The Ah domain of the mouse. Induction of proteins by the carcinogen 3-methylcholanthrene.
The effect of the carcinogen 3-methylcholanthrene (MCA) on protein accumulation in mouse tissues was examined. Administration of the hydrocarbon (250 mg/kg, intraperitoneally) to high-responder C57BL/6 (B6) mice resulted in the induction of five proteins in liver tissue. Quantitative analysis revealed that maximal induction of all five proteins occurred 2 days after MCA administration, with liver protein concentrations returning close to control values by 7 days after the treatment. No consistent effects on the concentrations of other liver proteins were seen. Cell-fractionation studies demonstrate that these proteins appear to be non-microsomal in origin. The induction of the five proteins was tissue-specific, since MCA had no effect on protein accumulation in the B6-mouse kidney, spleen or heart. In addition, their induction appeared to be correlated with the Ah locus, since MCA administration had no effect on the concentrations of the five proteins in the liver of the low-responder DBA/2 (D2) mouse strain. Comparing the extent and time course of this induction with that of previously characterized MCA-induced enzymes, we suggest that these five proteins may represent a new, previously unidentified, set of MCA-induced proteins.


Simulation Training in Obstetrics.
Simulation now permeates all levels of training in obstetrics and maternal-fetal medicine. We will review the role of obstetric simulation through the continuum of training and practice. Simulation allows learners to acquire skills in a nonthreatening environment while avoiding harm to patients. Simulation in obstetrics evolved from a learning tool for students and residents, to a method for experienced physicians to learn new procedures and reenter the full breadth and depth of practice. Specialty boards and credentialing organizations recognize simulation training as an innovative approach to assess and assure technical, clinical, and teamwork skills.


Amphoteric natural starch-coated polymer nanoparticles with excellent protein corona-free and targeting properties.
The protein corona on nano drug carriers is an important well-known biological issue that often induces biological incompatibility and screens the targeting molecules on the surfaces of carriers, thus causing a loss of targeting specificity. Although polyethylene glycol (PEG) and zwitterionic polymers have been widely used as anti-fouling materials, there still remain critical challenges for their use as protein-corona agents for drug delivery and targeting. Here, we have designed novel amphoteric natural starch-stabilized core-shell colloidal nanoparticles with more efficient protein corona-free properties, under long term circulation, at different protein concentrations and in different protein charge environments, compared to typical anti-fouling materials such as PEG and zwitterionic polymers. More importantly, the starch-coated polymer nanoparticles can be further functionalized by antibodies to achieve additional excellent targeting and cell internalization capabilities for their use in photodynamic therapy. Our findings demonstrate a novel protein-free or anti-fouling natural material that is very promising for use as highly efficient nano drug carriers and marine coatings.


Temporal variability of two contrasting transient pollution events in a pastoral stream.
Two transient pollution events were monitored in a pastoral stream in southwestern Kenya to evaluate their relative contribution to diffuse pollution. Peak loads of pollutants during storm-induced transients were within 3-4 orders of magnitude higher than the short-lived (30-60 minutes) diurnal episodes provoked by in-stream activities of people and livestock. Transient yields were striking during storm-induced events; 778,000, 8,400, 550 and 100 kg day(-1) for suspended solids, BOD(5), total P and total N, respectively, compared to wet weather base flow (150, 30, 0.8 and 1.4 kg day(-1), for the same parameters, respectively). Two forms of concentration-discharge relationships were observed: increases in concentration for turbidity, suspended solids, BOD(5), total P and the faecal indicator bacteria at the peak of the stream hydrograph, and concurrent decreases in concentration for conductivity and total N. Following each storm-induced transient event, a marked improvement in water quality was observed within 48-72 hrs of the receding limb of the stream hydrograph before the next base low was established. It was concluded that storm-induced transients are exceedingly important for the mobilization of pollutants from diffuse sources but both transient events affect stream-channel processes, especially water quality, with the possibility of attendant consequences on the health of riparian inhabitants.


3-Hydroxy-2-oxindole Derivatives Containing Sulfonamide Motif: Synthesis, Antiviral Activity, and Modes of Action.
3-Hydroxy-2-oxindole motif constitutes a core structure in numerous natural products and imparts notable biological activities. Here, we describe the design and synthesis of four series of novel 3-substituted-3-hydroxy-2-oxindole derivatives containing sulfonamide moiety along with their antiviral activities against potato virus Y (PVY). Compound 10b displayed optimal antiviral activity and superior anti-PVY activity compared with the lead compound and commercial Ningnanmycin in terms of curative and protective effects. Additionally, 10b considerably inhibited PVY systemic infection in Nicotiana benthamiana. Physiological and biochemical analyses revealed that the activities of the four crucial defense-related enzymes increased in the tobacco plant following treatment with 10b. RNA-sequencing analysis revealed that 10b substantially induced the upregulation of 38 differentially expressed genes, which were enriched in the photosynthesis pathway. These findings suggest that 10b is a promising antiviral agrochemical that can effectively control PVY infection and trigger plant host immunity to develop virus resistance. This study provides novel molecular entities and ideas for developing new pesticides.


Effects of beta-adrenoreceptor-blocking drugs in patients with Raynaud's phenomenon.
Digital vasospastic phenomena have been reported to result from use of nonselective and cardioselective beta-adrenoreceptor-blocking drugs. The effects of 80 mg/day propranolol and 100 mg/day metoprolol on finger hemodynamics and clinical responses were compared with those of placebo in 16 patients with Raynaud's phenomenon. A double-blind, 2 week crossover study design was used with a 2 week washout placebo period between drugs. Total fingertip blood flow (FBF) as determined by venous occlusion plethysmography, fingertip capillary flow (FCF) as determined by radioisotope disappearance rate, and finger systolic blood pressure (FSP) were measured in a 28.3 degrees and a 20 degrees C room at the end of each period. Subjects kept diaries to record vasospastic attacks. There were no significant changes in FBF, FCF, or FSP in the warm or cool environment during drug treatment as compared with during the placebo period. A decrease in pulse rate occurred with both drugs and there was a decrease in blood pressure with metoprolol. There were no significant changes in the number of vasospastic attacks or in the patients' overall evaluation of their conditions while they were receiving the drugs. It is concluded that the presence of Raynaud's phenomenon is not a contraindication to the use of beta-adrenoreceptor-blocking drugs in the normotensive population.


On aging bone loss.
A survey was done of aging changes in compact and trabecular bone. During the past decade, noninvasive methods have demonstrated similar results for compact bone in large samples. Aging decreases of 3%/decade begin at about age 40 in both sexes and continue, but in women, an additional loss occurs after menopause, bringing their total rate of decrease to 9%/decade between ages 45 and 75. Results on trabecular bone loss are more variable, the majority indicating a slightly lower rate of loss (6% to 8% decade), beginning in young adulthood (20 to 40 years) in both sexes. These findings suggest that the common assumption about a large ongoing loss of trabecular bone after menopause may be erroneous. These assumptions are examined, as are the implications of the findings for calcium metabolism, anatomical correlations and fracture incidences.


Reduced strength, poor balance and concern about falls mediate the relationship between knee pain and fall risk in older people.
Pain is an independent risk factor for falling. One in two older community-dwelling people with musculoskeletal pain fall each year. This study examined physical, psychological and medical factors as potential mediators to explain the relationship between knee pain and falls. Three hundred and thirty-three community-dwelling people aged 70+ years (52% women) participated in this cohort study with a 1-year follow-up for falls. Participants completed questionnaires (medical history, general health and concern about falls) and underwent physical performance tests. Participants were classified into 'pain' and 'no pain' groups based on self-reported knee pain. Poisson Regression models were computed to determine the Relative Risk (RR) of having multiple falls and potential mediators for increased fall risk. One hundred and eighteen (36%) participants were categorised as having knee pain. This group took more medications and had more medical conditions (P < 0.01) compared to the no pain group. The pain group had poorer balance, physical function and strength and reported increased concern about falls. Sixty one participants (20%) reported ≥2 falls, with the pain group twice as likely to experience multiple falls over the 12 month follow up (RR = 2.0, 95% confidence interval (CI) = 1.27-3.13). Concern about falls, knee extension torque and postural sway with eyes closed were identified as significant and independent mediators of fall risk, and when combined explained 23% of the relationship between knee pain and falls. This study has identified several medical, medication, psychological, sensorimotor, balance and mobility factors to be associated with knee pain, and found the presence of knee pain doubles the risk of multiple falls in older community living people. Alleviating knee pain, as well as addressing associated risk factors may assist in preventing falls in older people with knee pain.


The role of the lateral frontal cortex in causal associative learning: exploring preventative and super-learning.
Prediction error--a mismatch between expected and actual outcome--is critical to associative accounts of inferential learning. However, it has proven difficult to explore the effects of prediction error using functional magnetic resonance imaging (fMRI) while excluding the confounding effects of stimulus novelty and incorrect responses. In this event-related fMRI study we used a three-stage experiment generating preventative- and super-learning conditions. In both cases, it was possible to generate prediction error within a causal associative learning experiment while subtracting the effects of novelty and error. We show that right lateral prefrontal cortex (PFC) activation is sensitive to the magnitude of prediction error. Furthermore, super-learning activation in this region of PFC correlates, across subjects, with the amount learned. We thus provide direct evidence for a brain correlate of the surprise-dependent mechanisms proposed by associative accounts of causal learning. We show that activity in right lateral PFC is sensitive to the magnitude, though not the direction, of the prediction error. Furthermore, its activity is not directly explicable in terms of novelty or response errors and appears directly related to the learning that arises out of prediction error.


[(18)F]FLT-PET imaging does not always "light up" proliferating tumor cells.
[(18)F]FLT (3'-Fluoro-3' deoxythymidine)-PET imaging was proposed as a tool for measuring in vivo tumor cell proliferation. The aim of this article was to validate the use of [(18)F]FLT-PET imaging for measuring xenograft proliferation and subsequent monitoring of targeted therapy. In exponentially growing xenografts, factors that could impact the outcome of [(18)F]FLT-PET imaging, such as nucleoside transporters, thymidine kinase 1, the relative contribution of DNA salvage pathway, and the ratio of FLT to thymidine, were evaluated. The [(18)F]FLT tracer avidity was compared with other proliferation markers. In a panel of proliferating xenografts, [(18)F]FLT or [(3)H]thymidine tracer avidity failed to reflect the tumor growth rate across different tumor types, despite the high expressions of Ki67 and TK1. When FLT was injected at the same dose level as used in the preclinical [(18)F]FLT-PET imaging, the plasma exposure ratio of FLT to thymidine was approximately 1:200. Thymidine levels in different tumor types seemed to be variable and exhibited an inverse relationship with the FLT tracer avidity. In contrast, high-dose administration of bromdeoxyuridine (BrdUrd; 50 mg/kg) yielded a plasma exposure of more than 4-fold higher than thymidine and leads to a strong correlation between the BrdUrd uptake and the tumor proliferation rate. In FLT tracer-avid models, [(18)F]FLT-PET imaging as a surrogate biomarker predicted the therapeutic response of CDK4/6 inhibitor PD-0332991. Tumor thymidine level is one of the factors that impact the correlation between [(18)F]FLT uptake and tumor cell proliferation. With careful validation, [(18)F]FLT-PET imaging can be used to monitor antiproliferative therapies in tracer-avid malignancies.


Effects of skeletal unloading on the vasomotor properties of the rat femur principal nutrient artery.
Spaceflight and prolonged bed rest induce deconditioning of the cardiovascular system and bone loss. Previous research has shown declines in femoral bone and marrow perfusion during unloading and with subsequent reloading in hindlimb-unloaded (HU) rats, an animal model of chronic disuse. We hypothesized that the attenuated bone and marrow perfusion may result from altered vasomotor properties of the bone resistance vasculature. Therefore, the purpose of this study was to determine the effects of unloading on the vasoconstrictor and vasodilator properties of the femoral principal nutrient artery (PNA), the main conduit for blood flow to the femur, in 2 wk HU and control (CON) rats. Vasoconstriction of the femoral PNA was assessed in vitro using norepinephrine, phenylephrine, clonidine, KCl, endothelin-1, arginine vasopressin, and myogenic responsiveness. Vasodilation through endothelium-dependent [acetylcholine, bradykinin, and flow-mediated dilation (FMD)] and endothelium-independent mechanisms [sodium nitroprusside (SNP) and adenosine] were also determined. Vasoconstrictor responsiveness of the PNA from HU rats was not enhanced through any of the mechanisms tested. Endothelium-dependent vasodilation to acetylcholine (CON, 86 ± 3%; HU, 48 ± 7% vasodilation) and FMD (CON, 61 ± 9%; HU, 11 ± 11% vasodilation) were attenuated in PNAs from HU rats, while responses to bradykinin were not different between groups. Endothelium-independent vasodilation to SNP and adenosine were not different between groups. These data indicate that unloading-induced decrements in bone and marrow perfusion and increases in vascular resistance are not the result of enhanced vasoconstrictor responsiveness of the bone resistance arteries but are associated with reductions in endothelium-dependent vasodilation.


Treating children in residential group psychotherapy.
The underlying principle in this approach to group treatment is provision of protective limits. In such a model, the therapist is required to operate as a benevolent authority. These children are offered a new view of authority that is firm, consistent, and nonpunitive. As a result, group members come to rely on the safety present in the group experience to develop greater awareness of their feelings and needs. In essence, their emotional needs are recognized and addressed directly, which supports emotional and social development and adaptation. By learning to control their behavior and by understanding their needs, these children can also come to learn how to get along with each other. For these children such achievements represent significant changes in the way they view themselves, as well as the world around them.


Suppression of virus replication by prostaglandin A is associated with heat shock protein synthesis.
The antiviral action of cyclopentenone prostaglandins (PGs) is generally associated with alterations in the synthesis and/or maturation of specific virus proteins. In particular, inhibition of Sendai virus (SV) replication in African green monkey kidney cells by PGA1 has been shown to be a cell-mediated event, due to alterations in SV protein glycosylation and accompanied by the induction of a cellular polypeptide of Mr 74K. In this report we identify this protein as a heat shock protein (HSP) related to the major 70K HSP group (HSP70). Induction of HSP70 synthesis by PGA1 was found to be dose-dependent, and an accumulation of HSP70 comparable to that occurring after heat shock could be obtained at concentrations of PGA1 that did not inhibit macromolecular synthesis in uninfected cells, but caused a dramatic block of virus replication in SV-infected cells. Induction of HSP70 by PGA1 occurred at the transcriptional level and was not affected by SV infection. HSP70 synthesis was evident between 2 and 3 h after PGA1 treatment, maximal at 12 h and went back to control levels by 26 h after the addition of PGA1, thus preceding virus protein synthesis. Finally, of several PGs tested, only those which possess antiviral activity induced the synthesis of HSP70. These results, together with the observation that suppression of HSP70 synthesis by actinomycin D also abolishes the PGA1-induced alteration of SV glycoproteins, suggest that HSP70 could play a role in the block of virus replication by cyclopentenone PGs.


Effect of methylphenidate and folic Acid on ADHD symptoms and quality of life and aggression: a randomized double blind placebo controlled clinical trial.
This clinical trial examines the effect of augmentation of methylphenidate (MPH) with folic acid to improve quality of life, and to treat aggression and ADHD symptoms. Participants of this eight week randomized double blind placebo controlled clinical trial were 49 children with ADHD. They were randomly assigned into one of the two groups: the first group receiving methylphenidate (10 to 20mg/day) plus folic (5mg/day), and the second group receiving methylphenidate plus placebo. Parent-reported ADHD symptoms and Overt Aggression Scale score were the outcome measures. Quality of life was assessed as well. Assessments were performed at pre-intervention, and at one month and two months after starting the interventions using repeated measure analysis. The mean age of children was 9.6(2.7) years. Age and gender were not associated with the groups. ADHD symptoms significantly decreased in both groups during the trial. However, no difference was observed between the groups. Moreover, aggression non-significantly decreased in both groups. Meanwhile, there was no difference between the two groups in efficacy for treating different types of aggressive behaviors including: verbal aggression, physical aggression against people, physical aggression against properties or objects, and aggression against self (self-injurious behavior). While methylphenidate improved quality of life of children with ADHD, folic acid did not improve it more than placebo. Both medications were well tolerated. considering the marked limitations of this trial, this primarily report suggests that methylphenidate may improve ADHD symptoms and the quality of life of children with ADHD. Current evidence does not support that folic acid as an adjuvant is effective for treating ADHD symptoms or aggression, or the improving quality of life of children with ADHD.


The effect of musical experience on emotional self-reports and psychophysiological responses to dissonance.
To study the influence of musical education on emotional reactions to dissonance, we examined self-reports and physiological responses to dissonant and consonant musical excerpts in listeners with low (LE: n=15) and high (HE: n=13) musical experience. The results show that dissonance induces more unpleasant feelings and stronger physiological responses in HE than in LE participants, suggesting that musical education reinforces aversion to dissonance. Skin conductance (SCR) and electromyographic (EMG) signals were analyzed according to a defense cascade model, which takes into account two successive time windows corresponding to orienting and defense responses. These analyses suggest that musical experience can influence the defense response to dissonance and demonstrate a powerful role of musical experience not only in autonomic but also in expressive responses to music.


CRISPs Function to Boost Sperm Power Output and Motility.
Fertilization requires sperm to travel long distances through the complex environment of the female reproductive tract. Despite the strong association between poor motility and infertility, the kinetics of sperm tail movement and the role individual proteins play in this process is poorly understood. Here, we use a high spatiotemporal sperm imaging system and an analysis protocol to define the role of CRISPs in the mechanobiology of sperm function. Each of CRISP1, CRISP2, and CRISP4 is required to optimize sperm flagellum waveform. Each plays an autonomous role in defining beat frequency, flexibility, and power dissipation. We thus posit that the expansion of the CRISP family from one member in basal vertebrates, to three in most mammals, and four in numerous rodents, represents an example of neofunctionalization wherein proteins with a common core function, boosting power output, have evolved to optimize different aspects of sperm tail performance.


A study on the tricarboxylic acid cycle and the synthesis of acetylcholine in the lobster nerve.
1. The pattern of metabolism of (14)C-labelled substrates in the lobster nerve suggested a normal tricarboxylic acid cycle with a slow turnover. 2. Acetylcholine was synthesized from [2-(14)C]acetate, [2-(14)C]pyruvate and [1,5-(14)C]citrate, implying the presence of acetate thiokinase, choline acetylase and citrate-cleavage enzyme. 3. [2-(14)C]Acetate was the best precursor. 4. The formation of acetyl-CoA from citrate was limited, probably by the citrate-cleavage enzyme, although the magnitude of the reversed reactions of the tricarboxylic acid cycle was large when compared with that of the forward reactions. 5. The relative magnitude of the two pathways (acetyl-CoA and carbon dioxide fixation) in pyruvate utilization was nearly equal. 6. The probable presence of metabolic compartments in the lobster nerve is discussed.


I-CARE randomized clinical trial integrating depression and acute coronary syndrome care in low-resource hospitals in China: Design and rationale.
Depression and acute coronary syndromes (ACS) are both common public health challenges. Patients with ACS often develop depression, which in turn adversely affects prognosis. Low-cost, sustainable, and effective service models that integrate depression care into the management of ACS patients to reduce depression and improve ACS outcomes are critically needed. Integrating Depression Care in ACS patients in Low Resource Hospitals in China (I-CARE) is a multicenter, randomized controlled trial to evaluate the efficacy of an 11-month integrated care (IC) intervention compared to usual care (UC) in management of ACS patients. Four thousand inpatients will be recruited and then randomized in a 1:1 ratio to an IC intervention consisting of nurse-led risk factor management, group-based counseling supplemented by individual problem-solving therapy, and antidepressant medications as needed, or to UC. The primary outcomes are depression symptoms measured by the Patient Health Questionnaire-9 at 6 and 12 months. Secondary endpoints include anxiety measured by the Generalized Anxiety Disorder-7; quality of life measured by the EQ-5D at 6 and 12 months; and major adverse events including the combined end point of all-cause death, suicide attempts, nonfatal myocardial infarction, nonfatal stroke, and all-cause rehospitalization at yearly intervals for a median follow-up of 2 years. Analyses of the cost-effectiveness and cost-utility of IC also will be performed. I-CARE trial will be the largest study to test the effectiveness of an integrated care model on depression and cardiovascular outcomes among ACS patients in resource-limited clinical settings.


Enhanced cell-specific ablation in zebrafish using a triple mutant of Escherichia coli nitroreductase.
Transgenic expression of bacterial nitroreductase (NTR) facilitates chemically-inducible targeted cell ablation. In zebrafish, the NTR system enables studies of cell function and cellular regeneration. Metronidazole (MTZ) has become the most commonly used prodrug substrate for eliciting cell loss in NTR-expressing transgenic zebrafish due to the cell-specific nature of its cytotoxic derivatives. Unfortunately, MTZ treatments required for effective cell ablation border toxic effects, and, thus, likely incur undesirable nonspecific effects. Here, we tested whether a triple mutant variant of NTR, previously shown to display improved activity in bacterial assays, can solve this issue by promoting cell ablation in zebrafish using reduced prodrug treatment regimens. We generated several complementary transgenic zebrafish lines expressing either wild-type or mutant NTR (mutNTR) in specific neural cell types, and assayed prodrug-induced cell ablation kinetics using confocal time series imaging and plate reader-based quantification of fluorescent reporters expressed in targeted cell types. The results show that cell ablation can be achieved in mutNTR expressing transgenic lines with markedly shortened prodrug exposure times and/or at lower prodrug concentrations. The mutNTR variant characterized here can circumvent problematic nonspecific/toxic effects arising from low prodrug conversion efficiency, thus increasing the effectiveness and versatility of this selective cell ablation methodology.


Racial and ethnic disparities in awareness of genetic testing for cancer risk.
Racial and ethnic disparities in awareness of genetic testing for cancer risk are substantial. This study assesses the relative importance of contributing factors to gaps in awareness of genetic testing for cancer risk across racial and ethnic groups. Data from the 2005 National Health Interview Survey (N=25,364) were analyzed in 2009 to evaluate the contribution of demographic factors, SES, health status, nativity/length of residency in the U.S., personal/family history of cancer, and perceived cancer risk to racial and ethnic disparities in genetic testing awareness for cancer risk. The contribution of each factor was assessed using the Fairlie decomposition technique. About 48% of non-Hispanic whites reported that they had heard about genetic testing, followed by 31% of blacks, 28% of Asians, and 19% of Hispanics. Education and nativity/length of residency in the U.S. explained 26% and 30% of the gap between whites and Hispanics, respectively. Education accounted for 22% of the white-black gap, with residential region explaining another 11%. Nativity/length of residency in the U.S. explained 51% of the white-Asian gap. The relative importance of factors contributing to racial and ethnic disparities in genetic testing awareness is specific to the particular groups under comparison. Diverse, culturally competent approaches are needed to improve awareness for different racial and ethnic groups.


Bridging the gap between systems biology and synthetic biology.
Systems biology is an inter-disciplinary science that studies the complex interactions and the collective behavior of a cell or an organism. Synthetic biology, as a technological subject, combines biological science and engineering, allowing the design and manipulation of a system for certain applications. Both systems and synthetic biology have played important roles in the recent development of microbial platforms for energy, materials, and environmental applications. More importantly, systems biology provides the knowledge necessary for the development of synthetic biology tools, which in turn facilitates the manipulation and understanding of complex biological systems. Thus, the combination of systems and synthetic biology has huge potential for studying and engineering microbes, especially to perform advanced tasks, such as producing biofuels. Although there have been very few studies in integrating systems and synthetic biology, existing examples have demonstrated great power in extending microbiological capabilities. This review focuses on recent efforts in microbiological genomics, transcriptomics, proteomics, and metabolomics, aiming to fill the gap between systems and synthetic biology.


Characterization of the inflammatory infiltrate during IgE-mediated late phase reactions in the skin of normal and atopic dogs.
In canine and human atopic patients, the intracutaneous injection of offending allergens is followed by the development of both immediate and late-phase reactions. The present study was performed to expand on the characterization and dynamics of inflammatory cell subsets during IgE-mediated late-phase reactions in canine skin. Three normal dogs and three Dermatophagoides farinae-allergic dogs were selected for this experiment. All dogs were challenged intradermally with mite allergen, purified anticanine IgE antibodies (positive control) or phosphate-buffered saline (negative control). Skin biopsies were obtained before and 6, 12 and 24 h post-injection. Sections were stained with metachromatic and eosinophil-specific histological stains. Additionally, we used an immunohistochemical method with antibodies specific for canine leukocyte antigens. This study confirmed the occurrence of a late-phase reaction in atopic skin following allergen challenge, and in normal and atopic canine skin after intradermal injection of IgE-specific antibodies. Whereas early emigrating dermal cells were composed chiefly of neutrophil and activated eosinophil granulocytes, there was an influx of alpha beta T-lymphocytes and dermal dendritic cells in later stages of the late-phase reactions. Because IgE-mediated late-phase reactions resemble spontaneous atopic canine skin lesions, both at macroscopic and microscopic levels, we propose the use of similar challenges to study the anti-inflammatory effects of anti-allergic drugs in a pre-clinical setting.


Contemporary management of wartime vascular trauma.
The treatment of wartime injuries has led to advances in the diagnosis and treatment of vascular trauma. Recent experience has stimulated a reappraisal of the management of such injuries, specifically assessing the effect of explosive devices on injury patterns and treatment strategies. The objective of this report is to provide a single-institution analysis of injury patterns and management strategies in the care of modern wartime vascular injuries. From December 2001 through March 2004, all wartime evacuees evaluated at a single institution were prospectively entered into a database and retrospectively reviewed. Data collected included site, type, and mechanism of vascular injury; associated trauma; type of vascular repair; initial outcome; occult injury; amputation rate; and complication. Liberal application of arteriography was used to assess these injuries. The results of that diagnostic and therapeutic approach, particularly as it related to the care of the blast-injured patient, are reviewed. Of 3057 soldiers evacuated for medical evaluation, 1524 (50%) sustained battle injuries. Known or suspected vascular injuries occurred in 107 (7%) patients, and these patients comprised the study group. Sixty-eight (64%) patients were wounded by explosive devices, 27 (25%) were wounded by gunshots, and 12 (11%) experienced blunt traumatic injury. The majority of injuries (59/66 [88%]) occurred in the extremities. Nearly half (48/107) of the patients underwent vascular repair in a forward hospital in Iraq or Afghanistan. Twenty-eight (26%) required additional operative intervention on arrival in the United States. Vascular injuries were associated with bony fracture in 37% of soldiers. Twenty-one of the 107 had a primary amputation performed before evacuation. Amputation after vascular repair occurred in 8 patients. Of those, 5 had mangled extremities associated with contaminated wounds and infected grafts. Sixty-seven (63%) patients underwent diagnostic angiography. The most common indication was mechanism of injury (42%), followed by abnormal examination (33%), operative planning (18%), or evaluation of a repair (7%). This interim report represents the largest analysis of US military vascular injuries in more than 30 years. Wounding patterns reflect past experience with a high percentage of extremity injuries. Management of arterial repair with autologous vein graft remains the treatment of choice. Repairs in contaminated wound beds should be avoided. An increase in injuries from improvised explosive devices in modern conflict warrants the more liberal application of contrast arteriography. Endovascular techniques have advanced the contemporary management and proved valuable in the treatment of select wartime vascular injuries.


Lactobacillus rhamnosus GG reverses mortality of neonatal mice against Salmonella challenge.
Pathogenic infection is one of the major causes of death in newborns. Antibiotic based therapies are still the major mode of treatment for infection. Increased usage of antibiotics leads to selective evolution of microorganisms and causes diseases in adulthood. Attempts to develop alternatives to antibiotics did not yield much success. A recent viable trend is to identify novel probiotics that could alleviate problems associated with over usage of antibiotics. We screened three different Lactobacillus species to establish their efficacy in neonates in protecting against Salmonella challenge. The methodologies employed are metagenomics, metabonomics, transcriptional profiling, molecular assays and behavioral studies. Among the three probiotics used, only Lactobacillus rhamnosus GG (LGG) treatment of the neonates resulted in rescuing of 80% of the Salmonella-infected mice. We have shown that LGG (MTCC #1408) can prevent Salmonella mediated infection in neonates. In the current report, results from histopathology, gene expression, neutrophil infiltration, metabolite and metataxonomic profiling, and protein level data suggested that LGG treatment of the neonates enhanced anti-inflammatory cytokine expression and increased the gut barrier function. The current report establishes the potential use of LGG in clinical intervention of infectious diseases.


Stable transformation of tobacco by electroporation: evidence for plasmid concatenation.
Electroporation (electric field-mediated DNA transfer) of tobacco protoplasts in the presence of the linearized plasmid pMON200 has led to the formation of transgenic plants. Defined electric shocks were delivered by capacitive discharges with readily available, low-cost electrical components. This transformation procedure is simple and efficient and may suggest a quick method for determining the appropriate electric fields for new cell systems. An optimal transformation frequency of 2.2 X 10(-4) (based on the number of cells subjected to the shock) was obtained with a single 2000-V/cm, 250-microseconds-duration capacitive discharge. Calli transformed to kanamycin resistance have been regenerated into whole plants. Southern blots of DNA from the transgenic plants demonstrate the integration of the selectable marker gene (neomycin phosphotransferase) at single or multiple genomic sites. In some cases, the plasmid appears to be integrated intact; in others, it is rearranged. The blots also provide evidence of plasmid recircularization and/or the formation of head-to-head and head-to-tail concatemers in most of the plants analyzed. Although some plants apparently have multiple integration sites, analysis of progeny obtained by self-fertilization of the transgenic plants indicates that the kanamycin-resistance marker is inherited as a single dominant gene.


A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype.
Isolated Complex I deficiency is the most common paediatric mitochondrial disease presentation, associated with poor prognosis and high mortality. Complex I comprises 44 structural subunits with at least 10 ancillary proteins; mutations in 29 of these have so far been associated with mitochondrial disease but there are limited genotype-phenotype correlations to guide clinicians to the correct genetic diagnosis. Patients were analysed by whole-exome sequencing, targeted capture or candidate gene sequencing. Clinical phenotyping of affected individuals was performed. We identified a cohort of 10 patients from 8 families (7 families are of unrelated Irish ancestry) all of whom have short stature (<9th centile) and similar facial features including a prominent forehead, smooth philtrum and deep-set eyes associated with a recurrent homozygous c.64T>C, p.Trp22Arg NDUFB3 variant. Two sibs presented with primary short stature without obvious metabolic dysfunction. Analysis of skeletal muscle from three patients confirmed a defect in Complex I assembly. Our report highlights that the long-term prognosis related to the p.Trp22Arg NDUFB3 mutation can be good, even for some patients presenting in acute metabolic crisis with evidence of an isolated Complex I deficiency in muscle. Recognition of the distinctive facial features-particularly when associated with markers of mitochondrial dysfunction and/or Irish ancestry-should suggest screening for the p.Trp22Arg NDUFB3 mutation to establish a genetic diagnosis, circumventing the requirement of muscle biopsy to direct genetic investigations.


Impact of Laterality on Cumulative Survival in Patients Diagnosed with Retinoblastoma: A Retrospective Cohort Analysis of 1925 Cases in the Surveillance, Epidemiology, and End Results (SEER) Program.
Retinoblastoma is an intraocular cancer with potentially severe clinical consequences if left untreated. Diagnostic and clinical management guidelines are strictly dependent on nature of laterality. This analysis aims to characterize the influence of laterality on survival in patients diagnosed with retinoblastoma. This retrospective cohort analysis utilized the Surveillance, Epidemiology, and End Results (SEER) program for population-based clinical data from 1975 to 2016, a period of 41 years. Univariable and multivariable Cox regression assessed survival with laterality as the primary independent predictor of mortality. Adjustment for demographical and clinical variables was performed. N = 1925 patients with a valid cause of death classification. Mean±SD age was 2.35±2.020 years (range 0-74). At the time of diagnosis, 819 (42.1%) patients were between 0 and 1 year of age, 469 (24.1%) patients were between 1 and 2 years, 350 (18.0%) patients were between 2 and 3 years, 147 (7.6%) patients were between 3 and 4 years, and 68 (3.5%) patients were between 4 and 5 years of age. The hazard of univariable cause-specific death is 55.6% and 52.9% lower for retinoblastoma patients with left-sided origin and right-sided origin as compared to patients with bilateral origin, respectively (HR = 0.444, CI 0.247-0.800, p = 0.007; HR = 0.471, CI 0.267-0.832, p = 0.009). After adjusting for confounding variables, the hazard of other-cause death for retinoblastoma patients is significantly less for left-sided origin (HR = 0.364, CI 0.140-0.946, p = 0.038) and right-sided origin (HR = 0.190, CI 0.066-0.549, p = 0.002) as compared to patients with retinoblastomas of bilateral origin. Prognostication of survival is significantly influenced by the nature of laterality in retinoblastoma. Unilateral retinoblastomas showcase increased promise for long-term cause-specific and other-cause survival compared to cases of retinoblastoma arising from bilateral origin.


[Early detection of developmental disorders: the need for a new perspective].
Early detection of abnormality in young children (aged 0-7) in the Netherlands is to be organized on two levels. First, regional cooperation between child-health professionals and institutions will be stimulated in order to form a nationwide network of 'multidisciplinary teams', with the task of coordinating early detection in a specific area. These teams are to advise parents and professionals in those cases where a child's development is suspected of being 'at risk'. The second part of the program is a campaign to promote the idea of early detection among the population. The aim is to develop the 'signalizing' and diagnostic abilities of parents, teachers and child-health professionals through education and training. The subject of early detection seemed and still seems to be a focus of different interests, and of conflicts of competence between different groups and schools of professionals and different institutions. In this article some of the main conflicting issues are discussed. One of the important problems concerning early detection is the question of defining normality and abnormality. It is concluded that in the case of early detection of both somatic and psychosomatic disorder there can be no such thing as an absolute scientific rationality, as is often suggested. Theoretical frameworks underlying methods of early detection are influenced by social, cultural and historical factors, and thus form a social construction. Finally a protocol-approach is being suggested, a method that might clear some of the problems concerning the content and organizational procedures of the Dutch system for early detection.


[Atrial flutter and atrial fibrillation by DDD stimulation].
136 patients were followed after implantation a DDD pacemaker (PM) for a total of 1,919 patient-months (m = 14.1 months/patient). 22/136 patients had one or more episodes of atrial flutter or fibrillation (AF) postoperatively. In 121/136 patients (group A) AF had not been documented before, in 4 it was unknown at the time of implantation, but was verified retrospectively (group B). 11 patients (group C) had a positive history of previous AF. Post implantation 7.4% in group A and 81.8% in group C developed AF. In patients with sick sinus syndrome (SSS) the incidence was 10/37 (27%), in those with AV block (AV) 6/77 (7.8%) and in cases with both SSS and AV 6/22 (27.3%). The first AF episode occurred during the implantation itself (n = 2) or during the hospital course in 9/22 patients (A: 11%, B/C: 64% early attacks), and later on in 13 with a time delay of 1-24 months (m = 8.5, 8 patients) in group A and 2-15 months (m = 6.6, 4 patients) in groups B/C. 2 patients of group C had no AF episodes post implantation. In the individual patient the number of attacks ranged from 1 to 3 (10.4/100 patient-months) in group A and from 1 to 6 (20.1/100 patient-months) in groups B/C. During AF 16/22 patients had a ventricular rate of 110-185, m = 132 bpm. In 6 patients the tachycardia was mediated by the PM and in 10 by fast intrinsic AV conduction. 1 patient with SSS, 2 with SSS + AV (spontaneous ventricular rate less than 45 bpm) and 3 with AV needed ventricular backup-pacing during AF. In 7 patients a total of 15 attacks of atrial flutter could be terminated by atrial overdrive pacing, in 5 of these episodes by temporary high rate A00 stimulation via the implanted pacemaker lead system. Otherwise AF was converted to sinus rhythm by antiarrhythmic drugs. After termination AF often recurred, but only 3 patients developed chronic atrial fibrillation. In 2 patients a ventricular rate greater than 180 bpm during AF reverted the PM to asynchronous mode, a possible cause of ventricular fibrillation in one. No other complications due to the PM itself have been encountered. AF, therefore, common during DDD pacing, even in patients without any AF history before implant. Both the incidence and the recurrence of AF depend on the presence or absence of previous atrial arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS)


Odontogenic Tumors: A Review of 675 Cases in Eastern Libya.
The aim of this study was to determine the relative frequency of odontogenic tumors (OTs) in an Eastern Libyan population based on the 2005 World Health Organization (WHO) classification, and also to compare the actual data with previous studies. We retrieved and analyzed 85 OTs from a total of 675 tumors and tumor-like lesions of the oral and perioral structures, for gender, age, tumor site, and frequency. The diagnosis was based on the most recent WHO (2005) classification of OTs. OTs constituted 12.6% of all oral/jaw tumors and tumor-like lesions. Ameloblastoma (28.2%) was the most common type, followed by keratocystic odontogenic tumor (25.2%) and odontoma (19.9%). The male: female ratio was 1.2:1, and maxilla: mandible ratio 1:2. The mean age of occurrence of tumors was 29 years with a peak incidence between 10 and 40 years. OTs are relatively common lesion in this Libyan Population, but the incidence of tumors is neither similar to Caucasians nor Sub-Saharan population.


Physician Initial Assessment Times Based on CTAS Scores: Are We Meeting the Recommendations?
The Canadian Triage and Acuity Scale prioritizes patient care in the emergency department (ED) by setting recommendations for physician initial assessment (PIA) times. However, adherence to the recommended PIA times may not be possible due to increasing ED visits, overcrowding and patient boarding in the ED. We conducted a retrospective review of adult patients who visited four community EDs from January 2016 to December 2017 and found that the overall compliance with the recommended PIA times was low. This brings into question the utility of the current target PIA times and prompts the need for changes downstream to enable quicker patient assessments.


Increased iron availability resulting from increased CO2 enhances carbon and nitrogen metabolism in the economical marine red macroalga Pyropia haitanensis (Rhodophyta).
Ocean acidification caused by rising CO2 is predicted to increase the concentrations of dissolved species of Fe(II) and Fe(III), leading to the enhanced photosynthetic carbon sequestration in some algal species. In this study, the carbon and nitrogen metabolism in responses to increased iron availability under two CO2 levels (390 μL L-1 and 1000 μL L-1), were investigated in the maricultivated macroalga Pyropia haitanensis (Rhodophyta). The results showed that, elevated CO2 increased soluble carbonhydrate (SC) contents, resulting from enhanced photosynthesis and photosynthetic pigment synthesis in this algae, but declined its soluble protein (SP) contents, resulting in increased ratio of SC/SP. This enhanced photosynthesis performance and carbon accumulation was more significant under iron enrichment condition in seawater, with higher iron uptake rate at high CO2 level. As a key essential biogenic element for algae, Fe-replete functionally contributed to P. haitanensis photosynthesis. Increased SC fundamentally provided carbon skeletons for nitrogen assimilation. The significant increase of carbon and nitrogen assimilation finally contributed to enhanced growth in this alga. This was also intuitively reflected by respiration that provided energy for cellular metabolism and algal growth. We propose that, in the predicted scenario of rising atmospheric CO2, P. haitanensis is capable to adjust its physiology by increasing its carbon and nitrogen metabolism to acclimate the acidified seawater, at the background of global climate change and simultaneously increased iron concentration due to decreased pH levels.


Effect of exciton self-trapping and molecular conformation on photophysical properties of oligofluorenes.
Electronic absorption and fluorescence transitions in fluorene oligomers of differing lengths are studied experimentally and using density functional theory (DFT) and time-dependent DFT. Experimental values are determined in two ways: from the measured molar absorption coefficient and from the radiative rate deduced from a combination of fluorescence quantum yield and lifetime measurements. Good agreement between the calculated and measured transition dipoles is achieved. In both theory and experiment a gradual increase in transition dipoles with increasing oligomer length is found. In absorption the transition dipole follows an approximately n(0.5) dependence on the number of fluorene units n for the range of 2 < or = n < or = 12, whereas a clear saturation of the transition dipole with oligomer length is found in fluorescence. This behavior is attributed to structural relaxation of the molecules in the excited state leading to localization of the excitation (exciton self-trapping) in the middle of the oligomer for both twisted and planar backbone conformations. Twisted oligofluorene chains were found to adopt straight or bent geometries depending on alternation of the dihedral angle between adjacent fluorene units. These different molecular conformations show the same values for the transition energies and the magnitude of the transition dipole.


A novel missense mutation of Wilms' Tumor 1 causes autosomal dominant FSGS.
FSGS is a clinical disorder characterized by focal scarring of the glomerular capillary tuft, podocyte injury, and nephrotic syndrome. Although idiopathic forms of FSGS predominate, recent insights into the molecular and genetic causes of FSGS have enhanced our understanding of disease pathogenesis. Here, we report a novel missense mutation of the transcriptional regulator Wilms' Tumor 1 (WT1) as the cause of nonsyndromic, autosomal dominant FSGS in two Northern European kindreds from the United States. We performed sequential genome-wide linkage analysis and whole-exome sequencing to evaluate participants from family DUK6524. Subsequently, whole-exome sequencing and direct sequencing were performed on proband DNA from family DUK6975. We identified multiple suggestive loci on chromosomes 6, 11, and 13 in family DUK6524 and identified a segregating missense mutation (R458Q) in WT1 isoform D as the cause of FSGS in this family. The identical mutation was found in family DUK6975. The R458Q mutation was not found in 1600 control chromosomes and was predicted as damaging by in silico simulation. We depleted wt1a in zebrafish embryos and observed glomerular injury and filtration defects, both of which were rescued with wild-type but not mutant human WT1D mRNA. Finally, we explored the subcellular mechanism of the mutation in vitro. WT1(R458Q) overexpression significantly downregulated nephrin and synaptopodin expression, promoted apoptosis in HEK293 cells and impaired focal contact formation in podocytes. Taken together, these data suggest that the WT1(R458Q) mutation alters the regulation of podocyte homeostasis and causes nonsyndromic FSGS.


Scattering of dipole-mode vector solitons: theory and experiment.
We study, both theoretically and experimentally, the scattering properties of optical dipole-mode vector solitons-radially asymmetric composite self-trapped optical beams. First, we analyze the soliton collisions in an isotropic two-component model with a saturable nonlinearity, and demonstrate that in many cases the scattering dynamics of the dipole-mode solitons allows us to classify them as "molecules of light"-extremely robust spatially localized objects which survive a wide range of interactions and display many properties of composite states with a rotational degree of freedom. Next, we study the composite solitons in an anisotropic nonlinear model that describes photorefractive nonlinearities, and also present a number of experimental verifications of our analysis.


Induction of specific microRNAs inhibits cutaneous wound healing.
Chronic nonhealing wounds, such as venous ulcers (VUs), are a widespread and serious medical problem with high morbidity and mortality. The molecular pathology of VUs remains poorly understood, impeding the development of effective treatment strategies. Using mRNA expression profiling of VUs biopsies and computational analysis, we identified a candidate set of microRNAs with lowered target gene expression. Among these candidates, miR-16, -20a, -21, -106a -130a, and -203 were confirmed to be aberrantly overexpressed in a cohort study of 10 VU patients by quantitative PCR and in situ hybridizations. These microRNAs were predicted to target multiple genes important for wound healing, including early growth response factor 3, vinculin, and leptin receptor (LepR). Overexpression of the top up-regulated miRNAs, miR-21 and miR-130a, in primary human keratinocytes down-regulated expression of the endogenous LepR and early growth response factor 3. The luciferase reporter assay verified LepR as a direct target for miR-21 and miR-130a. Both miR-21 and miR-130a delayed epithelialization in an acute human skin wound model. Furthermore, in vivo overexpression of miR-21 inhibited epithelialization and granulation tissue formation in a rat wound model. Our results identify a novel mechanism in which overexpression of specific set of microRNAs inhibits wound healing, resulting in new potential molecular markers and targets for therapeutic intervention.


A comprehensive multimodal dataset for contactless lip reading and acoustic analysis.
Small-scale motion detection using non-invasive remote sensing techniques has recently garnered significant interest in the field of speech recognition. Our dataset paper aims to facilitate the enhancement and restoration of speech information from diverse data sources for speakers. In this paper, we introduce a novel multimodal dataset based on Radio Frequency, visual, text, audio, laser and lip landmark information, also called RVTALL. Specifically, the dataset consists of 7.5 GHz Channel Impulse Response (CIR) data from ultra-wideband (UWB) radars, 77 GHz frequency modulated continuous wave (FMCW) data from millimeter wave (mmWave) radar, visual and audio information, lip landmarks and laser data, offering a unique multimodal approach to speech recognition research. Meanwhile, a depth camera is adopted to record the landmarks of the subject's lip and voice. Approximately 400 minutes of annotated speech profiles are provided, which are collected from 20 participants speaking 5 vowels, 15 words, and 16 sentences. The dataset has been validated and has potential for the investigation of lip reading and multimodal speech recognition.


Molecular model of a soluble guanylyl cyclase fragment determined by small-angle X-ray scattering and chemical cross-linking.
Soluble guanylyl/guanylate cyclase (sGC) converts GTP to cGMP after binding nitric oxide, leading to smooth muscle relaxation and vasodilation. Impaired sGC activity is common in cardiovascular disease, and sGC stimulatory compounds are vigorously sought. sGC is a 150 kDa heterodimeric protein with two H-NOX domains (one with heme, one without), two PAS domains, a coiled-coil domain, and two cyclase domains. Binding of NO to the sGC heme leads to proximal histidine release and stimulation of catalytic activity. To begin to understand how binding leads to activation, we examined truncated sGC proteins from Manduca sexta (tobacco hornworm) that bind NO, CO, and stimulatory compound YC-1 but lack the cyclase domains. We determined the overall shape of truncated M. sexta sGC using analytical ultracentrifugation and small-angle X-ray scattering (SAXS), revealing an elongated molecule with dimensions of 115 Å × 90 Å × 75 Å. Binding of NO, CO, or YC-1 had little effect on shape. Using chemical cross-linking and tandem mass spectrometry, we identified 20 intermolecular contacts, allowing us to fit homology models of the individual domains into the SAXS-derived molecular envelope. The resulting model displays a central parallel coiled-coil platform upon which the H-NOX and PAS domains are assembled. The β1 H-NOX and α1 PAS domains are in contact and form the core signaling complex, while the α1 H-NOX domain can be removed without a significant effect on ligand binding or overall shape. Removal of 21 residues from the C-terminus yields a protein with dramatically increased proximal histidine release rates upon NO binding.


Christianity and epilepsy.
Epileptic seizures have been known from time immemorial. Throughout the ages, however, ideas concerning the aetiology and treatment of epilepsy have changed considerably. Epilepsy is mentioned many times in the Pentateuch, where it is portrayed as a mysterious condition, whose symptoms, course and contingencies evade rational laws and explanations. In the Middle Ages, the accepted view which prevailed in social consciousness was that patients with epilepsy were possessed by Satan and other impure spirits. One common method of treatment of epileptic seizures was to submit the patient to cruel exorcisms. Patients were frequently injured in the process and some of them even died. Our understanding of epilepsy and its social consequences has improved considerably within the last century. The most significant progress as far as diagnosis and treatment of epilepsy is concerned took place in the last four decades of the twentieth century. Although we now know much more about epilepsy than we used to, this knowledge is still insufficiently popularized.


The role of transforming growth factor beta in thyroid autoimmunity: current knowledge and future perspectives.
The complex mechanisms, which are related to the pathophysiology and the development of autoimmune thyroid diseases, involve transforming growth factor beta (TGF-β) and its interplay with the immune system. The aim of this review is to examine the role of TGF-β regarding thyroid autoimmunity and explore the potent role of this molecule either as a diagnostic or prognostic marker or a therapeutic target regarding autoimmune thyroid diseases. TGF-β is clearly a master regulator of the immune response, exerting either inhibitory or facilitatory effects on cells of the immune system. Thus, this molecule is involved in the pathogenesis and development of autoimmune thyroid diseases. Recent research has revealed the involvement of TGF-β in the pathophysiology of autoimmune thyroid diseases. The role of TGF-β in the development of autoimmune thyroid diseases varies, depending on its concentrations, the type of the activated TGF-β signalling pathway, the genetic predisposition of the patient and the pathophysiologic stage of the disease. TGF-β could emerge as a useful diagnostic or prognostic marker for the evolution of thyroid autoimmunity. Promising perspectives for the effective therapeutic use of TGF-β regarding thyroid autoimmunity exist. The main treatment approaches incorporate either enhancement of the immunosuppressive role of TGF-β or inhibition of its facilitatory role in the autoimmune thyroid diseases. Further research towards deeper understanding of TGF-β physiology and clinical application of its possible therapeutic role regarding thyroid autoimmunity is needed.


Living in an oasis: Rapid transformations, resilience, and resistance in the North Water Area societies and ecosystems.
Based on lake sediment data, archaeological findings, and historical records, we describe rapid transformations, resilience and resistance in societies and ecosystems, and their interactions in the past in the North Water area related to changes in climate and historical events. Examples are the formation of the polynya itself and the early arrival of people, ca. 4500 years ago, and later major human immigrations (different societies, cultural encounters, or abandonment) from other regions in the Arctic. While the early immigrations had relatively modest and localised effect on the ecosystem, the later-incoming culture in the early thirteenth century was marked by extensive migrations into and out of the area and abrupt shifts in hunting technologies. This has had long-lasting consequences for the local lake ecosystems. Large natural transformations in the ecosystems have also occurred over relatively short time periods related to changes in the polynya. Finally, we discuss the future perspectives for the North Water area given the many threats, but also opportunities.


The use of artificial intelligence and deep learning reconstruction in urological computed tomography: Dose reduction at ghost level.
The objective of the study is to demonstrate that with the use of artificial intelligence (AI) in computed tomography (CT), radiation doses of CT kidney-ureter-bladder (KUB) and CT urogram (CTU) can be reduced to less than that of X-ray KUB and CT KUB, respectively, while maintaining the good image quality. We reviewed all CT KUBs (n = 121) performed in September 2019 and all CTUs (n = 74) performed in December 2019 at our institution. The dose length product (DLP) of all CT KUBs and each individual phase of CTU were recorded. DLP of each scan done with new scanner (Canon Aquilion One Genesis with AiCE [CAOG]) which uses AI and deep learning reconstruction (DLR) were compared against traditional non-AI scanner (GE OPTIMA 660 [GEO-660]). We also compared DLPs of both scanners against the United Kingdom, National Diagnostic Reference Levels (NDRL) for CT. One hundred and twenty-one patient's CT KUBs and 74 patient's CTUs were reviewed. For CT KUB group, the mean DLP of 81/121 scans done using AI/DLR scanner (CAOG) was 77.8 mGy cm (1.16 mSv), while the mean DLP of 40/121 CT KUB done with GEO-660 was 317.1 mGy cm (4.75 mSv). For CTU group, the mean DLP for 46/74 scans done using AI/DLR scanner (CAOG) was 401.9 mGy cm (6 mSv), compared to mean DLP of 1352.6 mGy cm (20.2 mSv) from GEO-660. We propose that CT scanners using AI/DLR method have the potential of reducing radiation doses of CT KUB and CTU to such an extent that it heralds the extinction of plain film XR KUB for follow-up of urinary tract stones. To the best of our knowledge, this is the first study comparing CT KUB and CTU doses from new scanners utilizing AI/DLR technology with traditional scanners using hybrid iterative reconstruction technology. Moreover, we have shown that this technology can markedly reduce the cumulative radiation burden in all urological patients undergoing CT examinations, whether this is CT KUB or CTU.


Directed expression of Gata2, Mash1, and Foxa2 synergize to induce the serotonergic neuron phenotype during in vitro differentiation of embryonic stem cells.
Investigation of serotonergic neuronal activity and its relationship to disease has been limited by a lack of physiologically relevant in vitro cell models. Serotonergic neurons derived from embryonic stem cells (ESCs) could provide a platform for such studies and provide models for use in drug discovery. Here, we report enhancement of serotonergic differentiation using a genetic approach. Expression of Gata2 increased the yield of serotonergic neurons. Enhancement was only achieved when Gata2 was expressed under the control of the tissue-specific promoter of the transcription factor Nkx6.1. High levels of Gata2 expression in ESCs compromised pluripotency and induced non-neuronal differentiation. Combined directed expression of Gata2, proneural gene Mash1, and forkhead transcription factor Foxa2 further enhanced serotonergic neural differentiation, resulting in a 10-fold increase in serotonin content. These neurons were also capable of depolarization (KCl, 30 mM)-induced elevations of intracellular Ca(2+) . The presence of sonic hedgehog during differentiation produced a further modest increase in numbers (1.5-fold). Transgene expression did not influence the number of tyrosine hydroxylase positive neurons in the cultures after 20 days, implying that Gata2, Mash1, and Foxa2 modulate in vitro differentiation at a time beyond the decision-point for dopaminergic or nondopaminergic commitment. This study demonstrates that the directed expression of specific transcription factors enhances serotonergic neuron differentiation in vitro and highlights the importance of transgene expression at the right stage of ESC differentiation to effect the generation of a desired neural subtype.


Latency of the pupil light reflex: sample rate, stimulus intensity, and variation in normal subjects.
To investigate the clinical usefulness of the latency of the pupil light reflex by optimizing its measurement, characterizing its variability, and determining the sensitivity of pupil latency as a function of stimulus input in normal subjects. Computerized binocular infrared pupillography was performed in 14 eyes of seven healthy subjects. Pupils were recorded simultaneously at 60 and 1000 Hz. Each eye was alternatively stimulated eight times for 50 ms every 2.5 seconds, increasing by 0.5 log units over a 2.0-log-unit range. To determine intersubject and intereye variability, 98 eyes of 49 healthy subjects were recorded at 60 Hz over a 3.0-log-unit range (15 degrees radius stimulation, four repetitions at each intensity). Accuracy and resolution of latency were limited by the number of light reflexes used to estimate the average latency and were significantly affected by sampling rate when the number of reflexes recorded was fewer than four. Binocular recording and interpolation of the 60-Hz recording to 300 Hz added resolution to the latency. Biological variability contributed more to interindividual variability than did measurement variability. The range of intereye afferent asymmetry of latency in normal subjects was only between 8.3 and 35 ms-less with brighter stimulus intensity. An optimal method for determination of the onset of the pupil light reflex was devised that consisted of filtering, interpolation of pupil recordings, and analysis of the first and second derivative of the pupil movement. Most of the variability in latency as a function of intensity in normal subjects was due to interindividual variation and latency was well matched between the two eyes of the subjects.


Information processing by community health nurses using mobile health (mHealth) tools for early identification of suicide and depression risks in Fiji Islands.
High rates of depression and suicide and a lack of trained psychiatrists have emerged as significant concerns in the low-income and middle-income countries (LMICs) such as the Pacific Island Countries (PICs). Readily available smartphones were leveraged with community health nurses (CHNs) in task-sharing for early identification of suicide and depression risks in Fiji Islands, the largest of PICs. This investigation examines how CHNs can efficiently and effectively process patient information about depression and suicide risk for making diagnostic and management decisions without compromising safety. The research is driven by the theoretical framework of text comprehension (knowledge representation and interpretation) and decision-making. Mobile health (mHealth) Application for Suicide Risk and Depression Assessment (ASRaDA) was designed to include culturally useful clinical guidelines for these disorders. A representative sample of 48 CHNs was recruited and presented with two clinical cases (depression and suicide) in a simulated setting under three conditions: No support, paper-based and mobile-based culturally valid guideline support. Data were collected as the nurses read through the scenarios, 'thinking aloud', before summarising, diagnoses and follow-up recommendations. Transcribed audiotapes were analysed using formal qualitative discourse analysis methods for diagnostic accuracy, comprehension of clinical problems and reasoning patterns. Using guidelines on ASRaDA, the CHNs took less time to process patient information with more accurate diagnostic and therapeutic decisions for depression and suicide risk than with paper-based or no guideline conditions. A change in reasoning pattern for nurses' information processing was observed with decision support.DiscussionAlthough these results are shown in a mental health setting in Fiji, there are reasons to believe they are generalisable beyond mental health and other lower-to-middle income countries. Culturally appropriate clinical guidelines on mHealth supports efficient information processing for quick and accurate decisions and a positive shift in reasoning behaviour by the nurses. However, translating complex qualitative patient information into quantitative scores could generate conceptual errors. These results are valid in simulated conditions.


[The Doppler palm test].
In 384 hands the patency of the arterial arch was investigated by means of both the Allen test and the Doppler palmar arch test as developed by the authors. While the Allen test is purely subjective and gives a high proportion of false results especially in shocked patients, the Doppler palmar arch test is based on two objective criteria: 1. Demonstration of reversed flow in the distal section of the radial artery on proximal compression. 2. Demonstration of pulsatile flow in the radial thumb artery even on compression of the radial artery. The Doppler palmar arch test eliminates all negative aspects of the Allen test and is therefore definitely more reliable than the latter. It is easy to perform for investigators having little experience with Doppler sonography. The time consumed is not greater than with the Allen test.


Natural course of sensitization to cow's milk and hen's egg in childhood atopic dermatitis: ETAC study group.
Sensitization to food allergens has been implicated in the pathogenesis of atopic diseases, in particular atopic dermatitis (AD). The aim of the present paper is to investigate the natural course of sensitization to egg and to cow's milk and its relationship with the severity of AD. The placebo intention-to-treat population of the ETACTM (Early Treatment of the Atopic Child) study consisted of 397 children with AD aged 12-24 months (mean+ SD: 17.2 + 4.1 months) who were followed for 18 months. All children were examined for objective SCORing Atopic Dermatitis (SCORAD) and specific IgE amongst other, to egg and to cow's milk at inclusion and after 3, 12 and 18 months. Fifteen patients were excluded from this analysis due to major protocol violations thus leaving 382 patients in the analysed population. Sensitization to egg and to cow's milk was more common in atopic children with severe AD at all time-points. At inclusion, children sensitized to both egg and to cow's milk had the most severe AD (Kruskall-Wallis test P= 0.007). The degree of sensitization expressed in RAST classes was significantly related to the severity of AD. Furthermore, children sensitized to egg or to cow's milk at inclusion had a higher risk of persistence of AD (84% and 67%, respectively, vs. 57% in those not sensitized) and a higher objective SCORAD after 18 months follow-up. We found an association between severity of AD and sensitization to egg or to cow's milk. Moreover, sensitization to egg, and to a lesser extent cow's milk, indicates a worse outcome of AD in terms of persistence and severity of the disease.


Narrative review: molecular and genetic profiling of oligometastatic non-small cell lung cancer.
The objectives of this review are to discuss: the definition, clinical and biologic features of oligometastatic non-small cell lung cancer (NSCLC), as well as the concept of treating oligoprogression in oligometastatic NSCLC. A substantial proportion of patients diagnosed with lung cancer present with metastatic disease, and a large portion of patients who present with localized disease later develop metastases. Oligometastatic NSCLC is defined as an intermediate state between localized and widespread metastatic disease, where there may be a role for curative localized therapy approach by treating the primary tumor and all metastases with radiotherapy or surgery. Despite the increasing application of this approach in patients with lung cancer, the identification of patients who might benefit from this approach is yet to be well characterized. After a systematic review of the literature, a PubMed search was performed using the English language and the key terms: oligometastatic, non-small cell lung cancer (NSCLC), localized consolidative treatment (LCT), biomarkers, biologic features, clinical features. Over 500 articles were retrieved between 1889-2021. A total of 178 papers discussing the definition, clinical and biologic factors leading to oligometastatic NSCLC were reviewed and included in the discussion of this paper. Oligometastatic NSCLC is a unique entity. Identifying patients who have oligometastatic NSCLC accurately using a combination of clinical and biologic features and treating them with localized consolidative approach appropriately results in improvement of outcome. Further understanding of the molecular mechanisms driving the formation of oligometastatic NSCLC is an important area of focus for future studies.


Discovery and implementation of a novel pathway for n-butanol production via 2-oxoglutarate.
One of the European Union directives indicates that 10% of all fuels must be bio-synthesized by 2020. In this regard, biobutanol-natively produced by clostridial strains-poses as a promising alternative biofuel. One possible approach to overcome the difficulties of the industrial exploration of the native producers is the expression of more suitable pathways in robust microorganisms such as Escherichia coli. The enumeration of novel pathways is a powerful tool, allowing to identify non-obvious combinations of enzymes to produce a target compound. This work describes the in silico driven design of E. coli strains able to produce butanol via 2-oxoglutarate by a novel pathway. This butanol pathway was generated by a hypergraph algorithm and selected from an initial set of 105,954 different routes by successively applying different filters, such as stoichiometric feasibility, size and novelty. The implementation of this pathway involved seven catalytic steps and required the insertion of nine heterologous genes from various sources in E. coli distributed in three plasmids. Expressing butanol genes in E. coli K12 and cultivation in High-Density Medium formulation seem to favor butanol accumulation via the 2-oxoglutarate pathway. The maximum butanol titer obtained was 85 ± 1 mg L-1 by cultivating the cells in bioreactors. In this work, we were able to successfully translate the computational analysis into in vivo applications, designing novel strains of E. coli able to produce n-butanol via an innovative pathway. Our results demonstrate that enumeration algorithms can broad the spectrum of butanol producing pathways. This validation encourages further research to other target compounds.


Predictive value of plasma biomarkers for mortality and organ failure development in patients with acute respiratory distress syndrome.
To evaluate the predictive value of 6 different biomarkers in the development of multiple-organ failure (MOF) and mortality in a contemporary prospective cohort of acute respiratory distress syndrome (ARDS). Patients with ARDS admitted to a tertiary referral center during an 8-month period were included. Plasma sample collection of 6 different biomarkers on days 1, 3, and 5 after ARDS onset was performed (von Willebrand factor, thrombin-antithrombin III complex, plasminogen activator inhibitor 1, interleukin 8, receptor for advanced glycation end-products, and club cell secretory protein). Main outcomes included hospital mortality and development of MOF. Logistic regression models for MOF and mortality prediction were created including biomarkers levels and clinical predictors. One hundred patients were included in the study. Do-not-resuscitate status and McCabe score were independently associated with increased mortality. None of the 6 biomarkers measured at the time of ARDS diagnosis predicted hospital mortality. After adjustment for important clinical characteristics, elevated day-1 interleukin 8 levels were associated with the development of MOF. Addition of biomarkers did not improve mortality prediction in this cohort of ARDS. Association between elevated interleukin 8 levels and progression of organ failures suggests an important role of exaggerated inflammatory response in the development of MOF.


Passive diffusion accounts for the majority of intracellular nanovesicle transport.
During membrane trafficking, a vesicle formed at the donor compartment must travel to the acceptor membrane before fusing. For large carriers, it is established that this transport is motor-driven; however, the mode by which small vesicles, which outnumber larger carriers, are transported is poorly characterized. Here, we show that intracellular nanovesicles (INVs), a substantial class of small vesicles, are highly mobile within cells and that this mobility depends almost entirely on passive diffusion (0.1-0.3 μm2 s-1). Using single particle tracking, we describe how other small trafficking vesicles have a similar diffusive mode of transport that contrasts with the motor-dependent movement of larger endolysosomal carriers. We also demonstrate that a subset of INVs is involved in exocytosis and that delivery of cargo to the plasma membrane during exocytosis is decreased when diffusion of INVs is specifically restricted. Our results suggest that passive diffusion is sufficient to explain the majority of small vesicle transport.


Polypeptide specificities of measles virus-reactive T cell lines and clones derived from a patient with multiple sclerosis.
Eleven cloned and uncloned measles virus-specific T cell lines were generated from peripheral blood lymphocytes obtained from a patient with multiple sclerosis and were assayed for measles polypeptide specificity. Three clones reacted specifically with the fusion (F) protein and one recognized the hemagglutinin (HA). Two reacted with whole virus but not with any of the purified proteins. Five cell lines proliferated in response to multiple measles polypeptides. The addition of anti-HA or anti-F monoclonal antibodies to two of the multispecific cell lines each resulted in partial suppression of the proliferative response to whole virus by the cell lines. Two of the three F-reactive clones recognized antigen in association with a subgroup of HLA-DR4; the third responded to F only in the presence of autologous antigen-presenting cells. Of the two clones that reacted only with whole virus, one was restricted to DP3 and one to autologous cells. The HA-specific clone was DP3 restricted. Several cell lines recognized multiple measles polypeptides in association with a single HLA antigen. Recognition of individual measles polypeptides does not segregate with specific genetic restriction elements.


Optimized reactive silencers composed of closely-spaced elongated side-branch resonators.
This paper reports a theoretical study of the sound propagation in a rectangular waveguide loaded by closely-spaced elongated side-branch resonators forming a simple low-frequency broadband reactive silencer. Semi-analytical calculations account for the evanescent modes both in the main waveguide and side-branch resonators and for the viscothermal losses in the silencer elements. Reasonable accuracy is maintained in the evaluation of transmission, reflection, and absorption coefficients, while the calculation time is reduced by a few hundred times in comparison with the finite element method. Therefore, the proposed method is particularly suitable for optimization procedure. The lengths of the individual equally spaced side-branch resonators are optimized by a heuristic evolutionary algorithm that maximizes the minimum transmission loss (TL) over a pre-defined frequency range. Numerical results indicate that the minimum TL of the optimized silencers is reduced due to the destructive effect of the evanescent coupling from the resonators of the nearest side-branches. In the opposite, the TL increases linearly with the number of the side-branch resonators.


Wild-type myoblasts rescue the ability of myogenin-null myoblasts to fuse in vivo.
Skeletal muscle is formed via a complex series of events during embryogenesis. These events include commitment of mesodermal precursor cells, cell migration, cell-cell recognition, fusion of myoblasts, activation of structural genes, and maturation. In mice lacking the bHLH transcription factor myogenin, myoblasts are specified and positioned correctly, but few fuse to form multinucleated fibers. This indicates that myogenin is critical for the fusion process and subsequent differentiation events of myogenesis. To further define the nature of the myogenic defects in myogenin-null mice, we investigated whether myogenin-null myoblasts are capable of fusing with wild-type myoblasts in vivo using chimeric mice containing mixtures of myogenin-null and wild-type cells. Chimeric embryos demonstrated that myogenin-null myoblasts readily fused in the presence of wild-type myoblasts. However, chimeric myofibers did not express wild-type levels of muscle-specific gene products, and myofibers with a high percentage of mutant nuclei appeared abnormal, suggesting that the wild-type nuclei could not fully rescue mutant nuclei in the myofibers. These data demonstrate that myoblast fusion can be uncoupled from complete myogenic differentiation and that myogenin regulates a specific subset of genes with diverse function. Thus, myogenin appears to control not only transcription of muscle structural genes but also the extracellular environment in which myoblast fusion takes place. We propose that myogenin regulates the expression of one or more extracellular or cell surface proteins required to initiate the muscle differentiation program.


Guidelines for identification and treatment of individuals with attention deficit/hyperactivity disorder and associated fetal alcohol spectrum disorders based upon expert consensus.
The association of attention deficit/hyperactivity disorder (ADHD) and fetal alcohol spectrum disorders (FASD) results in a complex constellation of symptoms that complicates the successful diagnosis and treatment of the affected individual. Current literature lacks formal guidelines, randomized control trials, and evidence-based treatment plans for individuals with ADHD and associated FASD. Therefore, a meeting of professional experts was organized with the aim of producing a consensus on identification and treatment guidelines that will aid clinicians in caring for this unique patient population. Experts from multiple disciplines in the fields of ADHD and FASD convened in London, United Kingdom, for a meeting hosted by the United Kingdom ADHD Partnership (UKAP; www.UKADHD.com ) in June 2015. The meeting provided the opportunity to address the complexities of ADHD and FASD from different perspectives and included presentations, discussions, and group work. The attendees worked towards producing a consensus for a unified approach to ADHD and associated FASD. The authors successfully came to consensus and produced recommended guidelines with specific regards to identification and assessment, interventions and treatments, and multiagency liaisons and care management, highlighting that a lifespan approach to treatment needs to be adopted by all involved. Included in the guidelines are: 1) unique 'red flags', which when identified in the ADHD population can lead to an accurate associated FASD diagnosis, 2) a treatment decision tree, and 3) recommendations for multiagency care management. While clinically useful guidelines were achieved, more research is still needed to contribute to the knowledge base about the diagnosis, treatment, and management of those with ADHD and associated FASD.


The sequence motifs that are involved in SV40 enhancer function also control SV40 late promoter activity.
The simian virus 40 (SV40) enhancer element is constituted of two domains which contain sequences important for late transcription (M. Ernoult-Lange, F. Omilli, D. O'Reilly and E. May, J. Virol. 61, 167-176, 1987). By analysing a series of clustered point mutations generated throughout the enhancer region we mapped domain I from nt 232 to 272 and domain II from nt 184 to 216. These two domains which are required for late promoter activity both in the presence and in the absence of T antigen correspond closely to the domains B and A respectively, identified for enhancer function (M. Zenke, T. Grundström, H. Matthes, M. Wintzerith, C. Schatz, A. Wildeman and P. Chambon, EMBO J., 5, 387-397, 1986). Similarly to the enhancer function the late promoter elements defined by these two domains contain multiple sequence motifs. Moreover there is a striking overlap between the sequence motifs within domain A, active for early enhancer function and those within domain II involved in efficient late transcription.


Local anesthetics QX 572 and benzocaine act at separate sites on the batrachotoxin-activated sodium channel.
We have studied the effect of local anesthetics QX 572, which is permanently charged, and benzocaine, which is neutral, on batrachotoxin-activated sodium channels in mouse neuroblastoma N18 cells. The dose-response curves for each drug suggest that QX 752 and benzocaine each act on a single class of binding sites. The dissociation constants are 3.15 X 10(-5) M for QX 572 and 2.65 X 10(-4) M for benzocaine. Equilibrium and kinetic experiments indicate that both drugs are competitive inhibitors of batrachotoxin. When benzocaine and QX 572 are present with batrachotoxin, they are much more effective at inhibiting Na+ flux than would be predicted by a one-site model. Our results indicate that QX 572 and benzocaine bind to separate sites, each of which interacts competitively with batrachotoxin.


Yield improvement strategies for the production of secondary metabolites in plant tissue culture: silymarin from Silybum marianum tissue culture.
Plant cell culture can be a potential source for the production of important secondary metabolites. This technology bears many advantages over conventional agricultural methods. The main problem to arrive at a cost-effective process is the low productivity. This is mainly due to lack of differentiation in the cultured cells. Many approaches have been used to maximise the yield of secondary metabolites produced by cultured plant cells. Among these approaches: choosing a plant with a high biosynthetic capacity, obtaining efficient cell line for growth and production of metabolite of interest, manipulating culture conditions, elicitation, metabolic engineering and organ culture. This article gives an overview of the various approaches used to maximise the production of pharmaceutically important secondary metabolites in plant cell cultures. Examples of using these different approaches are shown for the production of silymarin from Silybum marianum tissue culture.


Evidence that PAR-1 and PAR-2 mediate prostanoid-dependent contraction in isolated guinea-pig gallbladder.
We have investigated the ability of protease-activated receptor-1 (PAR-1), PAR-2, PAR-3 and PAR-4 agonists to induce contractile responses in isolated guinea-pig gallbladder. Thrombin, trypsin, mouse PAR-1 activating (SFLLRN-NH(2)) peptide, and mouse PAR-2 activating (SLIGRL-NH(2)) and human PAR-2 activating (SLIGKV-NH(2)) peptides produced a concentration-dependent contractile response. Mouse PAR-4 activating (GYPGKF-NH(2)) peptide, the mouse PAR-1 reverse (NRLLFS-NH(2)) peptide, the mouse PAR-2 reverse (LRGILS-NH(2)) and human PAR-2 reverse (VKGILS-NH(2)) peptides caused negligible contractile responses at the highest concentrations tested. An additive effect was observed following the contractile response induced by either trypsin or thrombin, with the addition of a different PAR agonist (SFLLRN-NH(2) and SLIGRL-NH(2), respectively). Desensitization to PAR-2 activating peptide attenuated the response to trypsin but failed to attenuate the response to PAR-1 agonists, and conversely desensitization to PAR-1 attenuated the response to thrombin but failed to alter contractile responses to PAR-2 agonists. The contractile responses produced by thrombin, trypsin, SFLLRN-NH(2) and SLIGRL-NH(2) were markedly reduced in the presence of the cyclo-oxygenase inhibitor, indomethacin, whilst the small contractile response produced by NRLLFS-NH(2) and LRGILS-NH(2) were insensitive to indomethacin. The contractile responses to thrombin, trypsin, SFLLRN-NH(2) and SLIGRL-NH(2) were unaffected by the presence of: the non-selective muscarinic antagonist, atropine; the nitric oxide synthase inhibitor, L-NAME; the sodium channel blocker, tetrodotoxin; the combination of selective tachykinin NK(1) and NK(2) receptor antagonists, (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2] octane chloride (SR140333) and (S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino-2-(3, 4-dichlorophenyl)-butyl] benzamide (SR48968), respectively. The results indicate that PAR-1 and PAR-2 activation causes contractile responses in the guinea-pig gallbladder, an effect that is mediated principally by prostanoid release, and is independent of neural mechanisms.


The effects of graduated stimulus change on the acquisition of a simple discrimination in severely retarded boys.
Methods were compared for teaching severely retarded boys to discriminate the position of a 0.75-in. black square and to press the response key closest to it. Seven boys were given trial-and-error training; one learned the task. The six boys who did not learn were presented with a program of graduated stimulus changes. All but one acquired the performance, and he was under appropriate control during the program. When he reached the criterion stimuli, he reverted to a position-based response learned during trial-and-error training. Six similar subjects were presented with graduated stimulus training alone. All six learned the criterion discrimination with few or no errors. Both groups were tested for retention of the criterion performance 35 days after training was completed. Two boys who had near-perfect criterion discrimination performances showed no signs of retention after 35 days. These boys had a history of trial-and-error training.


Incidence and risk factors for postoperative delirium after lumbar spine surgery.
Retrospective database analysis. A population-based database was analyzed to characterize the incidence, hospital costs, mortality, and risk factors associated with postoperative delirium after lumbar decompression (LD) and lumbar fusion (LF) surgical procedures. Postoperative delirium is a common complication after surgery in the elderly that leads to increased hospitalization, cost, and other adverse outcomes. The incidence of delirium after lumbar spine surgery has not been discussed in this literature. Data from the Nationwide Inpatient Sample were obtained from 2002-2009. Patients undergoing LD or LF for degenerative pathologies were identified. Patient demographics, comorbidities, length of stay, discharge disposition, costs, and mortality were assessed. SPSS version 20 was used for statistical analysis using independent T tests for discrete variables and χ2 tests for categorical data. Logistic regression was performed to identify independent predictors of delirium. A P value of less than 0.001 was used to denote significance. A total of 578,457 LDs and LFs were identified in the United States from 2002-2009. Of these, 292,177 were LDs and 286,280 were LFs. The overall incidence of delirium was 8.4 events per 1000 cases. Patients undergoing LF had a statistically greater incidence of delirium than patients undergoing LD (11.8 vs. 5.0 per 1000; P < 0.001). Patients experiencing delirium were significantly older and more likely to be female than nonaffected patients (P < 0.001). Patients with delirium in both cohorts demonstrated significantly greater comorbidities, length of stay, greater costs, and more frequent discharge to skilled nursing facilities (P < 0.001). The presence of delirium in LD-treated patients was associated with an increased mortality rate (6.1 vs. 0.8 per 1000; P < 0.001). Logistic regression demonstrated that independent predictors of delirium included older age (≥65 yr), alcohol/drug abuse, depression, psychotic disorders, neurological disorders, deficiency anemia, fluid/electrolyte disorders, and weight loss. The results of our study demonstrated an overall incidence of 8.4 events per 1000 lumbar spine surgical procedures. Overall analysis demonstrated an increased incidence of delirium in older females with greater comorbid conditions. Delirium was found to be associated with increased length of stay, costs, and mortality in all patients undergoing lumbar spine surgery. We recommend that physicians put greater effort into recognizing risk factors of delirium and diagnosing it in a timely manner to mitigate its effects. 3.


Intravenous immunoglobulin therapy for recurrent spontaneous abortion: a meta-analysis.
Published randomized trials of the use of intravenous immunoglobulins (IVIG) as a treatment for recurrent spontaneous abortion (RSA) have produced conflicting results. The purpose of this study was to conduct a systematic review of the current evidence to evaluate the effectiveness of IVIG for RSA. After a thorough search of the literature, four randomized, double-blind trials comparing IVIG with placebo for treatment of RSA were included in the meta-analysis. Live birth rates for each treatment group were extracted, and the overall odds ratio (OR) and absolute treatment effect for IVIG were calculated. Two of the trials showed an increase in successful pregnancy outcome with IVIG treatment and two did not. The overall OR was 1.48 (95% CI, 0.84-2.60) in favor of IVIG, with an absolute treatment effect of 10.1% (95% CI, -4.8-24.6). Excluding pregnancy failures with an obvious cause produced statistically significant results, but this approach may be subject to bias. This meta-analysis suggests that IVIG may have a role in the treatment of recurrent abortion, but as yet no conclusive evidence is available.


The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity, cholesterol esterification and the expression of low-density lipoprotein receptors in cultured monocyte-derived macrophages.
Human blood monocytes cultured in medium containing 20% whole serum showed the greatest activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and [14C]acetate incorporation into non-saponifiable lipids around the 7th day after seeding, the period of greatest growth. Although there was enough low-density lipoprotein (LDL) in the medium to saturate the LDL receptors that were expressed by normal cells at that time, HMG-CoA reductase activity and acetate incorporation were as high in normal cells as in cells from familial-hypercholesterolaemic (FH) patients. Both the addition of extra LDL, which interacted with the cells by non-saturable processes, and receptor-mediated uptake of acetylated LDL significantly reduced reductase activity and increased incorporation of [14C]oleate into cholesteryl esters in normal cells and cells from FH patients ('FH cells'), and reduced the expression of LDL receptors in normal cells. Pre-incubation for 20h in lipoprotein-deficient medium apparently increased the number of LDL receptors expressed by normal cells but reduced the activity of HMG-CoA reductase in both normal and FH cells. During subsequent incubations the same rate of degradation of acetylated LDL and of non-saturable degradation of LDL by FH cells was associated with the same reduction in HMG-CoA reductase activity, although LDL produced a much smaller stimulation of oleate incorporation into cholesteryl esters. In normal cells pre-incubated without lipoproteins, receptor-mediated uptake of LDL could abolish reductase activity and the expression of LDL receptors. The results suggested that in these cells, receptor-mediated uptake of LDL might have a greater effect on reductase activity and LDL receptors than the equivalent uptake of acetylated LDL. It is proposed that endogenous synthesis is an important source of cholesterol for growth of normal cells, and that the site at which cholesterol is deposited in the cells may determine the nature and extent of the metabolic events that follow.


STAT3 expression in salivary gland tumours.
The aim of the present study was to evaluate the signal transducer and activator of transcription (STAT3) expression, which is constitutively active in different types of malignant tumours, in salivary gland tumours. Fifty biopsies of salivary gland tumours (9 pleomorphic adenomas, 12 adenoid cystic carcinomas, 7 epithelial-myoepithelial carcinomas, 10 polymorphous low-grade adenocarcinomas and 12 mucoepidermoid carcinomas) and 10 normal salivary glands were immunohistochemically labeled for STAT3 and Phospho-STAT3 (STAT3P). The labeled sections were qualitatively and quantitatively evaluated. The results showed that, in normal salivary gland, STAT3 was expressed in cytoplasm and STAT3P in nuclei of all tissue cells, except in large mucous acinar cells for which both antibodies were negative. In pleomorphic adenoma, the expression was the same as in normal glands. In malignant tumours, there were variations in the expression of these antibodies. The most important one was the presence of STAT3 in the nuclei of the malignant tumour cells, most evident in the cribriform-type of adenoid cystic carcinoma. Both loss and variation of STAT3P expression were also observed. The presence of STAT3 in the nuclei of malignant salivary gland tumours may represent an important event in oncogenesis probably contributing to tumour cell proliferation while blocking apoptosis. However, further investigation will be necessary to support this hypothesis.


Satisfaction levels with a community night nursing service.
To compare the satisfaction levels of patients and carers with a community night nursing service. Thirty seven patients and 23 carers completed satisfaction postal questionnaires. Respondents were further subdivided into acute, chronic and terminally ill patients and their carers. Satisfaction levels with the service were generally high, although respondents from the terminally ill group showed the lowest levels of satisfaction overall. The Kruskal-Wallis test showed that results between the groups were not significantly different (Chi-square (chi2) test = 3.52; df = 2; P = 0.172). Although the results demonstrated positive levels of satisfaction with the community night nursing service, there were some respondents who indicated a low level of satisfaction. This could be explained by patients' and carers' lack of autonomy and inadequate provision of psychological care.