Catabolism of newly formed triglyceride-rich lipoproteins and serum high density lipoproteins in rats fed soybean phospholipid and soybean oil.
Previous research has shown that serum cholesterol and apolipoprotein (apo) A-I were lower and serum apoB was higher in rats fed soybean phospholipid (PL) than in rats fed soybean oil. Secretion of cholesterol and apoA-I, but not apoB, from the liver and intestine was lower in rats fed soybean PL. In the present study catabolism of newly formed triglyceride (TG)-rich lipoproteins, from the liver and intestine, and of serum high density lipoproteins (HDL) were compared in rats fed soybean PL and in rats fed soybean oil. The following results were seen: Feeding of soybean PL was related to more TG and less cholesterol in intestinal lymph chylomicrons (CM) and hepatic very low density lipoproteins (VLDL) than was feeding of soybean oil. A lesser amount of the TG, labeled with [3H]oleate in CM and hepatic VLDL, was incorporated into the adipose tissue and muscle in vivo. The clearance of CM-TG from plasma was higher, but that of VLDL-TG and apoB labeled with [3H]lysine was lower. The catabolism of 125I-labeled HDL from the plasma was lower while hepatic uptake of 125I-labeled HDL, in vivo and in vitro, was higher. These results indicate that soybean PL modifies the catabolism of the respective serum lipoproteins. Therefore, we suggest that changes in both the catabolism and secretion of lipoproteins are responsible for the altered serum lipid and apolipoprotein patterns found in rats fed soybean PL.


Tubulin Folding Cofactor D Deficiency: Missing the Diagnosis With Whole Exome Sequencing.
Two siblings with an early onset of a neurodegenerative disease were presented with muscular hypotonia, secondary microcephaly, and severe developmental delay. Seizures were refractory to treatment but could be controlled with a ketogenic diet. Over the course of 5 years, whole exome sequencing (WES) was performed twice in both children. The first time the diagnosis was missed. The next one revealed compound heterozygous mutations in the gene coding for the tubulin folding cofactor D. Technical improvements in WES mandated a new investigation after a few years in children where the diagnosis has not been found.


From consensus to action: knowledge transfer, education and influencing policy on sports concussion.
To: (1) provide a review of knowledge transfer (KT) and related concepts; (2) look at the impact of traditional and emerging KT strategies on concussion knowledge and education; (3) discuss the value and impact of KT to organisations and concussion-related decision making and (4) make recommendations for the future of concussion education. Qualitative literature review of KT and concussion education literature. PubMed, Medline and Sport Discus databases were reviewed and an internet search was conducted. The literature search was restricted to articles published in the English language, but not restricted to any particular years. Altogether, 67 journal articles, 21 websites, 1 book and 1 report were reviewed. The value of KT as part of concussion education is increasingly becoming recognised. Target audiences benefit from specific learning strategies. Concussion tools exist, but their effectiveness and impact require further evaluation. The media is valuable in drawing attention to concussion, but efforts need to ensure that the public is aware of the right information. Social media as a concussion education tool is becoming more prominent. Implementation of KT models is one approach which organisations can use to assess knowledge gaps; identify, develop and evaluate education strategies and use the outcomes to facilitate decision-making. Implementing KT strategies requires a defined plan. Identifying the needs, learning styles and preferred learning strategies of target audiences, coupled with evaluation, should be a piece of the overall concussion education puzzle to have an impact on enhancing knowledge and awareness.


Spontaneous spike-wave discharges in rat neocortex and their relation to behaviour.
A certain proportion of laboratory rats of various strains show spontaneous nonconvulsive ECoG seizures in the form of bursts of spike-and-wave discharges (SWD). Since in the majority of behavioural experiments the EEG is not controlled, the experimenter is usually unaware of this fact. The purpose of the present work was to find out whether the SWD trait is related to the rats behavioural performance in selected test situations. The experiment was performed on two groups of male Wistar rats, outbreds, aged six (group 6M, n = 17) and 24 months (group 24M, n = 14). First, in both groups the following forms of behaviour were assessed: (1) seeking water reward in an 8-arm radial maze, (2) exploration of a new object, (3) inhibition of a locomotor response (passive avoidance), and (4) paw-lick response to a thermal stimulus (54.5 degrees C) applied to the feet before and after intermittent footshock. The rats were then implanted with intrabrain electrodes and the level of SWD activity was assessed. Rats of the 24M group, compared with those of the 6M one, showed a significantly shorter exploratory response to a new object and diminished responsiveness to heat. The groups did not differ, however, in passive avoidance and radial maze performance. The analysis of 3-h ECoG sections revealed SWD bursts in 73% and nearly 93% of rats from groups 6M and 24M, respectively. The groups did not differ in the number of bursts or in the total duration of SWD activity. A correlation analysis of pooled data from both groups revealed that the exploration time of a new object was significantly (negatively) correlated with the number of SWD episodes. The total duration of SWD activity, and the number of perseveration errors in the radial maze, was significantly (positively) correlated with the total duration of SWD activity. The results suggest that SWD rats are behaviourally impaired in some test situations.


Flow graphs: interweaving dynamics and structure.
The behavior of complex systems is determined not only by the topological organization of their interconnections but also by the dynamical processes taking place among their constituents. A faithful modeling of the dynamics is essential because different dynamical processes may be affected very differently by network topology. A full characterization of such systems thus requires a formalization that encompasses both aspects simultaneously, rather than relying only on the topological adjacency matrix. To achieve this, we introduce the concept of flow graphs, namely weighted networks where dynamical flows are embedded into the link weights. Flow graphs provide an integrated representation of the structure and dynamics of the system, which can then be analyzed with standard tools from network theory. Conversely, a structural network feature of our choice can also be used as the basis for the construction of a flow graph that will then encompass a dynamics biased by such a feature. We illustrate the ideas by focusing on the mathematical properties of generic linear processes on complex networks that can be represented as biased random walks and their dual consensus dynamics, and show how our framework improves our understanding of these processes.


The Impact of Intestinal Microorganisms and Their Metabolites on Type 1 Diabetes Mellitus.
Type 1 diabetes mellitus (T1DM) is an autoimmune disease with a complex etiology comprising numerous genetic and environmental factors; however, many of the mechanisms underlying disease development remain unclear. Nevertheless, a critical role has recently been assigned to intestinal microorganisms in T1DM disease pathogenesis. In particular, a decrease in intestinal microbial diversity, increase in intestinal permeability, and the translocation of intestinal bacteria to the pancreas have been reported in patients and animal models with T1DM. Moreover, intestinal microbial metabolites differ between healthy individuals and patients with T1DM. Specifically, short-chain fatty acid (SCFA) production, which contributes to intestinal barrier integrity and immune response regulation, is significantly reduced in patients with T1DM. Considering this correlation between intestinal microorganisms and T1DM, many studies have investigated the potential of intestinal microbiota in preventive and therapeutic strategies for T1DM. The aim of this review is to provide further support for the notion that intestinal microbiota contributes to the regulation of T1DM occurrence and development. In particular, this article reviews the involvement of the intestinal microbiota and the associated metabolites in T1DM pathogenesis, as well as recent studies on the involvement of the intestinal microbiota in T1DM prevention and treatment. Intestinal microbes and their metabolites contribute to T1DM occurrence and development and may become a potential target for novel therapeutics.


An in vitro evaluation of fit of zirconium-oxide-based ceramic four-unit fixed partial dentures, generated with three different CAD/CAM systems, before and after porcelain firing cycles and after glaze cycles.
The purpose of this study was to assess in vitro the marginal fit of four-unit fixed partial dentures (FPDs) produced using three different computer aided design/computer aided manufacturing (CAD/CAM) all-ceramic systems before and after porcelain firing cycles and after glaze cycles. An acrylic resin model of a maxillary arch was fabricated. Teeth #6 and 9 were prepared; teeth #7 and 8 were absent. Forty-five four-unit zirconium-oxide-based ceramic FPDs were made following conventional impression and master cast techniques: 15 were made with the Everest system, 15 with the Procera system, and 15 with the Lava system. Marginal gaps along vertical planes were measured for each bridge before (Time 0) and after (Time 1) porcelain firing cycles and after glaze cycles (Time 2) using a total of 8 landmarks (4 for tooth #6 and 4 for tooth #9) by means of a microscope at a magnification of x50. MANOVA was performed to determine whether the 8 landmarks, jointly considered, differed between CAD/CAM systems and time phases. Two-way ANOVA was performed to investigate in detail, for each landmark, how gap measurements were related to CAD/CAM systems and time phases. Differences were considered to be significant at p < 0.05. The mean values of the Everest system (microm) were: 63.37 (Time 0), 65.34 (Time 1), and 65.49 (Time 2); the mean values of the Lava system (microm) were: 46.30 (Time 0), 46.79 (Time 1), and 47.28 (Time 2); the mean values of the Procera system (microm) were: 61.08 (Time 0), 62.46 (Time 1), and 63.46 (Time 2). MANOVA revealed quantitative differences of the 8 landmarks, jointly considered, between the three CAD/CAM systems (p < 0.0001), but it did not reveal any quantitative differences among the three time phases (p > 0.4). Two-way ANOVA revealed that the Lava system produced gap measurements statistically smaller than the Everest and Procera systems (p < 0.0001 for each landmark). Within the limitations of this study, it was concluded that the three zirconium-oxide-based ceramic CAD/CAM systems demonstrated a comparable and acceptable marginal fit; however, the Lava system produced gap measurements statistically smaller than the Everest and Procera systems. The porcelain firing cycles and the glaze cycles did not affect the marginal fit of the zirconium-oxide-based ceramic CAD/CAM systems.


Importance of the intracytoplasmic domain of the simian immunodeficiency virus (SIV) envelope glycoprotein for pathogenesis.
SIVmac1A11 and SIVmac239 are nonpathogenic and pathogenic molecular clones in rhesus macaques, respectively. Although these viruses exhibit approximately 98% nucleotide and amino acid sequence homology, differences are found in the length of the translation frames for several genes. SIVmac239 has a premature stop codon in nef, whereas SIVmac1A11 has a premature stop codon in vpr and two premature stop codons in the intracytoplasmic domain of the env-transmembrane (TM) subunit. Recombinant viruses, constructed through reciprocal exchange of large DNA restriction enzyme fragments between SIVmac1A11 and SIVmac239, were evaluated in adult rhesus macaques. This in vivo analysis revealed that two or more regions of the SIVmac genome were essential for high virus load and disease progression (Marthas et al., 1993. J. Virol. 67, 6047-6055). An important gap in knowledge remaining from this study was whether the premature stop codons in env-TM of recombinant virus SIV1A11/239gag-env/1A11 (Full-length vpr and nef, two stop codons in env-TM) reverted to coding triplets in vivo. Here, we report that viral sequences in macaques, which succumbed to an AIDS-like disease after infection with SIV1A11/239gag-env/1A11, exhibited reversion of both env-TM stop codons. In addition, antibodies to the intracytoplasmic domain of env-TM were detected in macaques containing revertant virus and showing disease; this finding indicates that this domain of the env glycoprotein was expressed in vivo. Thus selection for viral variants with full-length env-TM demonstrated that the cytoplasmic domain of the SIVmac env glycoprotein plays a role in viral persistence and immunodeficiency in primates.


Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck.
The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) was overexpressed in squamous cell carcinoma of the head and neck (HNSCC). Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in head and neck tissue. Mean levels of COX-2 mRNA were increased by nearly 150-fold in HNSCC (n = 24) compared with normal oral mucosa from healthy volunteers (n = 17). Additionally, there was about a 50-fold increase in amounts of COX-2 mRNA in normal-appearing epithelium adjacent to HNSCC (n = 10) compared with normal oral mucosa from healthy volunteers. Immunoblotting demonstrated that COX-2 protein was present in six of six cases of HNSCC but was undetectable in normal oral mucosa from healthy subjects. Immunohistochemical analysis showed that COX-2 was expressed in both HNSCC and adjacent normal-appearing epithelium. Taken together, these results suggest that COX-2 may be a target for the prevention or treatment of HNSCC.


NLRC5 deficiency does not influence cytokine induction by virus and bacteria infections.
Nucleotide-binding domain and leucine rich repeat containing gene family receptors (NLRs) are cytosolic proteins that respond to a variety of pathogen and host components to induce inflammatory cytokines. NLRC5 is a recently identified member of the NLR family that has been implicated in positive and negative regulation of antiviral innate immune responses. To clarify whether NLRC5 controls antiviral innate immunity in vivo, we generated NLRC5-deficient mice. Macrophages and dendritic cells derived from NLRC5-deficient mice induced relatively normal levels of IFN-β, IL-6, and TNF-α after treatment with RNA viruses, DNA viruses, and bacteria. The serum cytokine levels after polyinosinic-polycytidylic acid infection were also comparable between control and NLRC5-deficient mice. NLRC5 overexpression promoted IL-1β production via caspase-1, suggesting that NLRC5 constitutes an inflammasome. However, there was no reduction of IL-1β in NLRC5-deficient cells in response to known inflammasome activators, suggesting that NLRC5 controls IL-1β production through an unidentified pathway. These findings indicate that NLRC5 is dispensable for cytokine induction in virus and bacterial infections under physiologic conditions.


Nanomaterials for detection of biomolecules and delivering therapeutic agents in theragnosis: A review.
Nanomaterials are emerging facts used to deliver therapeutic agents in living systems. Nanotechnology is used as a compliment by implementing different kinds of nanotechnological applications such as nano-porous structures, functionalized nanomaterials, quantum dots, carbon nanomaterials, and polymeric nanostructures. The applications are in the initial stage, which led to achieving several diagnoses and therapy in clinical practice. This review conveys the importance of nanomaterials in post-genomic employment, which includes the design of immunosensors, immune assays, and drug delivery. In this view, genomics is a molecular tool containing large databases that are useful in choosing an apt molecular inhibitor such as drug, ligand and antibody target in the drug delivery process. This study identifies the expression of genes and proteins in analysis and classification of diseases. Experimentally, the study analyses the design of a disease model. In particular, drug delivery is a boon area to treat cancer. The identified drugs enter different phase trails (Trails I, II, and III). The genomic information conveys more essential entities to the phase I trials and helps to move further for other trails such as trails-II and III. In such cases, the biomarkers play a crucial role by monitoring the unique pathological process. Genetic engineering with recombinant DNA techniques can be employed to develop genetically engineered disease models. Delivering drugs in a specific area is one of the challenging issues achieved using nanoparticles. Therefore, genomics is considered as a vast molecular tool to identify drugs in personalized medicine for cancer therapy.


Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX.
Denosumab has been shown to reduce the incidence of vertebral, nonvertebral, and hip fractures. The aim of the current study was to determine whether the antifracture efficacy of denosumab was dependent on baseline fracture probability assessed by FRAX. The primary data of the phase 3 FREEDOM study of the effects of denosumab in women with postmenopausal osteoporosis were used to compute country-specific probabilities using the FRAX tool (version 3.2). The outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. At baseline, the median 10-year probability of a major osteoporotic fracture (with bone mineral density) was approximately 15% and for hip fracture was approximately 5% in both groups. In the simplest model adjusted for age and fracture probability, treatment with denosumab over 3 years was associated with a 32% (95% confidence interval [CI] 20% to 42%) decrease in clinical osteoporotic fractures. Denosumab reduced fracture risk to a greater extent in those at moderate to high risk. For example, at 10% probability, denosumab decreased fracture risk by 11% (p = 0.629), whereas at 30% probability (90th percentile of study population) the reduction was 50% (p = 0.001). The reduction in fracture was independent of prior fracture, parental history of hip fracture, or secondary causes of osteoporosis. A low body mass index (BMI) was associated with greater efficacy. Denosumab significantly decreased the risk of clinical osteoporotic fractures in postmenopausal women. Overall, the efficacy of denosumab was greater in those at moderate to high risk of fracture as assessed by FRAX.


Moving Toward Summative Competency Assessment to Individualize the Postclerkship Phase.
In the move toward competency-based medical education, leaders have called for standardization of learning outcomes and individualization of the learning process. Significant progress has been made in establishing defined expectations for the knowledge, skills, attitudes, and behaviors required for successful transition to residency training, but individualization of educational processes to assist learners in reaching these competencies has been predominantly conceptual to date. The traditional time-based structure of medical education has posed a challenge to individualization within the curriculum and has led to more attention on innovations that facilitate transition from medical school to residency. However, a shift of focus to the clerkship-to-postclerkship transition point in the undergraduate curriculum provides an opportunity to determine how longitudinal competency-based assessments can be used to facilitate intentional and individualized structuring of the long-debated fourth year.This Perspective demonstrates how 2 institutions-the University of Virginia School of Medicine and the University of Michigan Medical School-are using competency assessments and applying standardized outcomes in decisions about individualization of the postclerkship learning process. One institution assesses Core Entrustable Professional Activities for Entering Residency, whereas the other has incorporated Accreditation Council for Graduate Medical Education core competencies and student career interests to determine degrees of flexibility in the postclerkship phase. Individualization in addition to continued assessment of performance presents an opportunity for intentional use of curriculum time to develop each student to be competently prepared for the transition to residency.


Detecting negative response bias with the Fake Bad Scale, Response Bias Scale, and Henry-Heilbronner Index of the Minnesota Multiphasic Personality Inventory-2.
The 28-item Response Bias Scale (RBS) and 15-item Henry-Heilbronner Index (HHI) are new validity scales within the Minnesota Multiphasic Personality Inventory-2, designed to detect over-reporting of cognitive and somatic symptomology, respectively. The 43-item Lees-Haley Fake Bad Scale (FBS) was designed to detect noncredible symptom presentations within a personal injury setting. The current study examined the predictive validity of these scales in a criterion-groups design involving head-injured litigants. Archival data were collected and two groups were created using the Slick, Sherman, and Iverson ([1999]. Diagnostic criteria for malingered neurocognitive dysfunction: Proposed standards for clinical practice and research. The Clinical Neuropsychologist, 13, 545-561) Criteria for Probable Negative Response Bias. Results yielded excellent to acceptable discrimination ability for the validity scales, including an area under the curve of 0.83 for FBS, 0.82 for RBS, and 0.73 for HHI. Findings suggest that the FBS, RBS, and HHI perform as well as the other validity scales in discriminating over-reporting within a head-injured litigant setting.


Predictive outcomes of APACHE II and expanded SAPS II mortality scoring systems in coronary care unit.
We investigated the predictive values of the expanded Simplified Acute Physiology Score (SAPS) II and Acute Physiologic Score and Chronic Health Evaluation (APACHE) II score in predicting in-hospital mortality in coronary care unit (CCU) patients. In this study, expanded SAPS II and APACHE II scores were calculated in the CCU of a single-center tertiary hospital. Patients admitted to CCU with any cardivascular indication were included in the study. Both scores were calculated according to previously determined criteria. Calibration and discrimination abilities of the scores in predicting in-hospital mortality were tested with Hosmer-Lemeshow goodness-of-fit C chi-square and receiver operating characteristics (ROC) curve analyses. A total of 871 patients were included in the analysis. The goodness-of-fit C chi-square test showed that both scores have a good performance in predicting survivors and nonsurvivors in CCU. Expanded SAPS II score has a sensitivity of 80% and a specificity of 91.8% with the cut-off value of 5.55, while APACHE II has a sensitivity of 75.9% and a specificity of 87.4% with the cut-off value of 16.5 in predicting mortality. Expanded SAPS II and APACHE II scores have good ability to predict in-hospital mortality in CCU patients. Therefore, they can be used as a tool to predict short-term mortality in cardiovascular emergencies.


Rapid methods for biochemical testing of anaerobic bacteria.
Rapid biochemical tests for nitrate, indole, gelatin, starch, esculin, and o-nitrophenyl-beta-D-galactopyranoside were performed on 112 strains of anaerobic bacteria. All tests were incubated under aerobic conditions, and results were recorded within 4 h. The tests for nitrate, indole, and starch showed a 95% or greater correlation when compared to the standard biochemical tests. Tests for esculin and gelatin showed an agreement of 86 and 77%, respectively. PathoTec test strips for nitrate, indole, esculin, o-nitrophenyl-beta-D-galactopyranoside, Voges-Proskauer, and urease were also tested and showed encouraging results.


A conserved human germline V kappa gene directly encodes rheumatoid factor light chains.
The full-length gene that encodes the light chain variable regions of an idiotypically related group of human IgM kappa rheumatoid factors (RFs) has been cloned and sequenced. The deduced amino acid sequence is identical to four separate RF proteins. These results prove that genes capable of encoding human anti-IgG autoantibody light chains without any somatic mutation are present in the kappa gene repertoire of normal people.


Abuse potential assessment of the dual orexin receptor antagonist daridorexant in rats.
Drugs that act on the central nervous system (CNS) and have sedative effects can lead to abuse in humans. New CNS-active drugs often require evaluation of their abuse potential in dedicated animal models before marketing approval. Daridorexant is a new dual orexin receptor antagonist (DORA) with sleep-promoting properties in animals and humans. It was approved in 2022 in the United States and Europe for the treatment of insomnia disorder. Nonclinical evaluation of abuse potential of daridorexant using three specific rat models assessing reinforcement, interoception, and withdrawal. Reinforcing effects of daridorexant were assessed in an operant rat model of intravenous drug self-administration. Similarity of interoceptive effects to those of the commonly used sleep medication zolpidem was tested in an operant drug discrimination task. Withdrawal signs indicative of physical dependence were evaluated upon sudden termination of chronic daridorexant treatment. Rat experiments were conducted at a dose range resulting in daridorexant plasma concentrations equaling or exceeding those achieved at the clinically recommended dose of 50 mg in humans. Daridorexant had no reinforcing effects, was dissimilar to zolpidem in the drug discrimination task, and did not induce any withdrawal-related signs upon treatment discontinuation that would be indicative of physical dependence. Daridorexant showed no signs of abuse or dependence potential in rats. Our data indicate that daridorexant, like other DORAs, has a low potential for abuse in humans.


Growth on D-lyxose of a mutant strain of Escherichia coli K12 using a novel isomerase and enzymes related to D-xylase metabolism.
Escherichia coli K12 cannot grow on D-lyxose, but a mutant was isolated which can utilize D-lyxose as sole source of carbon and energy for growth. D-Lyxose is transported into the bacteria by the D-xylose permease. The mutant constitutively synthesizes a new isomerase which is not inducible in the parent strain under any of the conditions tested. This enzyme, whose native substrate appears to be D-mannose, fortuitously converts D-lyxose into D-xylulose. Its structural gene is located at around 85 min on the E. coli genetic map, away from other known isomerase genes. D-Xylulose is subsequently catabolized by the enzymes of the normal D-xylose metabolic pathway. D-Mannose isomerase was partially purified and some of its properties were examined.


Relationship of inferior vena cava filter usage in post-surgical patients by various surgical and medical subspecialists.
Venous thromboembolism is a common and often fatal problem in postsurgical patients. These patients are usually treated with either therapeutic anticoagulation or the placement of inferior vena cava (IVC) filters. Controversy surrounds the use of IVC filters, because no data exist proving survival benefit. In this study, 264 inpatient medical records of patients who underwent major surgical procedures and had the diagnosis of deep venous thrombosis or pulmonary embolism were examined. Among these patients, those who received IVC filters were identified, and the documented indications for filter placement were reviewed. Rates of IVC filter placement per venous thromboembolism event and specific indications were examined across surgical subspecialties and by type of medical consultant. Sixty percent of patients received IVC filters. IVC filter placement rates varied significantly across surgical subspecialties (p <0.0001), with the highest rate in the orthopedic surgery subgroup (80%). Rates of IVC filter use also differed significantly (p <0.0007) between medical consultants who specialized in antithrombotic medicine (46.8%) and those who did not (68.3%). Significant differences also existed in specific indications for filter placement between medical and surgical subspecialties. In conclusion, most of this study's population received IVC filters. Rates of IVC filter placement varied by the specialties of surgeons and medical consultants. The heterogeneity of treatment strategies coupled with the lack of data for this patient population highlights the need for future prospective studies to guide evidence-based treatment.


[Scientific rationale for a scheme for the environmental and hygienic assessment of a solid domestic waste burial ground].
A scheme for the environmental and hygienic assessment of a functioning solid domestic waste (SDW) burial ground was experimentally tested, by taking into account regional features. The study involved the assessment of climatic, geological, and hydrogeological features of the region, the sanitary-and-hygienic assessment of the activity of a SDW burial ground, and the hygienic assessment of ambient air, soil, and water in the SDW burial ground functioning area. The developed scheme may be used to modify a manufacturing inspection program.


The effect of monooctanoin on retained common duct stones.
Monooctanoin is a medium-chain diglyceride that is effective in dissolving cholesterol gallstones in vitro. The in vivo efficacy of monooctanoin was evaluated in eight patients who had monooctanoin infused through the T tube to dissolve retained common duct stones. Five of eight (62%) experienced success. Abdominal cramps and diarrhea were the only side effects, and these resolved by temporarily stopping the infusion or decreasing the rate of the infusion. Since bilirubinate stones accounted for the three failures, the composition of the stone is the determining factor in selecting a treatment plan for retained common duct stones. Retained cholesterol stones can be successfully treated within 4 to 7 days by T-tube infusion of monooctanoin. Pigment stones should be removed by extraction through the T-tube tract or by endoscopic papillotomy.


Heat Stress-Induced Fetal Intrauterine Growth Restriction Is Associated with Elevated LPS Levels Along the Maternal Intestine-Placenta-Fetus Axis in Pregnant Mice.
The exacerbation of the greenhouse effect has made heat stress (HS) an important risk factor for the occurrence of intrauterine growth restriction (IUGR). The experiment aims to uncover the effects of maternal HS on IUGR and its mechanisms. The results showed that HS leads to decreased maternal and fetal birth weights, accompanied by increased serum oxidative stress and cortisol levels. Moreover, HS inflicted significant damage to both the intestinal and placental barriers, altering maternal gut microbiota and increasing intestinal LPS levels. As a result, LPS levels increased in maternal serum, placenta, and fetus. Furthermore, HS damaged the intestinal structure, intensifying inflammation and disrupting the redox balance. The placenta exposed to HS exhibited changes in the placental structure along with disrupted angiogenesis and decreased levels of nutritional transporters. Additionally, the leakage of LPS triggered placental JNK and ERK phosphorylation, ultimately inducing severe placental inflammation and oxidative stress. This study suggests that LPS translocation from the maternal intestine to the fetus, due to a disrupted gut microbiota balance and compromised intestinal and placental barrier integrity, may be the primary cause of HS-induced IUGR. Furthermore, increased LPS leakage leads to placental inflammation, redox imbalance, and impaired nutrient transport, further restricting fetal growth.


Evaluation of four whole-cell Leptospira-based serological tests for diagnosis of urban leptospirosis.
Four serologic assays for leptospirosis had sensitivities of 72 to 88% and specificities of 88 to 100% in the setting of highly endemic urban transmission, indicating that assays using enzyme-linked immunosorbency and rapid formats may be used as alternatives to the microscopic agglutination test for diagnosing urban leptospirosis. Testing a second sample will be required in cases with an initial negative result, since sensitivity was low (46 to 68%) during the first week of illness.


Invasive pneumococcal disease burden and implications for vaccine policy in urban Bangladesh.
We undertook active population-based surveillance in 5,000 urban households among children < 5 years old to determine invasive pneumococcal disease (IPD) incidence, serotype distribution, clinical presentation, and antimicrobial resistance, which have not been previously described in population-based studies from the region. IPD was documented by blood culture isolation. From 01 April 2004 to 31 March 2006, 5,903 blood cultures were collected from 6,167 eligible children. Streptococcus pneumoniae was isolated from 34 pneumococcal patients; IPD was clinically associated with pneumonia (24%), upper respiratory infection (62%), and febrile syndromes (14%). Overall, IPD and 13-valent serotype-related IPD incidences were 447 and 276 episodes/100,000 child-years, respectively. Peak IPD incidence occurred during the cool dry seasons. Penicillin, cotrimoxazole, chloramphenicol, and ciprofloxacin resistances were 2.9%, 82.4%, 14.7%, and 24.1%, respectively. Current conjugate vaccines should substantially reduce IPD, childhood pneumonia, and antimicrobial resistance in Bangladesh.


Biologically active synthetic fragments of epidermal growth factor: localization of a major receptor-binding region.
A primary receptor-binding region of mouse epidermal growth factor (EGF) was identified by comparing the relative affinities of selected synthetic fragments with overlapping sequences in the EGF receptor-binding assay, using human foreskin fibroblasts. Only synthetic peptides containing the amino acid residues 20-31 in the mouse EGF sequence showed the ability to compete with 125I-labeled EGF in binding to EGF receptors. The affinities of the cyclic EGF fragment [Ala20]EGF-(14-31) and the linear [(S-acetamidomethyl)-Cys20,31]-EGF-(20-31) were approximately 1/10(4) of the affinity of EGF. Despite their reduced receptor affinities, these two peptides exhibited the in vitro biological activities of native EGF, while fragments from other regions of the EGF molecule were devoid of these biological properties. The peptides induced DNA synthesis in human foreskin fibroblasts as measured by [3H]thymidine incorporation into DNA. They also induced EGF receptor clustering and activated the EGF-sensitive kinase, enhancing the autophosphorylation of EGF receptors in a dose-related manner. Moreover, a major antigenic determinant of EGF for rabbit anti-EGF antibodies was identified within this same localized region of the EGF molecule by competition experiments utilizing the synthetic EGF fragments. The predominant EGF antigenic determinant(s) was also found within the fragment [(S-acetamidomethyl)Cys20,31]-EGF-(20-31). The accessibility of the residues in positions 20-31 for antibody recognition is consistent with the conclusion that these residues constitute or contain a major receptor-binding region for EGF.


Clinical significance of programmed cell death-ligand 1 expression and the immune microenvironment at the invasive front of colorectal cancers with high microsatellite instability.
Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI-H); however, the specific cell types that respond to immune checkpoint therapy are unclear. Herein, we aimed to examine the expression of programmed cell death-ligand 1 (PD-L1) and related proteins in MSI-H and microsatellite-stable (MSS) CRCs to investigate the immune microenvironment at the tumor's invasive front. The MSI status was retrospectively assessed in 499 patients undergoing surgical resection of primary CRC; of these, 48 were classified as MSI-H. Propensity score matching was performed, and tissues from 36 and 37 patients with MSI-H and MSS CRCs, respectively, were immunohistochemically evaluated for PD-L1, PD-1, CD8 and CD68. PD-L1 expression was evaluated separately for tumor cells (PD-L1 [T]) and tumor-infiltrating myeloid cells in the stroma (PD-L1 [I]). PD-L1 (T) was positive in only 5.4% and 36.1% of MSS and MSI-H CRCs, while PD-L1 (I) was positive in 27% and 72.2% of these CRCs, respectively. The PD-L1 (T) and PD-L1 (I) expression levels in MSI-H CRCs significantly correlated with poor differentiation, lymphatic invasion and vascular invasion (p < 0.05), and with early-stage adenocarcinoma and high budding grade (p < 0.05), respectively. Significantly more PD-L1 (I), CD8-positive cells and CD68-positive macrophages were present at the invasive front than in the central tumor in MSI-H CRCs (p < 0.005). PD-L1 was expressed on both tumor cells and CD68/CD163-positive (M2) macrophages at the invasive front of MSI-H CRCs. In conclusion, PD-L1-positive tumor cells and M2-type tumor-associated macrophages may contribute to tumor invasion and immune escape at the invasive front.


Effect of gonadal steroid hormones on plasma growth hormone concentrations in sexually immature rainbow trout, Oncorhynchus mykiss.
In the present study we investigated the effects of gonadal steroid hormones on plasma growth hormone (GH), triiodothyronine (T3), and thyroxine (T4) levels in steroid-primed sexually immature rainbow trout, Oncorhynchus mykiss, in order to determine whether changes in plasma GH and thyroid hormone levels during sexual maturation are a result of elevated gonadal steroid levels or are an altered condition associated with reproduction (as proposed by Sumpter et al., 1991b). We found no significant correlation between plasma GH and condition factor in either of two cohorts of rainbow trout (1+ and 2+ year old fish) examined. To evaluate the effects of gonadal steroids on plasma GH and thyroid hormone levels, fed and fasted (4 weeks fasted) fish were given a slow-release implant of testosterone (T), 17beta-estradiol (E2), 17alpha-methyltestosterone (17alphaMT), or 5alpha-dihydrotestosterone (5alphaDHT) dissolved in coconut oil, or coconut oil alone (control). Blood samples were taken after 2 weeks and analyzed for GH, T3, and T4. Neither 17alphaMT nor 5alphaDHT had any effect on plasma GH levels in fed or fasted fish. However, plasma GH levels were elevated after E2 treatment in both fed and fasted (P </= 0.01) fish, and after T treatment in fasted but not fed fish (P < 0.01). The effects of gonadal steroid hormones on thyroid hormone levels were less clear. T3 levels were depressed in fed E2-primed fish (P < 0.05) and elevated in fasted T- and 17alphaMT-primed fish (P < 0.05). T4 levels were depressed in T- and 5alphaDHT-primed fed fish (P < 0.01) and elevated in fasted E2-primed fish (P < 0.01). These elevated GH levels associated with sexual maturation may be more clearly linked to elevated gonadal steroid levels rather than to changes in nutritional status. The effects of gonadal steroids on thyroid hormone levels are less clear.


LIM homeobox 8 (Lhx8) is a key regulator of the cholinergic neuronal function via a tropomyosin receptor kinase A (TrkA)-mediated positive feedback loop.
Basal forebrain cholinergic neurons play an important role in cognitive functions such as learning and memory, and they are affected in several neurodegenerative diseases, including Alzheimer disease and Down syndrome. Despite their functional importance, the molecular mechanisms of functional maturation and maintenance of these cholinergic neurons after the differentiation stage have not been fully elucidated. This study demonstrates that the LIM homeobox 8 (Lhx8) transcription factor regulates cholinergic function in rat septal cholinergic neurons in primary cultures from E18.5 embryos and in the adult brain. Lhx8 expression modulated tropomyosin receptor kinase A (TrkA) expression in septal cholinergic neurons in vitro and in vivo, resulting in regulated acetylcholine release as an index of cholinergic function. In addition, Lhx8 expression and function were regulated by nerve growth factor (NGF), and the effect of NGF was potentiated by Lhx8-induced TrkA expression. Together, our findings suggest that positive feedback regulation between Lhx8, TrkA, and NGF is an important regulatory mechanism for cholinergic functions of the septum.


Association of iris surface features with iris parameters assessed by swept-source optical coherence tomography in Asian eyes.
To characterise the association of iris surface features (crypts, furrows and colour) with iris volume and curvature assessed by swept-source optical coherence tomography (SSOCT) in Asian eyes. Iris crypts (by number and size) and furrows (by number and circumferential extent) were graded from iris photographs. Iris colour was measured by a customised algorithm written on MATLAB (MathWorks, Natick, Massachusetts, USA). The iris was imaged by SSOCT (SS-1000, CASIA, Tomey, Nagoya, Japan). The associations of surface features with iris parameters were analysed using a generalised estimating equation. A total of 1704 subjects (3297 eyes) were included in the analysis. The majority was Chinese (86.4%), and 63.2% were females, and their mean age (±SD) was 61.4±6.6 years. After adjusting for age, sex, ethnicity, pupil size and corneal arcus, higher iris crypt grade was independently associated with smaller iris volume (β=-0.54, p<0.001), whereas darker irides and higher iris furrow grade were associated with larger iris volume (β=-0.041, p<0.001) and (β=0.233, p<0.001), respectively. Lighter coloured irides with more crypts and/or more furrows were also associated with less convexity (crypts: β=-0.003, p=0.03; furrows: β=-0.004, p=0.007; and colour: β=-0.001, p=0.005). Iris surface features were highly correlated with iris volume and curvature. Irides with more crypts have a smaller volume; and darker irides with more furrows have a larger volume. Lighter irides with more crypts and/or furrows have less convexity.


Auxotrophy to Xeno-DNA: an exploration of combinatorial mechanisms for a high-fidelity biosafety system for synthetic biology applications.
Biosafety is a key aspect in the international Genetically Engineered Machine (iGEM) competition, which offers student teams an amazing opportunity to pursue their own research projects in the field of Synthetic Biology. iGEM projects often involve the creation of genetically engineered bacterial strains. To minimize the risks associated with bacterial release, a variety of biosafety systems were constructed, either to prevent survival of bacteria outside the lab or to hinder horizontal or vertical gene transfer. Physical containment methods such as bioreactors or microencapsulation are considered the first safety level. Additionally, various systems involving auxotrophies for both natural and synthetic compounds have been utilized by iGEM teams in recent years. Combinatorial systems comprising multiple auxotrophies have been shown to reduced escape frequencies below the detection limit. Furthermore, a number of natural toxin-antitoxin systems can be deployed to kill cells under certain conditions. Additionally, parts of naturally occurring toxin-antitoxin systems can be used for the construction of 'kill switches' controlled by synthetic regulatory modules, allowing control of cell survival. Kill switches prevent cell survival but do not completely degrade nucleic acids. To avoid horizontal gene transfer, multiple mechanisms to cleave nucleic acids can be employed, resulting in 'self-destruction' of cells. Changes in light or temperature conditions are powerful regulators of gene expression and could serve as triggers for kill switches or self-destruction systems. Xenobiology-based containment uses applications of Xeno-DNA, recoded codons and non-canonical amino acids to nullify the genetic information of constructed cells for wild type organisms. A 'minimal genome' approach brings the opportunity to reduce the genome of a cell to only genes necessary for survival under lab conditions. Such cells are unlikely to survive in the natural environment and are thus considered safe hosts. If suitable for the desired application, a shift to cell-free systems based on Xeno-DNA may represent the ultimate biosafety system. Here we describe different containment approaches in synthetic biology, ranging from auxotrophies to minimal genomes, which can be combined to significantly improve reliability. Since the iGEM competition greatly increases the number of people involved in synthetic biology, we will focus especially on biosafety systems developed and applied in the context of the iGEM competition.


[International cooperation at Public Health: proposals to a debate].
In the available literature, there is no study devoted to international cooperation in public health. This paper aims to partly fill this gap, raising and examining the state of art in this area as well as how it interferes in the evaluation of post-graduate programs. The study used secondary data available at CAPES "Indicators Journals", during the years of 1998 to 2006. It also analyzes foreign scholarships and special programs of cooperation of CAPES from 2005 to 2009 through a quantitative descriptive methodology. It shows that international cooperation in the area is relatively developed in a variety of themes and diverse partnerships, focusing in the United States. It is observed a positive correlation between the number of international cooperation and a high-concept program into the evaluation of CAPES, the last triennium of evaluation. The sub-areas where there is more cooperation are, in order: epidemiology; planning, and others. There is a variety of institutions, themes and subareas involved in international cooperation that could be a positive indicator in the evaluation, but as far as was possible to infer, no significant correlation in this direction was found.


The effect of electronic medical record application on the length of stay in a Chinese general hospital: a department- and disease-focused interrupted time-series study.
A key purpose of electronic medical records (EMR) introduced in medical institutions is to improve work efficiency. The average length of stay (LOS) is just an important indicator to evaluate work efficiency of medical care in hospitals. Recently, there have been reports about effects of EMR application on LOS in medical institutions, but they have been mostly based on the overall analysis of a region or a hospital and not of specific clinical departments and diseases or based on longer time periods. Therefore, in this study, we selected four clinical departments and four diseases with the largest number of inpatients from January 2004 to December 2012 in a Chinese 3A general hospital and used an interrupted time-series method by the departments and diseases to analyze the relationship of EMR application and LOS. Through our analyses, we concluded that, under unadjusted condition, LOS were all reduced (P < 0.001) after EMR application in four departments and for four diseases. After adjustment by gender, age or admission condition, LOS still all decreased after EMR application (P < 0.05) regardless of departments or diseases. The trend changes in LOS reversed from increasing to decreasing in the orthopedics department (coefficient: 0.016 to -0.079), the cardiovascular surgery department (coefficient: 0.007 to -0.126) and all departments overall (coefficient: 0.004 to -0.070), as well as for the intervertebral disc disorders (coefficient: 0.026 to -0.068). Furthermore, the decreasing trend gained a larger slope in the cardiology department (coefficient: -0.017 to -0.023), the neurology department (coefficient: -0.012 to -0.043) and for the coronary heart disease (coefficient: -0.010 to -0.018), the ventricular septal defect (coefficient: -0.024 to -0.059), and the cerebral infarction (coefficient: -0.031 to -0.040). Together, these findings indicate that EMR application coincided with a decrease in LOS and may have a contribution to the decrease.


Primary care: questions raised by a definition.
In Defining Primary Care: An Interim Report, the Institute of Medicine offers a set of attributes for primary care that raise many unresolved empirical and philosophical questions. For instance, the "integrated nature" of primary care immediately challenges the validity of the content of research in primary care using data such as ICD-9 codes, which, by nature, reduce patients to disaggregated sets of problems rather than coherent wholes. Likewise, considering accessibility as a hallmark of primary care focuses attention on how health care is organized, and whether depending on primary care-trained professionals as the necessary or ideal first point of access might be a deterrent to the delivery of optimal care among some populations. Primary care clinicians should and will be held accountable for achieving the attributes of practice that make primary care unique. This paper provides a detailed examination of the Institute's definition, and identifies many aspects that require additional thought and research before these attributes can be applied as criteria for the evaluation of primary care practice.


Ocular motor abnormalities in Parkinsonian syndromes.
Oculomotor abnormalities can be observed in all Parkinsonian syndromes (PS). Nevertheless, due to the considerable overlap of oculomotor pathology in Parkinsonism, oculomotor changes are not generally considered to contribute substantially to the differential diagnosis of PS. Here we review the characteristics of oculomotor disturbances in the major PS, we provide a survey of the current concepts of the underlying neural physiology of oculomotor control and a summary of the major recording techniques for eye movements. The main focus of this review is to outline the subtle differences between apparently similar oculomotor alterations in Parkinson's disease (PD) and atypical neurodegenerative PS that can contribute to the early differential diagnosis of these entities.


Interim evaluation of the Secondary 2 Program of Project P.A.T.H.S.: insights based on the experimental implementation phase.
An interim evaluation was conducted to understand the implementation quality of the Tier 1 Program (Secondary 2 Curriculum) of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programs) in the Experimental Implementation Phase. Twenty-five schools were randomly selected to participate in personal and/or telephone interviews to provide information on the implementation details of the program and perceived attributes of the worker-support scheme ("Co-Walker Scheme"). Results showed that a majority of the workers perceived that the students had positive responses to the program and the program was helpful to the students. They also identified several good aspects in the program and the Co-Walker Scheme, albeit expressing some negative comments on the program design and difficulties in the implementation process. In conjunction with other findings reported previously, the present findings suggest that the Tier 1 Program is well received by different stakeholders and it promotes the positive development of secondary school students in Hong Kong.


Epithelia Use Butyrophilin-like Molecules to Shape Organ-Specific γδ T Cell Compartments.
Many body surfaces harbor organ-specific γδ T cell compartments that contribute to tissue integrity. Thus, murine dendritic epidermal T cells (DETCs) uniquely expressing T cell receptor (TCR)-Vγ5 chains protect from cutaneous carcinogens. The DETC repertoire is shaped by Skint1, a butyrophilin-like (Btnl) gene expressed specifically by thymic epithelial cells and suprabasal keratinocytes. However, the generality of this mechanism has remained opaque, since neither Skint1 nor DETCs are evolutionarily conserved. Here, Btnl1 expressed by murine enterocytes is shown to shape the local TCR-Vγ7(+) γδ compartment. Uninfluenced by microbial or food antigens, this activity evokes the developmental selection of TCRαβ(+) repertoires. Indeed, Btnl1 and Btnl6 jointly induce TCR-dependent responses specifically in intestinal Vγ7(+) cells. Likewise, human gut epithelial cells express BTNL3 and BTNL8 that jointly induce selective TCR-dependent responses of human colonic Vγ4(+) cells. Hence, a conserved mechanism emerges whereby epithelia use organ-specific BTNL/Btnl genes to shape local T cell compartments.


Seizures: A Rare Presentation of Autonomic Dysreflexia in a Young Adult with Complete Spinal Cord Injury.
Autonomic dysreflexia (AD) is a common complication for individuals with cervical or upper-mid thoracic spinal cord injury (SCI). It is a life-threatening emergency; however, it is rarely encountered by many emergency physicians, thus, ongoing awareness of the topic is necessary. An 18-year-old man with cervical spinal cord injury presented to the Emergency Department with headache, nausea, elevated blood pressure, and seizures. He was treated with antiepileptics and transferred to the pediatric intensive care unit (PICU). The PICU care team recognized AD as the cause of the seizure, secondary to a clogged suprapubic catheter causing overdistension of his bladder. Once replaced, over 1 liter of urine drained from his bladder and his autonomic symptoms resolved. He became hypotensive and required fluid resuscitation, but no further seizures occurred. Why Should an Emergency Physician Be Aware of This? Although rare, AD can result in seizures, intracerebral hemorrhage, or even death if not recognized or treated appropriately. Emergency physicians should recognize headaches, facial flushing, and sweating as early symptoms of AD, along with acute elevation in blood pressure (noting that baseline blood pressure may be lower in individuals with SCI). Management involves evaluating and treating noxious stimuli below the level of neurologic injury. Symptom management alone, without resolution of the underlying issue, can add to morbidity and mortality.


Homochiral columns constructed by chiral self-sorting during supramolecular helical organization of hat-shaped molecules.
A library of dendronized cyclotriveratrylene (CTV) crowns substituted with chiral, racemic, or achiral peripheral alkyl chains, including enantiopure R and S branched alkyls, "racemic by mixture", "racemic by synthesis", n-octyl, and n-dodecyl groups was synthesized. In solvophobic solvents and in bulk they self-assemble in helical columns. Their solution and bulk shape-persistent supramolecular structures were determined by a complementary combination of circular dichroism (CD) and UV in solution and thin film, microspot CD in thin film, differential scanning calorimetry combined with fiber X-ray diffraction, computer simulation, and molecular models. In solution, self-assembly via a cooperative mechanism generates single-handed columns from enantiopure CTVs and mixtures of right- and left-handed columns from racemic by mixture, racemic by synthesis, other combinations of R and S, and even from achiral compounds. In bulk state all supramolecular columns form a 3D hexagonal crystalline phase, Φ(h)(k) (P6₃ symmetry), that can be obtained only from single-handed columns and a columnar hexagonal 2D liquid crystal, Φ(h). The highest order Φ(h)(k) consists of enantiopure single-handed columns that are slightly distorted 12-fold triple helices. The "hat-shaped" dendronized CTV assembles in bent-branch pine-tree columns that allow interdigitation of alkyl groups in adjacent columns regardless of their direction. Enantiomerically rich, racemic, and achiral compositions undergo deracemization in the crystal state by transfer of the transient disc-like conformer of dendronized CTV from column to column during crown inversion. Solid state NMR experiments identified motional processes that allow such transfer. This unprecedented supramolecular chiral self-sorting will impact the creation of functions in complex systems.


[Endonuclease activity in the blood serum of rats undergoing nonuniform gamma irradiation].
During the first hours following nonuniform gamma-irradiation (the nonuniformity coefficient was 3:1 and 5:1 with a dose change along the axis directed cranio-caudally and caudo-cranially), endonuclease activity (pH 5.75) in the blood serum increased with the dose which was estimated with a reference to total utilization of the substrate. Supercoiled plasmid DNA served as the substrate. The transformation of a supercoiled form of plasmid DNA into an open circular form was the criterion of estimation of nuclease activity. It was shown that the increase in the nuclease activity correlated with the increase in the nonuniformity coefficient.


Quantitative trait loci and differential gene expression analyses reveal the genetic basis for negatively associated β-carotene and starch content in hexaploid sweetpotato [Ipomoea batatas (L.) Lam.].
β-Carotene content in sweetpotato is associated with the Orange and phytoene synthase genes; due to physical linkage of phytoene synthase with sucrose synthase, β-carotene and starch content are negatively correlated. In populations depending on sweetpotato for food security, starch is an important source of calories, while β-carotene is an important source of provitamin A. The negative association between the two traits contributes to the low nutritional quality of sweetpotato consumed, especially in sub-Saharan Africa. Using a biparental mapping population of 315 F1 progeny generated from a cross between an orange-fleshed and a non-orange-fleshed sweetpotato variety, we identified two major quantitative trait loci (QTL) on linkage group (LG) three (LG3) and twelve (LG12) affecting starch, β-carotene, and their correlated traits, dry matter and flesh color. Analysis of parental haplotypes indicated that these two regions acted pleiotropically to reduce starch content and increase β-carotene in genotypes carrying the orange-fleshed parental haplotype at the LG3 locus. Phytoene synthase and sucrose synthase, the rate-limiting and linked genes located within the QTL on LG3 involved in the carotenoid and starch biosynthesis, respectively, were differentially expressed in Beauregard versus Tanzania storage roots. The Orange gene, the molecular switch for chromoplast biogenesis, located within the QTL on LG12 while not differentially expressed was expressed in developing roots of the parental genotypes. We conclude that these two QTL regions act together in a cis and trans manner to inhibit starch biosynthesis in amyloplasts and enhance chromoplast biogenesis, carotenoid biosynthesis, and accumulation in orange-fleshed sweetpotato. Understanding the genetic basis of this negative association between starch and β-carotene will inform future sweetpotato breeding strategies targeting sweetpotato for food and nutritional security.


Effects of neuroserpin on clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke.
Neuroserpin (NSP) is known for its neuroprotective effects. The aim of this study was to investigate the relationship between NSP level and clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke. A total of 133 patients with acute cerebral infarction (ischemia group) and 44 controls were recruited. The modified Rankin Scale (mRS) was used to determine the functional outcome three months after onset. We investigated the relationship between serum NSP levels [on admission and a decrease in NSP levels (10 days after admission versus on admission)] and serum levels of several inflammatory markers. We confirmed that NSP levels on admission in the ischemia group were significantly higher than those in the control group. NSP levels in patients with good outcomes were significantly higher than those in patients with poor outcomes. NSP levels on admission were associated with having a good outcome in these patients. We found that a larger decrease in NSP levels (on admission vs. 10 days after admission) was correlated with lower serum levels of IL-6, IL-1β, and ICAM-1 10 days after admission. A larger decrease in NSP levels related to lower levels of inflammatory marker, while higher NSP levels were associated with lower inflammatory markers and better functional outcomes. Decreasing the infarct size may play a role in this process. These results provide more evidence of the neuroprotective effect of NSP in cerebral ischemic patients. Decrease in the Serum NSP level and NSP level at admission may be considered as potential predictive factors for outcome of acute ischemic stroke.


Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations.
Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.


A test bed for insect-inspired robotic control.
Flying insects are remarkable examples of sophisticated sensory-motor control systems. Insects have solved the fundamental challenge facing the field of mobile robots: robust sensory-motor mapping. Control models based on insects can contribute much to the design of robotic control systems. We present our work on a preliminary robotic control system inspired by current behavioural and physiological models of the fruit fly, Drosophila melanogaster. We designed a five-degrees-of-freedom robotic system that serves as a novel simulation/mobile robot hybrid. This design has allowed us to implement a fly-inspired control system that uses visual and mechanosensory feedback. Our results suggest that a simple control scheme can yield surprisingly robust fly-like robotic behaviour.


Development of a non-extracted 'two-site' immunoradiometric assay for corticotropin utilizing extreme amino- and carboxy-terminally directed antibodies.
The development of a 'two-site' immunoradiometric assay (i.r.m.a.) for the direct estimation of human corticotropin-(1-39)-peptide in plasma is described. The assay is based on the simultaneous addition of 125I-labelled sheep anti-(N-terminal corticotropin) IgG (immunoglobulin G) antibodies and rabbit anti-(C-terminal corticotropin) antiserum to standards and unknowns (0.5 ml) followed by 18h incubation. The use of solid-phase reagents was avoided in order to minimize non-specific effects and the time required for reactants to reach equilibrium. Instead, the separation of corticotropin-bound from free labelled antibody is achieved by the addition of sheep anti-(rabbit IgG) antiserum, which precipitates bound labelled antibody by complex-formation with rabbit anti-corticotropin antibodies, which are also hormone-bound. Several 125I-labelled sheep anti-(N-terminal corticotropin) IgG preparations were assessed in the i.r.m.a. Although each was derived from antisera raised to a thyroglobulin conjugate of synthetic corticotropin-(1-24)-peptide (Synacthen), purification of immunoglobulins before iodination by selective immunoadsorption resulted in preparations with distinct specificities which demonstrated marked differences in binding to intact human corticotropin-(1-39)-peptide. These preparations are compared in combination with two rabbit anti-(C-terminal corticotropin) antisera. A 'two-site' assay based on the use of 125I-labelled sheep anti-[ corticotropin-(2-16)-peptide] IgG and rabbit anti-[corticotropin-(34-39)-peptide] antiserum was optimized, since steric inhibition of antibody binding was avoided with this combination and because the measurement of only intact human corticotropin-(1-39)-peptide and not fragments was assured by the use of terminal antibodies. This i.r.m.a. is characterized by rapid equilibration of reactants, a wide 'operating range' (the precision of dose estimates was less than 4% over the range 30-2200 pg/ml) and high sensitivity [8 pg of corticotropin/ml (95% confidence interval 3.7-12.0) (4 pg minimal detectable mass) can be detected directly in plasma].


The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected.
Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a "total ancestry" estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries--a phenomenon described and intended as the "whitening of Brazil"--is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations.


Case report: the use of a resin retained bridge with movable joint.
The use of resin retained bridge work is commonplace within dental practice. Factors that may affect long term success include the type of metal used and surface preparation, the resin, operator technique, the surface area of the tooth, differing movement of the abutment teeth and occlusal forces. A clinical case is reported in which a resin retained bridge with a movable joint was used to restore missing anterior teeth in a 15 year old girl with a developing occlusion.


A new PK/PD target for assessing efficacy of micafungin against Candida parapsilosis.
Pharmacokinetic/pharmacodynamic (PK/PD) targets of echinocandins failed to support current clinical breakpoints of Candida parapsilosis as the PTA is low for susceptible isolates despite the good clinical efficacy of echinocandins against these infections. We therefore investigated the effect of micafungin against C. parapsilosis using an in vitro PK/PD in the presence of 10% human serum. Three susceptible (MIC = 0.5-2 mg/L) and one resistant (MIC > 8 mg/L) C. parapsilosis sensu stricto isolates were tested at two different inocula (104 and 103 cfu/mL) simulating micafungin human exposures in RPMI and in RPMI + 10% pooled human serum. The exposure-effect relationship tAUC0-24/MIC was described and different PK/PD targets were determined in order to calculate the PTA for the standard 100 mg IV q24h dose. A maximal effect was found at fCmax ≥ 4 mg/L in RPMI and tCmax ≥ 64 mg/L (fCmax = 0.08 mg/L) in the presence of serum for which in vitro PK/PD targets were 50 times lower. Stasis in the presence of serum was found at 272-240 tAUC0-24/MIC, close to the clinical PK/PD target (285 tAUC/MIC), validating the in vitro model. However, the PTA was low for susceptible isolates with EUCAST/CLSI MICs ≤ 2 mg/L. Among the different PK/PD targets investigated, the PK/PD target 28 tAUC/MIC associated with 10% of maximal effect with the low inoculum resulted in PTAs ≥ 95% for susceptible isolates with EUCAST/CLSI MICs ≤ 2 mg/L. A new PK/PD target was found for micafungin and C. parapsilosis that supports the current clinical breakpoint. This target could be used for assessing echinocandin efficacy against C. parapsilosis.


Morphometric assessment of the dermal microcirculation in patients with chronic venous insufficiency.
Ultrastructural assessments of the dermal microcirculation in patients with chronic venous insufficiency have been limited to qualitative morphologic descriptions of venous ulcer edges or venous stasis dermatitis. The purpose of this investigation was to quantify differences in endothelial cell structure and local cell type with emphasis on leukocytes and their relationship to arterioles, capillaries, and postcapillary venules (PCVs). Two 4.0 mm punch biopsies were obtained from areas of dermal stasis skin changes in the gaiter region of the leg, as well as from noninvolved areas of skin in the ipsilateral thigh, from 35 patients: CEAP class 4 (11 patients), class 5 (9 patients), class 6 (10 patients), and five normal skin biopsies from patients without chronic venous insufficiency. Electron microscopy was performed on sections at 6700x and 23,800x magnification. At 6700x endothelial cell thickness was determined, and the number of fibroblasts, leukocytes, and mast cells were recorded relative to their proximity to arterioles, capillaries, and PCVs. Similarly, at 23,800x endothelial cell vesicle density, interendothelial junctional widths, and basal lamina thickness (cuff width) were measured. Preliminary evaluation for the presence of transforming growth factor-beta 1 (TGF-beta 1) was performed on three patients using reverse transcriptase-polymerase chain reaction (RT-PCR). Quantitative measurements demonstrated increased mast cell content for class 4 and 5 patients around arterioles and PCVs and increased macrophage numbers for class 6 patients around PCVs (p < 0.05). Fibroblasts were the most common cells observed; however, no differences were demonstrated between groups. No differences were observed in interendothelial junctional widths or vesicle densities in arterioles, capillaries, or PCVs. Basal lamina thickness was increased only at the capillary level (p < 0.05). The results of RT-PCR for TGF-beta 1 messenger RNA were positive in the three patients studied. Our data suggest that (1) mast cells play a role in the pathogenesis of chronic venous insufficiency; (2) the effects of mast cells, macrophages, or both may be mediated in part by TGF-beta 1; and (3) capillary cuff formation is not associated with widened interendothelial gap junctions, but may be a result of enhanced vesicular transport rate or conformational changes in the interendothelial glycocalyx.


Severe traumatic brain injury management in Tanzania: analysis of a prospective cohort.
Given the high burden of neurotrauma in low- and middle-income countries (LMICs), in this observational study, the authors evaluated the treatment and outcomes of patients with severe traumatic brain injury (TBI) accessing care at the national neurosurgical institute in Tanzania. A neurotrauma registry was established at Muhimbili Orthopaedic Institute, Dar-es-Salaam, and patients with severe TBI admitted within 24 hours of injury were included. Detailed emergency department and subsequent medical and surgical management of patients was recorded. Two-week mortality was measured and compared with estimates of predicted mortality computed with admission clinical variables using the Corticoid Randomisation After Significant Head Injury (CRASH) core model. In total, 462 patients (mean age 33.9 years) with severe TBI were enrolled over 4.5 years; 89% of patients were male. The mean time to arrival to the hospital after injury was 8 hours; 48.7% of patients had advanced airway management in the emergency department, 55% underwent cranial CT scanning, and 19.9% underwent surgical intervention. Tiered medical therapies for intracranial hypertension were used in less than 50% of patients. The observed 2-week mortality was 67%, which was 24% higher than expected based on the CRASH core model. The 2-week mortality from severe TBI at a tertiary referral center in Tanzania was 67%, which was significantly higher than the predicted estimates. The higher mortality was related to gaps in the continuum of care of patients with severe TBI, including cardiorespiratory monitoring, resuscitation, neuroimaging, and surgical rates, along with lower rates of utilization of available medical therapies. In ongoing work, the authors are attempting to identify reasons associated with the gaps in care to implement programmatic improvements. Capacity building by twinning provides an avenue for acquiring data to accurately estimate local needs and direct programmatic education and interventions to reduce excess in-hospital mortality from TBI.


Device-associated infections rates in adult, pediatric, and neonatal intensive care units of hospitals in the Philippines: International Nosocomial Infection Control Consortium (INICC) findings.
This study investigated the rate of device-associated health care-associated infection (DA-HAI), microbiological profiles, bacterial resistance, length of stay (LOS), and mortality rate in 9 intensive care units (ICUs) of 3 hospital members of the International Nosocomial Infection Control Consortium (INICC) in the Philippines. This was an open-label, prospective cohort, active DA-HAI surveillance study of adult, pediatric, and newborn patients admitted to 9 tertiary care ICUs in the Philippines between January 2005 and December 2009, implementing methodology developed by the INICC. Data collection was performed in the participating ICUs, and data were uploaded and analyzed at the INICC headquarters using proprietary software. DA-HAI rates were registered based on definitions promulgated by the Centers for Disease Control and Prevention's National Healthcare Safety Network. Over a 5-year period, 4952 patients hospitalized in ICUs for a total of 40,733 days acquired 199 DA-HAIs, for an overall rate of 4.9 infections per 1,000 ICU-days. Ventilator-associated pneumonia posed the greatest risk (16.7 per 1,000 ventilator-days in the adult ICUs, 12.8 per 1,000 ventilator-days in the pediatric ICU, and 0.44 per 1,000 ventilator-days in the neonatal ICUs), followed by central line-associated bloodstream infections (4.6 per 1,000 catheter-days in the adult ICUs, 8.23 per 1,000 ventilator-days in the pediatric ICU, and 9.6 per 1,000 ventilator-days in the neonatal ICUs) and catheter-associated urinary tract infections (4.2 per 1,000 catheter-days in the adult ICUs and 0.0 in the pediatric ICU). DA-HAIs pose far greater threats to patient safety in Philippine ICUs than in US ICUs. The establishment of active infection control programs that involve infection surveillance and implement guidelines for prevention can improve patient safety and should become a priority.


Transplacental delivery of the Wnt antagonist Frzb1 inhibits development of caudal paraxial mesoderm and skeletal myogenesis in mouse embryos.
Axial structures (neural tube/notochord) and surface ectoderm activate myogenesis in the mouse embryo; their action can be reproduced, at least in part, by several molecules such as Sonic hedgehog and Wnts. Recently, soluble Wnt antagonists have been identified. Among those examined only Frzb1 was found to be expressed in the presomitic mesoderm and newly formed somites and thus its possible role in regulating myogenesis was investigated in detail. When presomitic mesoderm or newly formed somites were cultured with axial structures and surface ectoderm on a feeder layer of C3H10T1/2 cells expressing Frzb1, myogenesis was abolished or severely reduced in presomitic mesoderm and the three most recently formed somites. In contrast, no effect was observed on more mature somites. Inhibition of myogenesis did not appear to be associated with increased cell death since the final number of cells in the explants grown in the presence of Frzb1 was only slightly reduced in comparison with controls. In order to examine the possible function of Frzb1 in vivo, we developed a method based on the overexpression of the soluble antagonist by transient transfection of WOP cells with a Frzb1 expression vector and injection of transfected cells into the placenta of pregnant females before the onset of maternofoetal circulation. Frzb1, secreted by WOP cells, accumulated in the embryo and caused a marked reduction in size of caudal structures. Myogenesis was strongly reduced and, in the most severe cases, abolished. This was not due to a generalized toxic effect since only several genes downstream of the Wnt signaling pathway such as En1, Noggin and Myf5 were downregulated; in contrast, Pax3 and Mox1 expression levels were not affected even in embryos exhibiting the most severe phenotypes. Taken together, these results suggest that Wnt signals may act by regulating both myogenic commitment and expansion of committed cells in the mouse mesoderm.


[Validity of epidemiological surveys with low participation rates].
The purpose of the present study was to compare the characteristics of epidemiological survey non-respondents with the characteristics of respondents who participated by mail and phone. The study was based on data from questionnaires and registered data on socio-demographics. The Child Behavior Checklist for Ages 1-5 (CBCL/1-5) and "Experiences when answering a questionnaire" was mailed to 300 parents of children aged 18 months to five years. Parents who did not respond after a mail reminder were contacted by telephone. A total of 138 families replied to the mail contact, 99 replied after telephone contact, and we received no response from 63 families. No statistical differences in socio-demographic characteristics were found between the three groups. No statistical differences were found concerning the total problem behaviour score of the CBCL/1-5 between mail and phone responders. Parents who participated by phone thought more frequently than mail responders that questions on the CBCL/1-5 were ethically offensive, and that their own knowledge about child well-being and behaviour was unsatisfactory, p < 0,01. Non-participation is associated with parental attitudes towards ethical issues related to CBCL/1-5 and to poor parental knowledge about child well-being and behaviour. In spite of this, and although there was a low initial participation rate, it seems reasonable to assume that the results of child psychiatric epidemiological questionnaire surveys can be generalised.


Strain differences rather than hyperglycemia determine the severity of glomerulosclerosis in mice.
We reported that ROP, but not C57, mice were prone to glomerulosclerosis (GS) after nephron reduction (J Clin Invest 97:1242, 1996). In this study, we induced diabetes in ROP and C57 mice to determine if the glomerulosclerotic response was stimulus specific. We used the oligosyndactyly mutation (Os), to produce a congenital 50% reduction in nephron number. Stable hyperglycemia was induced by streptozotocin and mice were maintained for 12 weeks without insulin treatment. Glomerular hypertrophy occurred in diabetic ROP +/+ and C57 +/+ mice, but glomeruli of diabetic ROP +/+ mice had 1.92-fold higher laminin B1 and 1.5-fold higher tenascin mRNA levels than diabetic C57 +/+ mice. Diabetic ROP Os/+ mice had severe glomerulosclerosis with arteriolar and tubulointerstitial lesions while there was only moderate mesangial sclerosis in diabetic C57 Os/+ mice. Glomerular size was increased in all non-diabetic Os/+ mice. It was further increased in diabetic ROP Os/+ mice, but not in diabetic C57 Os/+ mice. Glomerular mRNA levels were higher in diabetic ROP OS/+ than in diabetic C57 OS/+ mice [alpha 1 (i.v.) collagen 3.2-fold, laminin B1 2.1-fold, and tenascin 1.6-fold]. Overall, our data further support the hypothesis that the susceptibility to glomerulosclerosis is inherited, and suggest that hyperglycemia serves principally as a triggering event in the development of diabetic nephropathy. Since the acceleration of diabetic nephropathy by nephron reduction was also largely strain dependent, it appears that the propensity to glomerulosclerosis is a general renal response and is not stimulus specific.


Placental 11beta-HSD2 activity, early postnatal clinical course, and adrenal function in extremely low birth weight infants.
The placental enzyme 11beta-hydroxysteroid dehydrogenase-2 (11beta-HSD2) transforms maternal cortisol to inactive cortisone. Fetal glucocorticoid excess due to reduced 11beta-HSD2 activity could make small preterm infants susceptible to early adrenal insufficiency when the maternal cortisol source is no longer sustained. We assessed whether placental 11beta-HSD2 activity is related to early adrenal insufficiency and postnatal clinical course in extremely low birth weight (<1000 g) infants. Mean gestational age of the 44 infants was 26.6 wk (range, 23.7-32.0), birth weight was 747 g (440-981), and relative birth weight was -1.9 SD (-4.9 to 1.0). We determined placental 11beta-HSD2 activity, baseline, and ACTH-stimulated cortisol and assessed illness severity by the Score of Neonatal Acute Physiology (SNAP). One standard deviation decrease in placental 11beta-HSD2 activity corresponded to a 1.85 (95% CI 0.55 to 3.14; p = 0.006) unit increase in SNAP score and 2.9 mm Hg decrease in minimum mean arterial pressure (95% CI 0.3 to 5.6 mm Hg; p = 0.03). Placental 11beta-HSD2 activity was not associated with cortisol concentrations, although the confidence interval of the ACTH-stimulated cortisol was close to zero: 1 SD increase corresponded to 17% (-18% to 49%) increase in ACTH-stimulated cortisol. Moreover, a 1 SD decrease in enzyme activity was associated with a hazard ratio for postnatal glucocorticoid treatment of 1.63 (95% CI 1.00 to 2.65); p = 0.05. In ELBW infants, lower placental 11beta-HSD2 activity is associated with more severe early postnatal illness and hypotension. Although an association with baseline or ACTH-stimulated cortisol was not seen, possible relationships with other components of the hypothalamic-pituitary-adrenal axis remain to be determined.


CD34(+) Liver Cancer Stem Cells Were Formed by Fusion of Hepatobiliary Stem/Progenitor Cells with Hematopoietic Precursor-Derived Myeloid Intermediates.
A large number of cancer stem cells (CSCs) were identified and characterized; however, the origins and formation of CSCs remain elusive. In this study, we examined the origination of the newly identified CD34(+) liver CSC (LCSC). We found that CD34(+) LCSC coexpressed liver stem cell and myelomonocytic cell markers, showing a mixed phenotype, a combination of hepatobiliary stem/progenitor cells (HSPCs) and myelomonocytic cells. Moreover, human xenografts produced by CD34(+) LCSCs and the parental cells, which CD34(+) LCSC was isolated from, coexpressed liver cancer and myelomonocytic markers, also demonstrating mixed phenotypes. The xenografts and the parental cells secreted albumin demonstrating their hepatocyte origin and also expressed cytokines [interleukin (IL)-1b, IL-6, IL-12A, IL-18, tumor necrosis factor-alpha (TNF-α), and CSF1] and chemokines (IL-8, CCL2, and CCL5). Expression of these cytokines and chemokines responded to the stimuli [interferon-γ (INF-γ), IL-4, and lipopolysaccharide (LPS)]. Furthermore, human xenografts and the parental cells phagocytized Escherichia coli. CD34(+) LCSC coexpressed CD45, demonstrating that its origin appears to be from a hematopoietic precursor. The percentage of cells positive for OV6, CD34, and CD31, presenting the markers of HSPC, hematopoietic, and myelomonocytic cells, increased under treatment of CD34(+) LCSC with a drug. Cytogenetic analysis showed that CD34(+) LCSC contained a greater number of chromosomes. HBV DNA integrations and mutations in CD34(+) LCSC and the parental cells were identical to those in the literature or the database. Thus, these results demonstrated that CD34(+) LCSCs were formed by fusion of HSPC with CD34(+) hematopoietic precursor-derived myeloid intermediates; it appears that this is the first report that human CSCs have been formed by the fusion. Therefore, it represents a significant step toward better understanding of the formation of human CSC and the diverse origins of liver cancers.


Difficulties in emotion regulation and risky driving among Lithuanian drivers.
Risky driving is a common cause of traffic accidents and injuries. However, there is no clear evidence of how difficulties in emotion regulation contribute to risky driving behavior, particularly in small post-Soviet countries. The present study aimed to investigate the relationship between difficulties in emotion regulation and self-reported risky driving behavior in a sample of Lithuanian drivers. A total of 246 nonprofessional Lithuanian drivers participated in a cross-sectional survey. Difficulties in emotion regulation were assessed using the Difficulties in Emotion Regulation Scale (DERS; Gratz and Roemer 2004), and risky driving behavior was assessed using the Manchester Driver Behaviour Questionnaire (DBQ; Lajunen et al. 2004). Males scored higher than females in aggressive violations and ordinary violations. Females scored higher for the nonacceptance of emotional responses, whereas males had more difficulties with emotional awareness than females. More difficulties in emotion regulation were positively correlated with driving errors, lapses, aggressive violations, and ordinary violations for both males and females. Structural equation modeling showed that difficulties in emotion regulation explained aggressive and ordinary violations more clearly than lapses and errors. When controlling for interactions among the distinct regulation difficulties, difficulties with impulse control and difficulties engaging in goal-directed behavior predicted risky driving. Furthermore, nonacceptance of emotional responses and limited access to emotion regulation strategies were related to less violations and more driving errors. Emotion regulation difficulties were associated with the self-reported risky driving behaviors of Lithuanian drivers. This provides useful hints for improving driver training programs in order to prevent traffic injuries.


Sexual victimization of boys. Experience at an adolescent medicine clinic.
Most information pertaining to male child sexual abuse victims is derived from cases presenting to the criminal-justice system, the mental-health system, hospital emergency rooms, and retrospective studies of college populations, all of which may be biased samples. This paper reports a six-year experience in an adolescent medicine clinic in which all medical interviews of adolescent males included questions about sexual molestation. Forty adolescent males reported sexual victimization during their preadolescent years. This study group of 40 was compared with a randomly selected age-matched group whose responses were negative to the same questions. None of the study group had previously been identified by medical or legal systems as having been molested. Twenty-five percent of the victimized males reported sexual dysfunction compared to 5% of the nonvictimized males, and 60% stated that the sexual abuse had a significant impact on their lives. Consequently, we conclude that questions about sexual molestation should be included as part of routine histories in adolescent clinics.


Increasing Levels of Urban Malnutrition with Rapid Urbanization in Informal Settlements of Katutura, Windhoek: Neighbourhood Differentials and the Effect of Socio-Economic Disadvantage.
Rapid urbanization and increasing urban poverty characterize much of Southern Africa, resulting in poor urban health. This study investigates inter-urban differences and determinants of undernutrition among marginalized communities. Using the 1992, 2000 and 2006/2007 Namibia Demographic and Health Survey data, we fitted hierarchical random intercept logit models, applied at 52 enumeration areas in the capital city (Windhoek), to estimate trends in undernutrition, and investigate risk factors associated with stunting and underweight. Findings demonstrate that undernutrition among children has risen (7.4% to 25.1%, p<0.001 for stunting; and 9.7% to 17.6%, p<0.001 for underweight, between 1992 and 2006/2007). The risk was pronounced for children from socioeconomically disadvantaged households (OR=1.53, 95% CI:[1.01, 2.31] for stunting and OR=2.16, 95% CI:[1.03, 4.89]for underweight). Evidence emerged of intra-urban variation in undernutrition. We argue that with increasing urbanization, comes the challenge of food insecurity and, consequently, malnutrition. For improved child health, urban planners should have targeted interventions for poor urban households and deprived neighbourhoods.


The influence of part-word phonotactic probability/neighborhood density on word learning by preschool children varying in expressive vocabulary.
The goal of this study was to examine the influence of part-word phonotactic probability/neighborhood density on word learning by preschool children with normal vocabularies that varied in size. Ninety-eight children (age 2 ; 11-6 ; 0) were taught consonant-vowel-consonant (CVC) nonwords orthogonally varying in the probability/density of the CV (i.e. body) and VC (i.e. rhyme). Learning was measured via picture naming. Children with the lowest expressive vocabulary scores showed no effect of either CV or VC probability/density, although floor effects could not be ruled out. In contrast, children with low or high expressive vocabulary scores demonstrated sensitivity to part-word probability/density with the nature of the effect varying by group. Children with the highest expressive vocabulary scores displayed yet a third pattern of part-word probability/density effects. Taken together, word learning by preschool children was influenced by part-word probability/density but the nature of this influence appeared to depend on the size of the lexicon.


Morality and the Brain: The Right Hemisphere and Doing Right.
Morality, the set of shared attitudes and practices that regulate individual behavior to facilitate cohesion and well-being, is a function of the brain, yet its localization is uncertain. Neuroscientific study of morality has been conducted by examining departures from moral conduct after neurologic insult and by functional neuroimaging of moral decision-making in cognitively intact individuals. These investigations have yielded conflicting results: Acquired sociopathy, a syndromic surrogate for acquired immorality, has been reported predominantly after right frontotemporal lesions, whereas functional neuroimaging during moral decision-making has demonstrated bilateral activation. Although morality is bilaterally represented, the right hemisphere is clinically more critical in light of focal lesion data suggesting that moral behavior is subserved by a network of right frontotemporal structures and their subcortical connections. Evolution may have endowed the brain with bilaterally represented but unilaterally right-dominant morality. The unilateral dominance of morality permits concentration of an essential social cognitive function to support the perceptual and executive operations of moral behavior within a single hemisphere; the bilateral representation of morality allows activation of reserve tissue in the contralateral hemisphere in the event of an acquired hemispheric injury. The observed preponderance of right hemisphere lesions in individuals with acquired immorality offers a plausible hypothesis that can be tested in clinical settings. Advances in the neuroscience of morality promise to yield potentially transformative clinical and societal benefits. A deeper understanding of morality would help clinicians address disordered conduct after acquired neurologic insults and guide society in bolstering public health efforts to prevent brain disease.


Hypotheses, rationale, design, and methods for evaluation of ischemic preconditioning assessed by sequential exercise tests in diabetic and non-diabetic patients with stable coronary artery disease--a prospective study.
Ischemic preconditioning is a powerful mechanism of myocardial protection and in humans it can be evaluated by sequential exercise tests. Coronary Artery Disease in the presence of diabetes mellitus may be associated with worse outcomes. In addition, some studies have shown that diabetes interferes negatively with the development of ischemic preconditioning. However, it is still unknown whether diabetes may influence the expression of ischemic preconditioning in patients with stable multivessel coronary artery disease. This study will include 140 diabetic and non-diabetic patients with chronic, stable coronary artery disease and preserved left ventricular systolic function. The patients will be submitted to two sequential exercise tests with 30-minutes interval between them. Ischemic parameters will be compared between diabetic and non-diabetic patients. Ischemic preconditioning will be considered present when time to 1.0 mm ST-segment deviation is greater in the second of two sequential exercise tests. Exercise tests will be analyzed by two independent cardiologists. Ischemic preconditioning was first demonstrated by Murry et al. in dog's hearts. Its work was reproduced by other authors, clearly demonstrating that brief periods of myocardial ischemia followed by reperfusion triggers cardioprotective mechanisms against subsequent and severe ischemia. On the other hand, the demonstration of ischemic preconditioning in humans requires the presence of clinical symptoms or physiological changes difficult to be measured. One methodology largely accepted are the sequential exercise tests, in which, the improvement in the time to 1.0 mm ST depression in the second of two sequential tests is considered manifestation of ischemic preconditioning.Diabetes is an important and independent determinant of clinical prognosis. It's a major risk factor for coronary artery disease. Furthermore, the association of diabetes with stable coronary artery disease imposes worse prognosis, irrespective of treatment strategy. It's still not clearly known the mechanisms responsible by these worse outcomes. Impairment in the mechanisms of ischemic preconditioning may be one major cause of this worse prognosis, but, in the clinical setting, this is not known. The present study aims to evaluate how diabetes mellitus interferes with ischemic preconditioning in patients with stable, multivessel coronary artery disease and preserved systolic ventricular function.


Characterization of the specific CD4+ T cell response against the F protein during chronic hepatitis C virus infection.
The hepatitis C virus (HCV) Alternate Reading Frame Protein (ARFP or F protein) presents a double-frame shift product of the HCV core gene. We and others have previously reported that the specific antibodies against the F protein could be raised in the sera of HCV chronically infected patients. However, the specific CD4(+) T cell responses against the F protein during HCV infection and the pathological implications remained unclear. In the current study, we screened the MHC class II-presenting epitopes of the F protein through HLA-transgenic mouse models and eventually validated the specific CD4(+) T cell responses in HCV chronically infected patients. DNA vaccination in HLA-DR1 and-DP4 transgenic mouse models, proliferation assay to test the F protein specific T cell response, genotyping of Chronic HCV patients and testing the F-peptide stimulated T cell response in the peripheral blood mononuclear cell (PBMC) by in vitro expansion and interferon (IFN)- γ intracellular staining. At least three peptides within HCV F protein were identified as HLA-DR or HLA-DP4 presenting epitopes by the proliferation assays in mouse models. Further study with human PBMCs evidenced the specific CD4(+) T cell responses against HCV F protein as well in patients chronically infected with HCV. The current study provided the evidence for the first time that HCV F protein could elicit specific CD4(+) T cell response, which may provide an insight into the immunopathogenesis during HCV chronic infection.