1% since 2010 whereas average Medicare payments rose 4.9%. Average reimbursement from private insurers and WC/NF claims decreased 16.2% and 8.5%, respectively, from 2010 to 2013; increasing 14.2% and 12.5%, respectively, from 2014 to 2016. From 2010 to 2016, reimbursement for private insurance decreased 9.3% and increased 8.2% for WC/NF claims. Since 2010, inflation-adjusted reimbursement for spinal procedures increased in our practice. There was a decline from 2010 to 2013. Increases occurred from 2014 to 2016 across all insurers. Medicaid payments more than doubled since 2010. 3.


Targeted Truth: An Experiment Testing the Efficacy of Counterindustry Tobacco Advertisements Targeted to Black Individuals and Sexual and Gender Minority Individuals.
Some groups disproportionately suffer from tobacco-related illnesses-in part, because the tobacco industry has strategically targeted these groups. To combat industry targeting, antitobacco media campaigns (eg, the truth campaign) have used analogous messaging strategies, describing the industry's targeted marketing practices to reach these vulnerable groups. We tested the efficacy of counterindustry tobacco advertisements targeted to vulnerable groups (Black individuals and sexual and gender minority [SGM] individuals). From March to July 2020, we recruited N = 1161 young adults in the United States, including n = 430 Black young adults and n = 452 SGM young adults (with n = 108 identifying as Black and SGM). In a web-based, between-subjects experiment, participants were randomized to watch one of four types of advertisement ("ad"): (1) ads from the truth antismoking campaign not targeted toward a specific vulnerable group, (2) Black-targeted truth ads, (3) SGM-targeted truth ads, or (4) unrelated control ads. We examined effects on support for tobacco control policies, counterindustry motivation, counterindustry beliefs, perceived effectiveness, and anger toward the industry. Relative to control, non-targeted ads increased policy support, and Black-targeted ads increased motivation and beliefs. Targeted ads elicited anger regardless of the audience targeted. However, in general, neither Black identity nor SGM identity moderated the effects of the targeted ads. We offer little evidence that targeted counterindustry ads are especially influential for their intended group. However, targeted counterindustry appeals may be successful at evoking industry anger regardless of the audience targeted. Counterindustry advertisements from the truth campaign targeting Black individuals and SGM individuals had limited effect on tobacco control policies, counterindustry motivation, and counterindustry beliefs. However, counterindustry ads evoked anger toward the industry regardless of ingroup status, which in turn was positively associated with anti-industry outcomes. These results, considered alongside the extant literature, suggest little benefit to developing targeted counterindustry tobacco campaigns for specific groups and instead point to the utility of developing campaigns that appeal to broader audiences.


Optimizing indications of impacting bone allograft transplantation in osteonecrosis of the femoral head.
The aim of this study was to report the medium-term outcomes of impaction bone allograft and fibular grafting for osteonecrosis of the femoral head (ONFH) and to define the optimal indications. A total of 67 patients (77 hips) with ONFH were enrolled in a single centre retrospective review. Success of the procedure was assessed using the Harris Hip Score (HHS) and rate of revision to total hip arthroplasty (THA). Risk factors were studied, including age, aetiology, duration of hip pain, as well as two classification systems (Association Research Circulation Osseous (ARCO) and Japanese Investigation Committee (JIC) systems). After a mean follow-up period of 8.61 years (SD 1.45), 81.3% (52/64) of enrolled cases had a good or excellent HHS at latest follow-up (declining to 76.0% (38/50) for those with more than eight years of follow-up). Overall survival was 92.1% at eight years' follow-up (95% CI 83.2% to 96.4%). A total of 12 hips (19.0%) failed (reoperation or HHS < 70 points) at final follow-up. Rate of success was adversely affected by increasing age, duration of pain, and more severe disease as measured using the ARCO and JIC classifications, but not by aetiology of the ONFH. We report favourable medium-term results of this procedure. Best outcomes can be expected in patients matching the following indications: younger than 40 years; less 12-month hip pain before surgery; femoral head collapse being less than 2 mm; and integrated lateral wall of femoral head. Cite this article: Bone Joint J 2020;102-B(7):838-844.


Engaging community-based veterans' organizations in health promotion programs.
Community organizations, such as churches, clubs, and senior centers, can be important locations for health programs. However, little is known about the organizational factors that influence participation and engagement in health programs. To learn more, we evaluated a community-based program designed to help US military veterans better manage their high blood pressure. The program involved training a pair of veterans to deliver health-related presentations at their local units. We found that factors such as larger meeting attendance size, rural location, age diversity, and member enthusiasm were positively associated with both a willingness to participate and a high level of engagement in program activities.


Mechanisms by which the surface expression of the glycosyl-phosphatidylinositol-anchored complement regulatory proteins decay-accelerating factor (CD55) and CD59 is lost in human leukaemia cell lines.
We have investigated the mechanisms of defects in the glycosyl-phosphatidylinositol (GPI)-anchored complement regulatory proteins delay-accelerating factor (DAF) and/or CD59 in a panel of human leukaemia cell lines that lack surface expression of these proteins: U937 (DAF+/CD59-), CEM (DAF-/CD59+), TALL (DAF-/CD59-) and a substrain of Ramos [Ramos(-)] (DAF-/CD59-). Northern blotting and reverse transcription-PCR revealed that the main cause of the DAF and/or CD59 deficiency is the failure of mRNA expression in most of the cell lines, except in Ramos(-) in which sufficient mRNA for DAF and CD59 was produced. U937, CEM and TALL cells were not defective in GPI anchor formation as assessed by the detection of other GPI-anchored proteins. No gene abnormality corresponding to DAF or CD59 was detected by Southern blotting. Thus the cause of the defects of DAF and/or CD59 in these leukaemia cell lines except for Ramos(-) is virtually undetectable steady-state levels of the relevant mRNA, most likely attributable to lack of transcription in these cell lines. On the other hand, Ramos(-) cells failed to generate a GPI anchor, whereas they normally expressed DAF and CD59 transcripts. The transfection of phosphatidylinositol-glycan class A (PIG-A) cDNA into Ramos(-) cells restored DAF and CD59 expression, indicating that the defective mechanism in GPI anchor formation is similar to that in paroxysmal noctural haemoglobinuria (PNH) cells, i.e. a deficiency of the PIG-A gene product. Thus the mechanisms of the defects of DAF and/or CD59 in human leukaemia cell lines are not uniform, and in most cases are different from that proposed to cause PNH.


Study of drug utilization pattern of antihyperglycemic agents in a South Indian tertiary care teaching hospital.
To determine the drug utilization pattern of antihyperglycemic agents (AHA) in a tertiary care teaching hospital. This was a prospective observational study. All the relevant data were collected and drug utilization pattern of AHA was determined. Direct cost associated with the use of antihyperglycemic medicines was calculated and consumption of the antihyperglycemic medicines was measured as defined daily dose (DDD)/100 bed-days. The adverse drug reactions (ADRs) related to anti-diabetic medicines were monitored. Chi square test (χ(2)), mean±standard deviation. During the study period, 350 patients diagnosed as diabetes mellitus (DM) were admitted. Insulin was prescribed as monotherapy to 81% and to 52% patients during hospital stay and discharge, respectively. Increase in utilization of insulin was recorded in majority of the patients due to presence of co-morbid conditions or resistance to oral hypoglycemic drugs. Use of insulin at the time of discharge decreased significantly (P<0.05) by 29%. Among the oral AHA, combination of glimepiride with metformin was more prevalent during hospital stay and at the time of discharge monotherapy of metformin followed by glimepiride was more prevalent. During hospital stay, cost of AHA was found to be Rs. 95.27 ± 119.03. The total antihyperglycemic drug consumption in the medicine ward during study period was 13.42 DDD/100 bed-days. Fifty ADRs were reported and descriptions of ADRs were found to be only hypoglycemia. The study exhibited a significant increase in the utilization of two drug combination therapies and monotherapy of oral AHA and decrease in the utilization of insulin at the time of discharge.


The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats.
The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed. The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus-dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence. The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus-dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24-hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing. Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal-regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca2+ /calmodulin-dependent protein kinase IIα and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks. In peripubertal rats, propofol anesthesia exposure affects memory retrieval and acquisition of new learning in the spatial and nonspatial, nonaversive learning tasks 24 hour after the treatment, along with the expression of molecules that participate in memory retrieval/reconsolidation in the dorsal hippocampus. These results may have clinical implications, favoring control of basic cognitive functions in older children after the propofol exposure.


IL22RA1/STAT3 Signaling Promotes Stemness and Tumorigenicity in Pancreatic Cancer.
Chronic inflammation is a feature of pancreatic cancer, but little is known about how immune cells or immune cell-related signals affect pancreatic cancer stemness and development. Our previous work showed that IL22/IL22RA1 plays a vital role in acute and chronic pancreatitis progression by mediating cross-talk between immune cells and acinar cells or stellate cells, respectively. Here, we find IL22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of patients with pancreatic cancer. The IL22RA1hi population from pancreatic cancer harbored higher stemness potential and tumorigenicity. Notably, IL22 promoted pancreatic cancer stemness via IL22RA1/STAT3 signaling, establishing the mechanism of regulation of cancer stemness by microenvironmental factors. Moreover, STAT3 was indispensable for the maintenance of IL22RA1hi cells. Overall, these findings provide a therapeutic strategy for patients with PDAC with high expression of IL22RA1.Significance: IL22RA1/STAT3 signaling enhances stemness and tumorigenicity in pancreatic cancer. Cancer Res; 78(12); 3293-305. ©2018 AACR.


Convolutional Neural Network of Atomic Surface Structures To Predict Binding Energies for High-Throughput Screening of Catalysts.
High-throughput screening of catalysts can be performed using density functional theory calculations to predict catalytic properties, often correlated with adsorbate binding energies. However, more complete investigations would require an order of 2 more calculations compared to the current approach, making the computational cost a bottleneck. Recently developed machine-learning methods have been demonstrated to predict these properties from hand-crafted features but have struggled to scale to large composition spaces or complex active sites. Here, we present an application of a deep-learning convolutional neural network of atomic surface structures using atomic and Voronoi polyhedra-based neighbor information. The model effectively learns the most important surface features to predict binding energies. Our method predicts CO and H binding energies after training with 12 000 data for each adsorbate with a mean absolute error of 0.15 eV for a diverse chemical space. Our method is also capable of creating saliency maps that determine atomic contributions to binding energies.


Fatty Acid Profiles of Leishmania major Derived from Human and Rodent Hosts in Endemic Cutaneous Leishmaniasis Areas of Tunisia and Algeria.
Leishmaniasis is a protozoal vector-borne disease that affects both humans and animals. In the Mediterranean Basin, the primary reservoir hosts of Leishmania spp. are mainly rodents and canids. Lipidomic approaches have allowed scientists to establish Leishmania spp. lipid profiles for the identification of cell stage specific biomarkers, drug mechanisms of action, and host immune response. Using an in silico approach of global network interaction between genes involved in fatty acid (FA) synthesis followed by the GC-MS approach, we were able to characterize the fatty acid profiles of L. major derived from human and rodent hosts. Our results revealed that the lipid profile of L. major showed similarities and differences with those already reported for other Leishmania species. Phospholipids are the predominant lipid class. FA composition of rodent parasites was characterized by a lower abundance of the precursor C18:2(n-6). One of the rodent clones, which also expressed the lowest lipid abundance in PL and TAG, was the least sensitive clone to the miltefosine drug and has the lowest infection efficiency. Our findings suggest that the lipid composition variation may explain the response of the parasite toward treatment and their ability to infect their host.


Update on lasers in urology 2014: current assessment on holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripter settings and laser fibers.
The purpose of the study was to review the existing literature on holmium:yttrium-aluminum-garnet laser lithotripsy regarding lithotripter settings and laser fibers. An online search of current and past peer-reviewed literature on holmium laser lithotripsy was performed on several databases, including PubMed, SciElo, and Google Scholar. Relevant studies and original articles about lithotripter settings and laser fibers were examined, and the most important information is summarized and presented here. We examine how the choice of lithotripter settings and laser fibers influences the performance of holmium laser lithotripsy. Traditional laser lithotripter settings are analyzed, including pulse energy, pulse frequency, and power levels, as well as newly developed long-pulse modes. The impact of these settings on ablation volume, fragment size, and retropulsion is also examined. Advantages of small- and large-diameter laser fibers are discussed, and controversies are highlighted. Additionally, the influence of the laser fiber is examined, specifically the fiber tip preparation and the lithotripter settings' influence on tip degradation. Many technical factors influence the performance of holmium laser lithotripsy. Knowing and understanding these controllable parameters allows the urologist to perform a laser lithotripsy procedure safely, efficiently, and with few complications.


Effects of prenatal cocaine exposure on the developing hippocampus: intrinsic and synaptic physiology.
A variety of neurological complications has been reported in infants exposed to cocaine during gestation. In the present study, intrinsic cell properties of hippocampal neurons from CA1, CA3, and dentate gyrus regions were measured and compared in tissue from neonatal rats exposed to saline or cocaine in utero. Synaptic properties of the CA1 pyramidal cell region were analyzed at postnatal day (P) 20 with the use of extracellular and intracellular recording techniques. In vitro intracellular recordings (n = 223) obtained at P10, P15 and P20 in tissue from cocaine- and saline-exposed animals revealed no differences in standard cell properties such as resting membrane potential, input resistance, time constant, and action potential amplitude or duration. Hippocampal slices from cocaine-exposed animals exhibited a marked reduction of spike frequency adaptation for all three types of principal hippocampal neurons (e.g., CA1, CA3, and granule cells). The amplitudes of afterhyperpolarizations following a spike train were also decreased in CA1 and CA3 cells in tissue from cocaine-exposed animals. Extracellular and intracellular recordings in the CA1 pyramidal cell region at P20 were obtained to assess and compare synaptic function in tissue from cocaine- and saline-exposed animals. In hippocampal slices from cocaine-exposed animals, synaptic responses in the CA1 region were characterized by multiple population spike activity and reduced inhibitory postsynaptic potentials. The reduction in fast inhibitory postsynaptic potential conductance was not associated with a change in reversal potential. These results suggest that gestational cocaine exposure induces significant changes in intrinsic and synaptic electrophysiological properties of hippocampal neurons in the developing animal. The cell and synaptic features are consistent with an increase in hippocampal excitability, which may contribute to the neurobehavioral deficits and epileptogenic predisposition reported in this infant population. As such, this in utero drug exposure model may provide a useful system in which to elucidate and study the basic cellular mechanisms underlying neurological complications associated with maternal cocaine abuse.


Nursing's professional respect as experienced by hospital and community nurses.
There is growing awareness that patient care suffers when nurses are not respected. Therefore, to improve outcomes for patients, it is crucial that nurses operate in a moral work environment that involves both recognition respect, a form of respect that ought to be accorded to every single person, and appraisal respect, a recognition of the relative and contingent value of respect modulated by the relationships of the healthcare professionals in a determined context. Research question/aim: The purpose of this study was to develop better understandings of perceptions of nursing's professional respect in community and hospital settings in England. The research design was qualitative. Focus groups were chosen as the most appropriate method for eliciting discussion about nursing's professional respect. Participants and research context: A total of 62 nurses who had been qualified for at least a year and were working in two localities in England participated in this study. Data were collected using 11 focus group sessions. The data were analysed by means of an inductive content analysis, extracting meaning units from the information retrieved and classifying the arising phenomena into conceptually meaningful categories and themes. Ethical considerations: To conduct the research, permission was obtained from the selected universities. Recognition respect of human beings was perceived as ingrained in the innermost part of nurses. Regarding appraisal respect, a great importance was placed on: the interactions among healthcare professionals, the time to build trust in these relationships, the influences of the workplace characteristics and nurses' professional autonomy and decision-making. Recognition respect of persons was embedded in the inmost part of nurses as individuals. Concerning appraisal respect, it was thought to be deeply enshrined in the inter- and intra-healthcare professional interactions. The forging of trusting relationships over time was deemed to be strongly associated with good quality interactions with other healthcare professionals.


Effect of height versus height/weight-based spinal bupivacaine on maternal hemodynamics for elective cesarean in short stature patients: a randomized clinical trial.
Doses of spinal bupivacaine adjusted to patient height or height/weight have been shown to provide hemodynamic stability during cesarean section. However, their effects in short stature parturients are unknown. In this double-blind, randomized clinical trial, we randomly assigned short parturients (height < 150 cm) undergoing elective cesarean section, to receive doses of intrathecal hyperbaric bupivacaine either height or height/weight-adjusted, in a 1:1 ratio. The primary outcome was post-spinal hypotension (defined as systolic blood pressure [SBP] < 90% of baseline between spinal administration and delivery of the baby). Secondary outcomes included severe post-spinal hypotension (SBP < 80% of baseline), post-delivery hypotension (SBP < 90% and < 80% of baseline), intraoperative bradycardia, nausea and vomiting, shivering, rescue analgesic needed, and spinal block characteristics. A total of 112 patients underwent randomization. Post-spinal hypotension (SBP < 90% of baseline) occurred in 52% of the patients in the height/weight group and in 55% in the height group (difference - 3.5%: 95% confidence interval [CI] - 22 to 14.8, P = 0.705). There was no significant difference between the two groups in the occurrences of post-spinal severe hypotension (SBP < 80% of baseline), post-delivery hypotension, and spinal block characteristics. Six patients (11%) in the height/weight group needed intraoperative rescue analgesic compared to none in the height group (P = 0.027). We found that height-based dosing in short parturients provides the optimal trade-off between intraoperative hemodynamic instability and provision of pain-free anesthesia. clinicaltrial.gov-NCT04082676. https://clinicaltrials.gov/ct2/show/NCT04082676 .


Examining the role of menthol cigarettes in progression to established smoking among youth.
Menthol, a flavoring compound added to cigarettes, makes cigarettes more appealing to youth and inexperienced smokers and increases cigarettes' abuse liability. However, limited studies are available on menthol's role in smoking progression. To assess the association between menthol in cigarettes and progression to established smoking, we used five waves of data from the Evaluation of Public Education Campaign on Teen Tobacco Cohort Study, a nationally representative longitudinal survey of U.S. youth conducted as part of "The Real Cost" evaluation. We used discrete time survival analysis to model the occurrence of two event outcomes-progression to established, current smoking and progression to established, frequent smoking-using a logit model with a menthol use indicator as the key explanatory variable. Based on this framework, we estimated the effect of prior menthol use on the odds of smoking progression. In the progression to established, current smoking model, prior menthol use was significantly associated with progression [adjusted odds ratio (aOR) = 1.80, p < .05, confidence interval (CI) = (1.03-3.16)]. While results were in a similar direction for the model of progression to established, frequent smoking, the association between prior menthol use and this progression model did not reach significance [aOR = 1.56, CI = (0.80-3.03)]. The results suggest a relationship between using menthol cigarettes and progression from experimental to established, current smoking among youth. This study adds to a growing literature base that supports that menthol cigarettes, compared to nonmenthol cigarettes, put youth at increased risk for regular cigarette use.


Steroidogenic inhibition in testicular tissue of formaldehyde exposed rats.
Three groups of rats (n = 10) were subjected to intraperitoneal treatment of formaldehyde daily at doses of 5, 10 and 15 mg/kg body weight over a period of 30 days. Gradual diminution in body and testicular weight was observed in all treated groups. Leyding cell impairement was conspicuous in those given doses of 10 and 15 mg/kg. Inhibition of 3 beta-delta 5-hydroxy steroid dehydrogenase and accumulation of sudanophillic materials in testicular tissue of formaldehyde treated rats was recorded histochemically. Significant decline of serum testosterone was also observed in the same groups. Structural and functional impairement of Leydig cells after formaldehyde treatment caused steroidogenic inhibition.


Detection of diverse new Francisella-like bacteria in environmental samples.
Following detection of putative Francisella species in aerosol samples from Houston, Texas, we surveyed soil and water samples from the area for the agent of tularemia, Francisella tularensis, and related species. The initial survey used 16S rRNA gene primers to detect Francisella species and related organisms by PCR amplification of DNA extracts from environmental samples. This analysis indicated that sequences related to Francisella were present in one water and seven soil samples. This is the first report of the detection of Francisella-related species in soil samples by DNA-based methods. Cloning and sequencing of PCR products indicated the presence of a wide variety of Francisella-related species. Sequences from two soil samples were 99.9% similar to previously reported sequences from F. tularensis isolates and may represent new subspecies. Additional analyses with primer sets developed for detection and differentiation of F. tularensis subspecies support the finding of very close relatives to known F. tularensis strains in some samples. While the pathogenicity of these organisms is unknown, they have the potential to be detected in F. tularensis-specific assays. Similarly, a potential new subspecies of Francisella philomiragia was identified. The majority of sequences obtained, while more similar to those of Francisella than to any other genus, were phylogenetically distinct from known species and formed several new clades potentially representing new species or genera. The results of this study revise our understanding of the diversity and distribution of Francisella and have implications for tularemia epidemiology and our ability to detect bioterrorist activities.


Nursing diagnoses from ICNP® for people with metabolic syndrome.
To construct nursing diagnosis statements based on the International Classification for Nursing Practice (ICNP®) for people with metabolic syndrome, settled on the theoretical framework of Basic Human Needs. Descriptive study developed in four stages: 1) Identification and validation of terms relevant to care with health priority; 2) Cross-mapping of the terms identified with ICNP® terms; 3) Construction of the nursing diagnosis statements; and 4) Cross-mapping of constructed statements with the ones in ICNP®. Regarding terms extracted, 370 were validated based on the consensus (100%) among specialists, subsidizing the elaboration of 52 nursing diagnosis statements from ICNP® version 2015, distributed among the Basic Human Needs proposed by theoretical framework. It was possible to construct nursing diagnoses for people with metabolic syndrome based on the terms extracted from the literature, with a predominance of the need for "Health education and learning".


Advent and course of pastoralism in the kalahari.
It has long been thought that farming and herding were comparatively recent introductions into the Kalahari and that it has been a preserve of foraging "Bushmen" for thousands of years. Agropastoral Bantu-speakers were thought to have entered this region only within the last two centuries. However, fully developed pastoralism and metallurgy are now shown to have been established in the Kalahari from A.D. 500, with extensive grain agriculture and intracontinental trade added by A.D. 800. Archeological, linguistic, and historical evidence delineates the continuation of mixed economies in the region into the present. Consequences of this revised view for anthropological theory and for policy planning concerning contemporary Kalahari peoples are indicated.


Effects of piperlonguminine on lung injury in severe acute pancreatitis via the TLR4/NF-κB pathway.
Acute pancreatitis is an inflammatory response in the pancreas, involving activation of pancreatic enzymes. Severe acute pancreatitis (SAP) often causes systemic complications that affect distant organs, including the lungs. The aim of this study was to explore the therapeutic potential of piperlonguminine on SAP-induced lung injury in rat models. Acute pancreatitis was induced in rats by repetitive injections with 4% sodium taurocholate. Histological examination and biochemical assays were used to assess the severity of lung injury, including tissue damage, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), reactive oxygen species (ROS), and inflammatory cytokines. We found that piperlonguminine significantly ameliorated pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening in rats with SAP. In addition, NOX2, NOX4, ROS, and inflammatory cytokine levels in pulmonary tissues were notably decreased in piperlonguminine-treated rats. Piperlonguminine also attenuated the expression levels of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB). Together, our findings demonstrate for the first time that piperlonguminine can ameliorate acute pancreatitis-induced lung injury via inhibitory modulation of inflammatory responses by suppression of the TLR4/NF-κB signaling pathway.


CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells.
Human mesenchymal stem cells (hMSCs) display immunosuppressive properties in vitro and the potential has also been transferred successfully to clinical trials for treatment of autoimmune diseases. OX-2 (CD200), a member of the immunoglobulin superfamily, is widely expressed in several tissues and has recently been found from hMSCs. The CD200 receptor (CD200R) occurs only in myeloid-lineage cells. The CD200-CD200R is involved in down-regulation of several immune cells, especially macrophages. The present study on 20 hMSC lines shows that the CD200 expression pattern varied from high (CD200Hi) to medium (CD200Me) and low (CD200Lo) in bone marrow-derived mesenchymal stem cell (BMMSC) lines, whereas umbilical cord blood derived mesenchymal stem cells (UCBMSCs) were constantly negative for CD200. The role of the CD200-CD200R axis in BMMSCs mediated immunosuppression was studied using THP-1 human macrophages. Interestingly, hMSCs showed greater inhibition of TNF-α secretion in co-cultures with IFN-γ primed THP-1 macrophages when compared to LPS activated cells. The ability of CD200Hi BMMSCs to suppress TNF-α secretion from IFN-γ stimulated THP-1 macrophages was significantly greater when compared to CD200Lo whereas UCBMSCs did not significantly reduce TNF-α secretion. The interference of CD200 binding to the CD200R by anti-CD200 antibody weakened the capability of BMMSCs to inhibit TNF-α secretion from IFN-γ activated THP-1 macrophages. This study clearly demonstrated that the efficiency of BMMSCs to suppress TNF-α secretion of THP-1 macrophages was dependent on the type of stimulus. Moreover, the CD200-CD200r axis could have a previously unidentified role in the BMMSC mediated immunosuppression.


A redox-active porous coordination network film based on a Ru complex as a building block on an ITO electrode.
The combination of self-assembled monolayer (SAM) and layer-by-layer (LbL) growth methods for the construction of a surface porous film has the potential to incorporate a wide range of chemical functionalities on a solid surface. A novel redox-active Ru complex with 2,6-bis(N-pyridylbenzimidazolyl)-pyridine ligands (Ru complex 1), in which four peripheral pyridine groups act as coordination sites, was used as a building block for a porous coordination network film. By using (4-pyridyl)phenylphosphonic acid as a SAM primer layer on an ITO surface, the Ru complex 1 was immobilized by the successive reaction of PdCl2 on the ITO electrode in the LbL growth method. Multilayer growth was monitored by UV-vis spectra and cyclic voltammetry, in which the linear increases of both absorbance and the peak current were observed. This result indicated that the regular accumulation of Ru complex 1 onto the ITO surface took place. The permselectivity of the present porous coordination network structure was examined using redox-active molecular probes with different sizes and charges such as ferrocene, trimethylaminomethylferrocene, the Os bis(2,6-bis(N-methylbenzimidazolyl)-pyridine) complex, and tetrathiofulvarene (TTF). With the Os complex and cationic ferrocene, only the catalytic peak was observed as a prewave of the adsorbed Ru(II/III) peak at +0.73 V. On the other hand, the oxidation peak of ferrocene was observed around 0 V vs. Fc(+)/Fc even for nine-layered films in addition to the adsorbed Ru(II/III) peak. From these results, not only molecular size but also electrostatic interaction plays an important role in the permeation into the Ru complex 1 porous network film.


Interstitial telomeric sites and NORs in Hartmann's zebra (Equus zebra hartmannae) chromosomes.
Interstitial telomeric sites (ITSs) are considered as signatures of chromosomal rearrangements that take place during karyotype evolution. Understanding that equids have undergone rapid karyotype evolution compared with the average in other mammals, a search of these signatures was carried out in the Hartmann's mountain zebra (Equus zebra hartmannae; EZH) chromosomes. Six consistent ITSs were identified on five of the zebra chromosomes (EZH1p, 1q, 2q, 5q, 6q and 11q). The location of these ITSs coincided with fusion points of some of the evolutionarily conserved human-Hartmann's zebra chromosomal segments suggesting that the sequences are remnants of fusion events between ancestral chromosomes. Incidentally, three of the ITSs also matched with the presence of constitutive heterochromatin. Further, ribosomal gene clusters were localized on five zebra chromosomes and the data were compared with those in other equid species. The findings offer preliminary evidence on the likely evolution of some of the Hartmann's zebra chromosomes and add to the current search for clues that lead to the ancestral chromosomal configuration in equids.


NH3 as unique non-classical content-former within clathrate hydrates.
High quality FTIR spectra of aerosols of NH3-THF and NH3-TMO binary clathrate hydrates (CHs) have been measured. Our recently developed all-vapor sub-second approach to clathrate-hydrate formation combined with computational studies has been used to identify vibrational spectroscopic signatures of NH3 within the gas hydrates. The present study shows that there are three distinct NH3 types, namely, classical small-cage NH3, nonclassical small-cage NH3, and NH3 within the hydrate network. The network ammonia does not directly trigger the non-classical CH structure. Rather, the ammonia within the network structure perturbs the water bonding, introducing orientational defects that are stabilized by small and/or large cage guest molecules through H-bonding. This unusual behavior of NH3 within CHs opens a possibility for catalytic action of NH3 during CH-formation. Furthermore, impacts over time of the small-cage NH3-replacement molecules CO2 and CH4 on the structure and composition of the ternary CHs have been noted.


Effect of enzymic methylation of heterogeneous ribonucleoprotein particle A1 on its nucleic-acid binding and controlled proteolysis.
Recombinant unmethylated heterogeneous nuclear ribonucleoprotein particle (hnRNP) protein A1 was enzymatically methylated by nuclear protein/histone protein methylase I [Rajpurohit, Lee, Park, Paik and Kim (1994) J. Biol. Chem. 269, 1057-1082] and the effect of methylation on several physiocochemical properties was studied. The relative binding-affinity of methylated and unmethylated protein A1 to nucleic acid was quite different. This was observed by the elution behaviour of the protein A1 on a single-stranded DNA/cellulose column; the concentration of NaCl required to release the bound protein A1 was 0.59 M for the methylated and 0.63 M for the unmethylated, respectively. Employing isoelectrofocusing, pI values of the methylated and unmethylated proteins were found to be 9.41 and 9.48, respectively. Maximum fluorescence quenching of protein A1 in the presence of coliphage MS2-RNA was found to be 40% with methylated and 45% with unmethylated. When both species of protein A1 were subjected to controlled trypsin digestion, t1/2 of the methylated protein was 1.31 min and the unmethylated, 1.63 min. The difference in their t1/2 values was much greater in the presence of MS2-RNA; 2.4 min for the former and 4.3 min for the latter, indicating that the methylated species was less stabilized by the RNA than the unmethylated. All of the above results consistently suggested that the binding-property of hnRNP protein A1 to single-stranded nucleic acid was significantly reduced subsequent to its arginine-methylation. The biological significance of this observation is discussed.


Contactless, photoinitiated snap-through in azobenzene-functionalized polymers.
Photomechanical effects in polymeric materials and composites transduce light into mechanical work. The ability to control the intensity, polarization, placement, and duration of light irradiation is a distinctive and potentially useful tool to tailor the location, magnitude, and directionality of photogenerated mechanical work. Unfortunately, the work generated from photoresponsive materials is often slow and yields very small power densities, which diminish their potential use in applications. Here, we investigate photoinitiated snap-through in bistable arches formed from samples composed of azobenzene-functionalized polymers (both amorphous polyimides and liquid crystal polymer networks) and report orders-of-magnitude enhancement in actuation rates (approaching 10(2) mm/s) and powers (as much as 1 kW/m(3)). The contactless, ultra-fast actuation is observed at irradiation intensities <<100 mW/cm(2). Due to the bistability and symmetry of the snap-through, reversible and bidirectional actuation is demonstrated. A model is developed to elucidate the underlying mechanics of the snap-through, specifically focusing on isolating the role of sample geometry, mechanical properties of the materials, and photomechanical strain. Using light to trigger contactless, ultrafast actuation in an otherwise passive structure is a potentially versatile tool to use in mechanical design at the micro-, meso-, and millimeter scales as actuators, as well as switches that can be triggered from large standoff distances, impulse generators for microvehicles, microfluidic valves and mixers in laboratory-on-chip devices, and adaptive optical elements.


OUTCOMES OF AN INTRAVITREAL INJECTION CLINIC.
To examine the safety outcomes of an intravitreal injection-only clinic where patients needing long-term anti-vascular endothelial growth factor therapy are treated with injections at a predetermined interval for a set number of injections without an accompanying clinic visit. This is a retrospective chart review of all patients with exudative macular degeneration treated in an intravitreal injection clinic over a 4-year period. Data on the outcome measures of interest were gathered from electronic medical records. There were 556 patients who received 4,386 injections in the injection-only clinic in a total of 1,524 injection cycles. One hundred six cycles were interrupted. The most common causes for interruption were decreased vision in the injected eye (32), decreased vision in the fellow eye (23), flashing lights (6), pain (5), and irritation in the noninjected eye (2). Of patients who had interruption of the cycle, 32 had a new diagnosis (6 corneal abrasions, 6 exudative age-related macular degeneration in fellow eye). There were six instances of conversion to exudative age-related macular degeneration found in the other eye at a routine follow-up visit following the injection clinic. An injection-only clinic may provide a reasonable approach to streamline retina practices to ensure that patients receive timely injections.


Molecular Detection of Fusion Oncogenes in Zambian Patients with Acute Lymphoblastic Leukemia.
Chromosomal aberrations play a significant role in the pathogenesis of acute lymphoblastic leukemia (ALL) with prognostic and therapeutic implications. Despite the availability of molecular tools, low-resource settings struggle to diagnose the disease due to limited diagnostic capacity. The objective of this study was to detect common chromosomal aberrations in patients with ALL attending the University Teaching Hospital (UTH) in Lusaka, Zambia. In this prospective study, 19 blood samples from patients with ALL were screened for the presence of BCR-ABL, E2A-PBX1, MLL-AF4, and ETV6-RUNX1 fusion oncogenes using reverse transcriptase-polymerase chain reaction assay. Blood counts and clinical characteristics of patients were also assessed. The age of patients ranged from 1½ to 72 years and comprised 57.9% of males and 42.1% of females. The majority of these patients were children (68%), and adults only comprised 32%. Only BCR-ABL and E2A-PBX1 oncogenes were detected in 3/19 of cases. The BCR-ABL gene was detected in a 4-year-old female child and a 15-year-old child. Both cases were associated with hepatomegaly and anemia coupled with low hemoglobin, white blood cell, and platelet counts. E2A-PBX1 was detected in a 12-year-old child with lymphadenopathy and splenomegaly, coupled with low hemoglobin, white blood cell, and platelet counts. All the three patients who harbored these fusion oncogenes died. This is the first study from Zambia to investigate the presence of fusion oncogenes in leukemia patients, which were found only among the older children population. Based on these findings, we recommend that molecular diagnosis be made a priority for the younger leukemia patient population at UTH.


Posterior fusion for an unstable axial fracture dislocation.
Management of avulsion fractures in the upper cervical spine remains the subject of debate. Currently, most experts favor nonoperative management of an isolated injury. However, these injuries can be complicated by soft-tissue trauma, which may require a different clinical approach to management. Accurate diagnosis of soft-tissue injuries depends on the choice of imaging modality and consideration of unique patient-specific factors. A morbidly obese 34-year-old woman was involved in a low-velocity motor vehicle collision that caused a forceful extension of the cervical spine. Initial computed tomographic imaging demonstrated a displaced avulsion fracture of the C2 body and widening of the C2-C3 facet. However, subsequent imaging using magnetic resonance demonstrated more extensive injuries. Because bracing was not feasible due to cervical instability, the injury was treated with posterior C2-4 fusion and bone grafting. Even in low-velocity collisions and limited injury on imaging, patient-specific factors should be considered in management decisions. Magnetic resonance imaging showed significant ligamentous compromise and marked cervical instability, revealing potential damage to vulnerable neural structures. Magnetic resonance imaging should be considered in the initial approach to any patient with these injuries.


Breastfeeding knowledge, breastfeeding confidence, and infant feeding plans: effects on actual feeding practices.
To explore relationships among breastfeeding knowledge, breastfeeding confidence, and infant feeding plans and their effects on feeding practices in first-time breastfeeding mothers. Prospective descriptive design. Telephone interviews were conducted prenatally and at 6 weeks, 3 months, and 6 months postpartum. Seventy-four of 83 first-time mothers with prenatal intentions to breastfeed completed all study requirements. The majority were White (95%), between the ages of 21 and 30 years (73%), with a post-high school education (85%), and household incomes of more than 200% of the federal poverty guideline (88%). Breastfeeding knowledge, breastfeeding confidence, planned infant feeding method, planned breastfeeding duration, weeks of daily human milk substitute feeding, breastfeeding duration, achievement of breastfeeding goals. Breastfeeding knowledge was strongly correlated with breastfeeding confidence (r = .262; p = .025) and actual lactation duration (r = .455; p = .0001). Compared with women planning to exclusively breastfeed their infants, those planning to combination feed planned shorter breastfeeding duration (p = .022), reported shorter actual duration (p = .004), and were less likely to meet their breastfeeding goal (p = .034). The variables maternal education, breastfeeding knowledge, and weeks of daily human milk substitute feeding were used to develop a prediction equation that correctly categorized 93% of participants who met their breastfeeding goal and 90% of those who did not. Expectations and the actual breastfeeding experience differed among women planning to combination feed and those planning to exclusively breastfeed. Whether a cause or consequence, daily human milk substitute feeding was associated with negative breastfeeding outcomes.


[Prevalence of cardiovascular and metabolic risk factors in school students, university students, and women from community-based organizations in the districts of Lima, Callao, la Libertad and Arequipa, Peru 2011].
To determine the prevalence of arterial hypertension, and cardiovascular and metabolic risk factors in school students, college students and women from community-based organizations (CBO) in four districts in Peru. Cross-sectional study conducted in 2011 in the districts of Lima, Callao, La Libertad and Arequipa with school students, university students and women from CBOs. A survey, anthropometric measurements, blood pressure measurements and fasting blood sampling were conducted to determine glucose and lipid levels. Thus, prevalence of overweight, hypertension, hypercholesterolemia, suspected diabetes, and other variables, were calculated. The main outcome variable was prevalence of overweight. 1,127 people were included: 283 (25.1%) school students, 431 (38.3%) university students, and 413 women (36.6%) from CBOs. Non-response rates were 3%, 0% and 8%, respectively. The average ages in the three groups were 14.3 ± 0.9; 19.6 ± 2.8; and 46.1 ± 15.3 years, respectively. Prevalence of overweight/obesity (BMI ≥ 25) was 11.3%, 20.9%, and 73.4%; hypertension was 0.7%; 1.2%, and 12.8%; high cholesterol (≥ 200 mg/dL) was 5.2%, 11.5%, and 50.1%; and suspected diabetes was 1.4%; 1.0%, and 20.3% respectively in each group of school students, university students and women from CBOs. The prevalence of cardiovascular and metabolic risk factors generally increased in older age groups. In school and university aged groups, the most frequent problems were overweight and obesity, particularly abdominal obesity.


Birthing, Nativity, and Maternal Depression: Australia and the United States.
This study analyzes two birth cohort surveys, the Longitudinal Study of Australian Children (n=3944) and Early Childhood Longitudinal Study (n=7700), to examine variation in maternal depression by nativity, duration of residence, age at migration, and English proficiency in Australia and the United States. Both countries have long immigrant traditions and a common language. The results demonstrate that US immigrant mothers are significantly less depressed than native-born mothers, but maternal depression does not differ by nativity in Australia. Moreover, the association between duration of residence and maternal depression is not linear: recent arrivals and long-term residents exhibit the highest depression levels. Lack of English proficiency exacerbates maternal depression in Australia, but protects against depression in the United States. Differences in immigration regimes and welfare systems likely contribute to the differing salience of nativity for maternal depression.


Enhanced glucose oxidation in exercise-induced myocardial ischemia.
In animal models, dichloroacetate (DCA) facilitates recovery from severe myocardial ischemia by stimulating glucose oxidation. To evaluate the acute efficacy of DCA as a metabolic anti-ischemic intervention in patients with coronary artery disease (CAD) and exercise-induced myocardial ischemia in a clinical trial. Double-blind, randomized, crossover comparison of single dose (50 mg/kg intravenously) DCA versus placebo on clinical and electrocardiographic variables in seven patients with single vessel CAD and 34 patients with multiple vessel CAD during standard dynamic exercise testing. Blood pressure did not differ with placebo or DCA but mean heart rate was higher with DCA at rest (62 versus 59, P < 0.004) and at 5 mins of recovery (78 versus 75, P < 0.02). Exercise duration averaged 538 s with DCA and 534 s with placebo (not significant). Chest pain occurred in 14 patients in both tests, clinical ST depression occurred, in 34 placebo tests and 37 DCA tests (not significant). Body surface potential maps (BSPM) of the decrease in the area under the ST curve from rest to peak exercise averaged -5096 microV's with DCA and -5159 microV's with placebo (not significant). BSPM at 1 and 5 mins postexercise also showed no differences in rate of ST integral recovery. In the transient regional model of human myocardial ischemia induced by dynamic exercise, the acute administration of the pyruvate dehydrogenase agonist DCA was not associated with clinical or electrocardiographic moderation of, nor accelerated recovery from, ischemia. Whether DCA or metabolically similar agents that enhance oxidative metabolism are beneficial in other ischemic settings, such as the no-flow states of acute ST elevation myocardial infarction or angioplasty, requires further systematic evaluation.


Plasma amino acid turnover rates and pools in rabbits: in vivo studies using stable isotopes.
Gas chromatography--mass spectrometry of plasma amino acids has been used to determine the 15N enrichments of plasma glycine and alanine in rabbits in different metabolic states. Isotope-enrichment time-decay curves of plasma amino acids were linear over the course of the measurements after intravenous administration of a single dose of 15N-amino acid. Glycine and alanine pools and turnover rate constants were estimated from decay data. The effects of diurnal variation and fasting on glycine and alanine pool sizes, turnover rates, and flux in rabbits were studied to provide information on the effect of metabolic stress on amino acid kinetics in the whole body. The observations suggests that the transport of systemic glycine or alanine into the hepatocyte is under the control of a regulatory mechanism that compensates for decrease in the extracellular levels of the amino acids by enhancing the activity of the transport system. The volumes of the glycine and alanine pools were found to correspond to the extracellular space of rabbits, and the glycine and alanine pools can be identified as extracellular. We conclude that the plasma glycine and alanine 15N isotope-enrichment time-decay curves over the 1st h after a single intravenous dose of the amino acid represent mainly the hepatic uptake of glycine and alanine from the extracellular pool.


[Hemodynamic and rheologic aspects of the pathogenesis and prevention of cerebrovascular diseases].
Ultrasonography was used to study carotid and central hemodynamics in patients with cerebrovascular diseases and to analyze the factors responsible for reduction of cerebral blood supply. Comparative studies of the regulatory system for blood aggregation in patients elucidated the contribution of the system to the pathogenesis of cerebral hemorrhage and ischemia, defined the modes of preventing hemorrhagic and ischemic events in cerebrovascular diseases. The authors also discussed pathogenetic and prophylactic aspects of the diseases in childhood.


Intermediate frequency band digitized high dynamic range radiometer system for plasma diagnostics and real-time Tokamak control.
An intermediate frequency (IF) band digitizing radiometer system in the 100-200 GHz frequency range has been developed for Tokamak diagnostics and control, and other fields of research which require a high flexibility in frequency resolution combined with a large bandwidth and the retrieval of the full wave information of the mm-wave signals under investigation. The system is based on directly digitizing the IF band after down conversion. The enabling technology consists of a fast multi-giga sample analog to digital converter that has recently become available. Field programmable gate arrays (FPGA) are implemented to accomplish versatile real-time data analysis. A prototype system has been developed and tested and its performance has been compared with conventional electron cyclotron emission (ECE) spectrometer systems. On the TEXTOR Tokamak a proof of principle shows that ECE, together with high power injected and scattered radiation, becomes amenable to measurement by this device. In particular, its capability to measure the phase of coherent signals in the spectrum offers important advantages in diagnostics and control. One case developed in detail employs the FPGA in real-time fast Fourier transform (FFT) and additional signal processing. The major benefit of such a FFT-based system is the real-time trade-off that can be made between frequency and time resolution. For ECE diagnostics this corresponds to a flexible spatial resolution in the plasma, with potential application in smart sensing of plasma instabilities such as the neoclassical tearing mode (NTM) and sawtooth instabilities. The flexible resolution would allow for the measurement of the full mode content of plasma instabilities contained within the system bandwidth.


Natural resistance to tumors is a heterogeneous immunological phenomenon. Evidence for non-NK cell mechanisms.
The contribution of natural killer (NK) cells to natural antitumor resistance (NR) in syngeneic DBA/2 mice was examined. Subclones from two NK-resistant tumors, P815 and L5178Y, were selected for tumorigenicity in NR assays measuring the tumor frequency of threshold doses and the elimination of 131IUdR-labelled cells. In vivo variation in sensitivity to NR did not correlate with in vitro NK cytolysis for these clones, but did for a third pair of clones from the SL2 lymphoma selected on the basis of sensitivity or resistance to NK lysis. In another series of experiments it was found that a decrease in NK cytolysis of the (NK-sensitive) SL2-5 lymphoma in aged DBA/2 contrasted with an increased rate of elimination and lower tumor frequency, suggesting that the ontogeny of these phenomena was not related. In addition, while interferon treatment of the (NK-sensitive) SL2-5 produced a corresponding decrease in susceptibility to NK cytolysis in vitro and a reduction in the in vivo elimination of 131I-labelled cells, tumor of the NK-resistant phenotype, interferon-treated in the same way, remained NK-resistant and was more rapidly eliminated. The failure to observe correlative changes in NK cytolysis associated with heterogeneity in tumorigenicity and with age-related or interferon-induced changes in NR suggest that NR cannot be due solely to an NK effector mechanism.


Functional heterogeneity within neurotransmitter systems.
This paper reviews experiments that have revealed distinct differences between the dorsal and median raphe nuclei in the rat midbrain. The raphe nuclei appear to be hetrogeneous with respect to their anatomical projections to the forebrain, their relevance to specific behaviors, and their pharmacological responses. Startle response measures are useful indicators of the functional state of serotonergic system originating in the median raphe. As a way to study individual cells within the various raphe nuclei, microspectroflurimetric techniques are promising.


Trabulsiella odontotermitis sp. nov., isolated from the gut of the termite Odontotermes formosanus Shiraki.
Bacterial strains Eant 3-9(T) and Eant 3-3, isolated from the gut of the termite Odontotermes formosanus, were characterized using a polyphasic taxonomic approach. Cells of these organisms were Gram-negative, non-pigmented, rod-shaped, non-endospore-forming and facultatively anaerobic. Phenotypic, physiological and genetic characteristics of the two strains were highly similar. Phylogenetic analyses using 16S rRNA gene sequences showed that strain Eant 3-9(T) formed a monophyletic branch towards the periphery of the evolutionary radiation occupied by the genus Trabulsiella; its closest neighbour was Trabulsiella guamensis DSM 16940(T) (98.1 % similarity). Genomic DNA-DNA relatedness between strains Eant 3-9(T) and Eant 3-3 was 96+/-4 %, indicating that they belong to a single species. Eant 3-9(T) displayed DNA-DNA relatedness values of 48+/-5 and 14+/-3 % with T. guamensis DSM 16940(T) and Salmonella typhimurium ATCC 13311(T), respectively, indicating that Eant 3-9(T) warrants novel species status in the genus Trabulsiella. Eant 3-9(T) and Eant 3-3 could be further distinguished from T. guamensis DSM 16940(T) using whole-cell protein profiles and a range of physiological and biochemical characteristics. It is evident from genotypic and phenotypic data that Eant 3-9(T) represents a novel species in the genus Trabulsiella, for which the name Trabulsiella odontotermitis sp. nov. is proposed. The type strain is Eant 3-9(T) (=BCRC 17577(T)=LMG 23580(T)); Eant 3-3 is a reference strain.


A Rare Presentation of an Entrapment in a Liver Transplant Candidate Depicted by MDCT Angiography.
Hypertrophic caudate lobe veins can mimic a normal venous configuration. In cases of multiple vascular collaterals, Doppler evaluations must be conducted, and the flow direction of these veins as well as the IVC should be evaluated. If the flow in the IVC is reversed, Budd-Chiari syndrome should be suspected; moreover, at the supra diaphragmatic level, which may be considered a blind spot, particularly for radiologists, a web should be searched for in the area where the IVC opens into the right atrium. In this study, we present the unique findings of multidetector computed tomography (MDCT) angiography for a liver transplant candidate with Budd-Chiari syndrome caused by a web in the proximal IVC.


Unlocking policy synergies, challenges and contradictions influencing implementation of the Comprehensive Sexuality Education Framework in Zambia: a policy analysis.
Comprehensive sexuality education (CSE) has recently become salient, but adolescent sexual reproductive health and rights (ASRHR) challenges are still a global health problem. Studying policies which have implications for CSE implementation is a crucial but neglected issue, especially in low and middle-income countries (LMICs) like Zambia. We analyzed policy synergies, challenges and contradictions influencing implementation of CSE framework in Zambia. We conducted a document review and qualitative interviews with key stakeholders from Non-Governmental Organizations, as well as health and education ministries at the National and all (10) provincial headquarters. Our methods allowed us to capture valuable insights into the synergies, challenges and contradictions that exist in promoting CSE framework in Zambia. The study highlighted the synergies between policies that create opportunities for implementation of CSE through the policy window for adoption of sexual reproductive health and rights (SRHR) that opened around the 1990s in Zambia, promotion of inclusive development via education, adoption of an integrated approach in dealing with SRHR problems, and criminalization of gender-based violence (GBV). This analysis also identified the policy challenges and contradictions including restricted delivery of education on contraception in schools; defining childhood: dual legal controversies and implications for children, grey zones on the minimum age to access SRHR services; inadequate disability inclusiveness in SRHR legal frameworks; policy silences/contentious topics: LGBTQI + rights, abortion, and grey zones on the minimum age to access SRHR services. While many policies support the implementation of CSE in schools, the existence of policy silences and challenges are among the barriers affecting CSE implementation. Thus, policy reformulation is required to address policy silences and challenges to enhance effective promotion and integration of the CSE framework.


Cocaine-responsive gene expression changes in rat hippocampus.
Chronic cocaine use is known to elicit changes in the pattern of gene expression within the brain. The hippocampus plays a critical role in learning and memory and may also play a role in mediating behaviors associated with cocaine abuse. To profile the gene expression response of the hippocampus to chronic cocaine treatment, cDNA hybridization arrays were used to illuminate cocaine-regulated genes in rats treated non-contingently with a binge model of cocaine (45 mg/kg/day, i.p.) for 14 days. Validation of mRNA changes illuminated by hybridization array analysis was accomplished by measuring immunoreactive protein (via specific immunoblots). The induction of protein kinase Calpha, potassium channel 1.1, and metabotropic glutamate receptor 5 seen by hybridization arrays was confirmed at the level of protein. Immunoblot screening of previously described cocaine-responsive genes demonstrated increased levels of protein tyrosine kinase 2, beta-catenin, and protein kinase Cepsilon. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. The inductions of potassium channel 1.1, protein tyrosine kinase 2 and metabotropic glutamate receptor 5 are novel findings to hippocampal cocaine-responsive gene expression. These proteins have been shown to subserve learning and memory and/or long-term potentiation functions within the hippocampus. Additionally, these genes are known to interact with one another, forming a more complex pattern of gene expression changes. The findings suggest altered expression of genes with a number of different functions in the rat hippocampus after a 'binge' style of non-contingent cocaine administration. These changes in gene expression may play roles in neuronal plasticity and the behavioral phenomena associated with cocaine abuse.


Autoradiographic imaging and quantification of the high-affinity GHB binding sites in rodent brain using 3H-HOCPCA.
GHB (γ-hydroxybutyric acid) is a compound endogenous to mammalian brain with high structural resemblance to GABA. GHB possesses nanomolar-micromolar affinity for a unique population of binding sites, but the exact nature of these remains elusive. In this study we utilized the highly selective GHB analogue, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) as a tritiated version (3H-HOCPCA) to radioactively label the specific GHB high-affinity binding site and gain further insight into the density, distribution and developmental profile of this protein. We show that, in low nanomolar concentrations, 3H-HOCPCA displays excellent signal-to-noise ratios using rodent brain autoradiography, which makes it a valuable ligand for anatomical quantification of native GHB binding site levels. Our data confirmed that 3H-HOCPCA labels only the high-affinity specific GHB binding site, found in high density in cortical and hippocampal regions. The experiments revealed markedly stronger binding at pH 6.0 (Kd 73.8 nM) compared to pH 7.4 (Kd 2312 nM), as previously reported for other GHB radioligands but similar Bmax values. Using 3H-HOCPCA we analyzed the GHB binding protein profile during mouse brain development. Due to the high sensitivity of this radioligand, we were able to detect low levels of specific binding already at E15 in mouse brain, which increased progressively until adulthood. Collectively, we show that 3H-HOCPCA is a highly sensitive radioligand, offering advantages over the commonly used radioligand 3H-NCS-382, and thus a very suitable in vitro tool for qualitative and quantitative autoradiography of the GHB high-affinity site.


Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.
Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs). However, whether FXR is also involved in the maintenance of cell survival of MCDs under dehydration condition and hypertonic stress remains largely unknown. In the present study, we demonstrate that 24-hours water restriction selectively up-regulated renal medullary expression of FXR with little MCD apoptosis in wild-type mice. In contrast, water deprivation caused a massive apoptosis of MCDs in both global FXR gene-deficient mice and collecting duct-specific FXR knockout mice. In vitro studies showed that hypertonicity significantly increased FXR and tonicity response enhancer binding protein (TonEBP) expression in mIMCD3 cell line and primary cultured MCDs. Activation and overexpression of FXR markedly increased cell viability and decreased cell apoptosis under hyperosmotic conditions. In addition, FXR can increase gene expression and nuclear translocation of TonEBP. We conclude that FXR protects MCDs from hypertonicity-induced cell injury very likely via increasing TonEBP expression and nuclear translocation. This study provides insights into the molecular mechanism by which FXR enhances urine concentration via maintaining cell viability of MCDs under hyperosmotic condition.


Strategies to reduce dendritic cell activation through functional biomaterial design.
Dendritic cells play a key role in determining adaptive immunity, and there is growing interest in characterizing and manipulating the interactions between dendritic cells and biomaterial surfaces. Contact with several common biomaterials can induce the maturation of immature dendritic cells, but substrates that reduce dendritic cell maturation are of particular interest within the field of cell-based therapeutics where the goal is to reduce the immune response to cell-laden material carriers. In this study, we use a materials-based strategy to functionalize poly(ethylene glycol) hydrogels with immobilized immunosuppressive factors (TGF-β1 and IL-10) to reduce the maturation of immature dendritic cells. TGF-β1 and IL-10 are commonly employed as soluble factors to program dendritic cells in vitro, and we demonstrate that these proteins retain bioactivity towards dendritic cells when immobilized on hydrogel surfaces. Following stimulation with lipopolysaccharide (LPS) and/or cytokines, a dendritic cell line interacting with the surfaces of immunosuppressive hydrogels expressed reduced markers of maturation, including IL-12 and MHCII. The bioactivity of these immunomodulatory hydrogels was further confirmed with primary bone marrow-derived dendritic cells (BMDCs) isolated from non-obese diabetic (NOD) mice, as quantified by a decrease in activation markers and a significantly reduced capacity to activate T cells. Furthermore, by introducing a second signal to promote BMDC-material interactions combined with the presentation of tolerizing signals, the multifunctional PEG hydrogels were found to further increase signaling towards BMDCs, as evidenced by greater reductions in maturation markers.


Optimal-Flow Minimum-Cost Correspondence Assignment in Particle Flow Tracking.
A diversity of tracking problems exists in which cohorts of densely packed particles move in an organized fashion, however the stability of individual particles within the cohort is low. Moreover, the flows of cohorts can regionally overlap. Together, these conditions yield a complex tracking scenario that can not be addressed by optical flow techniques that assume piecewise coherent flows, or by multiparticle tracking techniques that suffer from the local ambiguity in particle assignment. Here, we propose a graph-based assignment of particles in three consecutive frames to recover from image sequences the instantaneous organized motion of groups of particles, i.e. flows. The algorithm makes no a priori assumptions on the fraction of particles participating in organized movement, as this number continuously alters with the evolution of the flow fields in time. Graph-based assignment methods generally maximize the number of acceptable particles assignments between consecutive frames and only then minimize the association cost. In dense and unstable particle flow fields this approach produces many false positives. The here proposed approach avoids this via solution of a multi-objective optimization problem in which the number of assignments is maximized while their total association cost is minimized at the same time. The method is validated on standard benchmark data for particle tracking. In addition, we demonstrate its application to live cell microscopy where several large molecular populations with different behaviors are tracked.


Children and Wild Foods in the Context of Deforestation in Rural Malawi.
There is growing recognition of the contribution of wild foods to local diets, nutrition, and culture. Yet disaggregation of understanding of wild food use by gender and age is limited. We used a mixed methods approach to determine the types, frequencies, and perceptions of wild foods used and sold by children in four villages in southern Malawi that have different levels of deforestation. Household and individual dietary diversity scores are low at all sites. All households consume one or more wild foods. Across the four sites, children listed 119 wild foods, with a wider variety at the least deforested sites than the most deforested ones. Older children can name more wild foods than younger ones. More children from poor households sell wild foods than from well-off households. Several reasons were provided for the consumption or avoidance of wild foods (most commonly taste, contribution to health, limited alternatives, hunger, availability, local taboos).


The relationship between perfectionism, self-perception of orofacial appearance, and mental health in college students.
In dental clinical practice, self-perception of orofacial appearance is highly correlated with treatment satisfaction. Therefore, it is important to explore factors correlated with self-perception of orofacial appearance. Perfectionism may be one such factor. This study investigated the role of perfectionism in self-perception of orofacial appearance. Participants completed an online questionnaire that included demographic data, a measure of perfectionism, a measure of self-perception of orofacial appearance (including body image, smile appearance concern, and self-esteem), and a measure of anxiety and depression. High perfectionism scores significantly predicted greater age, body image, smile appearance concern, and mental health scores and lower self-esteem scores (p < 0.005). After adjusting for possible confounding variables, smile appearance concern largely disappeared. Mental health acted as a mediator in the relationships between perfectionism and three orofacial appearance characteristics. High perfectionism predicted higher self-perception of body image, and lower mental health and self-esteem in college students. Mental health could mediate the relationships between perfectionism and self-perception of orofacial appearance.


The Yale-Brown Obsessive Compulsive Scale. II. Validity.
The development design and reliability of the Yale-Brown Obsessive Compulsive Scale have been described elsewhere. We focused on the validity of the Yale-Brown Scale and its sensitivity to change. Convergent and discriminant validity were examined in baseline ratings from three cohorts of patients with obsessive-compulsive disorder (N = 81). The total Yale-Brown Scale score was significantly correlated with two of three independent measures of obsessive-compulsive disorder and weakly correlated with measures of depression and of anxiety in patients with obsessive-compulsive disorder with minimal secondary depressive symptoms. Results from a previously reported placebo-controlled trial of fluvoxamine in 42 patients with obsessive-compulsive disorder showed that the Yale-Brown Scale was sensitive to drug-induced changes and that reductions in Yale-Brown Scale scores specifically reflected improvement in obsessive-compulsive disorder symptoms. Together, these studies indicate that the 10-item Yale-Brown Scale is a reliable and valid instrument for assessing obsessive-compulsive disorder symptom severity and that it is suitable as an outcome measure in drug trials of obsessive-compulsive disorder.


A constitutively expressed antifungal peptide protects Tenebrio molitor during a natural infection by the entomopathogenic fungus Beauveria bassiana.
Antimicrobial peptides have been well studied in the context of bacterial infections. Antifungal peptides have received comparatively less attention. Fungal pathogens of insects and their hosts represent a unique opportunity to study host-pathogen interactions due to the million of years of co-evolution they share. In this study, we investigated role of a constitutively expressed thaumatin-like peptide with antifungal activity expressed by the mealworm beetle Tenebrio molitor, named Tenecin 3, during a natural infection with the entomopathogenic fungus Beauveria bassiana. We monitored the effect of the expression of Tenecin 3 on the survival of infected hosts as well as on the progression of the fungal infection inside the host. Finally, we tested the activity of Tenecin 3 against B. bassiana. These findings could help improving biocontrol strategies and help understanding the evolution of antifungal peptides as a defense mechanism.


Atypical case of hemiconvulsions-hemiplegia-epilepsy syndrome revealing contralateral focal cortical dysplasia.
Hemiconvulsions-hemiplegia-epilepsy syndrome (HH/HHE) is a rare epileptic syndrome consisting of a prolonged unilateral convulsion producing a persisting hemiplegia, sometimes followed by epilepsy. We report on a 13-month-old male who presented with febrile left-sided HH syndrome with right hemispheric unilateral cytotoxic oedema followed by hemispheric atrophy on magnetic resonance imaging (MRI). Six months later the child progressively developed refractory focal epilepsy, including right hemiclonic seizures, and nearly continuous left frontal rhythmic spikes, suggesting the presence of a focal cortical dysplasia (FCD). A repeat MRI at 2 years of age showed left frontal FCD. This unusual case of dual pathology--right HH syndrome and left FCD--suggests that some other factor than the malformation determined the prolonged status and brain atrophy. The kinetics of regional cortical maturation could explain this unusual condition.


HTLV-I infection among prostitutes and pregnant women in Kinshasa, Zaïre: how important is high-risk sexual behavior?
High-risk sexual behavior as risk factor for human T-cell lymphotropic virus type I (HTLV-I) infection was assessed in cross-sectional studies with 1,183 prostitutes and 1,166 pregnant women in Kinshasa, Zaire. Eighty six (7.3%) prostitutes were positive for HTLV-I. The seroprevalence among prostitutes from the regions along the equator was 12.7%, whereas among prostitutes from the other regions it ranged between 0 and 4.3%. In the prostitutes from the high-prevalence regions, but not in the prostitutes from the low-prevalence regions, HTLV-I infection was associated with increasing age [odds ratio (OR) = 1.1 per year increment], active syphilis (OR = 2.3), and human immunodeficiency virus (HIV) infection (OR = 2.0). Forty three (3.7%) pregnant women were HTLV-I seropositive. Among the women from low-prevalence regions, there was no significant difference in HTLV-I seroprevalence between prostitutes (4.3%) and pregnant women (3.5%). In a group of 409 prostitutes who were observed for a mean duration of 23 months, the incidence of HTLV-I infection was 0.7 per 100 women-years, whereas the incidence of HIV infection was 9.8 per 100 women-years. We conclude that in Kinshasa prostitution per se was not associated with an increased risk of HTLV-I infection.


High prevalence of Plasmodium malariae and Plasmodium ovale in co-infections with Plasmodium falciparum in asymptomatic malaria parasite carriers in southwestern Nigeria.
Asymptomatic malaria parasite carriers do not seek anti-malarial treatment and may constitute a silent infectious reservoir. In order to assess the level of asymptomatic and symptomatic carriage amongst adolescents in a highly endemic area, and to identify the risk factors associated with such carriage, we conducted a cross-sectional survey of 1032 adolescents (ages 10-19 years) from eight schools located in Ibadan, southwestern Nigeria in 2016. Blood films and blood spot filter paper samples were prepared for microscopy and DNA analysis. The prevalence of asymptomatic malaria was determined using microscopy, rapid diagnostic tests and PCR for 658 randomly selected samples. Of these, we found that 80% of asymptomatic schoolchildren were positive for malaria parasites by PCR, compared with 47% and 9%, determined by rapid diagnostic tests and microscopy, respectively. Malaria parasite species typing was performed using PCR targeting the mitochondrial CoxIII gene, and revealed high rates of carriage of Plasmodium malariae (53%) and Plasmodium ovale (24%). Most asymptomatic infections were co-infections of two or more species (62%), with Plasmodium falciparum + P. malariae the most common (35%), followed by P. falciparum + P. malariae + P. ovale (21%) and P. falciparum + P. ovale (6%). Single infections of P. falciparum, P. malariae and P. ovale accounted for 24%, 10% and 4% of all asymptomatic infections, respectively. To compare the species composition of asymptomatic and symptomatic infections, further sample collection was carried out in 2017 at one of the previously sampled schools, and at a nearby hospital. Whilst the species composition of the asymptomatic infections was similar to that observed in 2016, the symptomatic infections were markedly different, with single infections of P. falciparum observed in 91% of patients, P. falciparum + P. malariae in 5% and P. falciparum + P. ovale in 4%.


Calcium-activated conductance in skate electroreceptors: voltage clamp experiments.
Voltage clamp experiments allow further characterization of the calcium-dependent repolarizing process in skate electroreceptor epithelium. Four current components are described: a prolonged capacity current, a leakage current, an early active current which flows inward across the lumenal membranes of the receptor cells, and a late current which flows outward. The leakage and capacity currents are linear and may be substracted from the total current, giving net active currents. The early active current is carried by calcium and does not undergo inactivation for at least several seconds. When large stimuli exceed the reversal potential for the early calcium current, the late current is suppressed. Reduction of the ionized calcium concentration in the lumen lowers the reversal potential for the early current and the suppression potential for the late current by the same amount. We conclude that the late current is initiated by a calcium influx into the cytoplasm. During pulses of moderate duration, activation of the late current does not begin until a fixed amount of calcium has entered the receptor cells. The required amount of calcium is reduced if a recent calcium influx has occurred. We suggest that the calcium-activated outward current is mediated by a distinct macromolecule that is insensitive to voltage. Such macromolecules are likely to have an important role in the regulation of electrical activity in excitable cells.


Somatic expansion in mouse and human carriers of fragile X premutation alleles.
Repeat expansion diseases result from expansion of a specific tandem repeat. The three fragile X-related disorders (FXDs) arise from germline expansions of a CGG•CCG repeat tract in the 5' UTR (untranslated region) of the fragile X mental retardation 1 (FMR1) gene. We show here that in addition to germline expansion, expansion also occurs in the somatic cells of both mice and humans carriers of premutation alleles. Expansion in mice primarily affects brain, testis, and liver with very little expansion in heart or blood. Our data would be consistent with a simple two-factor model for the organ specificity. Somatic expansion in humans may contribute to the mosaicism often seen in individuals with one of the FXDs. Because expansion risk and disease severity are related to repeat number, somatic expansion may exacerbate disease severity and contribute to the age-related increased risk of expansion seen on paternal transmission in humans. As little somatic expansion occurs in murine lymphocytes, our data also raise the possibility that there may be discordance in humans between repeat numbers measured in blood and that present in brain. This could explain, at least in part, the variable penetrance seen in some of these disorders.


Remifentanil maintains lower initial delayed nonmatching-to-sample accuracy compared to food pellets in male rhesus monkeys.
Emerging human laboratory and preclinical drug self-administration data suggest that a history of contingent abused drug exposure impairs performance in operant discrimination procedures, such as delayed nonmatching-to-sample (DNMTS), that are hypothesized to assess components of executive function. However, these preclinical discrimination studies have exclusively used food as the reinforcer and the effects of drugs as reinforcers in these operant procedures are unknown. The present study determined effects of contingent intravenous remifentanil injections on DNMTS performance hypothesized to assess 1 aspect of executive function, working memory. Daily behavioral sessions consisted of 2 components with sequential intravenous remifentanil (0, 0.01-1.0 μg/kg/injection) or food (0, 1-10 pellets) availability in nonopioid dependent male rhesus monkeys (n = 3). Remifentanil functioned as a reinforcer in the DNMTS procedure. Similar delay-dependent DNMTS accuracy was observed under both remifentanil- and food-maintained components, such that higher accuracies were maintained at shorter (0.1-1.0 s) delays and lower accuracies approaching chance performance were maintained at longer (10-32 s) delays. Remifentanil maintained significantly lower initial DNMTS accuracy compared to food. Reinforcer magnitude was not an important determinant of DNMTS accuracy for either remifentanil or food. These results extend the range of experimental procedures under which drugs function as reinforcers. Furthermore, the selective remifentanil-induced decrease in initial DNMTS accuracy is consistent with a selective impairment of attentional, but not memorial, processes. (PsycINFO Database Record


Various musculoskeletal manifestations of chronic renal insufficiency.
Musculoskeletal manifestations in chronic renal insufficiency are caused by complex bone metabolism alterations, now described under the umbrella term of chronic kidney disease mineral- and bone-related disorder (CKD-MBD), as well as iatrogenic processes related to renal replacement treatment. Radiological imaging remains the mainstay of disease assessment. This review aims to illustrate the radiological features of CKD-MBD, such as secondary hyperparathyroidism, osteomalacia, adynamic bone disease, soft-tissue calcifications; as well as features associated with renal replacement therapy, such as aluminium toxicity, secondary amyloidosis, destructive spondyloarthropathy, haemodialysis-related erosive arthropathy, tendon rupture, osteonecrosis, and infection.


Increased susceptibility to the epileptic effects of alcohol withdrawal following periodic electroconvulsive shocks.
There was a progressive intensification (kindling) of the motor seizure pattern when electroconvulsive shocks (ECSs) were administered to rats at 3-day intervals, but not when the inter-ECS interval was 1 hr. Similarly, the incidence of convulsive symptoms elicited by subsequent alcohol exposure and withdrawal was a function of the number of antecedent ECSs administered at 3-day, but not at 1-hr, intervals. Significant ECS-produced intensification of the alcohol withdrawal syndrome persisted for 3 weeks following ten periodic ECSs and occurred even when the motor seizures elicited by the antecedent ECSs were pharmacologically suppressed.


Diversity of cultivable protease-producing bacteria and their extracellular proteases associated to scleractinian corals.
Protease-producing bacteria play a vital role in degrading organic nitrogen in marine environments. However, the diversity of the bacteria and extracellular proteases has seldom been addressed, especially in communities of coral reefs. In this study, 136 extracellular protease-producing bacterial strains were isolated from seven genera of scleractinian corals from Luhuitou fringing reef, and their protease types were characterized. The massive coral had more cultivable protease-producing bacteria than branching or foliose corals. The abundance of cultivable protease-producing bacteria reached 106 CFU g-1 of coral. Phylogenetic analysis of 16S rRNA gene sequences revealed that the isolates were assigned to 24 genera, from which 20 corresponded to the phyla Firmicutes and Proteobacteria. Bacillus and Fictibacillus were retrieved from all coral samples. Moreover, Vibrio and Pseudovibrio were most prevalent in massive or foliose coral Platygyra and Montipora. In contrast, 11 genera were each identified in only one isolate. Nearly all the extracellular proteases from the bacteria were serine proteases or metalloproteases; 45.83% of isolates also released cysteine or aspartic proteases. These proteases had different hydrolytic ability against different substrates. This study represents a novel insight on the diversity of cultivable protease-producing bacteria and their extracellular proteases in scleractinian corals.


Histogenesis of exocrine pancreatic cancer in the hamster model.
There is strong evidence that induced pancreatic adenomas and carcinomas derive from ductal and ductular cells in the pancreas. We base our beliefs on our knowledge of the embryology and histology of the pancreas in Syrian golden hamsters, along with the sequential alterations that occur during exocrine pancreatic tumor formation. This concept also has been supported by much experimental evidence, including autoradiographic, immunologic and in vitro studies. We also present other viewpoints on the origin of pancreatic cancer histogenesis and outline certain areas of disagreement. We report the development of acinar cell lesions under certain experimental dietary conditions in hamsters (the lesions resemble those commonly seen in the rat pancreatic tumor model) and the nature of these lesions.


Somatization reconsidered: incorporating the patient's experience of illness.
The large and heterogeneous group of patients with "unexplained somatic symptoms," with or without coexisting psychiatric, "functional," or "organic" illnesses, provides continuing difficulty for clinicians. The construct of somatization artificially separates bodily and psychological symptoms that patients experience as a unified whole. Concurrent chronic illnesses make it difficult to exclude "general medical conditions." The diagnosis requires that the patient seek medical care. Conflict between patients' experiences of illness and physicians' diagnostic categories, and fear of blaming the patient, complicate naming and characterizing the illness. We recommend an approach to clinical care that involves exploring the patient's life context, finding mutually meaningful language to arrive at a name for the illness, normalizing the patient's bodily experience of distress, using a chronic disease model that attends to functioning, and addressing the physician's need for certainty and efficacy. Health systems can help coordinate care and avoid iatrogenic harm by appropriately controlling access to medical services.


Basic Cardiac Life Support: 2011 Singapore guidelines.
The core skills required in resuscitation of cardiac arrest individuals is referred to as Basic Cardiac Life Support or cardiopulmonary resuscitation (CPR). Once cardiac arrest (an unresponsive patient with no breathing or only gasping motions) is recognised, chest compressions should be initiated. Healthcare workers may choose to also check for a pulse to verify cardiac arrest if they are trained. The time taken for breathing check (and pulse check) should not exceed ten seconds. Good quality chest compressions are recommended with each being delivered with arms extended, elbows locked, shoulders vertically above the patient's chest and the heel of the palm on the lower half of the sternum. The rescuer should push hard and fast, with a compression of at least 5.0 cm,100 compressions per minute for adults and allow complete chest recoil after each compression. Every 30 chest compressions should be followed promptly by two quick and short ventilations (each 400-600 ml tidal volume) delivered within six seconds. Chest compression-only CPR is recommended for dispatcher-instructed CPR or if the rescuer, for any reason, is unable or unwilling to do mouth-tomouth ventilations. CPR should only be stopped when the patient wakes up or an emergency team arrives and takes over patient care, or if an automated external defibrillator were to prompt interruption of chest compressions for analysis of heart rhythm or delivery of shock.