Finite element model of the human lower cervical spine: parametric analysis of the C4-C6 unit.
In this study, a three-dimensional finite element model of the human lower cervical spine (C4-C6) was constructed. The mathematical model was based on close-up CT scans from a young human cadaver. Cortical shell, cancellous core, endplates, and posterior elements including the lateral masses, pedicle, lamina, and transverse and spinous processes, and the intervertebral disks, were simulated. Using the material properties from literature, the 10,371-element model was exercised under an axial compressive mode of loading. The finite element model response agreed with literature. As a logical step, a parametric study was conducted by evaluating the biomechanical response secondary to changes in the elastic moduli of the intervertebral disk and the endplates. In the stress analysis, the minimum principal compressive stress was used for the cancellous core of the vertebral body and von Mises stress was used for the endplate component. The model output indicated that an increase in the elastic modulii of the disk resulted in an increase in the endplate stresses at all the three spinal levels. In addition, the inferior endplate of the middle vertebral body responded with the highest mean compressive stress followed by its superior counterpart. Furthermore, the middle vertebral body produced the highest compressive stresses compared to its counterparts. These findings appear to correlate with experimental results as well as common clinical experience wherein cervical fractures are induced due to external compressive forces. As a first step, this model will lead to more advanced simulations as additional data become available.


Project STYLE: a multisite RCT for HIV prevention among youths in mental health treatment.
The study examined the efficacy of family-based and adolescent-only HIV prevention programs in decreasing HIV risk and improving parental monitoring and sexual communication among youths in mental health treatment. A randomized controlled trial (RCT) with 721 adolescents (ages 13-18 years) and their caregivers from mental health settings in three U.S. cities were randomly assigned to one of three theory-based, structured group interventions: family-based HIV prevention, adolescent-only HIV prevention, and adolescent-only health promotion. Interventions were delivered during an all-day workshop. Assessments were completed at baseline and three months postintervention. Compared with those in the health intervention, adolescents in the HIV prevention interventions reported fewer unsafe sex acts (adjusted rate ratio=.49, p=.01), greater condom use (adjusted relative change=59%, p=.01), and greater likelihood of avoiding sex (adjusted odds ratio=1.44, p=.05). They also showed improved HIV knowledge (p<.01) and self-efficacy (p<.05). The family-based intervention, compared with the other interventions, produced significant improvements in parent-teen sexual communication (p<.01), parental monitoring (p<.01), and parental permissiveness (p=.05). This RCT found that the HIV prevention interventions reduced sexual risk behavior over three months in a large, diverse sample of youths in mental health treatment and that the family-based intervention improved parental monitoring and communication with teens about sex. These interventions show promise.


Evaluation of toxicokinetic variables and arthropathic changes in juvenile rabbits after oral administration of an investigational fluoroquinolone, PD 117596.
To compare toxicokinetic variables and associated tissue drug concentrations with severity of articular lesions in weight-bearing joints of juvenile rabbits after oral administration of a fluoroquinolone. Ten 6- to 7-week-old, 800- to 1,200-g, New Zealand White rabbits. Rabbits were gavaged daily with the fluoroquinolone PD 117596 at 500 mg/kg of body weight for 5 days. Blood samples were collected on day 4 at preestablished times, up to 24 hours after drug administration. On day 5 gross lesion severity and prevalence were evaluated in the major weight-bearing joints, and tissue specimens were collected (60 minutes after drug administration). Serum and tissue drug concentrations were determined by microbiologic plate assay. Macroscopically, treatment rabbits had a high prevalence of arthropathy with the distal portion of the femur having the highest prevalence and severity of lesions. Grossly, alterations to articular cartilage included 1 to 4 mm in diameter vesicles or erosions. Histologically, vesicles were identified in the midzone or close to the zone of calcified cartilage of treatment rabbits. Chondrocyte cellularity was reduced in affected areas, and perivesicular regions had reduced staining with Safranin O. Correlation analysis of area under the curve values with total scores for lesion severity had a significant positive relationship. Our findings support the use of juvenile rabbits as a model for arthropathic changes induced by fluoroquinolone administration.


Identification of genes leading to glucocorticoid-induced leukemic cell death.
Glucocorticoidal steroids (GC) are capable of causing apoptotic death of many varieties of lymphoid cells; consequently, GC are used in therapy for many lymphoid malignancies. Gene transcription in the GC-treated cells is required for subsequent apoptosis, but only a few of the actual genes involved have been identified. We employed gene microarray analysis to find the network of genes involved in GC-evoked cell death, using three clones derived from the CEM lymphoid leukemia cell line. Clone C1-15 was resistant to GC-evoked apoptosis, although not necessarily to GC-induced gene transcription; the other two underwent apoptosis in the presence of GC. Clone C7-14 was subcloned from the apoptosis-sensitive parental C7 clone to establish karyotypic uniformity. The second sensitive clone, C1-6, was a spontaneous revertant from parental resistant clone C1. A period of > or = 24 h in the constant presence of receptor-occupying concentrations of synthetic GC dexamethasone (Dex) was necessary for apoptosis to begin. To identify the steps leading to this dramatic event, we identified the changes in gene expression in the 20-h period preceding the onset of overt apoptosis. Cells in the log phase of growth were treated with 10(-6) M Dex, and 2-20 h later, mRNA was prepared and analyzed using the Affymetrix HG_U95Av2 chip, containing probes for about 12,600 genes. Of these, approximately 6,000 were expressed above background. Comparisons of the basal and expressed genes in the three clones led to several conclusions: The Dex-sensitive clones shared the regulation of a limited set of genes. The apoptosis-resistant clone C1-15 showed Dex effects on a largely different set of genes. Promoter analysis of the regulated genes suggested that primary gene targets for GC often lack a classic GC response element.


Outcome prediction model for very elderly critically ill patients.
Very elderly critically ill patients have three possible hospital outcomes: discharge to home, discharge to a skilled nursing or rehabilitation facility, or death. The factors associated with these outcomes are unknown. To develop a three-outcome prediction model for very elderly critically ill patients. Retrospective chart abstraction with ordered logistic regression analysis. Academic medical center. Four hundred and fifty-five patients 85 yrs or older admitted to intensive care units (ICU) during 1996 and 1997. A fitted ordinal logistic regression predictive model was developed using data from 243 patients hospitalized in 1996, and validated on data from 212 patients hospitalized in 1997. Model variables include age, gender, baseline support level, type of ICU, heart rate at ICU admission, use of mechanical ventilation, vasopressors or a pulmonary artery catheter during the ICU stay, and the development of respiratory, neurologic or hematologic failure or sepsis while in the ICU. When tested on the 1997 data, the model was well calibrated and had a high discriminant index. This mathematical model can be used to predict the risks of these three hospital outcomes for this population of patients. These predictions can provide a context when discussing goals and expectations with patients, families, and other healthcare providers and to aid in hospital discharge planning.


Concentrations of essential trace elements in maternal serum and the effect on birth weight and newborn body mass index in sub-arctic and arctic populations of Norway and Russia.
This project is part of an assessment of the impact of environmental factors on human health in the Kola Peninsula of Russia and the neighboring arctic area of Norway. Pregnant women and their newborns were studied to explore a relationship between maternal status of essential metals and birth weight. Life-style information and serum specimens were collected from at least 50 consecutive mother-infant pairs from hospital delivery departments in three Russian and three Norwegian communities (N=151 and 167, respectively). Pregnancy outcomes were verified by consulting medical records. Copper, selenium and zinc in serum were determined by atomic absorption spectrometry and ferritin by an automated analyzer method. Mean birth weight and child's body mass index (BMIC) were significantly lower in the Russian group (p<0.001), with or without adjustment for gestational age. Copper, iron (as ferritin) and selenium serum concentrations were in the normal range, while zinc levels in both countries were mostly below the lower limit (10.8 micromol/L) of reported reference intervals. A positive correlation between zinc and birth weight or BMIC was only observed for concentrations exceeding 10.8 micromol/L. Analysis by quartiles showed that maternal urinary creatinine and birth weight were negatively correlated (p=0.001). The influence of the different elements on BMIC, grouped by quartiles, was significantly positive only for selenium (p=0.03) and ferritin (p=0.02), while there was no significant relationship for copper or zinc. Adjustment of birth weight and BMIC for gestational age did not alter substantially the various associations indicated. With the exception of zinc, the mineral status of delivering women in arctic and sub-arctic regions of Norway and western Russia appears to be adequate. The significantly lower BMIC for the Russian group suggests the likely occurrence of nutritional deficiencies during pregnancy in Russia. However, the significant contribution of a country factor in the predictive model implies that the maternal serum trace-element concentrations explored in this study are incomplete indicators of fetal undernourishment.


Electronic Health Record-Embedded Individualized Pain Plans for Emergency Department Treatment of Vaso-occlusive Episodes in Adults With Sickle Cell Disease: Protocol for a Preimplementation and Postimplementation Study.
Individuals living with sickle cell disease often require aggressive treatment of pain associated with vaso-occlusive episodes in the emergency department. Frequently, pain relief is poor. The 2014 National Heart, Lung, and Blood Institute evidence-based guidelines recommended an individualized treatment and monitoring protocol to improve pain management of vaso-occlusive episodes. This study will implement an electronic health record-embedded individualized pain plan with provider and patient access in the emergency departments of 8 US academic centers to improve pain treatment for adult patients with sickle cell disease. This study will assess the overall effects of electronic health record-embedded individualized pain plans on improving patient and provider outcomes associated with pain treatment in the emergency department setting and explore barriers and facilitators to the implementation process. A preimplementation and postimplementation study is being conducted by all 8 sites that are members of the National Heart, Lung, and Blood Institute-funded Sickle Cell Disease Implementation Consortium. Adults with sickle cell disease aged 18 to 45 years who had a visit to a participating emergency department for vaso-occlusive episodes within 90 days prior to enrollment will be eligible for inclusion. Patients will be enrolled in the clinic or remotely. The target analytical sample size of this study is 160 patient participants (20 per site) who have had an emergency department visit for vaso-occlusive episode treatment at participating emergency departments during the study period. Each site is expected to enroll approximately 40 participants to reach the analytical sample size. The electronic health record-embedded individualized pain plans will be written by the patient's sickle cell disease provider, and sites will work with the local informatics team to identify the best method to build the electronic health record-embedded individualized pain plan with patient and provider access. Each site will adopt required patient and provider implementation strategies and can choose to adopt optional strategies to improve the uptake and sustainability of the intervention. The study is informed by the Technology Acceptance Model 2 and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Provider and patient baseline survey, follow-up survey within 96 hours of an emergency department vaso-occlusive episode visit, and selected qualitative interviews within 2 weeks of an emergency department visit will be performed to assess the primary outcome, patient-perceived quality of emergency department pain treatment, and additional implementation and intervention outcomes. Electronic health record data will be used to analyze individualized pain plan adherence and additional secondary outcomes, such as hospital admission and readmission rates. The study is currently enrolling study participants. The active implementation period is 18 months. This study proposes a structured, framework-informed approach to implement electronic health record-embedded individualized pain plans with both patient and provider access in routine emergency department practice. The results of the study will inform the implementation of electronic health record-embedded individualized pain plans at a larger scale outside of Sickle Cell Disease Implementation Consortium centers. ClinicalTrials.gov NCT04584528; https://clinicaltrials.gov/ct2/show/NCT04584528. DERR1-10.2196/24818.


Histone H3 Thr 45 phosphorylation is a replication-associated post-translational modification in S. cerevisiae.
Post-translational histone modifications are crucial for the regulation of numerous DNA-templated processes, and are thought to mediate both alteration of chromatin dynamics and recruitment of effector proteins to specific regions of the genome. In particular, histone Ser/Thr phosphorylation regulates multiple nuclear functions in the budding yeast Saccharomyces cerevisiae, including transcription, DNA damage repair, mitosis, apoptosis and sporulation. Although modifications to chromatin during replication remain poorly understood, a number of recent studies have described acetylation of the histone H3 N-terminal alpha-helix (alphaN helix) at Lys 56 as a modification that is important for maintenance of genomic integrity during DNA replication and repair. Here, we report phosphorylation of H3 Thr 45 (H3-T45), a histone modification also located within the H3 alphaN helix in S. cerevisiae. Thr 45 phosphorylation peaks during DNA replication, and is mediated by the S phase kinase Cdc7-Dbf4 as part of a multiprotein complex identified in this study. Furthermore, loss of phosphorylated H3-T45 causes phenotypes consistent with replicative defects, and prolonged replication stress results in H3-T45 phosphorylation accumulation over time. Notably, the phenotypes described here are independent of Lys 56 acetylation status, and combinatorial mutations to both Thr 45 and Lys 56 of H3 cause synthetic growth defects. Together, these data identify and characterize H3-T45 phosphorylation as a replication-associated histone modification in budding yeast.


Insights into uveitis in association with spondyloarthritis from a large patient survey.
Uveitis is reported to be the most common extra-articular feature in spondyloarthritis (SpA). The objective of this study was to investigate the relationship between uveitis and SpA in a cohort identified from a survey. Eight hundred sixty-three respondents completed a survey conducted by the Spondylitis Association of America. Data on baseline demographics, quality of life, medication use, and joint involvement were compared in SpA patients with and without uveitis. Logistic regression analysis was used to identify characteristics associated with the presence of uveitis. Of the 863 respondents, 168 (19.5%) reported a diagnosis of uveitis. Baseline demographics including sex, age, and ethnicity were similar between the uveitis and no-uveitis groups. The presence of uveitis had a significant positive association with the use of the biologic drug infliximab (adjusted odds ratio [ORadj] = 1.66, P = 0.044), "lower jaw" involvement (ORadj = 1.60, P = 0.015), heel involvement (ORadj = 1.51, P = 0.023), and a diagnosis of arthritis associated with inflammatory bowel disease (ORadj = 1.92, P = 0.005). It had a significant negative association with the use of the biologic drug etanercept (ORadj = 0.49, P = 0.011) or a coexisting diagnosis of diabetes (ORadj = 0.02, P = 0.020). The relationship of uveitis to medication presumably reflects the choice of a specific tumor necrosis factor inhibitor in the setting of a history of uveitis. One prior study has also correlated heel pain and uveitis, thus supporting the validity of the association and suggesting potentially a common pathogenesis. Because diabetes has been proposed as a risk factor for uveitis, the negative association is surprising and may distinguish the pathogenesis of uveitis in association with SpA from other forms of uveitis.


Criticism or praise? The impact of verbal versus text-only computer feedback on social presence, intrinsic motivation, and recall.
The Computers Are Social Actors (CASA) paradigm asserts that human computer users interact socially with computers, and has provided extensive evidence that this is the case. In this experiment (n = 134), participants received either praise or criticism from a computer. Independent variables were the direction feedback (praise or criticism), and voice channel (verbal or text-only). Dependent variables measured via a computer-based questionnaire were recall, perceived ability, intrinsic motivation, and perceptions of the computer as a social entity. Results demonstrate that participants had similar reactions to computers as predicted by interpersonal communication research with participants who received text-only criticism reporting higher levels of intrinsic motivation, perceived ability, and recall. Additionally, the computer was seen as more intelligent. Implications for theory and application are discussed.


Outbreak of Peste des Petits Ruminants among Critically Endangered Mongolian Saiga and Other Wild Ungulates, Mongolia, 2016-2017.
The 2016-2017 introduction of peste des petits ruminants virus (PPRV) into livestock in Mongolia was followed by mass mortality of the critically endangered Mongolian saiga antelope and other rare wild ungulates. To assess the nature and population effects of this outbreak among wild ungulates, we collected clinical, histopathologic, epidemiologic, and ecological evidence. Molecular characterization confirmed that the causative agent was PPRV lineage IV. The spatiotemporal patterns of cases among wildlife were similar to those among livestock affected by the PPRV outbreak, suggesting spillover of virus from livestock at multiple locations and time points and subsequent spread among wild ungulates. Estimates of saiga abundance suggested a population decline of 80%, raising substantial concerns for the species' survival. Consideration of the entire ungulate community (wild and domestic) is essential for elucidating the epidemiology of PPRV in Mongolia, addressing the threats to wild ungulate conservation, and achieving global PPRV eradication.


Calcification in dermal fibroblasts from a patient with GGCX syndrome accompanied by upregulation of osteogenic molecules.
Gamma-glutamyl carboxylase (GGCX) gene mutation causes GGCX syndrome (OMIM: 137167), which is characterized by pseudoxanthoma elasticum (PXE)-like symptoms and coagulation impairment. Here, we present a 55-year-old male with a novel homozygous deletion mutation, c.2,221delT, p.S741LfsX100, in the GGCX gene. Histopathological examination revealed calcium deposits in elastic fibers and vessel walls, and collagen accumulation in the mid-dermis. Studies of dermal fibroblasts from the patient (GGCX dermal fibroblasts) demonstrated that the mutated GGCX protein was larger, but its expression level and intracellular distribution were indistinguishable from those of the wild-type GGCX protein. Immunostaining and an enzyme-linked immunosorbent assay showed an increase in undercarboxylated matrix gamma-carboxyglutamic acid protein (ucMGP), a representative substrate of GGCX and a potent calcification inhibitor, indicating that mutated GGCX was enzymatically inactive. Under osteogenic conditions, calcium deposition was exclusively observed in GGCX dermal fibroblasts. Furthermore, GGCX dermal fibroblast cultures contained 23- and 7.7-fold more alkaline phosphatase (ALP)-positive cells than normal dermal fibroblast cultures (n = 3), without and with osteogenic induction, respectively. Expression and activity of ALP were higher in GGCX dermal fibroblasts than in normal dermal fibroblasts upon osteogenic induction. mRNA levels of other osteogenic markers were also higher in GGCX dermal fibroblasts than in normal dermal fibroblasts, which including bone morphogenetic protein 6, runt-related transcription factor 2, and periostin (POSTN) without osteogenic induction; and osterix, collagen type I alpha 2, and POSTN with osteogenic induction. Together, these data indicate that GGCX dermal fibroblasts trans-differentiate into the osteogenic lineage. This study proposes another mechanism underlying aberrant calcification in patients with GGCX syndrome.


Traffic-related air pollution, preterm birth and term birth weight in the PIAMA birth cohort study.
Maternal exposure to air pollution has been associated with adverse pregnancy outcomes. Few studies took into account the spatial and temporal variation of air pollution levels. To evaluate the impact of maternal exposure to traffic-related air pollution during pregnancy on preterm birth and term birth weight using a spatio-temporal exposure model. We estimated maternal residential exposure to nitrogen dioxide (NO(2)), particulate matter (PM(2.5)) and soot during pregnancy (entire pregnancy, 1st trimester, and last month) for 3853 singleton births within the Dutch PIAMA prospective birth cohort study by means of temporally adjusted land-use regression models. Associations between air pollution concentrations and preterm birth and term birth weight were analyzed by means of logistic and linear regression models with and without adjustment for maternal physical, lifestyle, and socio-demographic characteristics. We found positive, statistically non-significant associations between exposure to soot during entire pregnancy and during the last month of pregnancy and preterm birth [adj. OR (95% CI) per interquartile range increase in exposure 1.08 (0.88-1.34) and 1.09 (0.93-1.27), respectively]. There was no indication of an adverse effect of air pollution exposure on term birth weight. In this study, maternal exposure to traffic-related air pollution during pregnancy was not associated with term birth weight. There was a tendency towards an increased risk of preterm birth with increasing air pollution exposure, but statistical power was low.


Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury.
Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2-3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.


Improved nucleic acid extraction protocols for Ganoderma boninense, G. miniatocinctum and G. tornatum.
The first and most crucial step of all molecular techniques is to isolate high quality and intact nucleic acids. However, DNA and RNA isolation from fungal samples are usually difficult due to the cell walls that are relatively unsusceptible to lysis and often resistant to traditional extraction procedures. Although there are many extraction protocols for Ganoderma species, different extraction protocols have been applied to different species to obtain high yields of good quality nucleic acids, especially for genome and transcriptome sequencing. Ganoderma species, mainly G. boninense causes the basal stem rot disease, a devastating disease that plagues the oil palm industry. Here, we describe modified DNA extraction protocols for G. boninense, G. miniatocinctum and G. tornatum, and an RNA extraction protocol for G. boninense. The modified salting out DNA extraction protocol is suitable for G. boninense and G. miniatocinctum while the modified high salt and low pH protocol is suitable for G. tornatum. The modified DNA and RNA extraction protocols were able to produce high quality genomic DNA and total RNA of ~ 140 to 160 µg/g and ~ 80 µg/g of mycelia respectively, for Single Molecule Real Time (PacBio Sequel® System) and Illumina sequencing. These protocols will benefit those studying the oil palm pathogens at nucleotide level.


Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery.
Although pre-clinical evidence has suggested that partial inhibition of myocardial fatty acid oxidation (FAO) and subsequent switch to greater glucose oxidation for ATP production can prevent ischemia/reperfusion injury, controversy about this approach persists. For example, mice with germline deletion of the FA transporter CD36, exhibited either impaired or unchanged post-ischemic functional recovery despite a 40-60% reduction in FAO rates. Because there are limitations to cardiac studies utilizing whole body CD36 knockout (totalCD36KO) mice, we have now generated an inducible and cardiomyocyte-specific CD36 KO (icCD36KO) mouse to better address the role of cardiomyocyte CD36 and its regulation of FAO and post-ischemic functional recovery. Four to six weeks following CD36 ablation, hearts from icCD36KO mice had significantly decreased FA uptake compared to controls, which was paralleled by significant reductions in intramyocardial triacylglycerol content. Analysis of cardiac energy metabolism using ex vivo working heart perfusions showed that reduced FAO rates were compensated by enhanced glucose oxidation in the hearts from icCD36KO mice. In contrast to the totalCD36KO mice, hearts from icCD36KO mice exhibited significantly improved functional recovery following ischemia/reperfusion (18min of global no-flow ischemia followed by 40min of aerobic reperfusion). This improved recovery was associated with lower calculated proton production prior to and following ischemia compared to controls. Moreover, the amount of ATP generated relative to cardiac work was significantly lower in the hearts from icCD36KO mice compared to controls, indicating significantly increased cardiac efficiency in the hearts from icCD36KO mice. These data provide genetic evidence that reduced FAO as a result of diminished CD36-mediated FA uptake improves post-ischemic cardiac efficiency and functional recovery. As such, targeting cardiomyocyte FA uptake and FAO via inhibition of CD36 in the adult myocardium may provide therapeutic benefit during ischemia-reperfusion.


Fecal MicroRNAs as novel biomarkers for colon cancer screening.
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, but currently available noninvasive screening programs have achieved only a modest decrease in mortality. MicroRNAs (miRNA) play an important role in a wide array of biological processes and are commonly dysregulated in neoplasia. We aimed to evaluate the feasibility of fecal miRNAs as biomarkers for colorectal neoplasia screening. Total RNA was extracted from freshly collected stool samples from 8 healthy volunteers and 29 samples collected via fecal occult blood testing from subjects with normal colonoscopies, colon adenomas, and CRCs. miRNA expression analyses were done with TaqMan quantitative reverse transcription-PCR for a subset of miRNAs. Illumina miRNA microarray profiling was done to evaluate the differences in expression patterns between normal colonic mucosa tissues and stool samples from healthy subjects. We efficiently extracted miRNAs from stool specimens using our developed protocol. Data from independent experiments showed high reproducibility for miRNA extraction and expression. miRNA expression patterns were similar in stool specimens among healthy volunteers, and reproducible in stool samples that were collected serially in time from the same individuals. miRNA expression profiles from 29 patients showed higher expression of miR-21 and miR-106a in patients with adenomas and CRCs compared with individuals free of colorectal neoplasia. Our data indicate that miRNAs could be extracted from stool easily and reproducibly. The stools of patients with colorectal neoplasms have unique and identifiable patterns of miRNA expression. Fecal miRNAs may be an excellent candidate for the development of a noninvasive screening test for colorectal neoplasms.


Caffeic acid phenethyl ester attenuates IgE-induced immediate allergic reaction.
Caffeic acid phenethyl ester (CAPE) is the active component of honey bee propolis extracts. The results of the current study demonstrate that CAPE attenuated immunoglobulin (Ig)E-mediated allergic response in mast cells. Oral administration of CAPE inhibited IgE-mediated passive cutaneous anaphylaxis. CAPE effectively reduced both histamine and serotonin (5-HT)-induced vascular permeability in rats. CAPE also reduced histamine and leukotrienes (LTs) release from isolated rat peritoneal mast cells. Moreover, CAPE suppressed contraction induced by histamine (3 × 10(-8)-3 × 10(-5) M), 5-HT (3 × 10(-9)-10(-6) M) and adenosine (3 × 10(-8)-10(-5) M) in guinea pig tracheal zigzag. These findings provide evidence that CAPE may serve as an effective therapeutic agent for allergic diseases.


Results of a mass screening program for colorectal cancer.
Following a series of educational newscasts about colorectal cancer that were aired on a local television news program, stool guaiac slide kits were distributed on request to 72,000 persons in Memphis. One or more slides were positive In 1310 (6%) of the 23,000 kits returned. Of the 1310 individuals with positive cultures, 597 (45%) saw a physician for further evaluation. Sixty-five of these persons received inadequate evaluations. Of the 532 individuals (90%) who received adequate evaluations, 154 (26%) had no evidence of pathology that would account for occult blood. Of the remaining 443 persons, 26 were found to have colorectal cancer, and 20 of these 26 persons were found to have surgically amenable lesions (Dukes' stages A through B2). In addition, 67 potentially precancerous polyps were found. Mass screening for colorectal cancer using guaiac slide tests, coupled with patient compliance for a screening protocol and adequate follow-up evaluation, has the potential to identify and treat early colorectal cancer.


Age of onset of first alcohol intoxication and subsequent alcohol use among urban American Indian adolescents.
The objective was to assess the effect of early onset intoxication on subsequent alcohol involvement among urban American Indian youth. The data come from the American Indian Research (AIR) project, a panel study of urban Indian youth residing in King County, Washington. Data were collected annually from the adolescent and his/her primary caregiver from the 1988-89 school year to the 1996-97 school year, providing a total of nine waves of data. Early intoxication (by age 14) was related to delinquency, family history of alcohol abuse or dependence, poverty, broken family structure, less family cohesiveness, and more family conflict. The effects of these characteristics were, therefore, partialed out in testing effects of early intoxication on later alcohol involvement. Two-part latent growth models of alcohol use and alcohol problems were specified. Effects of early onset intoxication on these trajectories, as well as lifetime alcohol abuse or dependence by the transition to young adulthood, were examined. Findings indicate that adolescents who experienced their first intoxication early (by age 14), used alcohol more heavily from the ages of 16 to 18, experienced more problems related to the alcohol's use from the ages of 16 to 18, and were more likely to have a diagnosed alcohol disorder by the final wave of data collection. Congruent with similar studies in the general population, early intoxication appears to be associated with a deleterious course of alcohol involvement during adolescence and into the transition to young adulthood among urban American Indian youth. Implications for prevention are discussed.


Determinants of Photolyase's DNA Repair Mechanism in Mesophiles and Extremophiles.
Light-driven DNA repair by extremophilic photolyases is of tremendous importance for understanding the early development of life on Earth. The mechanism for flavin adenine dinucleotide repair of DNA lesions is the subject of debate and has been studied mainly in mesophilic species. In particular, the role of adenine in the repair process is poorly understood. Using molecular docking, molecular dynamics simulations, electronic structure calculations, and electron tunneling pathways analysis, we examined adenine's role in DNA repair in four photolyases that thrive at different temperatures. Our results indicate that the contribution of adenine to the electronic coupling between the flavin and the cyclobutane pyrimidine dimer lesion to be repaired is significant in three (one mesophilic and two extremophilic) of the four enzymes studied. Our analysis suggests that thermophilic and hyperthermophilic photolyases have evolved structurally to preserve the functional position (and thus the catalytic function) of adenine at their high temperatures of operation. Water molecules can compete with adenine in establishing the strongest coupling pathway for the electron transfer repair process, but the adenine contribution remains substantial. The present study also reconciles prior seemingly contradictory conclusions on the role of adenine in mesophile electron transfer repair reactions, showing how adenine-mediated superexchange is conformationally gated.


Predictors of the trajectories of self-reported sleep disturbance in men with prostate cancer during and following radiation therapy.
To examine how self-reported ratings of sleep disturbance changed from the time of the simulation visit to four months after the completion of radiation therapy (RT) and to investigate whether specific patient, disease, and symptom characteristics predicted the initial levels of sleep disturbance and/or characteristics of the trajectories of sleep disturbance. Prospective longitudinal study. Two radiation therapy centers. Patients (n = 82) who underwent primary or adjuvant RT for prostate cancer. Changes in self-reported sleep disturbance were measured using the General Sleep Disturbance Scale (GSDS). Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale. Trait and state anxiety were measured using the Spielberger State-Trait Anxiety Inventory. Hierarchical linear modeling was used to answer the study aims. Self-reported sleep disturbance increased during the course of RT and then decreased following the completion of RT. Predictors of higher levels of sleep disturbance included younger age, higher levels of trait anxiety, higher levels of depressive symptoms, and higher levels of sleep disturbance at the initiation of RT. Sleep disturbance is a significant problem in patients with prostate cancer who undergo RT. Younger men with co-occurring depression and anxiety may be at greatest risk for sleep disturbance during RT.


Synthesis and Magnetic Properties of Maghemite (gamma-Fe(2)O(3)) Short-Nanotubes.
We report a rational synthesis of maghemite (gamma-Fe(2)O(3)) short-nanotubes (SNTs) by a convenient hydrothermal method and subsequent annealing process. The structure, shape, and magnetic properties of the SNTs were investigated. Room-temperature and low-temperature magnetic measurements show that the as-fabricated gamma-Fe(2)O(3) SNTs are ferromagnetic, and its coercivity is nonzero when the temperature above blocking temperature (T(B)). The hysteresis loop was operated to show that the magnetic properties of gamma-Fe(2)O(3) SNTs are strongly influenced by the morphology of the crystal. The unique magnetic behaviors were interpreted by the competition of the demagnetization energy of quasi-one-dimensional nanostructures and the magnetocrystalline anisotropy energy of particles in SNTs.


Patient and graft outcomes following liver transplantation for sarcoidosis.
End-stage liver disease as a consequence of hepatic sarcoidosis is a rare indication for liver transplantation. Consequently, there is a paucity of information on the pre-transplant findings and post-operative course of individuals transplanted for hepatic sarcoidosis. The purpose of this study was to evaluate our experience with liver transplantation for sarcoidosis. Cases were identified by review of the Mount Sinai Hospital liver transplant database. For each case, two control patients with other causes of liver failure matched for age, gender and date of transplant were selected for comparison. Hepatic sarcoidosis was the indication for liver transplantation in only seven of 2117 (0.3%) adult transplants performed from September 1988 to June 2004. The diagnosis of sarcoidosis was established by findings of extensive, non-caseating granulomas in pre-transplant liver biopsy specimens or in the native liver explant. Extrahepatic disease was limited to pulmonary involvement in four patients. Sarcoid cases were statistically more likely to have diabetes mellitus (100% vs. 21%, p = 0.001) and less likely to have antibodies to hepatitis C (0% vs. 50%, p = 0.047). Rates of acute cellular rejection were 57% in cases and 36% in controls (p = 0.397). Hepatic granulomas were identified in one patient at 5.6 yr of follow-up. Among cases, the 1-yr graft and patient survival rates were 100% and 5-yr graft and patient survival rates were 86%. The 1- and 5-yr graft and patient survival rates were comparable with those of patients transplanted for other indications.


Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma.
The airway response and cardiovascular and hypokalaemic effects of fenoterol, salbutamol, and terbutaline given in multiples of standard doses from metered-dose inhalers were studied in ten patients with mild asthma. In a double-blind, crossover, placebo-controlled study the subjects received 2, 6, and 18 puffs of each drug with intervals of 90 min, and forced expiratory volume in 1 s, heart rate, QTc interval, plasma potassium concentration, tremor, and bronchial reactivity to histamine were measured. All three drugs produced similar bronchodilatation. However, the rises in heart rate, QTc interval, and tremor and the fall in plasma potassium were greater after fenoterol than after salbutamol or terbutaline. The maximum mean (SD) increases in heart rate for fenoterol, salbutamol, and terbutaline were 29 (24) bpm, 8 (9) bpm, and 8 (14) bpm, respectively; falls in plasma potassium were 0.76 (0.62) mmol/l, 0.46 (0.32) mmol/l, and 0.52 (0.39) mmol/l, respectively. Fenoterol afforded no additional protection against histamine compared with salbutamol. These findings suggest that at doses based on those used in clinical practice fenoterol causes more adverse effects than salbutamol or terbutaline. The most likely explanation for these effects is that fenoterol has been marketed at a higher dose than the other beta 2-agonists; fenoterol may in addition be less selective for beta 2 receptors.


OmpF assembly mutants of Escherichia coli K-12: isolation, characterization, and suppressor analysis.
This paper describes a novel genetic method used to isolate mutations that alter proper assembly of OmpF in the outer membrane. The thermolabile nature of assembly intermediates allowed selection of temperature-sensitive mutations within the ompF gene. A variant allele of ompF (ompF-Dex) was used because it provided a convenient selectable phenotype (Dex+). Assembly mutants were isolated in two steps. First, amber mutations were obtained that mapped in ompF-Dex. This resulted in a Dex- phenotype. Starting with these Dex- strains, Dex+ revertants were isolated. Mutants that displayed a temperature-sensitive Dex+ phenotype were further characterized. Three such mutants possessed a single substitution within ompF that reverted the nonsense codon to a sense codon which replaced W214 with either an E or Q and Y231 with a Q residue in the mature OmpF protein. All three mutant OmpF proteins showed an assembly defect. This defect led to a substantial reduction in the amount of stable OmpF trimers with the concomitant increase of a high-molecular-weight form of OmpF which migrated at the top of the gel. Suppressor mutations were sought that corrected the assembly defect of OmpF. These extragenic suppressor mutations were mapped at 45 min on the Escherichia coli chromosome. The suppressor mutations displayed no allele specificity and were recessive to the wild-type allele. In the presence of a suppressor, mutant stable trimers appeared in an almost normal manner. The appearance of stable trimers concurred with a substantial loss of the high-molecular-weight OmpF species. At this stage, it is not clear whether the high-molecular-weight species of OmpF is a normal assembly intermediate or a dead-end assembly product. The results presented in this study raise the intriguing possibility of a chaperone-like activity for the wild-type suppressor gene product.


Socio-neuro risk factors for suicidal behavior in criminal offenders with psychotic disorders.
Relative to the general population, individuals with psychotic disorders have a higher risk of suicide. Suicide risk is also elevated in criminal offenders. Thus, psychotic-disordered individuals with antisocial tendencies may form an especially high-risk group. We built upon prior risk analyses by examining whether neurobehavioral correlates of social cognition were associated with suicidal behavior in criminal offenders with psychotic disorders. We assessed empathic accuracy and brain structure in four groups: (i) incarcerated offenders with psychotic disorders and past suicide attempts, (ii) incarcerated offenders with psychotic disorders and no suicide attempts, (iii) incarcerated offenders without psychotic disorders and (iv) community non-offenders without psychotic disorders. Established suicide risk variables were examined along with empathic accuracy and gray matter in brain regions implicated in social cognition. Relative to the other groups, offenders with psychotic disorders and suicide attempts had lower empathic accuracy and smaller temporal pole volumes. Empathic accuracy and temporal pole volumes were significantly associated with suicide attempts independent of other risk variables. The results indicate that brain and behavioral correlates of social cognition may add incremental value to models of suicide risk.


Solitary fibrous tumor of the anterior mediastinum: a rare extrapleural neoplasm.
Solitary fibrous tumors are uncommon spindle cell neoplasms originally thought to be restricted to the pleura. We describe a 62-year-old woman who presented with stridor and an anterior mediastinal mass. At thoracotomy, a 10.5 x 6.5 x 5.5 cm, circumscribed, firm mediastinal mass demonstrated no direct cardiac or pulmonary involvement. The tumor consisted of spindle cells organized in a patternless pattern with collagenous stroma and hemangiopericytoma-like vessels. Spindle cells were immunoreactive for CD34, CD99, desmin, vimentin and bcl-2 protein and a diagnosis of mediastinal solitary fibrous tumor was confirmed. The differential diagnosis of mediastinal solitary fibrous tumors is extensive and includes spindle cell thymoma, sarcomatoid carcinoma, malignant mesothelioma, inflammatory myofibroblastic tumor, peripheral nerve sheath tumors and various sarcomas. Despite their rarity in the mediastinum, solitary fibrous tumors can be recognized by their classic patternless morphology and immunophenotypic pattern. Their accurate classification is important, as solitary fibrous tumors are intermediate (rarely metastasizing) neoplasms that require complete surgical excision and long-term clinical follow-up for optimum therapy.


Water and ion losses during the cross-country phase of eventing.
Loss of total body water and ions during prolonged exercise can predispose the horse to health and performance problems. This study examined total body water (TBW) losses and extracellular (ECF) ion losses during the cross-country (XC) phase of Preliminary, Intermediate and Advanced Horse Trials and CCI level 3-day-events. Jugular venous blood samples and body mass (BM) were collected on 49 horses at rest, Pre-XC, Post-XC and following 30 min of recovery. Plasma was separated from blood cells within 10 min of collection. Plasma was analysed for [Na+], [K+], [Cl-], ionised [Ca+2], [glucose], [lactate] and packed cell volume (PCV) and plasma [protein] ([PP]). Distances ranged from 3000-6000 m for the XC phase with speeds of 500-570 m/min. In general, losses of TBW, Na+ and Cl- increased with increasing level of difficulty. Loss of TBW Post-XC ranged from 2-6.1% of resting values or 8.9-12.6 litres for the Preliminary level to mean +/- s.e. 20.4 +/- 1.8 litres for CCI. Losses of ECF ions ranged from 0.5-6.4% for Na+, 1.2-7.7% for Cl-, gains of 8% to losses of 23% for K+, and gains of 7% to losses of 11.7% for Ca+2 at 30 min Post-XC. There was little recovery following 30 min and deficits of 5.3 +/- 2.5 litres persisted overnight in horses that were tested. Plasma protein and PCV increased Post-XC and PCV remained elevated above resting values at 30 min recovery. It is concluded that significant water and ion losses occur and, in general, increase with increased level of difficulty. There was little change with 30 min of recovery and for some horses losses persisted overnight.


Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.
We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.


Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: screening in an infectious disease model.
Targeted delivery of rifampicin loaded microspheres to the alveolar macrophage, the host cell for Mycobacterium tuberculosis (MTB), may be an effective targeted approach to pulmonary tuberculosis therapy. A guinea pig infection model has been adopted as a post-treatment screening method for antimicrobial effect. Insufflation and nebulization methods of drug delivery were evaluated. Rifampicin alone (RIF, 1.03-1.72 mg/kg), within poly(lactide-co-glycolide) microspheres (R-PLGA, equivalent to 1.03-1.72 mg/kg) or polymer microparticles alone (PLGA) were administered by insufflation or nebulization, 24 h before bacterial aerosol exposure. Animals were infected with an aerosol containing a small number (2 x 10(5) cfu/mL) of virulent H37Rv strain of MTB. Lung and spleen tissue samples were collected 28 days after infection for quantitative bacteriology and histopathological analysis. There was a dose-effect relationship between insufflated R-PLGA and burden of bacteria in the lungs. In addition, guinea pigs treated with R-PLGA had a significantly smaller number of viable bacteria (P < 0.05), reduced inflammation and lung damage than lactose or saline control, PLGA or RIF treated animals. These studies indicate the potential of R-PLGA, delivered by insufflation or nebulization directly to the lungs, to affect the early development of pulmonary TB.


International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer.
Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥ 75% agreed or disagreed. There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz-Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥ 1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended. Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.


Metabolic syndrome and hepatic surgery.
In Europe, the prevalence of metabolic syndrome (MS) has reached the endemic rate of 25%. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of MS. Its definition is histological, bringing together the different lesions associated with hepatic steatosis (fat deposits on more than 5% of hepatocytes) without alcohol consumption and following exclusion of other causes. MS and NAFLD are implicated in the carcinogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). At present, HCC and ICC involving MS represent 15-20% and 20-30% respectively of indications for hepatic resection in HCC and ICC. Moreover, in the industrialized nations NAFLD is tending to become the most frequent indication for liver transplantation. MS patients combine the operative risk associated with their general condition and comorbidities and the risk associated with the presence and/or severity of NAFLD. Following hepatic resection in cases of HCC and ICC complicating MS, the morbidity rate ranges from 20 to 30%, and due to cardiovascular and infectious complications, post-transplantation mortality is heightened. The operative risk incurred by MS patients necessitates appropriate management including: (i) precise characterization of the subjacent liver; (ii) an accurately targeted approach privileging detection and optimization of treatment taking into account the relevant cardiovascular risk factors; (iii) a surgical strategy adapted to the histology of the underlying liver, with optimization of the volume of the remaining (postoperative) liver.


Adoptive cell therapy using engineered natural killer cells.
The generation of autologous T cells expressing a chimeric antigen receptor (CAR) have revolutionized the field of adoptive cellular therapy. CAR-T cells directed against CD19 have resulted in remarkable clinical responses in patients affected by B-lymphoid malignancies. However, the production of allogeneic CAR-T cells products remains expensive and clinically challenging. Moreover, the toxicity profile of CAR T-cells means that currently these life-saving treatments are only delivered in specialized centers. Therefore, efforts are underway to develop reliable off-the-shelf cellular products with acceptable safety profiles for the treatment of patients with cancer. Natural killer (NK) cells are innate effector lymphocytes with potent antitumor activity. The availability of NK cells from multiple sources and their proven safety profile in the allogeneic setting positions them as attractive contenders for cancer immunotherapy. In this review, we discuss advantages and potential drawbacks of using NK cells as a novel cellular therapy against hematologic malignancies, as well as strategies to further enhance their effector function.


Sorting things out: Assessing effects of unequal specimen biomass on DNA metabarcoding.
Environmental bulk samples often contain many different taxa that vary several orders of magnitude in biomass. This can be problematic in DNA metabarcoding and metagenomic high-throughput sequencing approaches, as large specimens contribute disproportionately high amounts of DNA template. Thus, a few specimens of high biomass will dominate the dataset, potentially leading to smaller specimens remaining undetected. Sorting of samples by specimen size (as a proxy for biomass) and balancing the amounts of tissue used per size fraction should improve detection rates, but this approach has not been systematically tested. Here, we explored the effects of size sorting on taxa detection using two freshwater macroinvertebrate bulk samples, collected from a low-mountain stream in Germany. Specimens were morphologically identified and sorted into three size classes (body size < 2.5 × 5, 5 × 10, and up to 10 × 20 mm). Tissue powder from each size category was extracted individually and pooled based on tissue weight to simulate samples that were not sorted by biomass ("Unsorted"). Additionally, size fractions were pooled so that each specimen contributed approximately equal amounts of biomass ("Sorted"). Mock samples were amplified using four different DNA metabarcoding primer sets targeting the Cytochrome c oxidase I (COI) gene. Sorting taxa by size and pooling them proportionately according to their abundance lead to a more equal amplification of taxa compared to the processing of complete samples without sorting. The sorted samples recovered 30% more taxa than the unsorted samples at the same sequencing depth. Our results imply that sequencing depth can be decreased approximately fivefold when sorting the samples into three size classes and pooling by specimen abundance. Even coarse size sorting can substantially improve taxa detection using DNA metabarcoding. While high-throughput sequencing will become more accessible and cheaper within the next years, sorting bulk samples by specimen biomass or size is a simple yet efficient method to reduce current sequencing costs.


The therapeutic potential of convalescent plasma therapy on treating critically-ill COVID-19 patients residing in respiratory care units in hospitals in Baghdad, Iraq.
The current COVID-19 pandemic needs unconventional therapies to tackle the resulted high morbidity and mortality. Convalescent plasma is one of the therapeutic approaches that might be of benefit. Forty nine early-stage critically-ill COVID-19 patients residing in Respiratory Care Units (RCU) of three hospitals in Baghdad, Iraq, were included: 21 received convalescent plasma while 28, namely control group, did not receive it. Recovery or death, length of stay in hospital, and improvement in the clinical course of the disease were monitored clinically along with laboratory monitoring through SARS-CoV-2 RNA detection via PCR, and SARS-CoV-2 IgG and IgM serological monitoring. Patients who received convalescent plasma showed reduced duration of infection in about 4 days and showed less death rate [1/21 versus 8/28 in control group]. In addition, all the patients who were given convalescent plasma showed high levels of SARS-CoV-2 IgG and IgM three days after plasma transfusion. Plasma from donors with high levels of SARS-CoV-2 IgG and donors with positive SRAS-CoV-2 IgM showed better therapeutic results than other donors. Convalescent plasma therapy is an effective therapy if donors with high level of SARS-Cov2 antibodies are selected and if recipients are at their early stage of critical illness, being no more than three days in RCUs.


Perceptions of Infertility and In Vitro Fertilization Treatment among Married Couples in Anambra State, Nigeria.
There is a high rate of infertility among couples in Nigeria. This challenge is perceived differently in each socio-cultural context in which it is experienced but solution to the problem is adversely affected by the people's perception of the phenomenon. This study thus explored the perceptions of infertility and in vitro fertilization (IVF) and how to enhance the use of IVF treatment among married couples. This was a cross-sectional survey in Anambra State, Nigeria involving household respondents (married couples) and hospital respondents (couples undergoing infertility evaluation). Structured questionnaire and key informant interview (KII) guide were used for data collection. Altogether 600 questionnaires were administered and 589 were validly completed and analysed. The main outcome measures included perceptions of infertility and IVF treatment, utilization of IVF treatment and association between some demographic variables and IVF utilization. The results showed that infertility was perceived majorly as - destiny/supernatural powers (17.1%), threat to men's procreativity/continuity of lineage (14.3%), women's problem only (15.6%). Solutions to the challenges were adversely affected by perception. The use of IVF treatment was low with misconceptions like it's too costly (15.4%) and unnatural (7.6%), giving rise to unmet need for assisted reproductive technology. Women (especially above 35 years) were more likely to accept IVF treatment than men. Reproductive health education and awareness creation should target the misconceptions about infertility/IVF and fertility treatment should be covered by national health insurance to reduce the cost of IVF treatment and improve its use in Anambra State.


Characteristics of patients with giant cell arteritis who experience visual symptoms.
Permanent vision loss is one of the most serious complications of giant cell arteritis (GCA) and therefore prompt diagnosis is paramount. However, diagnosis of GCA remains challenging due to its frequently non-specific presentation. Our aim was to identify differences in the characteristics of GCA patients with, and without, current visual symptoms. A cross-sectional survey was mailed to patients with a GCA Read code entered in their GP electronic medical record. Responders were categorised as those currently reporting a visual symptom or not. We compared general and GCA-specific characteristics in these two groups. The association of diagnostic delay with subsequent experience of visual symptoms was examined using unadjusted and adjusted linear regression analysis. 318 GCA patients responded to the survey (59.6%). Responders were predominantly female (69.8%), with a mean age of 73.7 years (SD 8.2). 28% reported current visual symptoms. There was no statistically significant difference in the general characteristics between those with and without visual symptoms. Of GCA-specific characteristics, pre-GCA diagnosis of diplopia (p = 0.018), temporary (p ≤ 0.001) or permanent visual problems (p = 0.001) and hoarseness (p = 0.004) were more common among those reporting current visual symptoms. There was no association between the extent of diagnostic delay and reporting of current visual symptoms. Though we found few characteristics to distinguish between GCA patients with or without current visual symptoms, diagnostic delay was not associated with current visual symptoms. Our findings highlighted the continued difficulty for clinicians to identify GCA patients at the highest risk of visual complications.


The challenge of electronic waste (e-waste) management in developing countries.
Information and telecommunications technology (ICT) and computer Internet networking has penetrated nearly every aspect of modern life, and is positively affecting human life even in the most remote areas of the developing countries. The rapid growth in ICT has led to an improvement in the capacity of computers but simultaneously to a decrease in the products lifetime as a result of which increasingly large quantities of waste electrical and electronic equipment (e-waste) are generated annually. ICT development in most developing countries, particularly in Africa, depends more on secondhand or refurbished EEEs most of which are imported without confirmatory testing for functionality. As a result large quantities of e-waste are presently being managed in these countries. The challenges facing the developing countries in e-waste management include: an absence of infrastructure for appropriate waste management, an absence of legislation dealing specifically with e-waste, an absence of any framework for end-of-life (EoL) product take-back or implementation of extended producer responsibility (EPR). This study examines these issues as they relate to practices in developing countries with emphasis on the prevailing situation in Nigeria. Effective management of e-waste in the developing countries demands the implementation of EPR, the establishment of product reuse through remanufacturing and the introduction of efficient recycling facilities. The implementation of a global system for the standardization and certification/labelling of secondhand appliances intended for export to developing countries will be required to control the export of electronic recyclables (e-scarp) in the name of secondhand appliances.


How to convene an international health or development commission: ten key steps.
The Commission on Investing in Health (CIH), an international group of 25 economists and global health experts, published its Global Health 2035 report in The Lancet in December 2013. The report laid out an ambitious investment framework for achieving a "grand convergence" in health-a universal reduction in deaths from infectious diseases and maternal and child health conditions-within a generation. This article captures ten key elements that the CIH found important to its process and successful outcomes. The elements are presented in chronological order, from inception to post-publication activities. The starting point is to identify the gap that a new commission could help to narrow. A critical early step is to choose a chair who can help to set the agenda, motivate the commissioners, frame the commission's analytic work, and run the commission meetings in an effective way. In selecting commissioners, important considerations are their technical expertise, ensuring diversity of people and viewpoints, and the connections that commissioners have with the intended policy audience. Financial and human resources need to be secured, typically from universities, foundations, and development agencies. It is important to set a clear end date, so that the commission's work program, the timing of its meetings and its interim deadlines can be established. In-person meetings are usually a more effective mechanism than conference calls for gaining commissioners' inputs, surfacing important debates, and 'reality testing' the commission's key findings and messages. To have policy impact, the commission report should ideally say something new and unexpected and should have simple messages. Generating new empirical data and including forward-looking recommendations can also help galvanize policy action. Finally, the lifespan of a commission can be extended if it lays the foundation for a research agenda that is then taken up after the commission report is published.


Attention-deficit/hyperactivity disorder symptoms and suicide ideation and attempts: Findings from the Adult Psychiatric Morbidity Survey 2007.
Adults with attention-deficit/hyperactivity disorder (ADHD) may have an increased risk of engaging in suicidal behavior. This study examined this association in the general adult population where there has been little research. Data came from the Adult Psychiatric Morbidity Survey 2007. This was a representative sample of the English adult household population aged ≥16 years (N=7403). The Adult ADHD Self-Report Scale (ASRS) was used to obtain information on ADHD symptoms. The Clinical Interview Schedule Revised (CIS-R) was used to assess six forms of common mental disorder (CMD). Information was also obtained on the lifetime and past 12-month occurrence of suicide ideation and attempts. Logistic regression analysis was used to examine these associations. After adjusting for comorbid disorders, adults with more ADHD symptoms had significantly higher odds for suicidal behavior. When a single cut-off point was used to classify ADHD (ASRS score ≥14), odds ratios ranged from 1.62 (lifetime suicide attempt) to 2.43 (past 12-month suicide ideation). When ADHD symptoms were categorized by strata (I: a score of 0-9; II: 10-13; III: 14-17; IV: 18-24), compared to adults in stratum I, those in stratum IV had odds ratios ranging from 2.16 (lifetime suicide ideation) to 3.68 (past 12-month suicide attempt). ADHD and suicide data came from self-reports which may have been affected by socially desirable responding. ADHD symptoms were linked to suicidal behavior after controlling for comorbid conditions. Health care professionals should be alerted to the increased suicide risk among adults with ADHD symptoms.


Community analysis of betaproteobacterial ammonia-oxidizing bacteria using the amoCAB operon.
The genes and intergenic regions of the amoCAB operon were analyzed to establish their potential as molecular markers for analyzing ammonia-oxidizing betaproteobacterial (beta-AOB) communities. Initially, sequence similarity for related taxa, evolutionary rates from linear regressions, and the presence of conserved and variable regions were analyzed for all available sequences of the complete amoCAB operon. The gene amoB showed the highest sequence variability of the three amo genes, suggesting that it might be a better molecular marker than the most frequently used amoA to resolve closely related AOB species. To test the suitability of using the amoCAB genes for community studies, a strategy involving nested PCR was employed. Primers to amplify the whole amoCAB operon and each individual gene were tested. The specificity of the products generated was analyzed by denaturing gradient gel electrophoresis, cloning, and sequencing. The fragments obtained showed different grades of sequence identity to amoCAB sequences in the GenBank database. The nested PCR approach provides a possibility to increase the sensitivity of detection of amo genes in samples with low abundance of AOB. It also allows the amplification of the almost complete amoA gene, with about 300 bp more sequence information than the previous approaches. The coupled study of all three amo genes and the intergenic spacer regions that are under different selection pressure might allow a more detailed analysis of the evolutionary processes, which are responsible for the differentiation of AOB communities in different habitats.


Estimating global agricultural effects of geoengineering using volcanic eruptions.
Solar radiation management is increasingly considered to be an option for managing global temperatures1,2, yet the economic effects of ameliorating climatic changes by scattering sunlight back to space remain largely unknown3. Although solar radiation management may increase crop yields by reducing heat stress4, the effects of concomitant changes in available sunlight have never been empirically estimated. Here we use the volcanic eruptions that inspired modern solar radiation management proposals as natural experiments to provide the first estimates, to our knowledge, of how the stratospheric sulfate aerosols created by the eruptions of El Chichón and Mount Pinatubo altered the quantity and quality of global sunlight, and how these changes in sunlight affected global crop yields. We find that the sunlight-mediated effect of stratospheric sulfate aerosols on yields is negative for both C4 (maize) and C3 (soy, rice and wheat) crops. Applying our yield model to a solar radiation management scenario based on stratospheric sulfate aerosols, we find that projected mid-twenty-first century damages due to scattering sunlight caused by solar radiation management are roughly equal in magnitude to benefits from cooling. This suggests that solar radiation management-if deployed using stratospheric sulfate aerosols similar to those emitted by the volcanic eruptions it seeks to mimic-would, on net, attenuate little of the global agricultural damage from climate change. Our approach could be extended to study the effects of solar radiation management on other global systems, such as human health or ecosystem function.


Mechanism of ion transfer in supported liquid membrane systems: electrochemical control over membrane distribution.
A polarization study carried out on a thin supported liquid membrane separating two aqueous compartments is presented. Transfer of both the ionized and uncharged form of an organic tracer dye, rhodamine B ([9-(2-carboxyphenyl)-6-diethylamino-3-xanthenylidene]-diethylammonium chloride), across supported liquid membranes composed of one of 1-octanol (octan-1-ol), 1,9-decadiene (deca-1,9-diene), 1,2-dichlorobenzene, or nitrophenyl octyl ether (1-(2-nitrophenoxy)octane) was studied using cyclic voltammetry and UV-vis absorption spectrophotometry. Concentration analysis indicates that the high membrane concentration of rhodamine B determines the ionic transfer observed via voltammetry, which is consistent with the low aqueous ionic concentration and large membrane/aqueous distribution of the molecule. The observed double-transfer voltammogram, although it has been largely neglected in previous literature, is a logical consequence of the presence of two liquid-liquid interfaces and is rationalized in terms of ion transfer across the two interfaces on either side of the membrane and supported by voltammograms obtained for a series of ions of varied lipophilicity. The bipolar nature of the voltammetric response offers an effective way of mass transport control via changing polarity of the applied voltage and finds immediate use in extraction, purification, and separation applications.


In silico discrimination of single nucleotide polymorphisms and pathological mutations in human gene promoter regions by means of local DNA sequence context and regularity.
DNA sequence features were sought that could be used for the in silico ascertainment of the likely functional consequences of single nucleotide changes in human gene promoter regions. To identify relevant features of the local DNA sequence context, we transformed into consensus tables the nucleotide composition of sequences flanking 101 promoter SNPs of type C<-->T or A<-->G, defined empirically as being either 'functional' or 'non-functional' on the basis of a standardised reporter gene assay. The similarity of a given sequence to these consensus tables was then measured by means of the Shapiro-Senapathy score. A decision rule with the potential to discriminate between empirically ascertained functional and non-functional SNPs was proposed that potentiated discrimination between functional and non-functional SNPs with a sensitivity of 80% and a specificity of 20%. Two further datasets (viz. disease-associated SNPs of types A<-->G and C<-->T (N = 75) and pathological promoter mutations (transitions, N = 114)) were retrieved from the Human Gene Mutation Database (HGMD; http://www.hgmd.org/) and analyzed using consensus tables derived from the functional and non-functional promoter SNPs; approximately 70% were correctly recognized as being of probable functional significance. Complexity analysis was also used to quantify the regularity of the local DNA sequence environment. Functional SNPs/mutations of type C<-->T were found to occur in DNA regions characterized by lower average sequence complexity as measured with respect to symmetric elements; complexity values increased gradually from functional SNPs and pathological mutations to functional disease-associated SNPs and non-functional SNPs. This may reflect the internal axial symmetry that frequently characterizes transcription factor binding sites.


New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep.
Glycine is a non-essential amino acid that has indispensable roles in both excitatory and inhibitory neurotransmission via N-methyl-D-aspartate type glutamate receptors and glycine receptors, respectively. We recently reported that glycine ingestion before bedtime significantly ameliorated subjective sleep quality in individuals with insomniac tendencies. Oral administration of glycine to rats was found to induce a significant increase in the plasma and cerebrospinal fluid glycine concentrations and a significant decrease in the core body temperature associated with an increase in cutaneous blood flow. The decline in the core body temperature might be a mechanism underlying glycine's effect on sleep, as the onset of sleep is known to involve a decrease in the core body temperature. Moreover, a low core body temperature is maintained during sleep in humans. Pharmacological studies investigating the mechanisms of glycine on sleep were also performed. In this review, we will describe both our recent findings regarding how and where orally administered glycine acts and findings from our rat study and human trials.


Treatment with Angiotensin-(1-7) reduces inflammation in carotid atherosclerotic plaques.
Angiotensin (Ang)-(1-7), acting through the receptor Mas, has atheroprotective effects; however, its role on plaque vulnerability has been poorly studied. Here, we investigated the expression of the renin-angiotensin system (RAS) components in stable and unstable human carotid plaques. In addition, we evaluated the effects of the chronic treatment with an oral formulation of Ang-(1-7) in a mouse model of shear stress-determined carotid atherosclerotic plaque. Upstream and downstream regions of internal carotid plaques were obtained from a recently published cohort of patients asymptomatic or symptomatic for ischaemic stroke. Angiotensinogen and renin genes were strongly expressed in the entire cohort, indicating an intense intraplaque modulation of the RAS. Intraplaque expression of the Mas receptor mRNA was increased in the downstream portion of asymptomatic patients as compared to corresponding region in symptomatic patients. Conversely, AT1 receptor gene expression was not modified between asymptomatic and symptomatic patients. Treatment with Ang-(1-7) in ApoE-/- mice was associated with increased intraplaque collagen content in the aortic root and low shear stress-induced carotid plaques, and a decreased MMP-9 content and neutrophil and macrophage infiltration. These beneficial effects were not observed in the oscillatory shear stress-induced plaque. In vitro incubation with Ang-(1-7) did not affect ICAM-1 expression and apoptosis on cultured endothelial cells. In conclusion, Mas receptor is up regulated in the downstream portions of human stable carotid plaques as compared to unstable lesions. Treatment with the oral formulation of Ang-(1-7) enhances a more stable phenotype in atherosclerotic plaques, depending on the local pattern of shear stress forces.


Zonal distribution of the cation lucigenin in rat liver: influence of taurocholate.
The yellow fluorescent cation lucigenin (LU) was used as a model compound to study acinar heterogeneity in transport of hydrophilic cations that enter the liver by adsorptive endocytosis. Hepatic uptake was fast and saturable. The extraction was about 50% in a cyclically perfused rat liver preparation in which endogenous bile salts were replaced by the infusion of taurocholate (TC). Fluorescence microscopy on 8-microns liver sections revealed a striking distribution pattern. LU appeared to be concentrated in micro- and macrovesicular structures in the cell. At the same time, LU skipped the first cells of the acinus, zone 1 in an antegrade and zone 3 in a retrograde perfusion. A downstream localization of the dye was the result. Single-pass perfusions with TC concentrations ranging from 0 to 180 microM showed that hepatic clearance of LU negatively correlated with the TC concentration (p less than 0.005). Clearance fell from 1.99 +/- 0.06 ml/min-g of liver(mean +/- SD) without TC to 1.61 +/- 0.21 with 45 microM TC and 1.65 +/- 0.12 with 180 microM TC. Moreover, in the absence of TC we observed a homogeneous distribution of LU. TC induced in the acinus a nonfluorescent upstream area that expanded with increasing TC concentration. We concluded that TC inhibited uptake of LU; a high medium concentration of TC in zone 1 (antegrade) was accompanied by a low uptake of LU in this zone, resulting in a downstream increasing acinar gradient. Hepatic uptake and acinar distribution of certain cationic drugs in vivo may, therefore, vary with the variable input of bile salts in the portal circulation and, hence, with nutritional status and the time of day.


Chemical changes in the photoreceptor outer segments due to iron induced oxidative stress: analysis by Fourier transform infrared (FT-IR) microspectroscopy.
Oxidative stress is thought to be an important pathogenic mechanism in many diseases of the retina. The purpose of this study was to investigate the chemical changes that are present in the photoreceptor outer segments of the retina following exposure to oxidative stress. Fourier transform infrared (FT-IR) microspectroscopy enables the characterization and semi-quantitation of chemical functional groups in microscopic regions of tissue sections. This technique was used to evaluate the chemical changes in the outer segments following exposure to ferrous sulfate, which promotes oxidative tissue damage. A reduction of C=C-H and C=O functional groups was observed in the outer segments of iron-injected eyes compared to vehicle-injected eyes at 3 days following injection, which is prior to major histological changes that occur by 7 days. These functional groups are found in docosahexaenoic acid (DHA), which is present at a high concentration in the outer segments. DHA contains a series of six cis-conjugated double bonds, which are vulnerable to free radical attack, and the reduction of these unsaturation group absorptions suggests that DHA was degraded and/or removed from the outer segments. An unexpected finding was that several other chemical functional groups increased in concentration over time in the outer segments of vehicle-injected eyes compared to non-injected eyes. These increases generally did not include C=C-H or C=O, which suggests that either DHA was being degraded while other organic molecules were being concentrated, or that production of DHA failed to be upregulated in vehicle-injected eyes. In summary, there was a loss of both C=C-H and C=O functional group concentrations in the outer segments of iron-injected eyes, and there was an increased concentration of several other chemical functional groups following trauma induced by vehicle injection.


Improving AfriPop dataset with settlement extents extracted from RapidEye for the border region comprising South-Africa, Swaziland and Mozambique.
For modelling the spatial distribution of malaria incidence, accurate and detailed information on population size and distribution are of significant importance. Different, global, spatial, standard datasets of population distribution have been developed and are widely used. However, most of them are not up-to-date and the low spatial resolution of the input census data has limitations for contemporary, national- scale analyses. The AfriPop project, launched in July 2009, was initiated with the aim of producing detailed, contemporary and easily updatable population distribution datasets for the whole of Africa. High-resolution satellite sensors can help to further improve this dataset through the generation of high-resolution settlement layers at greater spatial details. In the present study, the settlement extents included in the MALAREO land use classification were used to generate an enhanced and updated version of the AfriPop dataset for the study area covering southern Mozambique, eastern Swaziland and the malarious part of KwaZulu-Natal in South Africa. Results show that it is possible to easily produce a detailed and updated population distribution dataset applying the AfriPop modelling approach with the use of high-resolution settlement layers and population growth rates. The 2007 and 2011 population datasets are freely available as a product of the MALAREO project and can be downloaded from the project website.


A pharmacy too far? Equity and spatial distribution of outcomes in the delivery of subsidized artemisinin-based combination therapies through private drug shops.
Millions of individuals with malaria-like fevers purchase drugs from private retailers, but artemisinin-based combination therapies (ACTs), the only effective treatment in regions with high levels of resistance to older drugs, are rarely obtained through these outlets due to their relatively high cost. To encourage scale up of ACTs, the Affordable Medicines Facility--malaria is being launched to subsidize their price. The Government of Tanzania and the Clinton Foundation piloted this subsidized distribution model in two Tanzanian districts to examine concerns about whether the intervention will successfully reach poor, rural communities. Stocking of ACTs and other antimalarial drugs in all retail shops was observed at baseline and in four subsequent surveys over 15 months. Exit interviews were conducted with antimalarial drug customers during each survey period. All shops and facilities were georeferenced, and variables related to population density and proximity to distribution hubs, roads, and other facilities were calculated. To understand the equity of impact, shops stocking ACTs and consumers buying them were compared to those that did not, according to geographic and socioeconomic variables. Patterning in ACT stocking and sales was evaluated against that of other common antimalarials to identify factors that may have impacted access. Qualitative data were used to assess motivations underlying stocking, distribution, and buying disparities. Results indicated that although total ACT purchases rose from negligible levels to nearly half of total antimalarial sales over the course of the pilot, considerable geographic variation in stocking and sales persisted and was related to a variety of socio-spatial factors; ACTs were stocked more often in shops located closer to district towns (p<0.01) and major roads (p<0.01) and frequented by individuals of higher socioeconomic status (p<0.01). However, other antimalarial drugs displayed similar patterning, indicating the existence of underlying disparities in access to antimalarial drugs in general in these districts. As this subsidy model is scaled up across multiple countries, these results confirm the potential for increased ACT usage but suggest that additional efforts to increase access in remote areas will be needed for the scale-up to have equitable impact. Current Controlled Trials ISRCTN39125414.


Anchoring vignettes in the Health and Retirement Study: how do medical professionals and disability recipients characterize the severity of work limitations?
Recent studies report systematic differences in how individuals categorize the severity of identical health and work limitation vignettes. We investigate how health professionals and disability recipients characterize the severity of work limitations and whether their reporting patterns are robust to demographic, education, and health characteristics. We use the results to illustrate the potential impact of reporting heterogeneity on the distribution of work disability estimated from self-reported categorical health and disability data. Nationally representative data on anchoring disability vignettes from the 2004 Health and Retirement Study (HRS) are used to investigate how respondents with an occupation background in health and Social Security disability beneficiaries categorize work limitation vignettes. Using pain, cardiovascular health, and depression vignettes, we estimate generalized ordered probit models (N = 2,660 individuals or 39,681 person-vignette observations) that allow the severity thresholds to vary by respondent characteristics. We find that health professionals (excluding nurses) and disability recipients tend to classify identical work limitations as more severe compared to non-health professional non-disabled respondents. For disability recipients, the differences are most pronounced and particularly visible in the tails of the work limitations distribution. For health professionals, we observe smaller differences, affecting primarily the classification of mildly and moderately severe work limitations. The patterns for health professionals (excluding nurses) are robust to demographics, education, and health conditions. The greater likelihood of viewing the vignette person as more severely work limited observed among disability recipients is mostly explained by the fact that these respondents also tend to be in poorer health which itself predicts a more inclusive scale. Knowledge of reporting scales from health professionals and disabled individuals can benefit researchers in a broad range of applications in health and disability research. They may be useful as reference scales to evaluate disability survey data. Such knowledge may be beneficial when studying disability programs. Given the increasing availability of anchoring vignette data in surveys, this is a promising area for future evaluation research.


Genomic actions of estrogen receptor alpha: what are the targets and how are they regulated?
The estrogen receptor alpha (ERalpha) is a ligand-dependent transcription factor that regulates a large number of genes in many different target tissues and is important in the development and progression of breast cancer. ERalpha-mediated transcription is a complex process regulated at many different levels. The interplay between ligand, receptor, DNA sequence, cofactors, chromatin context, and post-translational modifications culminates in transcriptional regulation by ERalpha. Recent technological advances have allowed the identification of ERalpha target genes on a genome-wide scale. In this review, we provide an overview of the progress made in our understanding of the different levels of regulation mediated by ERalpha. We discuss the recent advances in the identification of the ERalpha-binding sites and target gene network and their clinical applications.


The effect of weather on peritoneal dialysis (PD) prescription: seasonal variation in PD dialysate utilization.
There have been no reports on peritoneal dialysis (PD) solution utilization since this treatment was developed in the 1920s. The aim of the present investigation was to investigate if weather affects PD prescription. This 10-year observational study used the Taiwan National Health Insurance Research Database. Claims for different concentrate PD dialysate were analyzed monthly. 2.5% and 4.25% PD solutes were defined as hypertonic solutions. Monthly outdoor mean temperature. Outcome and Measurement: The relationship between monthly mean of PD dialysate utilization and monthly outdoor temperature was analyzed by linear regression. Monthly mean PD dialysate utilization amount in 4 quarters was analyzed by ANOVA. During the 10-year study period, a clear seasonal variation in PD dialysate was observed. This seasonal variation was present regardless of age, gender, and the presence of hypertension, diabetes, and dyslipidemia. Monthly mean temperature was positively correlated to 1.5% dialysate utilization amount (r = 0.559, p < 0.001) and negatively correlated to 2.5% (r = -0.533, p < 0.001) and 4.25% (r = -0.410, p < 0.001) dialysate utilization amount. In longitudinal follow-up, hypertonic PD fluid utilization was higher in diabetic patients than in nondiabetic patients from the beginning of treatment. Thereafter, it increased rapidly and reached a plateau within 1 year. Analysis of ultrafiltration amount, blood pressure, and body weight was unfeasible due to the nature of the database. The utilization of differential strengths of PD solutions has a seasonal cyclic pattern, with more hypertonic PD solution utilized in winter and more hypotonic PD solution in summer.


Endogenous stem cell proliferation after central nervous system injury: alternative therapeutic options.
The continuous regeneration of glial cells arising from endogenous stem cell populations in the central nervous system (CNS) occurs throughout life in mammals. In the ongoing research to apply stem cell therapy to neurological diseases, the capacity to harness the multipotential ability of endogenous stem cell populations has become apparent. Such cell populations proliferate in response to a variety of injury states in the CNS, but in the absence of a supportive microenvironment they contribute little to any significant behavioral recovery. In the authors' laboratory and elsewhere, recent research on the regenerative potential of these stem cells in disease states such as spinal cord injury has demonstrated that the cells' proliferative potential may be greatly upregulated in response to appropriate growth signals and exogenously applied trophic factors. Further understanding of the potential of such multipotent cells and the mechanisms responsible for creating a favorable microenvironment for them may lead to additional therapeutic alternatives in the setting of neurological diseases. These therapies would require no exogenous stem cell sources and thus would avoid the ethical and moral considerations regarding their use. In this review the authors provide a brief overview of the enhancement of endogenous stem cell proliferation following neurological insult.


Association of cocaine- and amphetamine-related transcript, leptin and leptin receptor gene polymorphisms with anthropometric obesity phenotype indicators in South African learners.
Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys(109)Arg G allele was associated with an average reduction of 2.36 kg/m(2) in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. Our findings suggest that c.517A→G and Lys(109)Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group.


Preventing provider errors: online total parenteral nutrition calculator.
To describe the development of a pragmatic low-cost medical information system that reduces errors in the ordering of total parenteral nutrition (TPN) in the newborn intensive care unit at the Johns Hopkins Hospital. We designed an online total parenteral nutrition order entry system (TPNCalculator) using Internet technologies. Utilization, impact on medical errors, and user satisfaction were evaluated prior to and immediately after introduction of TPNCalculator (intervention 1) and after 2 years (intervention 2). Total software development time was 3 weeks. The number of orders was similar during the 3 periods: 0.39 orders per patient per day (N = 557) were received compared with 0.35 and 0.43 orders per patient per day (N = 471 and N = 656) in 2 intervention periods. During the control period, an average of 10.8 errors were detected per 100 TPN orders compared with 4.2 per 100 orders in the first intervention period (61% reduction of error rate) and 1.2 per 100 orders after 2 years and some redesign of TPNCalculator (89% reduction of error rate). We found a reduction in the following types of problems (intervention 1; intervention 2): calculation errors (100%; 100%), osmolality outside the allowed range (88%; 91%), and other knowledge problems (84%; 100%). There was a 35% increase in the number of incomplete forms in the first intervention period and a 100% reduction in the second. Rapid cycle development was used in the development of this application. Users of the system were enthusiastic and supportive and compared it favorably to the previous paper-based system. Low-cost, pragmatic approaches using Internet technology in the design of medical information systems can reduce medical errors and might pose a viable option for the prevention of adverse drug events.


New tools for sex identification and the study of sex allocation in birds.
The recent development of simple, DNA-based methods for the determination of an individual's sex will make possible large-scale studies of sex allocation and the consequence of gender in birds. Birds provide ideal systems for studying these questions in vertebrates, as so much is known about their biology and determinants of fitness. Until recently, however, little quantitative work has been possible because of the difficulty in determining gender in most cases. Recent studies suggest that biased sex allocation be more widespread in birds than has been realized.


Spine Cryoablation: Pain Palliation and Local Tumor Control for Vertebral Metastases.
Percutaneous cryoablation has emerged as a minimally invasive technique for the management of osseous metastases. The purpose of this study was to assess the safety and effectiveness of percutaneous imaging-guided spine cryoablation for pain palliation and local tumor control for vertebral metastases. Imaging-guided spine cryoablation was performed in 14 patients (31 tumors) with vertebral metastases refractory to conventional chemoradiation therapy or analgesics, to achieve pain palliation and local tumor control in this retrospective study. Spinal nerve and soft-tissue thermal protection techniques were implemented in all ablations. Patient response was evaluated by a pain numeric rating scale administered before the procedure and 1 week, 1 month, and 3 months after the procedure. Pre- and postprocedural analgesic requirements (expressed as morphine-equivalent dosages) were also analyzed at the same time points. Pre- and postprocedural cross-sectional imaging was evaluated in all patients to assess local control (no radiographic evidence of disease at the treated sites). Complications were monitored. Analysis of the primary end points was undertaken via paired-comparison procedures by using the Wilcoxon signed rank test. Thirty-one tumors were ablated in 14 patients (9 women and 5 men; 20-73 years of age; mean age, 53 years). The most common tumor location was in the lumbar spine (n = 14, 45%), followed by the thoracic spine (n = 8, 26%), sacrum (n = 6, 19%), coccyx (n = 2, 6%), and cervical spine (n = 1, 3%). There were statistically significant decreases in the median numeric rating scale score and analgesic usage at 1-week, 1-month, and 3-month time points (P < .001 for all). Local tumor control was achieved in 96.7% (30/31) of tumors (median follow-up, 10 months). Two patients had transient postprocedural unilateral lower extremity radiculopathy and weakness. Percutaneous imaging-guided spine cryoablation is a safe and effective treatment for pain palliation and local tumor control for vertebral metastases.