Multimodal CT provides improved performance for lacunar infarct detection.
Lacunar infarcts account for approximately 25% of acute ischemic strokes. Compared with NCCT alone, the addition of CTP improves sensitivity for detection of infarcts overall. Our aim was to systematically evaluate the diagnostic benefit and interobserver reliability of an incremental CT protocol in lacunar infarction. Institutional review board approval and patient consent were obtained. One hundred sixty-three patients presenting with a lacunar syndrome ≤4.5 hours from symptom onset were enrolled. Images were reviewed incrementally by 2 blinded readers in 3 separate sessions (NCCT only, NCCT/CTA, and NCCT/CTA/CTP). Diagnostic confidence was recorded on a 6-point scale with DWI/ADC as a reference. Logistic regression analysis calculated differences between actual and observed diagnoses, adjusted for confidence. Predictive effects of observed diagnostic accuracy and confidence score were quantified with the entropy r(2) value. Sensitivity, specificity, and confidence intervals were calculated accounting for multiple readers. Receiver operating characteristic analyses were compared among diagnostic strategies. Interobserver agreement was established with Cohen κ statistic. The final study cohort comprised 88 patients (50% male). DWI/ADC-confirmed lacunar infarction occurred in 59/88 (67%) with 36/59 (61%) demonstrating a concordant abnormal finding on CTP. Sensitivity for definite or probable presence of lacunar infarct increased significantly from 9.3% to 42.4% with incremental protocol use, though specificity was unchanged (range, 91.9%-95.3%). The observed diagnosis was significantly related to the actual diagnosis after adjusting for CTP confidence level (P = .04) and was 5.1 and 2.4 times more likely to confirm lacunar infarct than NCCT or CTA source images. CTP area under the curve (0.77) was significantly higher than that of CTA source images (0.68, P = .006) or NCCT (0.55, P < .001). CTP offers an improved diagnostic benefit over NCCT and CTA for the diagnosis of lacunar infarction.


Association of Retinal Nerve Fiber Layer Thinning With Current and Future Cognitive Decline: A Study Using Optical Coherence Tomography.
Identifing potential screening tests for future cognitive decline is a priority for developing treatments for and the prevention of dementia. To examine the potential of retinal nerve fiber layer (RNFL) thickness measurement in identifying those at greater risk of cognitive decline in a large community cohort of healthy people. UK Biobank is a prospective, multicenter, community-based study of UK residents aged 40 to 69 years at enrollment who underwent baseline retinal optical coherence tomography imaging, a physical examination, and a questionnaire. The pilot study phase was conducted from March 2006 to June 2006, and the main cohort underwent examination for baseline measures from April 2007 to October 2010. Four basic cognitive tests were performed at baseline, which were then repeated in a subset of participants approximately 3 years later. We analyzed eyes with high-quality optical coherence tomography images, excluding those with eye disease or vision loss, a history of ocular or neurological disease, or diabetes. We explored associations between RNFL thickness and cognitive function using multivariable logistic regression modeling to control for demographic as well as physiologic and ocular variation. Odds ratios (ORs) for cognitive performance in the lowest fifth percentile in at least 2 of 4 cognitive tests at baseline, or worsening results on at least 1 cognitive test at follow-up. These analyses were adjusted for age, sex, race/ethnicity, height, refraction, intraocular pressure, education, and socioeconomic status. A total of 32 038 people were included at baseline testing, for whom the mean age was 56.0 years and of whom 17 172 (53.6%) were women. A thinner RNFL was associated with worse cognitive performance on baseline assessment. A multivariable regression controlling for potential confounders showed that those in the thinnest quintile of RNFL were 11% more likely to fail at least 1 cognitive test (95% CI, 2.0%-2.1%; P = .01). Follow-up cognitive tests were performed for 1251 participants (3.9%). Participants with an RNFL thickness in the 2 thinnest quintiles were almost twice as likely to have at least 1 test score be worse at follow-up cognitive testing (quintile 1: OR, 1.92; 95% CI, 1.29-2.85; P < .001; quintile 2: OR, 2.08; 95% CI, 1.40-3.08; P < .001). A thinner RNFL is associated with worse cognitive function in individuals without a neurodegenerative disease as well as greater likelihood of future cognitive decline. This preclinical observation has implications for future research, prevention, and treatment of dementia.


Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans.
Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common. To report the identification of a mutation in the human CRYGS gene. A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out. The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (theta = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G-->T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011). This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.


Relative Age Effect in Physical Fitness Among Elementary and Junior High School Students.
The present study investigated characteristics of the relative age effect (RAE) among a general sample of Japanese elementary and junior high school students. Japan applies a unique annual age-grouping by birthdates between April 1 and March 31 of the following year for sport and education. Anthropometric and physical fitness data were obtained from 3,610 Japanese students, including height, weight, the 50-m sprint, standing long jump, grip strength, bent-leg sit-ups, sit and reach, side steps, 20-m shuttle run, and ball throw. We examined RAE-related differences in these data using a one-way analysis of variance by comparing students with birthdates in the first (April-September) versus second (October-March of the following year) semesters. We observed a significant RAE for boys aged 7 to 15 years on both anthropometric and fitness data, but a significant RAE for girls was only evident for physical fitness tests among elementary school and not junior high school students. Thus, a significant RAE in anthropometry and physical fitness was evident in a general sample of school children, and there were RAE gender differences among adolescents.


Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women.
Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (SD 118) ng/ml [208 (SD 122) ng/ml in wild-type and 225 (SD 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (SD 36) ng/ml in haemochromatosis patients, and 159 (SD 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes.


Is there an association between PEPFAR funding and improvement in national health indicators in Africa? A retrospective study.
The US President's Emergency Plan for AIDS Relief (PEPFAR) was reauthorized in June 2008 with a three-fold increase in funds, and a broader, more explicit mandate to improve health in the low- and middle-income countries that it funded. However, the ability of a disease-specific, or vertical, programme to have a spill-over effect and improve health outcomes has been questioned. In this study, we sought to examine associations between being designated as a PEPFAR focus country (and receiving increased PEPFAR funding) and non-HIV-specific health outcomes in the World Health Organization (WHO) Africa Region, the area most affected by the HIV/AIDS epidemic. A retrospective analysis of publicly available health outcomes data published by the World Health Organization was performed for all countries in the WHO Africa Region. Fractional changes in health indicators between 2000 and 2006 were calculated, and PEPFAR focus and non-focus countries were then compared. Overall, countries in the WHO Africa Region showed a small worsening in health outcomes status when all indicators were analyzed together and weighted equally. However, more health indicators improved than worsened over this six-year period. A comparison of PEPFAR focus and non-focus countries found no significant difference in the fractional change among 13 of 14 health indicators during the study period. This study suggests that vertical programmes, even one that is the scale of PEPFAR, may have little or no impact on health outcomes not explicitly targeted.


Genetic susceptibility to infectious disease.
Our understanding of the variation in individual clinical responses to pathogens has become increasingly relevant, particularly in the face of new emerging epidemics as well as the increasing number of multi-drug-resistant organisms. An effective immune response to infection has contributed to the development of host genetic diversity through selective pressure, with an increasing number of studies characterizing the role that host genetics plays in disease susceptibility. Knowledge of the role host mechanisms play in the pathogenesis of infectious disease can contribute to the design of new therapeutic strategies. Rapid advances in the field of human genomics offer great opportunities for adopting this approach to find new insights into pathogenesis.


Targeted transgene integration overcomes variability of position effects in zebrafish.
Zebrafish transgenesis is increasingly popular owing to the optical transparency and external development of embryos, which provide a scalable vertebrate model for in vivo experimentation. The ability to express transgenes in a tightly controlled spatio-temporal pattern is an important prerequisite for exploitation of zebrafish in a wide range of biomedical applications. However, conventional transgenesis methods are plagued by position effects: the regulatory environment of genomic integration sites leads to variation of expression patterns of transgenes driven by engineered cis-regulatory modules. This limitation represents a bottleneck when studying the precise function of cis-regulatory modules and their subtle variants or when various effector proteins are to be expressed for labelling and manipulation of defined sets of cells. Here, we provide evidence for the efficient elimination of variability of position effects by developing a PhiC31 integrase-based targeting method. To detect targeted integration events, a simple phenotype scoring of colour change in the lens of larvae is used. We compared PhiC31-based integration and Tol2 transgenesis in the analysis of the activity of a novel conserved enhancer from the developmentally regulated neural-specific esrrga gene. Reporter expression was highly variable among independent lines generated with Tol2, whereas all lines generated with PhiC31 into a single integration site displayed nearly identical, enhancer-specific reporter expression in brain nuclei. Moreover, we demonstrate that a modified integrase system can also be used for the detection of enhancer activity in transient transgenesis. These results demonstrate the power of the PhiC31-based transgene integration for the annotation and fine analysis of transcriptional regulatory elements and it promises to be a generally desirable tool for a range of applications, which rely on highly reproducible patterns of transgene activity in zebrafish.


Congenital Zika Syndrome in Puerto Rico, Beyond Microcephaly, A Multiorgan Approach.
Zika virus (ZIKV) infection was identified in Puerto Rico on December 2015, and the outbreak encouraged us to characterize clinical manifestations and laboratory findings of intrauterine exposed infants. Retrospective medical record review of infants born to mothers with confirmed ZIKV infection during pregnancy was performed from January 2016-June 2017. We included patients admitted to UPH Neonatal Intensive Care Unit or referred for follow-up at UPH High Risk Clinics. The database was approved by the University of Puerto Rico, Medical Sciences Campus, IRB. 191 infants born to ZIKV positive mothers during pregnancy were identified. Normal head sonogram was found in 93% of the normo cephalic infants. Ocular findings were reported in 50% of the patients with microcephaly and 31% of the normo-cephalics. Fifteen newborns (7.8%) presented with microcephaly, of which 73% showed calcifications in head sonogram, and had severe anomalies on brain MRI. Auditory brainstem response test was performed on all newborns, 80% were within normal limits. Among the group of infants born to mothers with Zika positive test 4% had microcephaly. Of concern to us is the fact that 31% of normo cephalic infants had ocular manifestations and 7% of them had findings on head sonogram. While microcephaly is the severest form of Congenital Zika Syndrome, ocular manifestations might characterize the spectrum of disease. These findings reiterate the importance of detailed neonatal evaluations of exposed infants.


Antibiotics in surgical treatment of acute abscesses.
A four-way, double-blind, prospective trial of treatment of abscesses by incision, curettage, and primary closure with and without antibiotic cover (clindamycin injection before operation or capsules after operation, or both) was conducted. There was no appreciable difference in mean healing time between the patients given both the antibiotic injection and the antibiotic capsules and those given the injection and placebo capsules, whereas healing times in those given the placebo injection and antibiotic capsules or placebo only were appreciably longer. Four of the patients who were not given the antibiotic injection developed bacteraemia; one patient who was given the antibiotic injection also developed a bacteraemia, but this was caused by clindamycin-resistant bacteria. These results show that a single injection of an effective antibiotic before operation is sufficient to protect the patient against bacteraemia and permit optimum healing.


Diffusion tensor imaging in orthostatic tremor: a tract-based spatial statistics study.
The pathogenesis of orthostatic tremor (OT) is unknown. We investigated OT-related white matter changes and their correlations with scores from a neuropsychological testing battery. Diffusion tensor imaging measures were compared between 14 OT patients and 14 age- and education-matched healthy controls, using whole-brain tract-based spatial statistics analysis. Correlations between altered diffusion metrics and cognitive performance in OT group were assessed. In all cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language), OT patients' cognitive performance was significantly worse than that of healthy controls. OT patients demonstrated altered diffusivity metrics not only in the posterior lobe of the cerebellum (left cerebellar lobule VI) and in its efferent cerebellar fibers (left superior cerebellar peduncle), but also in medial lemniscus bilaterally (pontine tegmentum), anterior limb of the internal capsule bilaterally, right posterior limb of the internal capsule, left anterior corona radiata, right insula, and the splenium of corpus callosum. No relationship was found between diffusion measures and disease duration in OT patients. Diffusion white matter changes, mainly those located in right anterior limb of the internal capsule, were correlated with poor performance on tests of executive function, visuospatial ability, verbal memory, and visual memory in OT patients. White matter changes were preferentially located in the cerebellum, its efferent pathways, as well as in the pontine tegmentum and key components of the frontal-thalamic-cerebellar circuit. Further work needs to be done to understand the evolution of these white matter changes and their functional consequences.


Recovery of nitrogen from saponification wastewater by struvite precipitation.
In general, saponification wastewater produced from the separation process of rare-earth elements contains high ammonium concentration. In this study, a series of experiments were conducted to investigate the parameters to enhance the struvite precipitation potential for ammonium removal from the wastewater having an ammonium concentration of 4,100 mg/L. Experimental results showed that increasing the dose and grain size of pre-formed struvite, which was added as the seeding material in struvite reaction, could increase ammonium removal. The removal efficiency increased 7.6% when the dose of pre-formed struvite with crystal grain size range of 0.098-0.150 mm increased from 0 g/L to 60 g/L. Additionally, struvite precipitation was tested with the intermittent addition of magnesium and phosphate to utilize the struvite crystals formed during the reaction process as the seeding material for the subsequent reaction. The results revealed that intermittently adding magnesium 7 times effectively enhanced ammonium removal by around 8%, which was equivalent to that of using pre-formed struvite as the seeding material. Furthermore, the chemical composition of the struvite recovered with intermittent addition of magnesium was characterized, showing the struvite could be used as fertilizer. An economic evaluation indicated that intermittent addition of magnesium 7 times can save 13.4% cost for recovering per kg NH(4)(+) compared to that of bulk addition.


Analysis of curated and predicted plastid subproteomes of Arabidopsis. Subcellular compartmentalization leads to distinctive proteome properties.
Carefully curated proteomes of the inner envelope membrane, the thylakoid membrane, and the thylakoid lumen of chloroplasts from Arabidopsis were assembled based on published, well-documented localizations. These curated proteomes were evaluated for distribution of physical-chemical parameters, with the goal of extracting parameters for improved subcellular prediction and subsequent identification of additional (low abundant) components of each membrane system. The assembly of rigorously curated subcellular proteomes is in itself also important as a parts list for plant and systems biology. Transmembrane and subcellular prediction strategies were evaluated using the curated data sets. The three curated proteomes differ strongly in average isoelectric point and protein size, as well as transmembrane distribution. Removal of the cleavable, N-terminal transit peptide sequences greatly affected isoelectric point and size distribution. Unexpectedly, the Cys content was much lower for the thylakoid proteomes than for the inner envelope. This likely relates to the role of the thylakoid membrane in light-driven electron transport and helps to avoid unwanted oxidation-reduction reactions. A rule of thumb for discriminating between the predicted integral inner envelope membrane and integral thylakoid membrane proteins is suggested. Using a combination of predictors and experimentally derived parameters, four plastid subproteomes were predicted from the fully annotated Arabidopsis genome. These predicted subproteomes were analyzed for their properties and compared to the curated proteomes. The sensitivity and accuracy of the prediction strategies are discussed. Data can be extracted from the new plastid proteome database (http://ppdb.tc.cornell.edu).


Effectiveness of tuberculosis chemotherapy correlates with resistance to Mycobacterium tuberculosis infection in animal models.
It is widely believed that persistent Mycobacterium tuberculosis inhabits necrotic lung granulomas in humans and that the microenvironmental conditions encountered therein render the bacilli phenotypically tolerant to antibiotics, accounting for the long duration required for successful treatment of tuberculosis (TB). To validate this belief, we directly compared the activity of rifampicin/isoniazid/pyrazinamide (RHZ) against chronic TB infection in guinea pigs, which exhibit caseous granulomas histologically resembling human caseous foci, and in mice, which lack necrotic granulomas. Guinea pigs and mice were aerosol-infected with M. tuberculosis CDC1551 and twice weekly treatment with RHZ was started 4 weeks later. Culture-positive relapse was assessed in subgroups of guinea pigs after 3 months and 4 months of treatment. All guinea pig lungs exhibited histological evidence of granulomas with central caseation, while mouse lungs exhibited cellular lesions at the initiation of antibiotic treatment. Guinea pig lungs became culture-negative after 2 months of RHZ given twice weekly at human-equivalent doses. Relapse rates in guinea pigs were 0% (0/10) both after 3 months and 4 months of treatment. In contrast, all mouse lungs remained culture-positive after 4 months of equivalent RHZ exposures. Caseous necrosis does not reduce the sterilizing activity of the standard antituberculosis regimen of RHZ. Our findings have important implications for the use of alternative animal models in testing novel TB drug regimens and for modelling M. tuberculosis persistence.


Tomographic correlation for Magerl's technique in C1-C2 arthrodesis in children.
To analyze through tomographic studies, the morphology and dimensions of the C1-C2 vertebrae in pediatric patients, to evaluate the possibility of application of Magerl's technique in these patients, and to contribute with data for the usage of the technique in safety. Forty normal cervical tomographies, from patients at an age range of 24-120 months of age and from both genders, were retrospectively analyzed. Data was statistically analyzed to obtain mean value and variations of each measurement: length from the C2's pedicle to C1's lateral mass, thickness of the pedicle of C2, the attack angle of the screw at the C2 isthmus with the horizontal axis and the distance from the odontoid to the anterior arch of C1. THE MEAN VALUES OBTAINED WERE: length right 30.86 mm, left 31.47 mm; thickness right 5.28 mm, left 5.26 mm; attack angle right 46.25(0) , left 44.50(0) ; distance from odontoid to anterior arch of C1 2,17 mm. The Magerl technique, after tomographic study, seems to be a viable option to be used in pediatric patients. Level of Evidence IV, Case Series.


Cutaneous toxoplasmosis after bone marrow transplantation with molecular confirmation.
Toxoplasmosis is a rare and often fatal complication of hematopoietic stem cell transplantation (HSCT). The diagnosis of toxoplasmosis is usually made at autopsy because of the variety of systemic manifestations and the difficulty of diagnosis by serologic methods in the severely immunocompromised patient. Cutaneous toxoplasmosis in this setting is extremely rare and is difficult to diagnose with certainty because of the morphologic similarity of Toxoplasma gondii to other organisms, such as Leishmania and Histoplasma species. We report a patient who developed systemic toxoplasmosis, manifested as encephalitis and cutaneous lesions, after HSCT. Findings of a skin biopsy led to a tentative histologic diagnosis of toxoplasmosis, confirmed by polymerase chain reaction (PCR) examination of the skin biopsy and cerebrospinal fluid. This is, to our knowledge, the first report of cutaneous toxoplasmosis diagnosed by skin biopsy confirmed by PCR and sequencing. This disease may be more common than is generally appreciated in severely immunocompromised patients. PCR is a valuable adjunct to diagnosis.


Accessibility over availability: associations between the school food environment and student fruit and green vegetable consumption.
No national studies have examined associations between (1) school food availability and accessibility and (2) secondary student fruit and vegetable (FV) consumption. This article uses 5 years of nationally representative data from secondary school students to examine associations between the school food environment and student fruit and green vegetable consumption. From 2008 to 2012, cross-sectional, nationally representative data from US middle and high school students were collected annually on self-reported fruit and green vegetable consumption. Each year, data from administrators at each relevant school were collected on food item availability (any venue) and accessibility (total number of school sources). Data were obtained from 10,254 eighth-grade students in 317 schools and 18,898 tenth- and 12th-grade students in 518 schools. Associations were estimated by multi-level models controlling for student- and school-level characteristics. Availability showed minimal association with student consumption. Candy/regular-fat snack accessibility was associated negatively with middle school fruit consumption. Salad bar availability and accessibility were positively associated with middle school green vegetable consumption; FV accessibility was associated positively with high school fruit and green vegetable consumption. Significant associations were consistent across student racial/ethnic and socioeconomic groups. Forthcoming USDA nutrition standards for school foods and beverages sold outside of reimbursable meal programs should result in the removal of school candy/regular-fat snacks. In deciding which items to make available under the new standards, schools should consider increasing the number of FV sources-including salad bars-thereby potentially increasing student FV consumption.


Catheter-Associated Urinary Tract Infection and Obstinate Biofilm Producers.
Biofilms, or colonies of uropathogen growing on the surface of indwelling medical devices, can inflict obstinate or recurring infection, thought-provoking antimicrobial therapy. This prospective analysis included 105 urine samples from catheterized patients receiving intensive care. Ensuing phenotypic identification, antibiotic sensitivity test was performed by modified Kirby-Bauer disc diffusion method following CLSI guidelines; MDR isolates were identified according to the combined guidelines of the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC). Biofilm-forming uropathogens were detected by the tissue culture plate (TCA) method. The predominant uropathogen in catheter-associated UTIs (CAUTIs) was Escherichia coli 57%, followed by Klebsiella pneumonia 15%, Pseudomonas aeruginosa 12%, Staphylococcus aureus 8%, Enterobacter spp. 3%, Enterococcus faecalis, Acinetobacter spp., and Proteus mirabilis 1.5%, of which 46% isolates were biofilm producers. Prime biofilm producers were Escherichia coli 33%, followed by Klebsiella pneumoniae 30%, Pseudomonas aeruginosa 20%, Staphylococcus aureus 10%, Acinetobacter, and Enterobacter 3.33%. Multidrug resistance associated with biofilm producers were greater than biofilm nonproducers. The Gram-negative biofilm producers found 96.15%, 80.76%, 73.07%, 53.84%, 53.84%, 46.15%, 19.23%, and 11.5% resistant to amoxyclave, ceftazidime, tetracycline, gentamicin, meropenem, nitrofurantoin, amikacin, imipenem, and fosfomycin, respectively. Gram-positive biofilm producers, however, were found 100% resistant to tetracycline, cloxacillin, and amoxyclave: 66.67% resistant to ampicillin while 33.33% resistant to gentamicin, ciprofloxacin, and nitrofurantoin. High antimicrobial resistance was observed in biofilm producers than non-biofilm producers. Of recommended antimicrobial therapies for CAUTIs, ampicillin and amoxicillin-clavulanate were the least active antibiotics, whereas piperacillin/tazobactam and imipenem were found as the most effectual for gram-negative biofilm producer. Likewise, amoxicillin-clavulanate and tetracycline were the least active antibiotics, whereas vancomycin, fosfomycin, piperacillin-tazobactam, and meropenem were found as the most effective antibiotic for Gram-positive biofilm producer. In the limelight, the activity fosfomycin was commendable against both Gram-positive and Gram-negative biofilm producers.


In vitro study of odor-evoked behavior in a terrestrial mollusk.
To explore neural mechanisms how olfactory information is processed in the brain and finally converted into behavior, it would be useful to have isolated whole brains that include both olfactory organs and motor output. In the present study, we identified an in vitro index of odor-evoked behavior in the terrestrial mollusk Limax and also studied the modulation of this in vitro index of the behavior. We determined that shortening of the mantle muscles is one of the withdrawal responses selectively induced by aversive odors and that the shortening is mediated by a pair of parietal nerves. We also identified a motoneuron (named the posterior visceral neuron, p-VN) that projects to the parietal nerve and innervates the mantle muscles. When we applied various odors to the nose in these isolated molluscan brains, only aversive odors induced discharges in the p-VN. These results indicate that p-VN discharges can serve as an in vitro index of odor-induced aversive behavior. We also identified a novel serotonergic neuron (named the posterior cerebral serotonergic cell, p-CSC). Discharges in the p-CSC released serotonin to the tentacle ganglion (TG); serotonin in the TG then inhibited odor-induced discharges in the p-VN, the in vitro index of aversive behavior. These results suggest that the serotonergic system is involved in the regulation of approach and avoidance behavior in Limax.


Statistics of the sparse spectrum turbulent phase.
A recently published sparse spectrum (SS) model of the phase front perturbations by atmospheric turbulence [J. Opt. Soc. Am. A 30, 479 (2013)] is based on the trigonometric series with discrete random support. The SS model enables fewer computational efforts, while preserving the wide range of scales typically associated with turbulence perturbations. We present an improved version of the SS model that accurately reproduces the power-law spectral density of the phase fluctuations in the arbitrary wide spectral band. We examine the higher-order statistics of the SS phase samples for four versions of the SS model. We also present the calculations of the long-exposure Strehl numbers and scintillation index for the different versions of the SS model. A nonoverlapping SS model with a log-uniform partition emerges as the most appropriate for the atmospheric turbulence representation.


Neuroprotection for ischemic stroke: past, present and future.
Neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection. Rigorously conducted experimental studies in animal models of brain ischemia provide incontrovertible proof-of-principle that high-grade protection of the ischemic brain is an achievable goal. Nonetheless, many agents have been brought to clinical trial without a sufficiently compelling evidence-based pre-clinical foundation. At this writing, around 160 clinical trials of neuroprotection for ischemic stroke have been initiated. Of the approximately 120 completed trials, two-thirds were smaller early-phase safety-feasibility studies. The remaining one-third were typically larger (>200 subjects) phase II or III trials, but, disappointingly, only fewer than one-half of these administered neuroprotective therapy within the 4-6h therapeutic window within which efficacious neuroprotection is considered to be achievable. This fact alone helps to account for the abundance of "failed" trials. This review presents a close survey of the most extensively evaluated neuroprotective agents and classes and considers both the strengths and weakness of the pre-clinical evidence as well as the results and shortcomings of the clinical trials themselves. Among the agent-classes considered are calcium channel blockers; glutamate antagonists; GABA agonists; antioxidants/radical scavengers; phospholipid precursor; nitric oxide signal-transduction down-regulator; leukocyte inhibitors; hemodilution; and a miscellany of other agents. Among promising ongoing efforts, therapeutic hypothermia, high-dose human albumin therapy, and hyperacute magnesium therapy are considered in detail. The potential of combination therapies is highlighted. Issues of clinical-trial funding, the need for improved translational strategies and clinical-trial design, and "thinking outside the box" are emphasized.


Genome-Wide Analysis of RNA Secondary Structure.
Single-stranded RNA molecules fold into extraordinarily complicated secondary and tertiary structures as a result of intramolecular base pairing. In vivo, these RNA structures are not static. Instead, they are remodeled in response to changes in the prevailing physicochemical environment of the cell and as a result of intermolecular base pairing and interactions with RNA-binding proteins. Remarkable technical advances now allow us to probe RNA secondary structure at single-nucleotide resolution and genome-wide, both in vitro and in vivo. These data sets provide new glimpses into the RNA universe. Analyses of RNA structuromes in HIV, yeast, Arabidopsis, and mammalian cells and tissues have revealed regulatory effects of RNA structure on messenger RNA (mRNA) polyadenylation, splicing, translation, and turnover. Application of new methods for genome-wide identification of mRNA modifications, particularly methylation and pseudouridylation, has shown that the RNA "epitranscriptome" both influences and is influenced by RNA structure. In this review, we describe newly developed genome-wide RNA structure-probing methods and synthesize the information emerging from their application.


New Deployable Expandable Electrodes in the Electroporation Treatment in a Pig Model: A Feasibility and Usability Preliminary Study.
The aim of the study is to evaluate the usability aspects of new deployable, expandable, electrode prototypes, in terms of suitability solutions for laparoscopic applications on the liver, endoscopic trans-oral and trans-anal procedures, electroporation segmentation in several steps, mechanical functionality (flexibility, penetrability), visibility of the electrode under instrumental guidance, compatibility of the electrode with laparoscopic/endoscopic accesses, surgical instruments, and procedural room and safety compatibility. The electroporation was performed on an animal model (Sus Scrofa Large White 60 kg) both in laparoscopy and endoscopy, under ultrasound guidance, and in open surgery. Electrodes without divergence, with needles coming out straight, parallel to each other, and electrodes with peripheral needles (four needles), diverging from the electrode shaft axis (electrode with non-zero divergence) have been tested. To cause an evaluable necrosis effect, the number of electrical pulses was increased to induce immediate liver cell death. Histological samples were analyzed by staining with Haematoxylin/Eosin or by immunohistochemical staining to confirm complete necrosis. The prototypes of expandable electrodes, tested in laparoscopy and endoscopy and in open surgery, respectively, are suitable in terms of usability, electroporation segmentation in several steps, mechanical functionality (flexibility, penetrability), visibility under instrumental guidance, compatibility with laparoscopic/endoscopic accesses, surgical instruments and procedural room safety, patient safety (no bleeding and/or perforation), and treatment efficacy (adequate ablated volume). Electroporation treatment using new deployable expandable electrode prototypes is safe and feasible. Moreover, electrode configurations allow for a gradual increase in the ablated area in consecutive steps, as confirmed by histology and immunohistochemistry.


In early arthritis patients, high HAQ at baseline and DAS28 at three months predict suboptimal outcomes at two years: a retrospective cohort study.
Early arthritis clinics (EAC) aim to improve rheumatoid arthritis (RA) outcomes by tailoring treatment targeting to remission. Our aim was to analyse disease course and relevant predictors over 2 years in early arthritis; we also assessed the applicability of the "treat-to-target approach" in a real-life EAC. Patients with early arthritis recruited at the EAC of the University Hospital of Heraklion were followed prospectively according to a follow-up protocol for two years, without implementing a pre-specified treatment protocol, to capture real-life practices. Early predictors of "suboptimal outcomes" (high disease activity or HAQ>1.0 at 2 years) and biologic DMARD (bDMARD) initiation were evaluated with multivariate logistic regression. Intensification of treatment at 3 and 6 months and subsequent long-term outcome were also assessed. 251 patients [RA (n=188), undifferentiated arthritis (n=63)] were included. Although both DAS28 and HAQ at 2 years improved significantly compared to baseline in RA patients [mean (SD) DAS28 and median (IQR) HAQ 3.70 (1.32) and 0.44 (0.75) at 2 years, p<0.001 for both compared to baseline], 43.7% still had moderate and 18.8% high disease activity. The most powerful predictor of suboptimal outcomes or bDMARD initiation in RA was high disease activity at three months (adjusted odds ratio 2.22 and 2.62, respectively). At three and six months 72.8% and 62.4% of patients with medium/high disease activity received treatment intensification, which resulted in significant decrease in disease activity at 2 years (p<0.001 for ΔDAS28). DAS28 at three months was the most powerful predictor of suboptimal disease outcome during a 2-year follow-up in early RA. Despite significant DAS reductions, more than 50% of patients have active disease at two years. Failure to fully implement the treat-to-target strategy in our cohort could account for the low remission rates.


[Identification of the basilar artery with transcranial Doppler sonography].
In 100 normal subjects the flow velocity in the terminal segments of the vertebral arteries and the basilar artery was investigated by suboccipital transcranial Doppler sonography. In normal cases, flow velocity and direction are not sufficient criteria to differentiate these arteries. Using anatomical and haemodynamical parameters it can be shown that a Doppler signal originating from the basilar artery cannot be expected in a depth of less than 85 mm, thus being deeper than it is usually reported in the literature. Due to methodological limitations, the basilar artery cannot be insonated in about 30% of cases.


Unpacking Peer Conversations in a Virtual Communitiy for Diabetes Self-Management Education and Support: Behavior Science and Linguistics Perspective.
Diabetes is a chronic disease that can be effectively managed and controlled using strategies such as self-management education and ongoing support. Virtual environments offer innovative and realistic settings where patients can achieve self-management education and obtain ongoing self-management support from peers and healthcare professionals. Transcribed real-time conversations in an innovative virtual community were analyzed using qualitative and linguistic analysis. These virtual interactions were manually coded to identify embedded behavior change techniques and linguistic features. Results showed 13 behavior change techniques were manifested. Further, language differences were observed between behavior change techniques and social support types. Our research can provide valuable insights into the design of effective digital health interventions that maximize sustained use of virtual environments, subsequently impacting self-management of chronic conditions such as diabetes.


Insulin, prostaglandins, and the pathogenesis of hypertension.
Hypertension is associated with hyperinsulinemia in the presence or absence of obesity or glucose intolerance. Physiological concentrations of insulin decrease the catecholamine-induced production of prostaglandin I2 (PGI2; prostacyclin) and PGE2, two potent vasodilators, in adipose tissue, one of the largest organs in the body. This finding suggests that hyperinsulinemia increases peripheral vascular resistance and blood pressure by inhibiting the stimulatory effect of adrenergic agonists (and perhaps other agonists) on the production of PGI2 and PGE2 in adipose tissue (and perhaps other tissues). This concept is supported by evidence that PGI2 and PGE2 modulate vascular reactivity in states of health and disease. For example, during insulin deficiency, i.e., in diabetic ketoacidosis, PGI2 and PGE2 production by adipose tissue are increased, and peripheral vascular resistance and blood pressure are decreased. This hypothesis is also supported by evidence that blood flow through rat and human adipose tissue is decreased in obesity and that insulin decreases the blood flow through adipose tissue in nonobese rats. Thus, insulin may regulate PGI2 and PGE2 production by adipose tissue (and possibly other tissues) through a wide range of concentrations with important physiological and clinical consequences.


MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers.
Homeobox genes encode transcription factors that are essential for normal development and are often dysregulated in cancers. The molecular mechanisms that cause their misregulation in cancers are largely unknown. In this study, we investigate the mechanism by which the Six1 homeobox protein, which has a crucial role during development, is frequently deregulated in several poor outcome, aggressive, metastatic adult human cancers, including breast cancer, ovarian cancer, hepatocellular carcinoma and pediatric malignancies such as rhabdomyosarcoma and Wilms' tumor. Our results reveal that miRNA-185 translationally represses Six1 by binding to its 3'-untranslated region. Analyses of ovarian cancers, pediatric renal tumors and multiple breast cancer cell lines showed decreased miR-185 expression, paralleling an increase in Six1 levels. Further investigation revealed that miR-185 impedes anchorage-independent growth and cell migration, in addition to suppressing tumor growth in vivo, implicating it to be a potent tumor suppressor. Our results indicate that miR-185 mediates its tumor suppressor function by regulating cell-cycle proteins and Six1 transcriptional targets c-myc and cyclin A1. Furthermore, we show that miR-185 sensitizes Six1-overexpressing resistant cancer cells to apoptosis in general and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in particular. Together, our findings suggest that the altered expression of the novel tumor suppressor miR-185 may be one of the central events that leads to dysregulation of oncogenic protein Six1 in human cancers.


Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials.
To evaluate the efficacy of pentoxifylline therapy in improving the walking capacity of patients with moderate intermittent claudication. A search of MEDLINE for trials published between 1976 and 1994 inclusive, and a bibliographic review of all articles retrieved. Randomized, placebo-controlled, double-blind clinical trials were selected that evaluated the pain-free walking distance (the distanced walked on a treadmill before the onset of calf pain) and the absolute claudication distance (the maximum distance walked on a treadmill) among patients with moderate intermittent claudication. Twelve study groups in 11 trials were included in the analysis. In addition to information regarding the trial design, patient characteristics, dosages and treatment periods, the means and standard deviations were collected for both the pain-free walking and absolute claudication distances. Trial quality was also assessed. Overall, there was a statistically significant improvement in the pain-free walking distance after pentoxifylline therapy (weighted mean difference 29.4 m [95% confidence interval (CI) 13.0 to 45.9 m]); this finding was based on a total sample of 612 patients (308 in the treatment groups and 304 in the control groups). A significant improvement was also noted in the absolute claudication distance (weighted mean difference 48.4 m [95% CI 18.3 to 78.6 m]); this was based on a total sample of 511 patients (258 in the treatment group and 253 in the control group). In a sensitivity analysis of the pain-free walking distance, significant treatment effects and no statistically significant heterogeneity were found when only trials were included that were "medically eligible" (involved patients with stage II disease and a pain-free walking distance of 50 to 200 m). In a similar sensitivity analysis of the absolute claudication distance, the two conditions resulting in a significant treatment effect and no significant heterogeneity were the inclusion of "medically eligible" trials and those with a shorter treatment duration (13 weeks or less). Pentoxifylline therapy may be efficacious in improving the walking capacity of patients with moderate intermittent claudication. However, properly conducted clinical trials are required to provide a true estimate of the benefit.


[New therapies for the treatment of advanced non-small cell lung cancer: inhibitors of the epidermal growth factor receptor and angiogenesis].
The recently developed 'targeted' therapies, epidermal growth factor receptor (EGFR) inhibitors and angiogenesis inhibitors, target specific tumour characteristics. EGFR inhibitors, such as gefitinib and erlotinib, can lead to remission, particularly in non-small cell lung cancer (NSCLC) with specific EGFR mutations. These mutations occur more frequently in Asians, women, non-smokers and those with adenocarcinomas. Other mutations in EGFR and K-ras genes lead to resistance. EGFR inhibitors offered no benefit to untreated patients with advanced NSCLC. In previously treated patients, however, erlotinib increased survival by 2 months. Optimal patient selection criteria for EGFR inhibitor therapy is still under investigation. The angiogenesis inhibitor bevacizumab is an antibody that targets vascular endothelial growth factor receptor. The addition of bevacizumab to chemotherapy increased median survival by 2 months when given as first-line therapy for advanced NSCLC. The combination of EGFR and angiogenesis inhibitors is a rational anticancer treatment and is being studied. These new therapies are expected to help improve and individualize the treatment of advanced NSCLC.


[Haemoglobinopathy in the 21st century: incidence, diagnosis and heel prick screening].
To determine the incidence of severe haemoglobinopathy, to evaluate the effect of heel prick screening, and to identify those children who do not benefit from this early diagnosis. Prospective descriptive study. Registration of all symptomatic and asymptomatic children who between 2003-2009 were newly diagnosed with the a severe form of a hereditary disorder concerning the formation of the alpha haemoglobin chain (HbH disease), or the beta haemoglobin chain (sickle cell disease or beta thalassaemia major) in the Netherlands. Registration was done by collecting anonymised reports from the Dutch Paediatric Surveillance Unit and TNO, and by additional questionnaires. During the study period, 48 children (range: 36-76) per year were diagnosed with severe haemoglobinopathy. The overall incidence was 2.5 per 10,000 live births. The incidence of sickle cell disease diagnosed by heel prick screening was 2.1 per 10,000 live births and of thalassaemia major 0.6 per 10,000 live births. In 7% of the children with sickle cell disease who were diagnosed without any form of screening, the diagnosis was made on (a life threatening) infection. Twenty-two percent of the children with a severe form of haemoglobinopathy were not born in the Netherlands. The parents of almost half of the children with sickle cell disease originally came from West- or Central Africa. The parents of children with thalassaemia major were mainly from Morocco or various Asiatic countries. The number of children with severe haemoglobinopathy in the Netherlands has trebled since 1992. In order for all children to benefit from early diagnosis and preventive treatment, it is advisable that children who originate from risk areas should be tested for haemoglobinopathy when they first arrive in the Netherlands.


Recommendations From a Chinese-Language Survey of Knowledge and Prevention of Skin Cancer Among Chinese Populations Internationally: Cross-sectional Questionnaire Study.
There is a paucity of studies assessing awareness and prevention of skin cancer among Chinese populations. The aim of the study is to compare attitudes and practices regarding skin cancer risks and prevention between Chinese Asian and North American Chinese populations and between Fitzpatrick scores. A cross-sectional, internet-based, 74-question survey in Chinese was conducted focusing on Han Chinese participants internationally. The survey included Likert-type scales and multiple-choice questions. All participants were required to read Chinese and self-identify as being 18 years or older and Chinese by ethnicity, nationality, or descent. Participants were recruited on the internet over a 6-month period from July 2017 through January 2018 via advertisements in Chinese on popular social media platforms: WeChat, QQ, Weibo, Facebook, and Twitter. Of the 113 completed responses collected (participation rate of 65.7%), 95 (84.1%) were ethnically Han Chinese, of which 93 (96.9%) were born in China and 59 (62.1%) were female. The mean age of these 95 participants was 35.8 (SD 13.3) years; 72 (75.8%) participants were born after 1975. Few but more North American Chinese reported that Chinese Asian populations received annual skin checks (4/30, 4.2% vs 0/65, 0%; P=.009) and believed that their clinician provided adequate sun safety education (13/30, 43.3% vs 15/65, 23.1%; P=.04). Participants with higher Fitzpatrick scores less frequently received sun safety education from a clinician (4/34, 11.8% vs 22/61, 36.1%; P=.02). More participants with lower Fitzpatrick scores used sunscreen (41/61, 67.2% vs 16/34, 47.1%; P=.05), but alternative sun protection use rates are similar across groups. Cultural differences and Fitzpatrick scores can affect knowledge and practices with respect to sun protection and skin cancer among social media-using Chinese Asian and North American Chinese communities based on respondent demographics. Most participants in all groups understood that people of color have some risk of skin cancer, but >30% of all groups across regions and Fitzpatrick scores are unaware of current skin protection recommendations, receive insufficient sun safety education, and do not use sunscreen. Outreach efforts may begin broadly with concerted public and private efforts to train and fund dermatologists to perform annual total body skin exams and provide more patient education. They should spark community interest through mass media and empower Chinese people to perform self-examinations and recognize risks and risk mitigation methods.


Hydrogen sulfide: a target to modulate oxidative stress and neuroplasticity for the treatment of pathological anxiety.
Introduction: Anxiety disorders result inhigh patient burden and utilization of healthcare resources. Evidence-based treatments for pathological anxiety include targeted psychotherapy and use of serotonin-augmenting agents. Limitations in access to cognitive behavioral therapy and potential disadvantages to the use of psychotropics make the need for novel approaches to therapeutics for pathological anxiety salient.Areas Covered: Neuroplasticity mechanisms, as well as managing oxidative stress and inflammatory cellular allostatic loads can decrease anxiety. The gasotransmitter hydrogen sulfide (H2S) can impact these mechanisms through a) maintaining intracellular reduced glutathione in the CNS to decrease oxidative stress; b) facilitating neuroplasticity in amygdalar regions via the 2B subunit of n-methyl-d-aspartate (NMDA) receptors, in conjunction with the cAMP messenger system and a CNS kinase, PKC-γ; and c) regulating intracellular Ca2+ homeostasis in neurons and glial cells, among others.Expert Opinion: Given the mounting evidence for the role of H2S in neuronal health and its potential to decrease pathological anxiety, the current challenge in H2S therapeutics remains finding an efficient delivery system of this gasotransmitter in a reliable, safe and nontoxic form to engage in clinical trials. Current efforts include H2S-delivering moieties attached to known drugs, natural sulfide-releasing compounds such as garlic, and the regulation of dysfunctional breathing through breathing retraining.


The association between benzodiazepine prescription and aberrant drug-related behaviors in primary care patients receiving opioids for chronic pain.
Benzodiazepine use has been associated with addiction-related risks, but little is known about its association with aberrant drug-related behaviors in patients receiving opioids for chronic pain. The authors examined the association between receipt of a benzodiazepine prescription and 2 aberrant drug-related behaviors, early opioid refills and illicit drug (cocaine) use in patients receiving opioids for noncancer chronic pain. This was a retrospective cohort study of 847 patients with ≥1 visit to either a hospital-based primary care clinic or one of two community health centers between September 1, 2011, and August 31, 2012. All patients received ≥3 opioid prescriptions written at least 21 days apart within 6 months, and ≥1 urine drug screen during the study period. A Cox proportional hazards model estimated the hazard of a second early opioid refill, defined as an opioid prescription written 7-25 days after the previous prescription for the same drug, as a function of time-varying benzodiazepine prescription. A logistic regression model examined the relationship between benzodiazepine prescription and a positive urine test for cocaine. Models were adjusted for demographics and mental/substance use disorder diagnoses. Twenty-three percent (n = 196) of patients received ≥1 benzodiazepine prescription during the study period. Twenty-two percent (n = 183) of patients had ≥2 early opioid refills, and 11% (n = 93) had ≥1 positive urine drug tests for cocaine. Receipt of benzodiazepine prescription was associated with an increased hazard of having a second early opioid refill, adjusted hazard ratio = 1.54 (95% confidence interval [CI]: 1.09-2.18), but not associated with a positive cocaine test, adjusted odds ratio = 1.07 (95% CI: 0.55-2.23). Among primary care patients receiving chronic opioid therapy, benzodiazepine prescription was associated with early opioid refills but not with cocaine use. Further research should better elucidate the risks and benefits of prescribing benzodiazepines to patients receiving opioids for chronic pain.


[Pharmacological analysis of the ontogenetic traits of the functional receptor activity of glial and neuronal GABA uptake and GABA-T activity in the rat hippocampus].
Studies have been made on the effect of GABA mimetics on epileptogenic focus in the hippocamp of growing rats. By the pattern of inhibition of this focus by these drugs, it is possible to evaluate the degree of functional maturation of the activity of GABA receptors, glial and neuronal uptake of GABA, and the activity of GABA-T. Higher sensitivity of GABA receptors in younger animals was found together with a higher functional role of glial uptake in GABA utilization. Functional activity of GABA-T and neuronal uptake of the mediator are of lower physiological significance in younger animals as compared to those in adults.


Regulation of androgen receptor levels: implications for prostate cancer progression and therapy.
Androgen deprivation has been the standard therapy for advanced and metastatic prostate cancer for over half a century, as prostate tumors are initially dependent on androgens for growth and survival. Unfortunately, in most patients undergoing androgen ablation, relapse (recurrent tumor growth) eventually occurs. The actions of the principal androgens, testosterone and dihydrotestosterone (DHT), are mediated via androgen receptors (ARs), ligand-activated transcription factors that belong to the nuclear receptor superfamily. Because of the presence of transcriptionally active ARs in tumors from recurrent or androgen-independent disease, there is a heightened interest in new therapeutic paradigms that target the AR and its regulatory pathways. The regulation of AR levels is highly complex with control exerted by several pathways and in a cell-, tissue-, and developmental-stage specific manner. Androgens are important regulators of AR mRNA and protein through transcriptional and post-transcriptional mechanisms. This article reviews the evidence implicating the AR in recurrent prostate cancer and discusses the multiple mechanisms that regulate AR levels in normal and neoplastic cells. The complexity of AR regulation suggests that there will be an ample array of potential new drug targets for modulating levels of this receptor, a key signaling molecule in prostate cancer.


Characterization of functionally active subribosomal particles from Thermus aquaticus.
Peptidyl transferase activity of Thermus aquaticus ribosomes is resistant to the removal of a significant number of ribosomal proteins by protease digestion, SDS, and phenol extraction. To define the upper limit for the number of macromolecular components required for peptidyl transferase, particles obtained by extraction of T. aquaticus large ribosomal subunits were isolated and their RNA and protein composition was characterized. Active subribosomal particles contained both 23S and 5S rRNA associated with notable amounts of eight ribosomal proteins. N-terminal sequencing of the proteins identified them as L2, L3, L13, L15, L17, L18, L21, and L22. Ribosomal protein L4, which previously was thought to be essential for the reconstitution of particles active in peptide bond formation, was not found. These findings, together with the results of previous reconstitution experiments, reduce the number of possible essential macromolecular components of the peptidyl transferase center to 23S rRNA and ribosomal proteins L2 and L3. Complete removal of ribosomal proteins from T. aquaticus rRNA resulted in loss of tertiary folding of the particles and inactivation of peptidyl transferase. The accessibility of proteins in active subribosomal particles to proteinase hydrolysis was increased significantly after RNase treatment. These results and the observation that 50S ribosomal subunits exhibited much higher resistance to SDS extraction than 30S subunits are compatible with a proposed structural organization of the 50S subunit involving an RNA "cage" surrounding a core of a subset of ribosomal proteins.


Androgens selectively modulate C-fos messenger RNA induction in the rat hippocampus following novelty.
We have previously shown that androgen receptors are found in high concentrations in hippocampal CA1 pyramidal cells. To begin to explore the possible roles for androgen receptors in this area of the brain, we studied the effects of endogenous and exogenous androgen on the behaviourally induced expression of cellular immediate early gene messenger RNAs. Adult male Fischer 344 rats were either gonadectomized, gonadectomized and given two Silastic capsules of dihydrotestosterone propionate at the time of surgery, or left intact. Three weeks later, animals were placed into a novel open field for 20 min. This behavioural paradigm caused region- and gene-specific increases of c-fos, jun-B, c-jun and zif268 messenger RNA in the hippocampus as determined by semi-quantitative in situ hybridization histochemistry. The removal of circulating androgen by gonadectomy potentiated, whereas dihydrotestosterone treatment of castrates attenuated, the behaviourally induced expression of c-fos messenger RNA in the CA1 region of the hippocampus. No changes in c-fos messenger RNA expression were detected in the CA3 or dentate gyrus regions where androgen receptor levels are low. Androgen status did not affect either the basal or stimulated expression of Jun-B, c-Jun or zif268 messenger RNA in any of the three cellular regions of the hippocampus examined. These results implicate androgen receptors in modulating the active response of hippocampal neurons to a behaviourally relevant stimulus. Since the products of cellular immediate genes can function to alter an array of downstream genes, the modulation of these genes in the hippocampus by gonadal hormones may have important ramifications for hippocampal function.


Lunasin abrogates monocytes to endothelial cells.
The adherence of monocytes to endothelial cells plays a causal role in the early development of atherosclerosis and is driven by several inflammatory stimuli, which includes oxidized low-density lipoprotein (ox-LDL). Lunasin, a natural peptide identified in soybean seeds, soy-derived food products, other grains and herbal plants, has been found to exert numerous biological activities, including anti-inflammatory and antioxidant properties. However, little is known regarding the mechanism of action of lunasin in ox-LDL-induced endothelial inflammation. The results of the present study indicate that lunasin significantly ameliorated ox-LDL-induced adhesion of THP-1 monocytes to the surface of human umbilical vein endothelial cells (HUVECs). Lunasin also suppressed expression of the adhesion molecules VCAM-1 and E-selectin, but not ICAM-1. Notably, the inhibitory mechanism of lunasin is associated with its stimulatory effects on expression of the KLF2 transcriptional factor. In addition, lunasin treatment could reverse the effects of ox-LDL on the expression of eNOS and PAI-1, the direct target genes of KLF2. Mechanistically, it was proven that the MEK5/ERK5 pathway mediates the effects of lunasin on KLF2 expression. Taken together, the results of this study suggest that dietary or supplementary intake of lunasin may have a prophylactic or therapeutic capacity in cardiovascular diseases such as atherosclerosis.


Mid-1990s review of Medicaid and Medicaid dentistry.
In light of a federal report on the extremely limited availability of preventive dental services for children under the Medicaid program, a review is provided of the evolving comparative share of general health expenditures and Medicaid funds that are spent on dental services. The findings indicate that during the 1990s, dentistry in general and within the Medicaid program occupies a continuing decreasing share of expenditures.


Identification of a third feline Demodex species through partial sequencing of the 16S rDNA and frequency of Demodex species in 74 cats using a PCR assay.
Demodex cati and Demodex gatoi are considered the two Demodex species of cats. However, several reports have identified Demodex mites morphologically different from these two species. The differentiation of Demodex mites is usually based on morphology, but within the same species different morphologies can occur. DNA amplification/sequencing has been used effectively to identify and differentiate Demodex mites in humans, dogs and cats. The aim was to develop a PCR technique to identify feline Demodex mites and use this technique to investigate the frequency of Demodex in cats. Demodex cati, D. gatoi and Demodex mites classified morphologically as the third unnamed feline species were obtained. Hair samples were taken from 74 cats. DNA was extracted; a 330 bp fragment of the 16S rDNA was amplified and sequenced. The sequences of D. cati and D. gatoi shared >98% identity with those published on GenBank. The sequence of the third unnamed species showed 98% identity with a recently published feline Demodex sequence and only 75.2 and 70.9% identity with D. gatoi and D. cati sequences, respectively. Demodex DNA was detected in 19 of 74 cats tested; 11 DNA sequences corresponded to Demodex canis, five to Demodex folliculorum, three to D. cati and two to Demodex brevis. Three Demodex species can be found in cats, because the third unnamed Demodex species is likely to be a distinct species. Apart from D. cati and D. gatoi, DNA from D. canis, D. folliculorum and D. brevis was found on feline skin.


A reflection on the work of Gianni Bonadonna from the viewpoint of the global challenge of adolescents and young adults with cancer.
Adolescents and young adults (AYAs - ages 15 to 39) constitute approximately 40% of the world's population and contribute an estimated one million new cases of cancer annually, the great majority in low- and middle-income countries (LMICs). In high-income countries (HICs) cancer is the commonest cause of disease-related death in AYAs, though overall 5-year survival rates now exceed 80%. A very different circumstance likely holds in LMICs, but accurate assessments are not readily available.Breast cancer accounts for 40% of tumours in female AYAs and this age group includes the peak incidence of Hodgkin lymphoma. The late Professor Gianni Bonadonna contributed importantly to improved survival in patients with these two diseases. Accordingly, he would be justifiably proud of the advances in AYA oncology that are being made in Italy, especially the impact of his colleagues at the Istituto Nazionale dei Tumori (INT). The initiatives of the Associazione Italiana Ematologia Pediatrica and the Società Italiana Adolescenti con Malattie Onco-ematologiche are particularly noteworthy, with the accomplishment of productive collaboration between paediatric and adult cancer care providers serving as a model for other countries to emulate.Exporting these advances can be successful through the vehicle of "twinning": establishing sustainable cooperation between institutions in HICs and partners in LMICs. Colleagues in Monza and at INT have been leaders in such programmes for decades. Cancer in AYAs remains a global challenge to which Gianni Bonadonna surely would have risen with enthusiasm and leadership while securing measurable achievements.


[The research on the quenching of fluorescence spectra of TOP I by iodine anion].
Comparing the fluorescence spectra of tobacco peroxidase I (TOP I) solution and the solutions titrated by iodine anions, the number of binding locus and the binding constant of iodine anion to TOP I were calculated by using the modified Stern-Volmer equation. The mechanism of the quenching of fluorescence spectra and the distribution of tryptophane residues in the TOP I molecule were discussed.


Guidelines, Consensus Statements, and Standards for the Use of Artificial Intelligence in Medicine: Systematic Review.
The application of artificial intelligence (AI) in the delivery of health care is a promising area, and guidelines, consensus statements, and standards on AI regarding various topics have been developed. We performed this study to assess the quality of guidelines, consensus statements, and standards in the field of AI for medicine and to provide a foundation for recommendations about the future development of AI guidelines. We searched 7 electronic databases from database establishment to April 6, 2022, and screened articles involving AI guidelines, consensus statements, and standards for eligibility. The AGREE II (Appraisal of Guidelines for Research & Evaluation II) and RIGHT (Reporting Items for Practice Guidelines in Healthcare) tools were used to assess the methodological and reporting quality of the included articles. This systematic review included 19 guideline articles, 14 consensus statement articles, and 3 standard articles published between 2019 and 2022. Their content involved disease screening, diagnosis, and treatment; AI intervention trial reporting; AI imaging development and collaboration; AI data application; and AI ethics governance and applications. Our quality assessment revealed that the average overall AGREE II score was 4.0 (range 2.2-5.5; 7-point Likert scale) and the mean overall reporting rate of the RIGHT tool was 49.4% (range 25.7%-77.1%). The results indicated important differences in the quality of different AI guidelines, consensus statements, and standards. We made recommendations for improving their methodological and reporting quality. PROSPERO International Prospective Register of Systematic Reviews (CRD42022321360); https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=321360.


On the magnetorotational instability and elastic buckling.
This paper demonstrates an equivalence between rotating magnetized shear flows and a stressed elastic beam. This results from finding the same form of dynamical equations after an asymptotic reduction of the axis-symmetric magnetorotational instability (MRI) under the assumption of almost-critical driving. The analysis considers the MRI dynamics in a non-dissipative near-equilibrium regime. Both the magnetic and elastic systems reduce to a simple one-dimensional wave equation with a non-local nonlinear feedback. Under transformation, the equation comprises a large number of mean-field interacting Duffing oscillators. This system was the first proven example of a strange attractor in a partial differential equation. Finding the same reduced equation in two natural applications suggests the model might result from other applications and could fall into a universal class based on symmetry.


Non-uniform adaptive angular spectrum method and its application to neural network assisted coherent beam combining.
Increasing the number of laser beams that can be coherently combined requires accurate and fast algorithms for compensating phase and alignment errors. The paper proposes to use a Fully Connected Artificial Neural Network (FCANN) to correct the beam positioning perturbations by evaluating the beam shifts and tilts from two images taken at slightly different locations. Then, since it is practically impossible to have a large enough experimental dataset to train the neural network, this approach required developing an accurate and fast simulation method to evaluate the beam propagation in arbitrary directions, overcoming the limitations occurring when the computation must be repeated a large number of times. The numerical approach is a variant of the Angular Spectrum (AS) method, called Non Uniform ADaptive Angular Spectrum (NUADAS) method, which relies on the combination of non-uniform and adaptive Fourier transform algorithms to allow the computation of an arbitrary field distribution in a plane that is shifted and tilted with respect to the source. The parallel implementation of the NUADAS method is discussed and the numerical and experimental validations are presented. Then, an FCANN is trained using the synthetic dataset generated with the NUADAS method and the results are discussed, demonstrating the viability of the proposed approach not only for coherent beam combing, but also in other beam alignment applications.


Acute cytomegalovirus infection in liver transplant recipients: An independent risk for venous thromboembolism.
Acute cytomegalovirus (CMV) infection is a commonly encountered complication in the post liver transplant setting. We present a case of a 71-year-old male with acute CMV infection, initially presenting with a gastrointestinal bleed due to acute CMV gastritis and later on complicated by acute venous thromboembolism occurring as an unprovoked event in the post liver transplant period. Traditional risk factors for venous thromboembolism have been well described in the medical literature. Sporadic cases of thromboembolism due to CMV infection in the immune compromised patients have been described, especially in the post kidney transplant patients. Liver transplant recipients are equally prone to CMV infection particularly in the first year after successful transplantation. Venous thromboembolism in this special population is particularly challenging due to the fact that these patients may have persistent thrombocytopenia and anticoagulation may be a challenge for the treating physician. Since liver transplantation is severely and universally limited by the availability of donor organs, we feel that this case report will provide valuable knowledge in the day to day management of these patients, whose clinical needs are complex and require a multidisciplinary approach in their care and management. Evidence and pathophysiology linking both the conditions is presented along with a brief discussion on the management, common scenarios encountered and potential impact in this special group of patients.


An update on research and outcomes in surgical management of vaginal mesh complications.
Stress urinary incontinence and pelvic organ prolapse are major quality of life conditions affecting millions of individuals. Transvaginal mesh materials have been proposed to supplant native tissue repairs. However, these materials have opened a new field, meshology, devoted to the management of mesh complications. This review highlights some of the recent developments in this subspecialty which often requires a multidisciplinary approach. With better imaging, the preoperative assessment of mesh complications has been enhanced. Specialized centers with high volumes are best suited to handle these challenging patients who fear the many risks of mesh removal and the uncertainties of their clinical status after the removal procedure(s). However, despite a better classification system recommended by specialized societies, the multidimensional outcome of these repair procedures will require the adoption of outcome tools which can cover several domains such as urinary incontinence, pelvic pain, dyspareunia, bladder infections, to name a few. The surgical approach to mesh removal is also evolving with some experts recommending complete removal while others prefer more selective excision. Finally, the long-term outcome of these mesh removal procedures is not yet fully known.


Twitch potentiation during fatiguing exercise in the elderly: the effects of training.
Twitch potentiation was studied during a fatigue paradigm involving intermittent maximum voluntary contractions (MVCs) of the tibialis anterior muscle in the elderly and in young adults. Resting twitch torques were similar between groups, but twitch potentiation was significantly greater (241% vs 166%) in the young; the recovery of the twitch after fatigue was similar between groups. Contraction time, time to peak torque and half-relaxation time were all significantly slower in the elderly. Following 12 weeks of resistance training in the elderly, there was no significant change in the twitch contractile properties at rest, but there was a significant main effect of training on the degree of twitch potentiation during the same fatigue protocol (peak potentiation 192% post-training vs 165% pretraining). These data suggest that the mechanism(s) responsible for twitch potentiation following MVCs may be influenced by both aging and training.


Sleep loss and postpartum psychosis.
Postpartum psychosis is a rare but severe psychiatric disorder. Its diagnostic status remains controversial, but several studies have shown that the majority of patients who develop psychosis immediately following childbirth suffer from bipolar disorder. The pathophysiology of postpartum psychosis is poorly understood, but factors such as primiparity, difficult labor, genetic predisposition, and hormonal changes have been suggested as etiological factors. This paper reviews the literature on the relationship of sleep disruption and postpartum psychosis. It is argued that sleep loss resulting from the interaction of various putative causal factors may be the final common pathway in the development of psychosis in susceptible women. Clinical significance of these findings, including strategies to prevent postpartum psychosis, are discussed and suggestions are made for future research directions.


Single-trial laser-evoked potentials feature extraction for prediction of pain perception.
Pain is a highly subjective experience, and the availability of an objective assessment of pain perception would be of great importance for both basic and clinical applications. The objective of the present study is to develop a novel approach to extract pain-related features from single-trial laser-evoked potentials (LEPs) for classification of pain perception. The single-trial LEP feature extraction approach combines a spatial filtering using common spatial pattern (CSP) and a multiple linear regression (MLR). The CSP method is effective in separating laser-evoked EEG response from ongoing EEG activity, while MLR is capable of automatically estimating the amplitudes and latencies of N2 and P2 from single-trial LEP waveforms. The extracted single-trial LEP features are used in a Naïve Bayes classifier to classify different levels of pain perceived by the subjects. The experimental results show that the proposed single-trial LEP feature extraction approach can effectively extract pain-related LEP features for achieving high classification accuracy.


HIV incidence and factors associated with HIV acquisition among injection drug users in St Petersburg, Russia.
The Russian HIV-1 epidemic has been driven by injection drug use. To determine HIV incidence and identify demographic and behavioral correlates of infection to facilitate the development of longitudinal HIV prevention programs. In 2002, a cohort of 520 injection drug users (IDU) in St Petersburg, Russia were recruited and tested and counseled for HIV-1. HIV-seronegative IDU were enrolled and reevaluated at 6 and 12 months. HIV testing was performed and sociodemographic and behavioral data were collected during each study visit. The relationship of sociodemographic and behavioral factors to HIV-1 incidence was assessed. Most enrolled subjects were young, male, living at home, educated, heroin users, and frequently shared needles and other injection paraphernalia. The retention rate at the 12 month follow-up was 80%. The HIV-1 incidence rate was 4.5/100 person-years. In univariate analysis, psychostimulant use, especially frequent use, three or more sex partners in the past 6 months, and females selling sex were associated with HIV seroconversion. In the multivariate analysis, psychostimulant use three or more times per week was the only factor still associated with HIV seroconversion. The high incidence of HIV infection places St Petersburg among the worst IDU-concentrated epidemics in Europe. Interventions targeting psychostimulant and heroin users and their accompanying behaviors such as frequent injections and increased sexual activity are needed immediately.


[Effect of interferon on the cAMP system in cells].
The increase in cAMP concentration in CaOv cells affected by alpha-interferon has been found to have a two wave character with the maximums at 4 and 24 h after the effect. The waves are due to the increase in adenylate cyclase activity and to the decrease in the activity of cAMP phosphodiesterase. The described changes were characteristic of the native and partially purified interferon and depended on the concentration of interferon used (optimal effect at 1200 IU/ml-1). It suffices to notice that the described effects were more largely expressed when the preparations of the native alpha-interferon were used. The correlation was noticed between the increase in adenylate cyclase activity, the decrease in cAMP phosphodiesterase and the concentration of the cyclic nucleotide as well as the expression of antiproliferative effect. The correlation was less significant for antiviral effect.


Impact of percutaneous transluminal angioplasty for treatment of cerebral vasospasm on subarachnoid hemorrhage patient outcomes.
Percutaneous transluminal angioplasty (PTA) has been introduced for treatment of symptomatic cerebral vasospasm in patients with subarachnoid hemorrhage (SAH). While angiographic improvement is consistently reported, clinical improvement following the procedure varies, and limited data is available regarding overall impact on outcome. The authors performed a retrospective analysis of all hospital admissions with aneurysmal SAH over a 6 year period. The length of stay, discharge outcomes (measured by modified Rankin scale [mRS] at discharge), and 1-year mortality among patients with SAH before (4 year period) and after (2 year period) institution of PTA for cerebral vasospasm were compared. Embolization for intracranial aneurysm was used as a therapeutic option throughout the study duration. The effect of institution of PTA for vasospasm after adjusting for age, clinical severity, and use of aneurysm embolization on both discharge outcomes and 1-year mortality in multivariate analysis was evaluated. A total of 146 patients with aneurysmal SAH were admitted during the study duration. There was no difference between the 89 patients admitted in pre-angioplasty period and 57 patients admitted in post-angioplasty period in regards to age, medical co-morbidities, and admission clinical severity of patients (measured by Hunt and Hess grade and Glasgow coma scale). A total of 18 (32%) patients underwent PTA with or without intra-arterial vasodilator treatment in the second period of the study. There was a non significant decrease in rates of severe disability and death (mRS 5-6) at discharge (45 vs. 33%, P = 0.09) and 1-year mortality (32 vs. 22%, P = 0.26) after introduction of PTA for cerebral vasospasm after adjusting for potential confounders. There was no significant difference between the two time periods in regards to length of stay. A non significant trend was noted with reduced rate of severe disability and mortality at discharge and 1-year mortality after the introduction of PTA for cerebral vasospasm associated with SAH without increasing the length of hospital stay.


Mutation of the Cyba gene encoding p22phox causes vestibular and immune defects in mice.
In humans, hereditary inactivation of either p22(phox) or gp91(phox) leads to chronic granulomatous disease (CGD), a severe immune disorder characterized by the inability of phagocytes to produce bacteria-destroying ROS. Heterodimers of p22(phox) and gp91(phox) proteins constitute the superoxide-producing cytochrome core of the phagocyte NADPH oxidase. In this study, we identified the nmf333 mouse strain as what we believe to be the first animal model of p22(phox) deficiency. Characterization of nmf333 mice revealed that deletion of p22(phox) inactivated not only the phagocyte NADPH oxidase, but also a second cytochrome in the inner ear epithelium. As a consequence, mice of the nmf333 strain exhibit a compound phenotype consisting of both a CGD-like immune defect and a balance disorder caused by the aberrant development of gravity-sensing organs. Thus, in addition to identifying a model of p22(phox)-dependent immune deficiency, our study indicates that a clinically identifiable patient population with an otherwise cryptic loss of gravity-sensor function may exist. Thus, p22(phox) represents a shared and essential component of at least 2 superoxide-producing cytochromes with entirely different biological functions. The site of p22(phox) expression in the inner ear leads us to propose what we believe to be a novel mechanism for the control of vestibular organogenesis.


Risk of epilepsy after febrile convulsions: a national cohort study.
To identify children with febrile convulsions, classify their febrile convulsions into simple and complex, and determine the number and type of subsequent afebrile seizures in those children. National population based study. United Kingdom. 16,004 neonatal survivors born during one week in April 1970. Information about febrile and afebrile seizures obtained from questionnaires at 5 and 10 years of age and from hospital records. Information was available for 14,676 of the cohort children. 398 (2.7%) of them had had at least one febrile convulsion. 16 children were known to be neurologically or developmentally abnormal before the first attack. Of the remaining 382 children, 305 had had a simple first febrile convulsion and 77 a complex first febrile convulsion. Thirteen of the 382 had had one or more afebrile seizures, nine of whom had developed epilepsy (recurrent afebrile seizures). A higher proportion of children with complex febrile convulsions (6/95) rather than simple febrile convulsions (3/287) developed epilepsy, the risk being highest for those who had had focal febrile convulsions (5/17; chi 2 = 39.9, p less than 0.001). Three of the 32 children who had prolonged febrile convulsions developed afebrile complex partial seizures. The risk of epilepsy after febrile convulsions is much less than reported in many hospital studies, and if febrile convulsions cause brain damage that leads to later epilepsy this is a rare occurrence.


Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases.
RNA-guided endonucleases (RGENs), derived from the prokaryotic adaptive immune system known as CRISPR/Cas, enable targeted genome engineering in cells and organisms. RGENs are ribonucleoproteins that consist of guide RNA and Cas9, a protein component originated from Streptococcus pyogenes. These enzymes cleave chromosomal DNA, whose sequence is complementary, to guide RNA in a targeted manner, producing site-specific DNA double-strand breaks (DSBs), the repair of which gives rise to targeted genome modifications. Despite broad interest in RGEN-mediated genome editing, these nucleases are limited by off-target mutations and unwanted chromosomal translocations associated with off-target DNA cleavages. Here, we show that off-target effects of RGENs can be reduced below the detection limits of deep sequencing by choosing unique target sequences in the genome and modifying both guide RNA and Cas9. We found that both the composition and structure of guide RNA can affect RGEN activities in cells to reduce off-target effects. RGENs efficiently discriminated on-target sites from off-target sites that differ by two bases. Furthermore, exome sequencing analysis showed that no off-target mutations were induced by two RGENs in four clonal populations of mutant cells. In addition, paired Cas9 nickases, composed of D10A Cas9 and guide RNA, which generate two single-strand breaks (SSBs) or nicks on different DNA strands, were highly specific in human cells, avoiding off-target mutations without sacrificing genome-editing efficiency. Interestingly, paired nickases induced chromosomal deletions in a targeted manner without causing unwanted translocations. Our results highlight the importance of choosing unique target sequences and optimizing guide RNA and Cas9 to avoid or reduce RGEN-induced off-target mutations.


The transcription factor BcLTF1 regulates virulence and light responses in the necrotrophic plant pathogen Botrytis cinerea.
Botrytis cinerea is the causal agent of gray mold diseases in a range of dicotyledonous plant species. The fungus can reproduce asexually by forming macroconidia for dispersal and sclerotia for survival; the latter also participate in sexual reproduction by bearing the apothecia after fertilization by microconidia. Light induces the differentiation of conidia and apothecia, while sclerotia are exclusively formed in the absence of light. The relevance of light for virulence of the fungus is not obvious, but infections are observed under natural illumination as well as in constant darkness. By a random mutagenesis approach, we identified a novel virulence-related gene encoding a GATA transcription factor (BcLTF1 for light-responsive TF1) with characterized homologues in Aspergillus nidulans (NsdD) and Neurospora crassa (SUB-1). By deletion and over-expression of bcltf1, we confirmed the predicted role of the transcription factor in virulence, and discovered furthermore its functions in regulation of light-dependent differentiation, the equilibrium between production and scavenging of reactive oxygen species (ROS), and secondary metabolism. Microarray analyses revealed 293 light-responsive genes, and that the expression levels of the majority of these genes (66%) are modulated by BcLTF1. In addition, the deletion of bcltf1 affects the expression of 1,539 genes irrespective of the light conditions, including the overexpression of known and so far uncharacterized secondary metabolism-related genes. Increased expression of genes encoding alternative respiration enzymes, such as the alternative oxidase (AOX), suggest a mitochondrial dysfunction in the absence of bcltf1. The hypersensitivity of Δbctlf1 mutants to exogenously applied oxidative stress--even in the absence of light--and the restoration of virulence and growth rates in continuous light by antioxidants, indicate that BcLTF1 is required to cope with oxidative stress that is caused either by exposure to light or arising during host infection.


Postoperative cognitive dysfunction is independent of type of surgery and anesthetic.
Postoperative cognitive dysfunction (POCD) has been documented after cardiac and noncardiac surgery. The type of surgery and anesthetic has been assumed to be associated with the incidence but there are few prospective data comparing the incidence after different procedures. In this study, we sought to determine the association of the type of surgical procedure and anesthesia on the incidence of POCD after procedures involving light sedation, general anesthesia for noncardiac surgery, and general anesthesia for cardiac surgery involving cardiopulmonary bypass. Eight neuropsychological tests were administered at baseline and at 7 days and 3 months postoperatively to subjects from 3 procedure groups and a nonoperative control group. Reliable change index was used to calculate POCD. The study sample consisted of subjects involved in 3 separate trials investigating coronary angiography (CA) (percutaneous diagnostic procedure) under sedation, major noncardiac surgery (total hip joint replacement [THJR] surgery) under general anesthesia, and coronary artery bypass graft (CABG) surgery under general anesthesia. Data were collected from 644 patients in the patient groups and 34 subjects in the control group. Neuropsychological results were available for POCD at day 7 for THJR surgery (n=162) and CABG surgery (n=281). The incidence of POCD at day 7 was 17% for THJR surgery and 43% for CABG surgery (adjusted odds ratio=0.2, 95% confidence interval [CI]: 0.1, 0.4; P<0.01). At 3 months, the incidence of POCD for all groups combined (n=636) was 17% (21% for CA under sedation, 16% for THJR surgery, and 16% for CABG surgery). The mean (95% CI) for the difference in proportions of POCD among groups was 0.00 (-0.07, 0.07) (P=0.91) for CABG versus THJR; -0.05 (-0.12, 0.03) (P=0.21) for CABG versus CA; and -0.05 (-0.13, 0.03) (P=0.24) for THJR versus CA. There were no significant differences among groups (adjusted odds ratio=1.21, 95% CI: 0.94, 1.55; P=0.13). The incidence of POCD in old and elderly patients at day 7 was higher after CABG surgery than THJR surgery, but POCD at 3 months was independent of the nature or the type of procedure or anesthetic when comparing CA, THJR, and CABG surgery groups. Cardiovascular risk factors were not predictive of POCD after any procedure.


Breathing patterns in infants utilizing respiratory inductive plethysmography.
Respiratory inductive plethysmography (RIP) is a method that can be used to assess breathing patterns in infants without an airway connection. Ribcage and abdomen transducers are used which require gain factor calculation for calibration. We employed a single position graphic (SPG) calibration technique for gain factor calculation in RIP to obtain breathing pattern data for 70 infants in the quietly awake state. The SPG technique utilizes selection of two breaths from a 20s run of breaths with different ribcage/pneumotachograph (RC/PNT) and abdomen/pneumotachograph (AB/PNT) ratios for the gain factor calculation. Validation of gain factors was performed by comparing volumes obtained simultaneously by RIP and PNT. In 46 of the infants, maintenance of gain factor accuracy was confirmed following position reversal. Revalidation after position change could not be accomplished in 24 infants who were aroused into an agitated state. Breathing patterns were collected by RIP alone on the 46 infants who remained accurately calibrated in the supine and prone positions. No significant correlations were found between breathing pattern data and anthropometric characteristics. When the infants were repositioned, no consistent pattern of change could be identified. This study suggests that the SPG technique provides time-efficient and accurate calibration of RIP in the newborn infant. Furthermore, accuracy is maintained through position change if the infant remains in the same behavioral state. Breathing pattern data presented is representative of normative values in the quietly awake state for our study population.


The role of accreditation in transforming health services management education.
The core function of the Accrediting Commission on Education for Health Services Administration (ACEHSA) is to improve quality in health services management education. All specialized accrediting agencies provide quality assurance by developing standards of quality, assessing programs and reporting to stakeholders, as part of their public accountability function (Council for Higher Education Accreditation). Standards of quality derive from the level of competency considered essential within the domain of practice of health services managers. Accreditation review by ACEHSA is oriented to quality improvement and quality assurance, which have different purposes and are difficult to accomplish in the same process. The purpose of this paper is to discuss ACEHSA's role in evaluating the quality of health services management education programs in North America. The first objective is to describe the process of defining quality and to identify the skills, knowledge and abilities derived from it. The second objective is to discuss the measurement of quality, including using standardized measures, and determining whether the purpose is quality improvement or quality assurance. The third objective is to examine how quality measures are reported, and how reporting impacts the quality assessment process. Finally, the future role of ACEHSA is discussed, with regard to benchmarking measures of quality and publicly reporting relative levels of academic program quality.


Toxic cyanobacteria in Florida waters.
The occurrence of toxic cyanobacterial blooms in Florida waters have become more prominent following increased growth, declining groundwater supplies, and identification of impaired surface waters as future drinking water sources. Cyanobacterial toxins have been identified in source waters used for drinking water supply and in post-treated drinking water during algal bloom events. Algal toxin concentrations in post-treated drinking water have exceeded existing and proposed World Health Organization guidelines for the oral consumption of microcystin and cylindrospermopsin. Severe dermatitis has also been reported by swimmers in Florida springs where Lyngbya mats have expanded. The prevalence and toxicity of cyanobacteria should be considered when developing appropriate Total Maximum Daily Loads for impaired Florida waters that do not currently meet their designated use. It could also support further efforts to characterize potential ecological and human health risks due to toxic cyanobacterial blooms. Identification of algal toxins in finished drinking water and reports of severe skin irritation following contact with toxic cyanobacteria should be utilized for justification and implementation of increased monitoring of potentially toxic cyanobacterial blooms by surface water managers and water utilities. Epidemiological studies may also be required in Florida to assess potential human health risks due to algal toxin consumption at the tap and for those exposed to cyanotoxic blooms during recreational use of lakes, springs and rivers. Without adequate water treatment and coordinated state-wide monitoring efforts, it is anticipated that the likelihood for human exposure to cyanobacteria and their toxins will increase as Florida becomes more dependent upon surface waters to supply a growing population and an expanding urban environment. Coordination and communication between surface water managers and public health officials at the local level will be critical to the overall protection of the environment and public health during toxic cyanobacterial bloom events.