[Results of the surgical treatment of tuberculous spondylitis].
Between 1972 and 1992 91 patients with tuberculous spondylitis were treated in the orthopaedic departments of the Universities of Münster and Mainz. The age of the patients at the time of operation was 41 years and 7 months on the average. The tuberculous spondylitis was mostly located in the lower dorsal and upper lumbar spine. Indications for a surgical treatment were the acute spondylitis, the deformation of the spine and imminent or already existing neurological deficiencies. The number of removed vertebrae averaged between 2 and 7. For the ventral spondylodesis we mostly used iliac or tibial bone-grafts. The own results are discussed in relation to the literature, especially the different therapeutic regimes are regarded.


The Efficacy of Lung Volume Reduction Coil Treatment in Patients with Severe Chronic Obstructive Pulmonary Disease (COPD) Type II Respiratory Failure.
Emphysema is a progressive and irreversible disease, proceeding with the decrease in elastic recoil which is connected to tissue damage caused by chronic inflammation. Lung volume reduction coil (LVRC) method in patients with an advanced level of emphysema and irresponsive to medical treatment is shown to provide increase in lung volumes and exercise capacity, decrease in dyspnea, and increase in quality of life. The purpose of this study is to reveal that LVRC treatment is also efficient in severe COPD patients with hypercapnic respiratory failure. Eleven cases with severe COPD and emphysema were included in the study. LVRC treatment method was applied in upper lobes of both lungs in patients with severe COPD (FEV1 < %45) and Type-2 respiratory insufficiency (PCO2 55-80 mmHg) who were having medical treatment and CPAP treatment. The patients were followed up for a period of twelve months using arterial blood gas analysis. Beginning with the first month of the LVRC treatment, PCO2 levels were found to be significantly decreased in all patients using arterial blood gas analysis. LVRC method can provide physiological and functional recovery and progress in quality of life in severe COPD cases. It is demonstrated that LVRC treatment caused significant decreases in carbon dioxide levels as well as causing improvement in life quality and respiratory function tests in the patients with hypercapnic respiratory failure.


Active transport and exchange diffusion of Cl across the isolated skin of Rana pipiens.
Transepithelial Cl influx and efflux were measured in pairs of frog skin (Rana pipiens) matched according to short-circuit current, tissue conductance, and transepithelial potential (TEP). The skins were bathed symmetrically in NaCl Ringer and voltage clamped at TEP values ranging from -60 to +60 mV. At 0 TEP, Cl influx and net inward Cl movement (in neq X h-1 X cm-2) were, respectively, 961 +/- 116 and 463 +/- 68 in NaCl Ringer, 509 +/- 52 and 202 +/- 53 in amiloride-treated skins, 4,168 +/- 777 and 1,444 +/- 447 in theophylline-treated skins, and 587 +/- 38 and 97 +/- 44 in Na-free Ringer. A correlation was discovered between short-circuit current and Cl fluxes corresponding to a 2:6:1 relationship between changes in active Na transport and active Cl transport. Deviations from the predicted Cl flux ratio indicate the presence of exchange diffusion in the range of spontaneously occurring TEPs, in contrast to observations on R. temporaria and R. esculenta. The experiments indicate that a substantial portion of transepithelial Cl movement proceeds transcellularly 1) via active Cl transport that is Na dependent, amiloride sensitive, stimulated by theophylline, and apparently correlated with active Na transport, and 2) by means of exchange diffusion that not only occurs under short-circuit conditions but also at positive TEPs. It is possible to explain both the exchange diffusion and the properties of active Cl transport by a Cl-HCO3 exchange system at the apical side of the transporting cell that interacts with a Na-H exchange mechanism, a notion consistent with the recent observation of an amiloride-induced decrease in intracellular pH.


Vitamin D status and pathway genes in five European autoimmune Addison's disease cohorts.
While vitamin D regulates immune cells, little is known about it in autoimmune Addison's disease (AAD). We investigated the vitamin D status in AAD patients from five European populations to assess its deficiency. In addition, we studied two case-control cohorts for vitamin D metabolism and pathway genes. Cross-sectional study. A total of 1028 patients with AAD from Germany (n = 239), Italy (n = 328), Norway (n = 378), UK (n = 44) and Poland (n = 39) and 679 controls from Germany (n = 301) and Norway (n = 378) were studied for 25(OH)D3 (primary objective). Secondary objectives (1,25(OH)2D3 and pathway genes) were examined in case-controls from Germany and Norway correlating 25(OH)D3 and single nucleotide polymorphisms within genes encoding the vitamin D receptor (VDR), 1-α-hydroxylase (CYP27B1), 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1) and vitamin D binding protein (GC/DBP). Vitamin D deficiency (25(OH)D3 10-20 ng/mL) was highly prevalent in AAD patients (34-57%), 5-22% were severely deficient (<10 ng/mL), 28-38% insufficient (20-30 ng/mL) and only 7-14% sufficient (>30 ng/mL). Lower 25(OH)D3 and 1,25(OH)2D3 levels were observed both in Norwegian and German AAD (P = 0.03/0.003 and P = 1 × 10-5/< 1 × 10-7, respectively) the former was associated with CYP2R1 (rs1553006) genotype G. Whereas controls achieved sufficient median 25(OH)D3 in summers (21.4 to 21.9 ng/mL), AAD patients remained largely deficient (18.0 to 21.2 ng/mL) and synthesize less 1,25(OH)2D3. Vitamin D deficiency and insufficiency are highly prevalent in AAD patients. The vitamin D status of AAD may be influenced by genetic factors and suggests individual vitamin D requirements throughout the year.


On the Correlation Between Tactile Stimulation and Pleasantness.
Several studies in the affective haptics research field showed the potential of using haptic technology to convey emotions in remote communications. In this context, it is of interest to simplify the haptic feedback without altering the informative content of the stimulus, with a two-fold advantage. On one side, it would allow the development of affective haptic devices whose technological complexity is limited, hence more compatible with wearability and portability requirements. On the other side, having a simplified set of stimuli would decrease the amount of data to be transmitted, thus improving the overall quality of remote haptic interactions. In this work, we investigated the correlation between the parameters regulating a caress-like stimulation and the perceived pleasantness. This was done by means of two experiments, in which we asked subjects to adjust the temperature and the motion velocity of a set of stimuli in order to find the most pleasant combination. Results indicated that subjects preferred different values of temperature and velocity of the stimulus depending on the proposed tactile stimulation. A small difference in the pleasantness ratings was observed between caresses provided with linear movements and those given as discrete sequences of taps. In particular, participants preferred linear movements set at 34.5 °C and 3.4 cms-1. As regards caress-like stimuli provided with discrete sequences of taps, the preferred temperature and velocity were 33.2 °C and 2.9 cms-1, respectively. The presence of vibration had a little effect on the perceived pleasantness.


Telehealth Use Following COVID-19 Within Patient-Sharing Physician Networks at a Rural Comprehensive Cancer Center: Cross-sectional Analysis.
In response to the COVID-19 pandemic, cancer centers rapidly adopted telehealth to deliver care remotely. Telehealth will likely remain a model of care for years to come and may not only affect the way oncologists deliver care to their own patients but also the physicians with whom they share patients. This study aimed to examine oncologist characteristics associated with telehealth use and compare patient-sharing networks before and after the COVID-19 pandemic in a rural catchment area with a particular focus on the ties between physicians at the comprehensive cancer center and regional facilities. In this retrospective observational study, we obtained deidentified electronic health record data for individuals diagnosed with breast, colorectal, or lung cancer at Dartmouth Health in New Hampshire from 2018-2020. Hierarchical logistic regression was used to identify physician factors associated with telehealth encounters post COVID-19. Patient-sharing networks for each cancer type before and post COVID-19 were characterized with global network measures. Exponential-family random graph models were performed to estimate homophily terms for the likelihood of ties existing between physicians colocated at the hub comprehensive cancer center. Of the 12,559 encounters between patients and oncologists post COVID-19, 1228 (9.8%) were via telehealth. Patient encounters with breast oncologists who practiced at the hub hospital were over twice as likely to occur via telehealth compared to encounters with oncologists who practiced in regional facilities (odds ratio 2.2, 95% CI 1.17-4.15; P=.01). Patient encounters with oncologists who practiced in multiple locations were less likely to occur via telehealth, and this association was statistically significant for lung cancer care (odds ratio 0.26, 95% CI 0.09-0.76; P=.01). We observed an increase in ties between oncologists at the hub hospital and oncologists at regional facilities in the lung cancer network post COVID-19 compared to before COVID-19 (93/318, 29.3%, vs 79/370, 21.6%, respectively), which was also reflected in the lower homophily coefficients post COVID-19 compared to before COVID-19 for physicians being colocated at the hub hospital (estimate: 1.92, 95% CI 1.46-2.51, vs 2.45, 95% CI 1.98-3.02). There were no significant differences observed in breast cancer or colorectal cancer networks. Telehealth use and associated changes to patient-sharing patterns associated with telehealth varied by cancer type, suggesting disparate approaches for integrating telehealth across clinical groups within this health system. The limited changes to the patient-sharing patterns between oncologists at the hub hospital and regional facilities suggest that telehealth was less likely to create new referral patterns between these types of facilities and rather replace care that would otherwise have been delivered in person. However, this study was limited to the 2 years immediately following the initial outbreak of COVID-19, and longer-term follow-up may uncover delayed effects that were not observed in this study period.


Caseous necrosis of the mitral annulus masquerading as an intracardiac mass.
Caseous necrosis of the mitral annulus is a rare condition which typically involves the posterior leaflet or annulus. We report the case of a 71-year-old female with extensive comorbidities, presenting with dyspnea and angina, who had an incidental echocardiographic finding of a mass on or near the mitral valve. The mass increased in size over the course of three years and was associated with severe mitral regurgitation. The mass was initially thought to be a myxoma, however, surgical exploration revealed caseous necrosis of the posterior mitral annulus. Following removal of the necrotic tissue and distorted mitral leaflet, a bioprosthetic mitral valve was implanted and the patient recovered uneventfully.


Involvement of the Interferon Signaling Pathways in Pancreatic Cancer Cells.
To examine interferon (IFN) signaling pathways in human pancreatic cancer cells and their therapeutic application for pancreatic ductal adenocarcinoma (PDAC). We examined the effects of IFNα on cytotoxicity, migration, as well as on the levels of toll-like receptor (TLR) signaling pathway-associated genes expression in pancreatic cancer cells. We also examined the additive effects of IFNα and poly(I-C) on tyrosine kinase inhibitor (TKI)-induced cytotoxicity. We performed transcriptome analysis (RNA-Seq) of clinical samples and compared the profile between pancreatic intraepithelial neoplasias (PanINs) and PDACs. IFNα suppressed cell viability and cell migration, and affected TLR signaling pathways, in pancreatic cancer cells. TLR3 is one of the potential genes involved in IFN-treated pancreatic cancer cells. Furthermore, similar to IFN, extracellular addition of poly(I-C) enhanced TKI-induced cytotoxicity in pancreatic cancer cells. RNA-Seq analysis demonstrated that IFN signaling is one of the potential pathways involved in the progression of PanIN to PDAC. IFN signaling may be involved in the development of PDAC. Treatments that target the IFN and TLR3 signaling pathways may be therapeutic options against PDAC.


Exploring experiences of cancer care in Wales: a thematic analysis of free-text responses to the 2013 Wales Cancer Patient Experience Survey (WCPES).
To provide the first systematic analysis of a national (Wales) sample of free-text comments from patients with cancer, to determine emerging themes and insights regarding experiences of cancer care in Wales. Thematic analysis of free-text data from a population-based survey. Adult patients with a confirmed cancer diagnosis treated within a 3-month period during 2012 in the 7 health boards and 1 trust providing cancer care in Wales. Free-text categorised by theme, coded as positive or negative, with ratios. Overarching themes are identified incorporating comment categories. 4672 respondents (of n=7352 survey respondents) provided free-text comments. Data were coded using a multistage approach: (1) coding of comments into general categories (eg, nursing, surgery, etc), (2) coding of subcategories within main categories (eg, nursing care, nursing communication, etc), (3) cross-sectional analysis to identify themes cutting across categories, (4) mapping of categories/subcategories to corresponding closed questions in the Wales Cancer Patient Experience Survey (WCPES) data for comparison. Most free-text respondents (82%, n 3818) provided positive comments about their cancer care, with 49% (n=2313) giving a negative comment (ratio 0.6:1, negative-to-positive). 3172 respondents (67.9% of free-text respondents) provided a comment mapping to 1 of 4 overarching themes: communication (n=1673, 35.8% free-text respondents, a ratio of 1.0:1); waiting during the treatment and/or post-treatment phase (n=923, 19.8%, ratio 1.5:1); staffing and resource levels (n=671, 14.4% ratio 5.3:1); speed and quality of diagnostic care (n=374, 8.0%, ratio 1.5:1). Within these areas, constituent subthemes are discussed. This study presents specific areas of concern for patients with cancer, and reveals a number of themes present across the cancer journey. While the majority of comments were positive, analysis reveals concerns shared by significant numbers of respondents. Timely communication can help to manage these anxieties, even where delays or difficulties in treatment may be encountered.


Interaction of leukocytes with vascular cells in culture.
The nature, kinetics and cofactor requirements of leukocyte adhesion to cultured vascular cells have been investigated in vitro, using a model system in which leukocyte suspensions are in continuous motion over the cultured cells. Adhesion is assessed by histological examination or by using 51Cr-labelled leukocytes. Leukocytes adhere preferentially to endothelial cell monolayers rather than to smooth muscle cells, adventitial fibroblasts or serum-coated glass. Arterial and venous endothelium are equally good substrates for leukocyte adhesion, and lymphocytes and granulocytes at the same suspension density adhere to endothelial cells in similar numbers. Adherence is greatest during the first 10 min, and is inversely related to flow rate. Numbers of leukocytes adhering to the cell monolayer are proportional to the initial concentration of leukocytes in suspension, although only 2--10% of the leukocytes adhere. Leukocytes that have adhered to the cell monolayer spread over the cells and then migrate, apparently through intercellular junctions. Adhesion requires Ca2+ or Mg2+ ions, but not plasma protein cofactors. Fewer leukocytes adhere to endothelial cells grown for 48 h in rapidly stirred medium than to cells grown under conventional, static conditions.


HIV-1 drug resistance-associated mutations among HIV-1 infected drug-naïve antenatal clinic attendees in rural Kenya.
Access to antiretroviral therapy (ART) has increased dramatically in Sub-Saharan Africa. In Kenya, 560,000 people had access to ART by the end of 2011. This scaling up of ART has raised challenges to the Kenyan health system due to emergence of drug resistant viruses among those on treatment and possible onward transmission. To counter this, and come up with an effective treatment strategy, it has become vital to determine baseline mutations associated with drug resistance among the circulating strains of HIV-1 in Kenya. The prevalence of mutations associated with drug resistance in HIV-1 protease (PR) and reverse transcriptase (RT) regions from 188 HIV-1 infected treatment-naïve pregnant women was investigated in Kapsabet, Nandi Hills and Kitale district hospitals of Kenya. Blood samples were collected between April 2005 and June 2006. The HIV-1 pol gene was amplified using primers for HIV-1 PR and RT and sequenced using the BigDye chemistry. The mutations were analyzed based on the IAS algorithm as well as the Stanford University HIV Drug Resistance Database. Based on the PR and RT sequences, HIV-1 subtypes A1 (n=117, 62.2%), A2 (n=2, 1.1%), D (n=27, 14.4%), C (n=13, 6.9%), G (n=3, 1.6%), and possible recombinants (n=26, 13.8%) were detected. Mutations associated with nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside RTI (NNRTI)-resistance were detected in 1.6% (3 of 188) and 1.1% (2 of 188), respectively. Mutations associated with PI resistance were detected in 0.5% (1 of 188) of the study population. The prevalence of drug resistance among drug-naïve pregnant women in rural North Rift, Kenya in 2006 was 3.2%. Major drug resistance mutations associated with PIs, NRTIs and NNRTIs do exist among treatment-naïve pregnant women in North Rift, Kenya. There is a need for consistent follow-up of drug-naïve individuals in this region to determine the impact of mutations on treatment outcomes.


Nursing students' relationships among meaning in life, well-being, and positive beliefs: A cross-sectional survey study.
Nursing educators have a core responsibility to develop nursing students' health promotion. The purpose of this study was to explore nursing students regarding their relationships among meaning in life, well-being, and positive beliefs. A cross-sectional survey design was adopted in this study. Purposive sampling was used. A total of 219 nursing students participated in the study. Quantitative analysis was utilized for the data analyses. The study found that nursing students had the following mean scores on the meaning in life, 4.33 (86.60%) standard deviation (SD) 0.79; well-being, 4.23 (84.60%) SD 0.78; and positive beliefs, 4.32 (86.40%) SD 0.75. The nursing students' characteristics, meaning in life, and well-being explained 79% of the variance in positive beliefs (adjusted R = 0.79, F = 114.57, P < .001). Nursing educators can promote meaning in life and well-being to nursing students as an effective way to increase their positive beliefs.


DNMT3B promoter polymorphism and risk of immune thrombocytopenic purpura in pediatric Egyptians.
Idiopathic (immune) thrombocytopenic purpura (ITP) is a heterogeneous clinical disorder characterized by immune-mediated platelet destruction. Epigenetic changes in gene expression, including DNA methylation and histone modifications, might contribute to autoimmunity. Polymorphisms of the DNA methyltransferase 3B (DNMT3B) gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between a single nucleotide polymorphism (SNP) in the promoter of DNMT3B gene and the risk for ITP in pediatric Egyptians. DNMT3B SNP was genotyped by PCR-restriction fragment length polymorphism in 71 pediatric ITP patients and 82 healthy controls matched for age and sex. The C/C wild genotype was not detected in ITP patients or in the controls. The frequencies of the T/T and C/T genotypes were 93.9 and 6.1% in the controls and 91.5 and 6.1% in ITP patients, respectively. There was no significant difference in either genotypes or allelic distribution between ITP patients and the controls. In conclusion, this polymorphism was almost equally distributed between ITP patients and the controls. These results demonstrated that this SNP may not be used as a stratification marker to predict the susceptibility to childhood ITP in Egypt.


Second Arterial Versus Venous Conduits for Multivessel Coronary Artery Bypass Surgery in California.
Whether a second arterial conduit improves outcomes after multivessel coronary artery bypass grafting remains unclear. Consequently, arterial conduits other than the left internal thoracic artery are seldom used in the United States. Using a state-maintained clinical registry including all 126 nonfederal hospitals in California, we compared all-cause mortality and rates of stroke, myocardial infarction, repeat revascularization, and sternal wound infection between propensity score-matched cohorts who underwent primary, isolated multivessel coronary artery bypass grafting with the left internal thoracic artery, and who received a second arterial conduit (right internal thoracic artery or radial artery, n=5866) or a venous conduit (n=53 566) between 2006 and 2011. Propensity score matching using 34 preoperative characteristics yielded 5813 matched sets. A subgroup analysis compared outcomes between propensity score-matched recipients of a right internal thoracic artery (n=1576) or a radial artery (n=4290). Second arterial conduit use decreased from 10.7% in 2006 to 9.1% in 2011 (P<0.0001). However, receipt of a second arterial conduit was associated with significantly lower mortality (13.1% versus 10.6% at 7 years; hazard ratio, 0.79; 95% confidence interval [CI], 0.72-0.87), and lower risks of myocardial infarction (hazard ratio, 0.78; 95% CI, 0.70-0.87) and repeat revascularization (hazard ratio, 0.82; 95% CI, 0.76-0.88). In comparison with radial artery grafts, right internal thoracic artery grafts were associated with similar mortality rates (right internal thoracic artery 10.3% versus radial artery 10.7% at 7 years; hazard ratio, 1.10; 95% CI, 0.89-1.37) and individual risks of cardiovascular events, but the risk of sternal wound infection was increased (risk difference, 1.07%; 95% CI, 0.15-2.07). Second arterial conduit use in California is low and declining, but arterial grafts were associated with significantly lower mortality and fewer cardiovascular events. A right internal thoracic artery graft offered no benefit over that of a radial artery, but did increase risk of sternal wound infection. These findings suggest surgeons should consider lowering their threshold for using arterial grafts, and the radial artery may be the preferred second conduit.


Effects of Early-Life Stress on Social and Anxiety-Like Behaviors in Adult Mice: Sex-Specific Effects.
Stressful events in an early postnatal period have critical implications for the individual's life and can increase later risk for psychiatric disorders. The aim of this study was to investigate the influence of early-life stress on the social behavior of adult male and female mice. C57Bl/6 mice were exposed to maternal separation (MS, 3 h once a day) or handling (HD, 15 min once a day) on postnatal day 2 through 14. Adult male and female mice were tested for social behavior in the social interaction test and for individual behavior in the plus-maze and open-field tests. Female mice exposed to maternal separation had increased social behavior and increased anxiety. MS male mice had no changes in social behavior but had significantly disrupted individual behavior, including locomotor and exploratory activity. Handling had positive effects on social behavior in males and females and decreased anxiety in males. Our results support the hypothesis that brief separation of pups from their mothers (handling), which can be considered as moderate stress, may result in future positive changes in behavior. Maternal separation has deleterious effects on individual behavior and significant sex-specific effects on social behavior.


Oral collagen-derived dipeptides, prolyl-hydroxyproline and hydroxyprolyl-glycine, ameliorate skin barrier dysfunction and alter gene expression profiles in the skin.
Oral supplementation with collagen hydrolysate (CH) has been shown to improve the condition of the skin in humans and experimental animals. Several hydroxyproline-containing oligo-peptides were previously detected in human peripheral blood after the ingestion of CH, and the two dipeptides, prolyl-hydroxyproline (PO) and hydroxyprolyl-glycine (OG), have been proposed to have beneficial effects on human health. When HR-1 hairless mice were fed a HR-AD diet, which lacked magnesium and zinc, transepidermal water loss (TEWL) increased and water content of stratum corneum decreased. In the present study, we investigated the effects of dietary PO and OG on skin barrier dysfunction in HR-1 hairless mice. Mice were fed a HR-AD diet with or without PO (0.15%) and OG (0.15%) for 35 consecutive days. The administration of PO and OG significantly decreased TEWL, and significantly increased water content of stratum corneum. A DNA microarray analysis of the dorsal skin revealed differences in gene expression between the group administered PO and OG and the control group. We also identified muscle-related Gene Ontology as a result of analyzing the up-regulated genes. These results suggested that the administration of PO and OG improved skin barrier dysfunction and altered muscle-related gene expression.


MR of thoracic cord compression caused by epidural extramedullary hematopoiesis in myelodysplastic syndrome.
Spinal cord compression caused by extramedullary hematopoiesis is a rare complication of chronic anemic states, most frequently occurring in patients with beta-thalassemia. We report the MR appearance of extramedullary hematopoiesis resulting in cord compression in a patient with a myelodysplastic syndrome, which was isointense with the spinal cord on T1-weighted images and markedly hypointense on fast spin-echo T2-weighted images, and that demonstrated enhancement.


[Leiomyosarcoma and rhabdomyosarcoma: rare tumors of the kidney].
Renal sarcoma represents 2.8% of all renal malignant tumours. The most common kind is leiomyosarcoma while rhabdomyosarcoma is the most unusual. Clinical presentation and diagnosis of both types of tumours are unspecific. Treatment is controversial and the overall prognosis poor. The present paper presents two cases, one leiomyosarcoma and one rhabdomyosarcoma which were treated surgically and were followed by chemo- and radiotherapy. A revision of the criteria for grading these as primary tumours of the kidney is also included.


Pathogenic tau-induced transposable element-derived dsRNA drives neuroinflammation.
Deposition of tau protein aggregates in the brain of affected individuals is a defining feature of "tauopathies," including Alzheimer's disease. Studies of human brain tissue and various model systems of tauopathy report that toxic forms of tau negatively affect nuclear and genomic architecture, identifying pathogenic tau-induced heterochromatin decondensation and consequent retrotransposon activation as a causal mediator of neurodegeneration. On the basis of their similarity to retroviruses, retrotransposons drive neuroinflammation via toxic intermediates, including double-stranded RNA (dsRNA). We find that dsRNA and dsRNA sensing machinery are elevated in astrocytes of postmortem brain tissue from patients with Alzheimer's disease and progressive supranuclear palsy and in brains of tau transgenic mice. Using a Drosophila model of tauopathy, we identify specific tau-induced retrotransposons that form dsRNA and find that pathogenic tau and heterochromatin decondensation causally drive dsRNA-mediated neurodegeneration and neuroinflammation. Our study suggests that pathogenic tau-induced heterochromatin decondensation and retrotransposon activation cause elevation of inflammatory, transposable element-derived dsRNA in the adult brain.


Distorted Born diffraction tomography applied to inverting ultrasonic field scattered by noncircular infinite elastic tube.
This study focuses on the application of ultrasonic diffraction tomography to noncircular 2D-cylindrical objects immersed in an infinite fluid. The distorted Born iterative method used to solve the inverse scattering problem belongs to the class of algebraic reconstruction algorithms. This method was developed to increase the order of application of the Born approximation (in the case of weakly-contrasted media) to higher orders. This yields quantitative information about the scatterer, such as the speed of sound and the attenuation. Quantitative ultrasonic imaging techniques of this kind are of great potential value in fields such as medicine, underwater acoustics and nondestructive testing.


The undergraduate teaching assistant experience offers opportunities similar to the undergraduate research experience.
There has been a growing concern in higher education about our failure to produce scientifically trained workers and scientifically literate citizens. Active-learning and research-oriented activities are posited as ways to give students a deeper understanding of science. We report on an undergraduate teaching assistant (UTA) experience and suggest that students who participate as a UTA obtain benefits analogous to those who participate as an undergraduate research assistant (URA). We examined the experiences of 24 undergraduates acting as UTAs in a general microbiology course. Self-reported gains by the UTAs were supported by observational data from undergraduates in the course who were mentored by the UTAs and by the graduate teaching assistants (GTAs) with whom the UTAs worked. Specifically, data from the UTAs' journals and self-reported Likert scales and rubrics indicated that our teaching assistants developed professional characteristics such as self-confidence and communication and leadership skills, while they acquired knowledge of microbiology content and laboratory skills. Data from the undergraduate Likert scale as well as the pre- and post-GTA rubrics further confirmed our UTA's data interpretations. These findings are significant because they offer empirical data to support the suggestion that the UTA experience is an effective option for developing skills and knowledge in undergraduates that are essential for careers in science. The UTA experience provides a valuable alternative to the URA experience.


Somnogenic relationships between tumor necrosis factor and interleukin-1.
Both tumor necrosis factor (TNF) and interleukin (IL)-1 are somnogenic cytokines. They also induce each other's production and both induce nuclear factor kappa B activation, which in turn enhances IL-1 and TNF transcription. We hypothesized that TNF and IL-1 could influence each other's somnogenic actions. To test this hypothesis, we determined the effects of blocking both endogenous TNF and IL-1 on spontaneous sleep and on sleep rebound after sleep deprivation in rabbits. Furthermore, the effects of inhibition of TNF on IL-1-induced sleep and the effects of blocking IL-1 on TNF-induced sleep were determined. A TNF receptor fragment (TNFRF), as a TNF inhibitor, and an IL-1 receptor fragment (IL-1RF), as an IL-1 inhibitor, were used. Intracerebroventricular injection of a combination of the TNFRF plus the IL-1RF significantly reduced spontaneous non-rapid eye movement sleep by 87 min over a 22-h recording period. Pretreatment of rabbits with the combination of TNFRF and IL-1RF also significantly attenuated sleep rebound after sleep deprivation. Furthermore, the TNFRF significantly attenuated IL-1-induced sleep but not fever. Finally, the IL-1RF blocked TNF-induced sleep responses but not fever. Results indicate that TNF and IL-1 cooperate to regulate physiological sleep.


Service Delivery and Patient Outcomes in Ryan White HIV/AIDS Program-Funded and -Nonfunded Health Care Facilities in the United States.
Outpatient human immunodeficiency virus (HIV) health care facilities receive funding from the Ryan White HIV/AIDS Program (RWHAP) to provide medical care and essential support services that help patients remain in care and adhere to treatment. Increased access to Medicaid and private insurance for HIV-infected persons may provide coverage for medical care but not all needed support services and may not supplant the need for RWHAP funding. To examine differences between RWHAP-funded and non-RWHAP-funded facilities and in patient outcomes between the 2 systems. The study was conducted from June 1, 2009, to May 31, 2012, using data from the 2009 and 2011 cycles of the Medical Monitoring Project, a national probability sample of 8038 HIV-infected adults receiving medical care at 989 outpatient health care facilities providing HIV medical care. Data were used to compare patient characteristics, service needs, and access to services at RWHAP-funded vs non-RWHAP-funded facilities. Differences in prescribed antiretroviral treatment and viral suppression were assessed. Data analysis was performed between February 2012 and June 2015. Overall, 34.4% of facilities received RWHAP funding and 72.8% of patients received care at RWHAP-funded facilities. With results reported as percentage (95% CI), patients attending RWHAP-funded facilities were more likely to be aged 18 to 29 years (8.5% [7.4%-9.5%] vs 5.0% [3.9%-6.2%]), female (29.2% [27.2%-31.2%] vs 20.1% [17.0%-23.1%]), black (47.5% [41.5%-53.5%] vs 25.8% [20.6%-31.0%]) or Hispanic (22.5% [16.4%-28.6%] vs 12.9% [10.6%-15.2%]), have less than a high school education (26.1% [24.0%-28.3%] vs 10.9% [8.7%-13.1%]), income at or below the poverty level (53.6% [50.3%-56.9%] vs 23.9% [19.7%-28.0%]), and lack health care coverage (25.0% [21.9%-28.1%] vs 6.1% [4.1%-8.0%]). The RWHAP-funded facilities were more likely to provide case management (76.1% [69.9%-82.2%] vs 15.4% [10.4%-20.4%]) as well as mental health (64.0% [57.0%-71.0%] vs 18.0% [14.0%-21.9%]), substance abuse (33.6% [27.0%-40.2%] vs 12.0% [8.0%-16.0%]), and other support services; patients attending RWHAP-funded facilities were more likely to receive these services. After adjusting for patient characteristics, the percentage prescribed ART antiretroviral therapy, reported as adjusted prevalence ratio (95% CI), was similar between RWHAP-funded and non-RWHAP-funded facilities (1.01 [0.99-1.03]), but among poor patients, those attending RWHAP-funded facilities were more likely to be virally suppressed (1.09 [1.02-1.16]). A total of 72.8% of HIV-positive patients received care at RWHAP-funded facilities. Many had multiple social determinants of poor health and used services at RWHAP-funded facilities associated with improved outcomes. Without facilities supported by the RWHAP, these patients may have had reduced access to services elsewhere. Poor patients were more likely to achieve viral suppression if they received care at a RWHAP-funded facility.


Quantitative MRI of Human Cartilage In Vivo: Relationships with Arthroscopic Indentation Stiffness and Defect Severity.
Objective To investigate the association of cartilage defect severity, as determined by the International Cartilage Repair Society (ICRS) grading with indentation stiffness and T2 relaxation time of magnetic resonance imaging (MRI), a biomarker for the integrity of articular cartilage. Design Twenty-one patients scheduled for arthroscopic were included in the study. Prior to arthroscopy, subjects underwent quantitative MRI of articular cartilage, namely T2 relaxation time mapping at 1.5 T. Within 2 months, subjects underwent arthroscopy, which also included ICRS grading and measurement of arthroscopic indentation stiffness. Arthroscopic evaluations and T2 mapping at anterior, central, and posterior medial and lateral femoral condyles were correlated using a colocalization scheme. Differences in Young's modulus, as derived by indentation tests, and T2 times between ICRS grades were analyzed using Mann-Whitney's U or Kruskal-Wallis H tests. The correlation between modulus and T2 times was analyzed using Spearman's rank correlation coefficients. Results Modulus and T2 showed significant topographical variation. In the anterior region of interest (ROI) on the medial condyle the modulus showed a negative association with ICRS grade ( P = 0.040) and the T2 times were longer in ICRS grade 2 compared with grades 0 and 1 ( P = 0.047). Similar, but nonsignificant associations were found in the central ROI on the medial condyle. No significant correlations were observed between the indentation modulus and T2 times. Conclusions Cartilage degeneration is identified both with mechanical indentation and T2 mapping in MRI. However, in this study, indentation stiffness and T2 relaxation time in vivo, were not associated.


Partial recN gene sequencing: a new tool for identification and phylogeny within the genus Streptococcus.
Partial sequences of the recN gene (1249 bp), which encodes a recombination and repair protein, were analysed to determine the phylogenetic relationship and identification of streptococci. The partial sequences presented interspecies nucleotide similarity of 56.4-98.2 % and intersubspecies similarity of 89.8-98 %. The mean DNA sequence similarity of recN gene sequences (66.6 %) was found to be lower than those of the 16S rRNA gene (94.1 %), rpoB (84.6 %), sodA (74.8 %), groEL (78.1 %) and gyrB (73.2 %). Phylogenetically derived trees revealed six statistically supported groups: Streptococcus salivarius, S. equinus, S. hyovaginalis/S. pluranimalium/S. thoraltensis, S. pyogenes, S. mutans and S. suis. The 'mitis' group was not supported by a significant bootstrap value, but three statistically supported subgroups were noted: Streptococcus sanguinis/S. cristatus/S. sinensis, S. anginosus/S. intermedius/S. constellatus (the 'anginosus' subgroup) and S. mitis/S. infantis/S. peroris/S. oralis/S. oligofermentans/S. pneumoniae/S. pseudopneumoniae. The partial recN gene sequence comparison highlighted a high percentage of divergence between Streptococcus dysgalactiae subsp. dysgalactiae and S. dysgalactiae subsp. equisimilis. This observation is confirmed by other gene sequence comparisons (groEL, gyrB, rpoB and sodA). A high percentage of similarity was found between S. intermedius and S. constellatus after sequence comparison of the recN gene. To study the genetic diversity among the 'anginosus' subgroup, recN, groEL, sodA, gyrB and rpoB sequences were determined for 36 clinical isolates. The results that were obtained confirmed the high genetic diversity within this group of streptococci.


Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased influenza A virus cleavage and replication.
Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic acid residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host cell membrane, which is mediated by host trypsin-like serine protease. We show data here demonstrating that the protease:antiprotease ratio is increased in the nasal mucosa of asthmatics and that these changes were associated with increased proteolytic activation of influenza. These data suggest that disruption of the protease balance in asthmatics enhances activation and infection of influenza virus.


Feeling of Ownership over an Embodied Avatar's Hand Brings About Fast Changes of Fronto-Parietal Cortical Dynamics.
When we look at our body parts, we are immediately aware that they belong to us and we rarely doubt about the integrity, continuity, and sense of ownership of our body. Despite this certainty, immersive virtual reality (IVR) may lead to a strong feeling of embodiment over an artificial body part seen from a first-person perspective (1PP). Although such feeling of ownership (FO) has been described in different situations, it is not yet understood how this phenomenon is generated at neural level. To track the real-time brain dynamics associated with FO, we delivered transcranial magnetic stimuli over the hand region in the primary motor cortex (M1) and simultaneously recorded electroencephalography (EEG) in 19 healthy volunteers (11 male/8 female) watching IVR renderings of anatomically plausible (full-limb) versus implausible (hand disconnected from the forearm) virtual limbs. Our data show that embodying a virtual hand is temporally associated with a rapid drop of cortical activity of the onlookers' hand region in the M1 contralateral to the observed hand. Spatiotemporal analysis shows that embodying the avatar's hand is also associated with fast changes of activity within an interconnected fronto-parietal circuit ipsilateral to the brain stimulation. Specifically, an immediate reduction of connectivity with the premotor area is paralleled by an enhancement in the connectivity with the posterior parietal cortex (PPC) which is related to the strength of ownership illusion ratings and thus likely reflects conscious feelings of embodiment. Our results suggest that changes of bodily representations are underpinned by a dynamic cross talk within a highly-plastic, fronto-parietal network.SIGNIFICANCE STATEMENT Observing an avatar's body part from a first-person perspective (1PP) induces an illusory embodiment over it. What remains unknown are the cortical dynamics underpinning the embodiment of artificial agents. To shed light on the physiological mechanisms of embodiment we used a novel approach that combines noninvasive stimulation of the cortical motor-hand area and whole-scalp electroencephalographic (EEG) recordings in people observing an embodied artificial limb. We found that just before the illusion started, there is a decrease of activity of the motor-hand area accompanied by an increase of connectivity with the parietal region ipsilateral to the stimulation that reflects the ratings of the embodiment illusion. Our results suggest that changes of bodily representations are underpinned by a dynamic cross talk within a fronto-parietal circuit.


Characterization of developmentally regulated epitopes of Schistosoma mansoni egg glycoprotein antigens.
The chemical and antigenic composition of a major group of concanavalin A-binding glycoprotein antigens of Schistosoma mansoni eggs was examined by the use of monoclonal antibodies. The individual glycoproteins of this group each displayed a very wide range of apparent m.w. and had isoelectric points of less than 5 when analyzed by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. These glycoproteins could be chemically labeled with 125Iodine by two different methods and biosynthetically labeled with 35S-methionine during in vitro synthesis by isolated eggs. By using five monoclonal antibodies, the individual egg glycoproteins were shown to share several antigenic determinants when analyzed by radioimmunoprecipitation and solid-phase binding assays. These epitopes were present in a high level, and the degree of expression appeared to be developmentally regulated. In addition, Schistosoma haematobium and Schistosoma japonicum eggs contained antigenically related glycoprotein antigens. Preliminary evidence suggests that the epitopes involve carbohydrate moieties.


Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.
The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4361), and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein gene (p=2.43×10(-08)). Furthermore, three European loci for TGs (APOA5, GCKR and LPL), and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We used cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalised to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans. This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; used the interpopulation heterogeneity to significantly restrict three previously known European GWA signals, and surveyed whether the European lipid GWA SNPs extend to the Mexican population.


Can prolonged sick leave after gynecologic surgery be predicted? An observational study in The Netherlands.
Sick leave frequently has been used as an outcome to evaluate minimal invasive surgery compared with conventional open surgery. However, sick leave is determined not only by the surgical approach. Recently, a postoperative recovery-specific quality-of-life questionnaire, the Recovery Index (RI-10), has been developed and validated. This study investigated the relation of the Recovery Index 10, the RI-6 (a subset of 6 questions), and the type of surgery to sick leave. The study enrolled 46 patients with a paid job scheduled for elective gynecologic surgery, who filled out the RI-10. After 8 weeks, the patients were approached by telephone to give information on their return to work. Of the 46 patients, 23 (50%) returned to work completely after 8 weeks, 14 (30%) resumed work partly, and 9 (20%) did not resume work at all. In the analysis, the patients who completely returned to work were compared with those who did not return or partially returned. Recovery as expressed in the RI-6 improved with time after surgery. It appeared that the measurement 2 weeks after surgery showed the best discriminative capacity to predict sick leave after 8 weeks, with an area under the curve of 0.88 (confidence interval, 0.74-1.03). The subjective postoperative recovery as expressed by the RI-6 is more closely related to the type of surgery (p = 0.001) sick leave is (p = 0.14). The subjective recovery scored by the patient on a questionnaire of six questions is a better outcome than sick leave for evaluating surgical approaches. If administered 2 weeks after surgery, it may predict prolonged sick leave.


A novel X-linked combined immunodeficiency disease.
A novel X-linked combined immunodeficiency disease was found in five living males in an extended family in the United States. The age of the affected males ranged from 2.5 to 34 yr. The most prominent clinical abnormalities were a paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. The principal immunologic features of the disorder were normal concentrations of serum immunoglobulins but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes, particularly the CD45RA+ subpopulations; diminished proliferative responses of blood T cells to allogeneic cells, mitogens and antigens; and decreased production of IL-2 by mitogen stimulated blood lymphocytes. Thus, affected males in this family carry an abnormal gene on their X chromosome that results in a combined immunodeficiency that is distinct from previously reported disorders.


Gray Matter Surface based Spatial Statistics (GS-BSS) in Diffusion Microstructure.
Tract-based spatial statistics (TBSS) has proven to be a popular technique for performing voxel-wise statistical analysis that aims to improve sensitivity and interpretability of analysis of multi-subject diffusion imaging studies in white matter. With the advent of advanced diffusion MRI models - e.g., the neurite orientation dispersion density imaging (NODDI), it is of interest to analyze microstructural changes within gray matter (GM). A recent study has proposed using NODDI in gray matter based spatial statistics (N-GBSS) to perform voxel-wise statistical analysis on GM microstructure. N-GBSS adapts TBSS by skeletonizing the GM and projecting diffusion metrics to a cortical ribbon. In this study, we propose an alternate approach, known as gray matter surface based spatial statistics (GS-BSS), to perform statistical analysis using gray matter surfaces by incorporating established methods of registration techniques of GM surface segmentation on structural images. Diffusion microstructure features from NODDI and GM surfaces are transferred to standard space. All the surfaces are then projected onto a common GM surface non-linearly using diffeomorphic spectral matching on cortical surfaces. Prior post-mortem studies have shown reduced dendritic length in prefrontal cortex region in schizophrenia and bipolar disorder population. To validate the results, statistical tests are compared between GS-BSS and N-GBSS to study the differences between healthy and psychosis population. Significant results confirming the microstructural changes are presented. GS-BSS results show higher sensitivity to group differences between healthy and psychosis population in previously known regions.


Multidisciplinary treatment and long-term outcomes in six patients with leiomyosarcoma of the inferior vena cava.
Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare primary soft tissue sarcoma. Few reports have detailed the tumor features, treatment strategies, and long-term outcomes in IVC LMS patients. The present report describes the treatment and long-term outcomes of six patients with IVC LMS. We reviewed six consecutive cases of IVC LMS treated at the University of Ulsan College of Medicine, Asan Medical Center from August 1998 to June 2010. The patients comprised five females and one male, and had a median age of 44 years (range, 25 to 64 years). All tumors were suprarenal. The tumors were located between the hepatic and renal veins (i.e., middle segment; n = 5 [83%]), or above the hepatic veins (i.e., upper segment; n = 1 [17%]). Prosthetic IVC replacement using polytetrafluoroethylene grafts was performed in five patients, and the remaining patient underwent only tumor resection and IVC ligation. There were no intraoperative or postoperative deaths. The mean tumor size was 9.3 cm (range, 5 to 20 cm), and five of the six tumors were high grade. The mean follow-up period was 80 months (range, 6 to 118 months). The median survival period was 94 months. Recurrence occurred in all patients. Distant recurrence resulted in three patients undergoing lung resection and three patients undergoing thigh muscle resection. IVC LMS is a rare but serious disease. Although surgical resection combined with chemoradiotherapy was not completely curative, it resulted in long-term patient survival, even in patients with advanced tumors.


Making a Difference in Malawi and Zambia Through Health Education and Public Health Best Practices.
A 2-year U.S. Department of State-funded project* was conducted with the purpose of engaging health professionals from Malawi and Zambia who are actively involved in health care and health education for marginalized populations to develop, implement, and evaluate health education and public health interventions/programs. Twenty-six health professionals from Malawi and Zambia, referred to as Global Health Fellows, participated in the 2-year program, of which the main training component was conducted in the United States. Fellows were exposed to health education and public health best practices and developed an action plan to address a health problem of concern in their respective communities/countries. After completion of the program, Fellows received $300 to implement their action plans. Teams of Americans involved in the training program participated in follow-up visits to Malawi and Zambia to observe real-time progress on Fellows' respective action plans. The project was successful in creating an educational experience focused on health education best practices as well as implementation of action plans to address selected health problems in Malawi and Zambia.


Norine: A powerful resource for novel nonribosomal peptide discovery.
Since its first release in 2008, Norine remains the unique resource completely devoted to nonribosomal peptides (NRPs). They are very attractive microbial secondary metabolites, displaying a remarkable diversity of structure and functions. Norine (http://bioinfo.lifl.fr/NRP) includes a database now containing more than 1160 annotated peptides and user-friendly interfaces enabling the querying of the database, through the annotations or the structure of the peptides. Dedicated tools are associated for structural comparison of the compounds and prediction of their biological activities. In this paper, we start by describing the knowledgebase and the dedicated tools. We then present some user cases to show how useful Norine is for the discovery of novel nonribosomal peptides.


First record of Ae. albopictus (Skuse 1894), in Central African Republic.
SUMMARY METHODS: Mosquito aquatic stages were collected in domestic and peri-domestic areas, and epidemic risk indexes (Breteau, Container) were calculated for each prospected location. Adult female mosquitoes were captured by human landing catches, while larvae were sampled by inspecting artificial and natural breeding sites in randomly selected premises. Seventy-eight adults Aedes albopictus were collected in Bangui and Bayanga. Mosquito biting rate and abundance were, respectively, 0.33-1.70 bites/human/hour and 14.6% in Bangui and 0.04-0.16 and 0.4% in Bayanga. Larval sampling revealed a large diversity of water container harbouring the species in Bangui, Bayanga, Nola and Salo including unused containers, old tires, vehicle carcasses, buckets, barrels and stem of bamboo. The epidemic risk indices were erratic according to the location, ranging between 1.5-27.6 for Breteau and 1.3-47.1 for Container. This is the first record of Ae. albopictus in two bioclimatic zones of CAR This observation emphasizes the need to further investigate its potential impact on dengue and chikungunya viruses transmission regarding their recent emergencies in Africa (Côte d'Ivoire, Senegal, Mali, Somalia, Gabon, Cape Verde Islands).


RETRACTED: Curcumin restores Nrf2 levels and prevents quinolinic acid-induced neurotoxicity.
Neurological diseases comprise a group of heterogeneous disorders characterized by progressive brain dysfunction and cell death. In the next years, these diseases are expected to constitute a world-wide health problem. Because excitotoxicity and oxidative stress are involved in neurodegenerative diseases, it becomes relevant to describe pharmacological therapies designed to activate endogenous cytoprotective systems. Activation of transcription factor Nrf2 stimulates cytoprotective vitagenes involved in antioxidant defense. In this work, we investigated the ability of the antioxidant curcumin to induce transcription factor Nrf2 in a neurodegenerative model induced by quinolinic acid in rats. Animals were administered with curcumin (400 mg/kg, p.o.) for 10 days, and then intrastriatally infused with quinolinic acid (240 nmol) on day 10 of treatment. Curcumin prevented rotation behavior (6 days post-lesion), striatal morphological alterations (7 days post-lesion) and neurodegeneration (1 and 3 days post-lesion) induced by quinolinic acid. Curcumin also reduced quinolinic acid-induced oxidative stress (measured as protein carbonyl content) at 6 h post-lesion. The protective effects of curcumin were associated to its ability to prevent the quinolinic acid-induced decrease of striatal intra-nuclear Nrf2 levels (30 and 120 min post-lesion), and total superoxide dismutase and glutathione peroxidase activities (1 day post-lesion). Therefore, results of this study support the concept that neuroprotection induced by curcumin is associated with its ability to activate the Nrf2 cytoprotective pathway and to increase the total superoxide dismutase and glutathione peroxidase activities.


[Effect of patient education on neuroleptic treatment of young psychotic patients].
This study verifies the effect of the neuroleptic treatment teaching module, the French translation of the Medication Management Module produced by the social skills training programs. Twenty patients from an outpatient clinic (with schizophreniform or schizoaffective schizophrenia) were assigned at random to a test group (n = 10) or a control group (n = 10). The pre-test evaluation found that the two groups were the same with regard to 13 significant parameters. The experimenters used French translations of well-known instruments, and the double-blind method was applied to their respective observations throughout the study. Results were obtained by applying the neuroleptic treatment teaching module three hours per week for two to three months. The post-test evaluation revealed that patients who had been exposed to the education module had an improved understanding of schizophrenia and the medication required to treat it than patients who had not been exposed. The dose of medication prescribed between pre- and post-test evaluations were able to more effectively stabilize patients who had received education than patients who had not. Nevertheless, the education module continues to have no significant effect on the symptomatology (according to the Brief Psychiatric Rating Scale) and final SAS-II social scores of schizophrenics.


Semen culture, leukocytospermia, and the presence of sperm antibodies in seminal hyperviscosity.
Seminal hyperviscosity is generally thought to reveal genitourinary infection. The aim of the present work was to study this hypothesis. A total of 65 semen samples were obtained from males presenting for infertility screening. The samples were evaluated according to WHO criteria and microbiologically investigated, including culturing for Mycoplasma hominis and Ureaplasma urealyticum, and microscopic observation of Chlamydia trachomatis by a direct fluorescence assay. Determination of local antisperm antibodies was performed. Semen was categorized according to consistency: normal (n = 31) and high (n = 34). No difference was recorded either in the number of positive cultures, or in the number of species found in each sample. The number of white blood cells and the percentage of antibody-bound sperm showed no difference in the groups under study. There was no association between seminal hyperviscosity, positivity in semen cultures, number of species isolated in semen cultures, leukospermia, or presence of sperm antibodies. Further studies should be performed considering the evolution of the genital-infected patients to clarify the etiology of the hyperviscosity.


Rationale of the surgical treatment of carotid kinking.
Elongation and tortuosity of the internal carotid artery (ICAET) is a common angiographic, angioMR or Duplex scanning finding: it can be "pure" and, in a great majority of cases, it is not correlated to neurological symptoms. It can be associated with atherosclerotic bifurcation plaque, therefore in this case, indications to surgery follow that of carotid stenosis. On the other hand in some patients ICAET seems potentially correlated to hemispheric or non hemispheric symptoms: ICAET may show as kinking with a wide or narrow acute angle, single (< shaped) or double (Z shaped), or less frequently as a coiling (S,U, or C shaped). Surgical indications are controversial. In the author's opinion, surgery may represent the safest tool in the prevention of a stroke due to carotid occlusion, in selected patients. The aim of this study is to describe the author's experience in the surgical treatment of carotid kinking not associated with significant atherosclerotic lesions. From March 1994 to March 2001, 29 patients (11 male, 18 female) with a pure ICAET underwent surgery. Patients presented hemispheric symptoms (24.13%), non hemispheric symptoms (41.3%) or both (27.5 %). Two asymptomatic patients (6.9%) underwent surgery because of contralateral carotid occlusion. The postoperative (within 30 days from operation) results, no mortality was observed, 1 patient presented a stroke (3.4%), and 1 patient had a TIA at awakening (negative cerebral CT scan). All patients with hemispheric symptoms (15 patients) had complete remission, whereas only 6 out of 12 patients (50%) presenting non-hemispheric symptoms had remission (1 patient underwent a controlateral ICAET correction). The natural history of symptomatic and asymptomatic ICAET is practically unknown, but in some cases selected indication to surgery is justified. Surgery was indicated for patients with transient ischaemic attacks ( hemispheric symptoms); in asymptomatic patients presenting a kinking with an angle inferior to 30 degrees, and a contralateral carotid artery occlusion; in patients with non hemispheric symptoms, after a screening to exclude all other possible neurological or non-neurological causes with duplex scan positive for significant increase of flow velocity in ICA and positive cerebral CT scan or MR scan for ischaemic lesions in the homolateral hemisphere, and/or a flow inversion in anterior cerebral artery or flow reduction in the middle cerebral artery, according to different head positions (rotation and flex-extension).


The spatial genetic differentiation of the legume pod borer, Maruca vitrata F. (Lepidoptera: Crambidae) populations in West Africa.
The legume pod borer, Maruca vitrata, is an endemic insect pest that causes significant yield loss to the cowpea crop in West Africa. The application of population genetic tools is important in the management of insect pests but such data on M. vitrata is lacking. We applied a set of six microsatellite markers to assess the population structure of M. vitrata collected at five sites from Burkina Faso, Niger and Nigeria. Observed polymorphisms ranged from one (marker 3393) to eight (marker 32008) alleles per locus. Observed and expected heterozygosities ranged from 0.0 to 0.8 and 0.0 to 0.6, respectively. Three of the loci in samples from Nigeria and Burkina Faso deviated significantly from Hardy-Weinberg Equilibrium (HWE), whereas no loci deviated significantly in samples from Niger. Analysis of molecular variance (AMOVA) indicated that 67.3% level of the genetic variation was within individuals compared to 17.3% among populations. A global estimate of F ST=0.1 (ENA corrected F ST=0.1) was significant (P⩽0.05) and corroborated by pairwise F ST values that were significant among all possible comparisons. A significant correlation was predicted between genetic divergence and geographic distance between subpopulations (R2=0.6, P=0.04), and cluster analysis by the program STRUCTURE predicted that co-ancestry of genotypes were indicative of three distinct populations. The spatial genetic variance among M. vitrata in West Africa may be due to limited gene flow, south-north seasonal movement pattern or other reproductive barriers. This information is important for the cultural, chemical and biological control strategies for managing M. vitrata.


PHOTODYNAMIC THERAPY WITH VERTEPORFIN PLUS INTRAVITREAL BEVACIZUMAB FOR CIRCUMSCRIBED CHOROIDAL HEMANGIOMA: 4 YEARS OF FOLLOW-UP.
To report the anatomical and functional response of combined photodynamic therapy and intravitreal injection of bevacizumab in a patient with symptomatic circumscribed choroidal hemangioma. The patient received a single-session full-fluence photodynamic therapy immediately followed by an intravitreal injection of bevacizumab (1.25 mg/0.05 mL). One week after combined therapy, an improvement of best-corrected visual acuity from count fingers to 20/60 and a significant decrease in subretinal fluid were noted. One month later, we observed decreased leakage on fluorescein angiography in all phases of the study. Three months after treatment, the best-corrected visual acuity improved to 20/25 and spectral domain optical coherence tomography scans showed return to normal foveal architecture with no subretinal fluid and completely flat tumor. These findings were maintained during 4 years of follow-up. Combination therapy was associated with a rapid and persistent resolution of subretinal fluid, improvement of best-corrected visual acuity, and visual stability at 4 years of follow-up.


Interaction between cadmium and aromatic DNA adducts in hprt mutagenesis during foetal development.
The foetus is exposed to multiple xenobiotics through the mother's circulation and this is possibly involved in the development of diseases in later life. Heavy metals and lipophilic genotoxins in umbilical cord blood of newborns may have synergistic effects on mutagenesis in the hypoxanthine-phosphoribosyltransferase (HPRT) reporter gene. Concentrations of zinc (Zn), lead (Pb) and cadmium (Cd) were determined in the peripheral and cord blood of 16 non-smoking and 9 smoking healthy mothers by atomic absorption spectrometry. Lipophilic DNA adducts in lymphocytes were determined in the same subjects by 32P-postlabelling and the HPRT-variant frequency was assessed by the evaluation of 6-thioguanine resistant cells. Although the Cd/Zn ratio was 2.5-fold higher in the blood of smoking women than in non-smoking women (1.0 +/- 0.2 and 0.4 +/- 0.1, respectively, P = 0.007), this difference could not be observed in umbilical cord blood (0.3 +/- 0.1 and 0.3 +/- 0.1, respectively, P = 0.66). Similarly, mean DNA adduct levels were increased in the lymphocytes of smoking women compared with non-smoking controls (0.99 +/- 0.31 adducts/10(8) nt and 0.43 +/- 0.12, respectively, P = 0.009), but were only marginally higher in the neonates of smokers than in their non-smoking counterparts (0.57 +/- 0.29 and 0.24 +/- 0.09, respectively, P = 0.38). Since Cd is known to effectively inhibit DNA repair, we hypothesized that concomitant exposure of neonates to Cd and genotoxic compounds may result in an increased fixation of DNA damage into somatic mutations. Indeed, the number of HPRT-variants per adduct (i.e. the mutagenic efficiency of adducts) correlated positively with the Cd concentrations in cord blood (r = 0.61, P = 0.001). These data suggest a molecular link between DNA damage, inhibition of DNA repair by Cd and in vivo mutagenesis during foetal development. Thus, exposure to heavy metals may enhance the mutagenic potential of DNA-damaging compounds and results in biologically relevant genotoxic effects in neonates.


CT brain perfusion protocol to eliminate the need for selecting a venous output function.
In CTP, an arterial input function is used for cerebral blood volume measurement. AIFs are often influenced by partial volume effects resulting in overestimated CBV. A venous output function is manually selected to correct for partial volume. This can introduce variability. Our goal was to develop a CTP protocol that enables AIF selection unaffected by partial volume. First, the effects of partial volume on artery sizes/types including the MCA were estimated by using a CTP phantom with 9 protocols (section thicknesses of 1, 1.8, and 5 mm and image resolutions of 0.5, 1, and 1.5 mm). Next, these protocols were applied to clinical CTP studies from 6 patients. The influence of the partial volume effect was measured by comparison of the time-attenuation curves from different artery locations with reference veins. AIFs from MCAs were unaffected by partial volume effects when using high image resolution (1 mm) and medium section thickness (1.8 mm). For the clinical data, a total of 104 arteries and 60 veins was selected. The data confirmed that high image resolution and thin section thickness enable selection of MCAs for AIFs free of partial volume influences. In addition, we found that large veins were not insusceptible to partial volume effects relative to large arteries, questioning the use of veins for partial volume correction. A CTP protocol with 1.8-mm section thickness and 1-mm image resolution allows AIF selection unaffected by partial volume effects in MCAs.


Direct Health-Care Costs and Productivity Costs Associated With Hypoglycemia in Adults With Type 1 and Type 2 Diabetes Mellitus That Participated in the Canadian Hypoglycemia Assessment Tool Program.
There is a paucity of information concerning the cost of hypoglycemia events in Canadians with type 1 or type 2 diabetes. The objective of this study was to estimate the direct health-care costs and indirect costs associated with hypoglycemia based on a Canadian cohort of 498 patients from the global Hypoglycemia Assessment Tool (HAT) study. A costing model was developed to estimate the direct costs related to experiencing hypoglycemia by using health-care resources associated with hospital admissions and additional clinical appointments that were prospectively reported 1 month after baseline in the HAT study. Data collected retrospectively on work absenteeism in the year prior to baseline were used to estimate the indirect costs of hypoglycemia events. All costs were annualized and reported in 2016 Canadian dollars. Of the 403 patients with diabetes who experienced hypoglycemia events in the first month after baseline (81%), 10 (2.5%) patients required hospitalization or clinical appointments. Over 1 year, the mean direct health-care costs were estimated to be C$90,300 (C$1,777 per patient) for hospitalizations and C$14,695 (C$204 per person) for additional clinical appointments. Work absenteeism resulted in a total annual indirect cost of C$20,937 for time off due to sick leave (C$500 per patient), arriving late (C$187 per patient) or leaving work early (C$128 per patient). The annual direct and indirect costs of hypoglycemia events total C$125,932. The impact of hypoglycemia events on health-care resource utilization and work productivity leads to substantial direct and indirect costs in Canadian patients with diabetes.


Forward genetic screens identified mutants with defects in trap morphogenesis in the nematode-trapping fungus Arthrobotrys oligospora.
Nematode-trapping fungi (NTF) are carnivorous fungi that prey on nematodes under nutrient-poor conditions via specialized hyphae that function as traps. The molecular mechanisms involved in the interactions between NTF and their nematode prey are largely unknown. In this study, we conducted forward genetic screens to identify potential genes and pathways that are involved in trap morphogenesis and predation in the NTF Arthrobotrys oligospora. Using Ethyl methanesulfonate and UV as the mutagens, we generated 5552 randomly mutagenized A. oligospora strains and identified 15 mutants with strong defects in trap morphogenesis. Whole-genome sequencing and bioinformatic analyses revealed mutations in genes with roles in signaling, transcription or membrane transport that may contribute to the defects of trap morphogenesis in these mutants. We further conducted functional analyses on a candidate gene, YBP-1, and demonstrate that mutation of that gene was causative of the phenotypes observed in one of the mutants. The methods established in this study might provide helpful insights for establishing forward genetic screening methods for other non-model fungal species.


Stable inducible expression of a functional rat liver organic anion transport protein in HeLa cells.
Recently we expression cloned a rat liver organic anion transport protein in Xenopus laevis oocytes (Jacquemin, E. Hagenbuch, B, Stieger, B., Wolkoff, A.W., and Meier, P.J.,(1994) Proc. Natl. Acad. Sci. U.S.A. 91, 133-137). In the present study, we have stably transfected the cDNA encoding this protein into HeLa cells by using a vector containing a zinc-inducible promoter. The parent cells have virtually no baseline transport of [35S]sulfobromophthalein, whereas the induced transfected cells express a novel 74-kDa protein and avidly transport this ligand. Transport by these cells is saturable (Km = 3.3 microM, Vmax = 257 pmol/min/mg protein), bidirectional, and highly temperature-dependent. In the presence of albumin, uptake of [35S]sulfobromophthalein requires the presence of extracellular Cl, whereas in the absence of albumin, this C1- dependence is not seen. These studies indicate that cellular uptake of sulfobromophthalein does not result from direct interaction with the plasma membrane lipid bilayer but rather requires the presence of a specific plasma membrane transporter.


FGF1 and insulin control lipolysis by convergent pathways.
Inexorable increases in insulin resistance, lipolysis, and hepatic glucose production (HGP) are hallmarks of type 2 diabetes. Previously, we showed that peripheral delivery of exogenous fibroblast growth factor 1 (FGF1) has robust anti-diabetic effects mediated by the adipose FGF receptor (FGFR) 1. However, its mechanism of action is not known. Here, we report that FGF1 acutely lowers HGP by suppressing adipose lipolysis. On a molecular level, FGF1 inhibits the cAMP-protein kinase A axis by activating phosphodiesterase 4D (PDE4D), which separates it mechanistically from the inhibitory actions of insulin via PDE3B. We identify Ser44 as an FGF1-induced regulatory phosphorylation site in PDE4D that is modulated by the feed-fast cycle. These findings establish the FGF1/PDE4 pathway as an alternate regulator of the adipose-HGP axis and identify FGF1 as an unrecognized regulator of fatty acid homeostasis.


[Cysticercus tenuicollis infection in a goat farm].
An outbreak of acute cysticercosis occurred in six female goats 2-4 years old and three 50 days old kids from a goat farm in northern Italy. Goats were usually recovered in stable with an outdoor paddock. Post-mortem examination showed a massive infection of Taenia hydatigena larvae in the liver, lungs and on the peritoneum. All recovered Cysticercus tenuicollis were at immature stage.


Changing bacteriology of adult community-acquired lung abscess in Taiwan: Klebsiella pneumoniae versus anaerobes.
Most literature regarding lung abscess focuses on anaerobic bacterial lung abscess, and aerobic gram-negative bacillary infection is less frequently discussed. This study was conducted to investigate the bacteriology of community-acquired lung abscess and to improve the empirical therapeutic strategy for adults with community-acquired lung abscess. We reviewed and analyzed data on 90 consecutive adult cases of bacteriologically confirmed community-acquired lung abscess treated during 1995-2003 at a tertiary university hospital in Taiwan. We found that a high proportion (21%) of cases of lung abscess were due to Klebsiella pneumoniae infection, which differs from the findings of previous studies. Lung abscess due to K. pneumoniae was associated with underlying diabetes mellitus (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.0-18.4; P = .039) and negatively correlated with a time from onset of symptoms to diagnosis of >30 days (OR, 0.2; 95% CI, 0.1-0.7; P = .008). A higher percentage of patients with K. pneumoniae lung abscess had concomitant bacteremia (OR, 9.4; 95% CI, 1.1-81.9; P = .032), delayed defervesence (OR, 9.2; 95% CI, 1.8-47.8; P = .004), and multiple cavities noted on radiographs (OR, 11.0; 95% CI, 1.3-94.9; P = .015), compared with patients with anaerobic bacterial lung abscess. The rate of nonsusceptibility to clindamycin and penicillin among anaerobes and Streptococcus milleri group isolates increased. K. pneumoniae has become a more common cause of lung abscess than before, and a high proportion of anaerobes and S. milleri strains have become resistant to penicillin and clindamycin. A beta-lactam/beta-lactamase inhibitor or second- or third-generation cephalosporin with clindamycin or metronidazole is suggested as empirical antibiotic therapy for community-acquired lung abscess.


Association of Fluoroquinolone Prescribing Rates With Black Box Warnings from the US Food and Drug Administration.
In 2013 and 2016, the US Food and Drug Administration (FDA) issued warnings and recommended limited use of fluoroquinolones for patients with certain acute conditions. It is not clear how prescribers have responded to these warnings. To analyze changes in prescribing of fluoroquinolones after the 2013 and 2016 FDA warnings and to examine the physician characteristics associated with these changes. This cross-sectional study used Medicare administrative claims data on Medicare fee-for-service beneficiaries and OneKey data on physicians and their organizations from January 1, 2011, to December 31, 2017. The sample was restricted to outpatient visits for sinusitis, bronchitis, and uncomplicated urinary tract infections. An interrupted time series approach was used to analyze the changes in the prescription rate after each FDA warning. Data analysis was performed between January 1, 2011, and December 31, 2017. Two FDA black box warnings released in August 2013 and July 2016. The main outcome was an indicator for fluoroquinolone prescriptions in 3 periods: before the 2013 warning (baseline period), after the 2013 warning but before the 2016 warning (postwarning period 1), and after the 2016 warning (postwarning period 2). The sample comprised 1 238 397 unique patients with a total of 2 720 071 outpatient acute care visits. Of this sample, 848 360 were women (68.5%), and the mean (SD) age was 69.7 (12.6) years. The immediate prescribing levels of fluoroquinolones in postwarning period 1 increased by 3.42 percentage points (95% CI, 3.23-3.62; P < .001) and declined by -0.77 percentage points (95% CI, -1.00 to -0.54; P < .001) in postwarning period 2. The prescribing trend increased by 0.08 percentage points per month (95% CI, 0.08-0.10; P < .001) in postwarning period 1 and 0.06 percentage points per month (95% CI, 0.04-0.08; P < .001) in postwarning period 2. In postwarning period 1, the prescribing levels for physicians who were affiliated with hospitals with a top 10th percentile case mix index vs those without such affiliation decreased by -1.13 percentage points (95% CI, -1.92 to -0.34; P = .005), whereas the levels for primary care physicians declined by -1.34 percentage points (95% CI, -1.78 to -0.88; P < .001) compared with non-primary care physicians in postwarning period 2. Physicians at teaching hospitals were the only ones who showed a decline in prescribing trend in postwarning period 1. This cross-sectional study found an overall decline in prescribing of fluoroquinolones after the release of FDA warnings. Understanding the association of physician and organizational characteristics with fluoroquinolone prescribing behavior may ultimately help to identify mechanisms to improve de-adoption.


Degradation of cardiac troponin I: implication for reliable immunodetection.
We have analyzed by different immunological methods the proteolytic degradation of cardiac troponin I (cTnI) in human necrotic tissue and in serum. cTnI is susceptible to proteolysis, and its degradation leads to the appearance of a wide diversity of proteolytic peptides with different stabilities. N- and C-terminal regions were rapidly cleaved by proteases, whereas the fragment located between residues 30 and 110 demonstrated substantially higher stability, possibly because of its protection by TnC. We conclude that antibodies selected for cTnI sandwich immunoassays should preferentially recognize epitopes located in the region resistant to proteolysis. Such an approach can be helpful for a much needed standardization of cTnI immunoassays and can improve the sensitivity and reproducibility of cTnI assays.


Future trends in contraceptive prevalence and method mix in the developing world.
This study reviews existing methodologies for projecting future trends in contraception, evaluates the validity of the assumptions underlying these projections, proposes methodological improvements, and assesses the prospects for new methods of contraception in the coming decade. Demand for contraception can be expected to continue to rise rapidly for the next few decades as populations continue to grow and fertility declines to approach replacement level. As a result of these trends, the number of contraceptive users in the developing world is expected to rise from 549 to 816 million during the next 25 years, according to the most recent UN projection. An examination of the projection methodology found it to be reasonable. Projecting the future distribution of specific contraceptive methods is more difficult. Method choice is affected by trends in several factors, including access to different methods, user characteristics, and technology. The procedure employed by the Futures Group to project method mix was found to be less than optimally designed, and a new methodology is, therefore, proposed.


Upregulation of Interleukin-33 in obstructive renal injury.
Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneys using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases.


Facilitating prelinguistic communication skills in young children with developmental delay.
Very little research has focused on the development and evaluation of intervention strategies designed to facilitate the acquisition of prelinguistic communication skills. We conducted two experiments to determine the effects of a milieu teaching approach on the acquisition and generalization of specific prelinguistic communication skills. In the first experiment, we utilized this intervention approach within a multiple baseline design to teach prelinguistic requesting, commenting, and vocal imitation to a single subject with Down syndrome and language delay. The results indicated that the intervention approach was effective at facilitating the child's use of these skills within the treatment setting. Therefore, in the second experiment we conducted a more comprehensive analysis of this approach with 4 subjects with mental retardation. Three of these subjects were taught to request, and 1 subject was taught both to request and to comment. The effects were experimentally evaluated with multiple baseline across subjects design. The results indicated that the intervention was effective in eliciting the intervention targets within the training setting for all 4 subjects. All 4 subjects showed evidence of generalization across stimulus materials, setting, teachers, and interaction style. There was also evidence of reciprocal effects on how classroom teachers in the generalization setting interacted with the subjects as a result of changes in the child's communication behavior.


Botulinum toxin for temporary corneal protection after surgery for vestibular schwannoma.
High-grade postoperative facial nerve paresis after surgery for vestibular schwannoma with insufficient eye closure involves a risk for severe ocular complications. When conservative measurements are not sufficient, conventional invasive treatments include tarsorrhaphy and eyelid loading. In this study, injection of botulinum toxin into the levator palpebrae muscle was investigated as an alternative for temporary iatrogenic eye closure. Injection of botulinum toxin was indicated by an interdisciplinary decision (neurosurgery and ophthalmology) in patients with a postoperative facial nerve paresis corresponding to a House-Brackmann Grade of IV or greater and documented abnormalities concerning corneal status such as keratopathia or conjunctival redness. Twenty-five IUs of botulinum toxin were injected transcutaneously and transconjunctivally. Six of 11 patients with high-grade paresis showed abnormal corneal findings in the early postoperative period. In 4 of these patients, botulinum toxin was injected; 1 patient declined the treatment, and in 1 patient it was not performed because of contralateral blindness. Temporary eye closure was achieved for 2 to 6 months in all cases. In all cases, facial nerve function had recovered sufficiently in terms of eye closure when the effect of botulinum toxin subsided. The application of botulinum toxin for temporary iatrogenic eye closure is an excellent low-risk and temporary alternative to other invasive measures for the treatment of postoperative high-grade facial nerve paresis when the facial nerve is anatomically intact.


Epidemiology of Recurrent Anterior Cruciate Ligament Injuries in National Collegiate Athletic Association Sports: The Injury Surveillance Program, 2004-2014.
An anterior cruciate ligament (ACL) rupture is a serious injury that can be career-ending in collegiate athletics. A rerupture after primary ACL reconstruction occurs in 1% to 11% of all athletes. To describe the epidemiology of recurrent ACL ruptures in the 25 National Collegiate Athletic Association (NCAA) sports in the NCAA Injury Surveillance Program (ISP) and to identify and compare sport-specific risk factors for a recurrent ACL rupture. Descriptive epidemiology study. Athletes who experienced a primary or recurrent ACL rupture between 2004 and 2014 were identified using data from the NCAA ISP. ACL ruptures occurred in 12 of 25 sports during the study period. We assessed the rates and patterns of primary and recurrent ACL ruptures and reported them as events per 10,000 athlete-exposures (AEs). Sex-comparable sports were compared using rate ratios. Rupture rates were compared using odds ratios, with P values <.05 indicating significance. Regular-season and postseason data were combined because of low counts of postseason events. Of 350,416 AEs, there were 1105 ACL ruptures, 126 of which were recurrent. The highest rates of recurrent ACL ruptures (per 10,000 AEs) were among male football players (15), female gymnasts (8.2), and female soccer players (5.2). Of sports played by athletes of both sexes, women's soccer had a significantly higher rate of recurrent ACL ruptures than men's soccer (rate ratio, 3.8 [95% CI, 1.3-15]). Among all sports, men had a significantly higher rate of recurrent ACL ruptures (4.3) than women (3.0) (P = .04). Overall, the ratio of recurrent to primary ACL ruptures decreased over the 10-year study period. Both women and men had a decreasing trend of recurrent to primary ACL ruptures, although women had a steeper decrease. These data can help identify athletes who are most at risk of recurrent ACL ruptures after ACL reconstruction and who may benefit from injury prevention programs.


Synergy-inducing chemokines enhance CCR2 ligand activities on monocytes.
The migration of monocytes to sites of inflammation is largely determined by their response to chemokines. Although the chemokine specificities and expression patterns of chemokine receptors are well defined, it is still a matter of debate how cells integrate the messages provided by different chemokines that are concomitantly produced in physiological or pathological situations in vivo. We present evidence for one regulatory mechanism of human monocyte trafficking. Monocytes can integrate stimuli provided by inflammatory chemokines in the presence of homeostatic chemokines. In particular, migration and cell responses could occur at much lower concentrations of the CCR2 agonists, in the presence of chemokines (CCL19 and CCL21) that per se do not act on monocytes. Binding studies on CCR2(+) cells showed that CCL19 and CCL21 do not compete with the CCR2 agonist CCL2. Furthermore, the presence of CCL19 or CCL21 could influence the degradation of CCL2 and CCL7 on cells expressing the decoy receptor D6. These findings disclose a new scenario to further comprehend the complexity of chemokine-based monocyte trafficking in a vast variety of human inflammatory disorders.


Use of ultra-performance liquid chromatography/time-of-flight mass spectrometry with nozzle-skimmer fragmentation for comprehensive quantitative analysis of secondary metabolites in Arabidopsis thaliana.
This study sought to develop techniques for LC/MS-based metabolomics and to verify that an MS/MS spectral tag (MS2T) could be used in practical secondary metabolite profiling. The retention time (RT), precursor ions, and fragment ions generated by nozzle-skimmer fragmentation were determined using ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) and compared with the MS2T. A standard mix was analyzed with UPLC/TOF-MS under the same conditions as were used to construct the MS2T. The difference in RT for the standards was less than 0.15 min and the average RSD was about 2.8%, suggesting that the analysis was highly repeatable. Both precursor ions and fragment ions were observed when the cone voltage was 75 V. Experimental data and fragmentation pattern in the MS2T annotation list were highly similar. Wild-type and cas-1 mutant Arabidopsis thaliana samples treated with an elicitor were analyzed using UPLC/TOF-MS. Sixty-five peaks were successfully annotated. Fragment ions were observed with nozzle-skimmer fragmentation in 50 of 65 (77%) peaks. The reliability of annotation may have increased as a result of fragment ions. Results of multivariate analysis suggested that cas-1 was related to induction of the biosynthesis of these flavonoids. The devised method facilitated practical secondary metabolite profiling.


Molecular identification and characterization of Tcmago and TcY14 in Taiwania (Taiwania cryptomerioides).
Mago nashi (Mago) and Y14 proteins are highly conserved among eukaryotes, and not only play important roles in oogenesis, embryogenesis and germ-line determination during animal development, but also participate in mRNA localization and splicing in cell growth. We identified mago (Tcmago) and Y14 (TcY14) homologues derived from expressed sequence tags of Taiwania cryptomerioides Hayata seedlings. Tcmago and TcY14 contain coding regions encoding 149 and 216 amino acids, respectively. Multiple amino acid sequence alignments as well as secondary and tertiary structure all predicted that TcMago and TcY14 possessed similar protein structures to the crystal structures of Drosophila melanogaster and human Mago and Y14 proteins. We demonstrated by yeast two-hybrid analysis and a GST pull-down assay that TcMago and TcY14 interacted in vivo and in vitro, confirming structural predictions of their interaction. TcMago and TcY14 were predominately localized in the nucleus. Whole mount in situ hybridization and immunolocalization showed that Tcmago and TcY14 were both detected in root hairs at the levels of transcription and protein expression. Overexpression of Tcmago in transgenic tobacco plants resulted in longer roots and a more complex root system. TcMago and TcY14 may have cellular functions similar to the Mago and Y14 proteins in animals and may be involved in root development in plants.


Effects of metabolic state on the regulation of melanocortin circuits.
Dysfunction in neurophysiological systems that regulate food intake and metabolism are at least partly responsible for obesity and related comorbidities. An important component of this process is the hypothalamic melanocortin system, where an imbalance can result in severe obesity and deficits in glucose metabolism. Exercise offers many health benefits related to cardiovascular improvements, hunger control, and blood glucose homeostasis. However, the molecular mechanism underlying the exercise-induced improvements to the melanocortin system remain undefined. Here, we review the role of the melanocortin system to sense hormonal, nutrient, and neuronal signals of energy status. This information is then relayed onto secondary neurons in order to regulate physiological parameters, which promote proper energy and glucose balance. We also provide an overview on the effects of physical exercise to induce biophysical changes in the melanocortin circuit which may regulate food intake, glucose metabolism and improve overall metabolic health.


A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature.
How receptor acquisition correlates with the functional maturation of natural killer (NK) cells is poorly understood. We used quantitative real-time polymerase chain reaction (PCR) assays to compare NKG2 and killer immunoglobulin-like receptor (KIR) gene expression in NK cells from allogeneic transplant recipients and their donors. Marked differences were observed in the NK subsets of recipients who had 8-fold more CD56(bright) cells, diminished KIR expression (except 2DL4), and increased NKG2A. In normal blood not all CD56(dim) cells express KIR, and a novel subpopulation of cells committed to the NK-cell lineage was defined. These cells, which comprise 19.4% +/- 2.8% of the CD56(dim) NK population in healthy donors, express the activating NKG2D and NKG2E receptors but no KIR or NKG2A. Although the CD56(dim) NKG2A(-) KIR(-) NK cells lack "at least one" inhibitory receptor for autologous MHC class I, they are not fully responsive, but rather functionally immature cells with poor cytotoxicity and IFN-gamma production. Upon culture with IL-15 and a stromal cell line, CD56(dim) and CD56(bright) KIR(-) NK cells proliferate, express KIR, and develop cytotoxicity and cytokine-producing potential. These findings have implications for the function of NK cells reconstituting after transplantation and support a model for in vivo development in which CD56(bright) cells precede CD56(dim) cells.


Pleural and pulmonary involvement in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease with a multisystem involvement. The clinical manifestations of this disease include an erythematous rash, oral ulcers, polyarthralgia, nonerosive arthritis, polyserositis, hematologic, renal, neurologic, pulmonary and cardiac abnormalties. The involvement of the respiratory system is frequent. Pleuro-pulmonary manifestations are present in almost half of the patients during the disease course and may be the presenting symptoms in 4-5% of patients with SLE. Complications directly associated to the disease include pleuritis with or without pleural effusion, alveolitis, interstitial lung disease, lupus pneumonitis, pulmonary hemorrhage, pulmonary arterial hypertension, and pulmonary thromboembolic disease. Complications due to secondary causes include pleuro-pulmonary manifestations of cardiac and renal failure, atelectasis due to diaphragmatic dysfunction, opportunistic pneumonia, and drug toxicity. The prevalence, clinical presentation, prognosis and response to treatment vary, depending on the pattern of involvement. As with other connective tissue diseases, early and specific therapeutic intervention may be indicated for many of these pleuro-pulmonary manifestations.


How video image size interacts with evidence strength, defendant emotion, and the defendant-victim relationship to alter perceptions of the defendant.
Courtroom video presentations can range from images on small screens installed in the jury box to images on courtroom video monitors or projection screens. Does video image size affect jurors' perceptions of information presented during trials? To investigate this we manipulated video image size as well as defendant emotion level presented during testimony (low, moderate), the defendant-victim relationship (spouses, strangers), and the strength of the evidence (weak, strong). Participants (N=263) read a case and trial summary, watched video of defendant testimony, and then answered a questionnaire. Larger screens generally accentuated what was presented (e.g., made stronger evidence seem stronger and weaker evidence seem weaker), acting mainly upon trial outcome variables (e.g., verdict). Non-trial outcomes (e.g., defendant credibility) were generally affected by defendant emotion level and the defendant-victim relationship. Researchers and attorneys presenting video images need to recognize that respondents may evaluate videotaped trial evidence differently as a function of how video evidence is presented.