Work-related carpal tunnel syndrome treatment: a cross-sectional study among 106 patients.
The objective is to assess the influence of sociodemographic, professional and clinical variables on the choice of treatment of work-related carpal tunnel syndrome (CTS). An exhaustive and trans-sectional study was conducted over a period of eight years, from 1st January 2006 to 31 December 2013 in the Department of Occupational Medicine at University Hospital of Mahdia, Tunisia. The study population was represented by patients with work-related carpal tunnel syndrome. Data collection was based on a questionnaire sheet, describing social, occupational and medical characteristics of patients. The study population was characterized by a large female dominance, representing 95.3% with an average age of 42±7.8 years. Patients medically treated represented 38.7% and 61.3% had had surgical treatment. After binary logistic regression, surgical indication of CTS was significantly correlated to diabetes (p=0.017), other musculoskeletal disorders (p=0.02), functional signs of CTS (acrocyanosis p=0.05; muscle weakness p=0.015; radiating pain p=0.01; painful discomfort of the hand, the forearm or arm p=0.027) and to the atrophy of thenar muscles (p=0.018). According to this study, the choice of therapy for occupational CTS depends only on clinical data. More detailed studies will be needed to refine these results.


Cyclophilins A and B oppositely regulate renal tubular epithelial cell phenotype.
Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial-mesenchymal transition (pEMT), proliferation, and further redifferentiation into specialized tubule epithelial cells (TECs). Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase (PPIase) activity of cyclophilin (Cyp) proteins, we hypothesized that cyclophilins could regulate TEC phenotype. Here we demonstrate that in cultured TECs, CypA silencing triggers loss of epithelial features and enhances transforming growth factor β (TGFβ)-induced EMT in association with upregulation of epithelial repressors Slug and Snail. This pro-epithelial action of CypA relies on its PPIase activity. By contrast, CypB emerges as an epithelial repressor, because CypB silencing promotes epithelial differentiation, prevents TGFβ-induced EMT, and induces tubular structures in 3D cultures. In addition, in the kidneys of CypB knockout mice subjected to unilateral ureteral obstruction, inflammatory and pro-fibrotic events were attenuated. CypB silencing/knockout leads to Slug, but not Snail, downregulation. CypB support of Slug expression depends on its endoplasmic reticulum location, where it interacts with calreticulin, a calcium-buffering chaperone related to Slug expression. As CypB silencing reduces ionomycin-induced calcium release and Slug upregulation, we suggest that Slug expression may rely on CypB modulation of calreticulin-dependent calcium signaling. In conclusion, this work uncovers new roles for CypA and CypB in modulating TEC plasticity and identifies CypB as a druggable target potentially relevant in promoting kidney repair.


Microbial succession in an inflated lunar/Mars analog habitat during a 30-day human occupation.
For potential future human missions to the Moon or Mars and sustained presence in the International Space Station, a safe enclosed habitat environment for astronauts is required. Potential microbial contamination of closed habitats presents a risk for crewmembers due to reduced human immune response during long-term confinement. To make future habitat designs safer for crewmembers, lessons learned from characterizing analogous habitats is very critical. One of the key issues is that how human presence influences the accumulation of microorganisms in the closed habitat. Molecular technologies, along with traditional microbiological methods, were utilized to catalog microbial succession during a 30-day human occupation of a simulated inflatable lunar/Mars habitat. Surface samples were collected at different time points to capture the complete spectrum of viable and potential opportunistic pathogenic bacterial population. Traditional cultivation, propidium monoazide (PMA)-quantitative polymerase chain reaction (qPCR), and adenosine triphosphate (ATP) assays were employed to estimate the cultivable, viable, and metabolically active microbial population, respectively. Next-generation sequencing was used to elucidate the microbial dynamics and community profiles at different locations of the habitat during varying time points. Statistical analyses confirm that occupation time has a strong influence on bacterial community profiles. The Day 0 samples (before human occupation) have a very different microbial diversity compared to the later three time points. Members of Proteobacteria (esp. Oxalobacteraceae and Caulobacteraceae) and Firmicutes (esp. Bacillaceae) were most abundant before human occupation (Day 0), while other members of Firmicutes (Clostridiales) and Actinobacteria (esp. Corynebacteriaceae) were abundant during the 30-day occupation. Treatment of samples with PMA (a DNA-intercalating dye for selective detection of viable microbial population) had a significant effect on the microbial diversity compared to non-PMA-treated samples. Statistical analyses revealed a significant difference in community structure of samples over time, particularly of the bacteriomes existing before human occupation of the habitat (Day 0 sampling) and after occupation (Day 13, Day 20, and Day 30 samplings). Actinobacteria (mainly Corynebacteriaceae) and Firmicutes (mainly Clostridiales Incertae Sedis XI and Staphylococcaceae) were shown to increase over the occupation time period. The results of this study revealed a strong relationship between human presence and succession of microbial diversity in a closed habitat. Consequently, it is necessary to develop methods and tools for effective maintenance of a closed system to enable safe human habitation in enclosed environments on Earth and beyond.


Heparanase expression upregulates platelet adhesion activity and thrombogenicity.
Heparanase is an endo-glucuronidase that specifically cleaves heparan sulfate (HS) and heparin polysaccharides. The enzyme is expressed at low levels in normal tissues, but is often upregulated under pathological conditions such as cancer and inflammation. Normal human platelets express exceptionally high levels of heparanase, but the functional consequences of this feature remain unknown. We investigated functional roles of heparanase by comparing the properties of platelets expressing high (Hpa-tg) or low (Ctr) levels of heparanase. Upon activation, Hpa-tg platelets exhibited a much stronger adhesion activity as compared to Ctr platelets, likely contributing to a higher thrombotic activity in a carotid thrombosis model. Furthermore, we found concomitant upregulated expression of both heparanase and CD62P (P-selectin) upon activation of mouse and human platelets. As platelets play important roles in tumor metastasis, these findings indicate contribution of the platelet heparanase to hyper-thrombotic conditions often seen in patients with metastatic cancer.


Factor V Leiden mutation-related chronic skin ulcers.
Chronic skin ulcers require extensive, systemic differential diagnosis; thus, they are difficult to diagnose and treat. Transient or persistent hypercoagulable states are among the rare causes of skin ulcers. Here, we present the case of a 27-year-old woman patient with recurrent, nonhealing skin ulcers of 8 years' duration, who had been treated unsuccessfully with various medications under different diagnoses at different clinics. On admission, a skin biopsy demonstrated occlusive vasculopathy, and the search for an inherited hypercoagulable state revealed a heterozygous factor V Leiden mutation. The patient was treated with anticoagulants and hyperbaric oxygen. On treatment, the skin lesions healed and did not recur.


Peptide nucleic acids harness dual information codes in a single molecule.
Nature encodes the information required for life in two fundamental biopolymers: nucleic acids and proteins. Peptide nucleic acid (PNA), a synthetic analog comprised of nucleobases arrayed along a pseudopeptide backbone, has the ability to combine the power of nucleic acids to encode information with the versatility of amino acids to encode structure and function. Historically, PNA has been perceived as a simple nucleic acid mimic having desirable properties such as high biostability and strong affinity for complementary nucleic acids. In this feature article, we aim to adjust this perception by highlighting the ability of PNA to act as a peptide mimic and showing the largely untapped potential to encode information in the amino acid sequence. First, we provide an introduction to PNA and discuss the use of conjugation to impart tunable properties to the biopolymer. Next, we describe the integration of functional groups directly into the PNA backbone to impart specific physical properties. Lastly, we highlight the use of these integrated amino acid side chains to encode peptide-like sequences in the PNA backbone, imparting novel activity and function and demonstrating the ability of PNA to simultaneously mimic both a peptide and a nucleic acid.


Design of a Small-Molecule Drug Conjugate for Prostate Cancer Targeted Theranostics.
Targeted therapy has become an effective strategy of precision medicine for cancer treatment. Based on the success of antibody-drug conjugates (ADCs), here we report a theranostic design of small-molecule drug conjugates (T-SMDCs) for targeted imaging and chemotherapy of prostate cancer. The structure of T-SMDCs built upon a polyethylene glycol (PEG) scaffold consists of (i) a chelating moiety for positron emission tomography (PET) imaging when labeled with (68)Ga, a positron-emitting radioisotope; (ii) a prostate specific membrane antigen (PSMA) specific ligand for prostate cancer targeting; and (iii) a cytotoxic drug (DM1) for chemotherapy. For proof-of-concept, such a T-SMDC, NO3A-DM1-Lys-Urea-Glu, was synthesized and evaluated. The chemical modification of Lys-Urea-Glu for the construction of the conjugate did not compromise its specific binding affinity to PSMA. The PSMA-mediated internalization of (68)Ga-labeled NO3A-DM1-Lys-Urea-Glu displayed a time-dependent manner, allowing the desired drug delivery and release within tumor cells. The antiproliferative activity of the T-SMDC showed a positive correlation with the PSMA expression level. Small animal PET imaging with (68)Ga-labeled NO3A-DM1-Lys-Urea-Glu exhibited significantly higher uptake (p < 0.01) in the PSMA positive PC3-PIP tumors (4.30 ± 0.20%ID/g) at 1 h postinjection than in the PSMA negative PC3-Flu tumors (1.12 ± 0.42%ID/g). Taken together, we have successfully designed and synthesized a T-SMDC system for prostate cancer targeted imaging and therapy.


Compassion-based interventions for people with long-term physical conditions: a mixed methods systematic review.
Compassion-based interventions show promise in enhancing well-being and reducing distress, but little is known about their applications for people with long-term physical conditions. This study explores compassion-based interventions for this population: what are their differing elements (content, structure, tailoring, use of technology), feasibility and acceptability, effects and experienced benefits? A mixed-methods systematic review was conducted. Four bibliographic databases were searched without study design restrictions. Meta-synthesis was used to integrate quantitative results of effects and qualitative results of experienced benefits. Twenty studies met the inclusion criteria. Most studies targeted people with cancer or persistent pain. Interventions were either comprehensive with 6-12 face-to-face sessions, or brief based on a single compassion exercise. Feasibility and accessibility were highly rated by participants. Amongst a plethora of outcomes, reductions in depression and anxiety were the most common findings. Our qualitative synthesis yielded experienced benefits of (1) acceptance of the condition; (2) improved emotion regulation skills; (3) reduced feelings of isolation. There was minimal overlap between quantitative and qualitative outcomes. While the field is still in its infancy, this review highlights the potential benefits of compassion-based interventions for people with long-term physical conditions and discusses recommendations for further intervention research and development.


Characterization of the plant-specific BREVIS RADIX gene family reveals limited genetic redundancy despite high sequence conservation.
To date, the function of most genes in the Arabidopsis (Arabidopsis thaliana) genome is unknown. Here we present the first analysis of the novel, plant-specific BRX (BREVIS RADIX) gene family. BRX has been identified as a modulator of root growth through a naturally occurring loss-of-function allele. The biochemical function of BRX is enigmatic, however several domains in BRX are conserved in the proteins encoded by the related BRX-like (BRXL) genes. The similarity between Arabidopsis BRXL proteins within these domains ranges from 84% to 93%. Nevertheless, analysis of brx brx-like multiple mutants indicates that functional redundancy of BRXLs is limited. This results mainly from differences in protein activity, as demonstrated by assaying the propensity of constitutively expressed BRXL cDNAs to rescue the brx phenotype. Among the genes tested, only BRXL1 can replace BRX in this assay. Nevertheless, BRXL1 does not act redundantly with BRX in vivo, presumably because it is expressed at a much lower level than BRX. BRX and BRXL1 similarity is most pronounced in a characteristic tandem repeat domain, which we named BRX domain. One copy of this domain is also present in the PRAF (PH, RCC1, and FYVE)-like family proteins. The BRX domain mediates homotypic and heterotypic interactions within and between the BRX and PRAF protein families in yeast (Saccharomyces cerevisiae), and therefore likely represents a novel protein-protein interaction domain. The importance of this domain for BRX activity in planta is underscored by our finding that expression of the C-terminal fragment of BRX, comprising the two BRX domains, is largely sufficient to rescue the brx phenotype.


Comparative Molecular Dynamics Study on Tri-n-butyl Phosphate in Organic and Aqueous Environments and Its Relevance to Nuclear Extraction Processes.
A refined model for tri-n-butyl phosphate (TBP), which uses a new set of partial charges generated from our ab initio density functional theory calculations, has been proposed in this study. Molecular dynamics simulations are conducted to determine the thermodynamic properties, transport properties, and the microscopic structures of liquid TBP, TBP/water mixtures, and TBP/n-alkane mixtures. These results are compared with those obtained from four other TBP models, previously described in the literature. We conclude that our refined TBP model appears to be the only TBP model from this set that, with reasonable accuracy, can simultaneously predict the properties of TBP in bulk TBP, in organic diluents, and in aqueous solution. The other models only work well for two of the three systems mentioned above. This new TBP model is thus appropriate for the simulation of liquid-liquid extraction systems in the nuclear extraction process, where one needs to simultaneously model TBP in both aqueous and organic phases. It is also promising for the investigation of the microscopic structure of the organic phase in these processes and for the characterization of third-phase formation, where TBP again interacts simultaneously with both polar and nonpolar molecules. Because the proposed TBP model uses OPLS-2005 Lennard-Jones parameters, it may be used with confidence to model mixtures of TBP with other species whose parameters are given by the OPLS-2005 force field.


Prevalence and correlates of being overweight or obese in college.
Recent statistics indicate that over one-third of college students are currently overweight or obese, however, the impact of weight in this population from academic and psychiatric perspectives is not fully understood. This study sought to examine the prevalence of overweight and obesity in college students and its association with stress, mental health disorders and academic achievement. A total of 1765 students completed the College Student Computer User Survey (CSCUS) online at a large Midwestern United States University. Responders were classified by weight as normal, overweight or obese based on body mass index. Data were stratified by sex, with cross-tabulation and t-tests, one-way analysis of variance, and logistic regression for analysis. A total of 492 (27.9%) students were overweight (20.2%; range 25.01-29.98) or obese (7.7%; range 30.04-71.26). Overweight and obesity were associated with significantly lower overall academic achievement, more depressive symptoms, and using diet pills for weight loss. Obese males had significantly higher rates of lifetime trichotillomania while overweight and obese females reported higher rates of panic disorder. Higher educational institutions should be aware of the significant burden associated with overweight and obesity in students, and of the differing demographic and clinical associations between overweight or obesity in men and women.


Frequency of peripherally inserted central catheter complications in children.
This study examined the frequency and types of complications with peripherally inserted central catheters (PICCs) placed in immunocompetent pediatric patients for parenteral antimicrobial therapy. It also sought to determine risk factors associated with those complications. Complications occurred at a frequency of 19.3/1000 PICC days, and greater than 30% of PICCs developed at least one complication. Risk factors for complication include double-lumen PICCs, PICCs placed in the femoral vein, younger age, and greater number of daily doses.


Stenotrophomonas maltophilia: an emerging global opportunistic pathogen.
Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa. Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed.


Downregulation of Choline Kinase-Alpha Enhances Autophagy in Tamoxifen-Resistant Breast Cancer Cells.
Choline kinase-α (Chk-α) and autophagy have gained much attention, as they relate to the drug-resistance of breast cancer. Here, we explored the potential connection between Chk-α and autophagy in the mechanisms driving to tamoxifen (TAM) resistance, in estrogen receptor positive (ER+) breast cancer cells (BCCs). Human BCC lines (MCF-7 and TAM-resistant MCF-7 (MCF-7/TAM) cells) were used. Chk-α expression and activity was suppressed by the transduction of shRNA (shChk-α) with lentivirus and treatment with CK37, a Chk-α inhibitor. MCF-7/TAM cells had higher Chk-α expression and phosphocholine levels than MCF-7 cells. A specific downregulation of Chk-α by the transduction of shChk-α exhibited a significant decrease in phosphocholine levels in MCF-7 and MCF-7/TAM cells. The autophagy-related protein, cleaved microtubule-associated protein light chain 3 (LC3) and autophagosome-like structures were significantly increased in shChk-α-transduced or CK37-treated MCF-7 and MCF-7/TAM cells. The downregulation of Chk-α attenuated the phosphorylation of AKT, ERK1/2, and mTOR in both MCF-7 and MCF-7/TAM cells. In MCF-7 cells, the downregulation of Chk-α resulted in an induction of autophagy, a decreased proliferation ability and an activation of caspase-3. In MCF-7/TAM cells, despite a significant decrease in proliferation ability and an increase in the percentage of cells in the G0/G1 phase of the cell cycle, the downregulation of Chk-α did not induced caspase-dependent cell death and further enhanced autophagy and G0/G1 phase arrest. An autophagy inhibitor, methyladenine (3-MA) induced death and attenuated the level of elevated LC3 in MCF-7/TAM cells. Elucidating the interplay between choline metabolism and autophagy will provide unique opportunities to identify new therapeutic targets and develop novel treatment strategies that preferentially target TAM-resistance.


Age differences in personal values: Universal or cultural specific?
Prior studies on value development across adulthood have generally shown that as people age, they espouse communal values more strongly and agentic values less strongly. Two studies investigated whether these age differences in personal values might differ according to cultural values. Study 1 examined whether these age differences in personal values, and their associations with subjective well-being, showed the same pattern across countries that differed in individualism-collectivism. Study 2 compared age differences in personal values in the Canadian culture that emphasized agentic values more and the Chinese culture that emphasized communal values more. Personal and cultural values of each individual were directly measured, and their congruence were calculated and compared across age and cultures. Findings revealed that across cultures, older people had lower endorsement of agentic personal values and higher endorsement of communal personal values than did younger people. These age differences, and their associations with subjective well-being, were generally not influenced by cultural values. (PsycINFO Database Record


Neuropsychological test performance and cognitive reserve in healthy aging and the Alzheimer's disease spectrum: a theoretically driven factor analysis.
Accurate measurement of cognitive function is critical for understanding the disease course of Alzheimer's disease (AD). Detecting cognitive change over time can be confounded by level of premorbid intellectual function or cognitive reserve and lead to under- or over-diagnosis of cognitive impairment and AD. Statistical models of cognitive performance that include cognitive reserve can improve sensitivity to change and clinical efficacy. We used confirmatory factor analysis to test a four-factor model composed of memory/language, processing speed/executive function, attention, and cognitive reserve factors in a group of cognitively healthy older adults and a group of participants along the spectrum of amnestic mild cognitive impairment to AD (aMCI-AD). The model showed excellent fit for the control group (χ(2) = 100; df = 78; CFI = .962; RMSEA = .049) and adequate fit for the aMCI-AD group (χ(2) = 1750; df = 78; CFI = .932; RMSEA = .085). Although strict invariance criteria were not met, invariance testing to determine if factor structures are similar across groups yielded acceptable absolute model fits and provide evidence in support of configural, metric, and scalar invariance. These results provide further support for the construct validity of cognitive reserve in healthy and memory impaired older adults.


Melatonin receptors MT1 and MT2 are expressed in spermatozoa from several seasonal and nonseasonal breeder species.
Melatonin is a ubiquitous and multipurpose molecule, and one of its roles is to regulate reproduction in some seasonal mammals. Our group has previously reported the variation in the melatonin levels in ram seminal plasma along the year and identified MT1 and MT2 receptors in ram spermatozoa. The objective of this study was to elucidate whether the presence of melatonin receptors (MT1 and MT2) in the sperm plasma membrane, and melatonin in the seminal plasma is related to seasonal breeding. For this purpose, the presence of melatonin receptors and the levels of melatonin in seminal plasma have been examined in several species: donkey and stallion as long-day breeders; red deer as a wild, short-day, highly seasonal breeder (epididymal spermatozoa); bull as a conventional nonseasonal breeder; boar as a seasonal breeder under management techniques; and dog as possible a seasonal breeder not regulated by melatonin. We have detected measurable levels of melatonin in the seminal plasma of all ejaculated semen samples (from donkey, stallion, boar, bull, and dog). Also, and for the first time, we have demonstrated the presence of MT1 and MT2 melatonin receptors in the spermatozoa of all these species, regardless their type of reproduction or sperm source (ejaculated or epididymal), using indirect immunofluorescence techniques and Western blotting. Our findings suggest that melatonin and melatonin receptors may be universally distributed in the reproductive system of mammals and that the sperm melatonin receptors cells may not be necessarily related with seasonal reproduction. Furthermore, the presence of MT1 at the cytoplasmic droplet in immature ejaculated stallion spermatozoa found in one sample and epididymal red deer spermatozoa suggests that melatonin may be involved in specific functions during spermatogenesis and sperm maturation, like protecting spermatozoa from oxidative damage, this activity being mediated through these receptors.


Glucose-6-phosphate dehydrogenase deficiency and borderline deficiency: association with neonatal hyperbilirubinemia.
To characterize the occurrence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its association with neonatal hyperbilirubinemia. This study involved an evaluation of G6PD data for 2656 newborns from a universal newborn screening program. Mean G6PD activity was 14.2 ± 3.3 U/g Hb. Some 2.71% of the newborns were G6PD-deficient, and 1.77% had borderline G6PD activity, with male and female predominance, respectively. G6PD deficiency was more prevalent in newborns of Sephardic Jew and Muslim Arab backgrounds. The infants with G6PD deficiency had higher bilirubin levels at the time of discharge from the nursery. Infants with low and borderline G6PD activity were more likely to require phototherapy (22.2% and 25.5%, respectively, vs 7.6% of infants with normal G6PD activity; P < .005) and to have more referrals for exacerbation of jaundice (15.3% and 14.9%, respectively, vs 6.1%; P < .005). Mean G6PD activity was higher in preterm infants born at 27-34 weeks gestational age compared with those born later (16.3 ± 1.8 U/g Hb vs 14.8 ± 2.0 U/g Hb). Based on sex distribution and theoretical genetic calculations for the rate of heterozygous females, we propose that the range of borderline G6PD activity should be 2-10 U/g Hb rather than the currently accepted range of 2-7 U/g Hb. There is association between G6PD deficiency and significant neonatal hyperbilirubinemia. Increased risk is also associated with borderline G6PD activity. The suggested new range for borderline G6PD activity should enhance the identification of females at risk. G6PD activity is higher in preterm infants.


Correlation of C2 fractures and vertebral artery injury.
Retrospective review of prospectively collected data. Vertebral artery injuries (VAI) occur commonly after cervical spine trauma. No study has yet examined the association between VAI and specific variants of C2 fractures. To evaluate the incidence of VAI (as defined by magnetic resonance imaging/angiography [MRI/A]) in subtypes of C2 fractures. To define the association between the incidence, morphology, and severity of C2 fractures, based on fracture angulation and comminution, and the occurrence of VAI. Patients admitted to the hospital with C2 fractures between October 2006 and December 2008 to a tertiary care referral center were identified through a prospectively maintained database. Computed tomography (CT) and MRI/A studies were individually reviewed to evaluate the specific C2 fracture type and the occurrence of VAI. Fracture displacement and angulation were measured. Incidence of VAI was compared between different types and subtypes of C2 fractures. The effects of displacement and angulation of the fracture, morphology of foramen transversarium fracture, patient age, and patient gender on VAI were also analyzed. One hundred one patients were identified with C2 fractures that met inclusion criteria, and 18 (17.8%) had VAI by MRI/A. There was no correlation between fracture types and VAI. However, in subtype analysis, there was a correlation of VAI with traumatic spondylolisthesis of axis (TSA) and greater degree of angulation (P = 0.0023), communition fracture (P = 0.0341), and presence of bone fragment(s) within the foramen transversarium (P = 0.0075). Multivariate logistic regression indicated that age, gender and the presence of fragments within foramen transversarium were associated with greater risk of VAI. Vertebral artery injuries are more likely to occur in C2 fractures with comminuted fractures involving the foramen transversarium, with fractures manifesting bony fragment(s) within the foramen transversarium, or with fractures having greater angulation. These risk factors should be considered when a patient presents with isolated axis fracture.


The effect of lactation length on greenhouse gas emissions from the national dairy herd.
Many governments have signed up to greenhouse gas emission (GHGE) reduction programmes under their national climate change obligations. Recently, it has been suggested that the use of extended lactations in dairy herds could result in reduced GHGE. Dairy GHGE were modelled on a national basis and the model was used to compare emissions from lactations of three different lengths (305, 370 and 440 days), and a current 'base' scenario on the basis of maintaining current milk production levels. In addition to comparing GHGE from the average 'National Herd' under these scenarios, results were used to investigate how accounting for lactations of different lengths might alter the estimation of emissions calculated from the National Inventory methodology currently recommended by Intergovernmental Panel on Climate Change. Data for the three lactation length scenarios were derived from nationally recorded dairy performance information and used in the GHGE model. Long lactations required fewer milking cows and replacements to maintain current milk yield levels than short ones, but GHGEs were found to rise from 1214 t of CO2 equivalent (CE)/farm per year for lactations of 305 days to 1371 t CE/farm per year for 440-day lactations. This apparent anomaly can be explained by the less efficient milk production (kg milk produced per kg cow weight) found in later lactation, a more pronounced effect in longer lactations. The sensitivity of the model to changes in replacement rate, persistency and level of milk yield was investigated. Changes in the replacement rate from 25% to 20% and in persistency by −10% to +20% resulted in very small changes in GHGE. Differences in GHGE due to the level of milk yield were much more dramatic with animals in the top 10% for yield, producing about 25% less GHGE/year than the average animal. National Inventory results were investigated using a more realistic spread of lactation lengths than recommended for such calculations using emissions calculated in the first part of the study. Current UK emission calculations based on the National Inventory were 329 Gg of methane per year from the dairy herd. Using the national distribution of lactation lengths, this was found to be an underestimate by about 10%. This work showed that the current rise in lactation length or a move towards calving every 18 months would increase GHGE by 7% to 14% compared with the current scenario, assuming the same milk yield in all models. Increased milk yield would have a much greater effect on reducing GHGE than changes to lactation length, replacement rate or persistency. National Inventory methodology appears to underestimate GHGE when the distribution of lactation lengths is considered and may need revising to provide more realistic figures.


A cell-based high-throughput screening assay for posttranscriptional utrophin upregulation.
Duchenne muscular dystrophy (DMD) is a devastating muscle-wasting disease caused by mutations in the dystrophin gene. Utrophin is a homologue of dystrophin that can compensate for its absence when overexpressed in DMD animal models. Utrophin upregulation is therefore a promising therapeutic approach for DMD. Utrophin is regulated at both transcriptional and posttranscriptional levels. Transcriptional regulation has been studied extensively, and assays have been described for the identification of utrophin promoter-targeting molecules. However, despite the profound impact that posttranscriptional regulation has on utrophin expression, screening assays have not yet been described that could be used to discover pharmaceuticals targeting this key phase of regulation. We describe the development and validation of a muscle cell line-based assay in which a stably expressed luciferase coding sequence is flanked by the utrophin 5'- and 3'-untranslated regions (UTRs). The assay was validated using the posttranscriptional regulation of utrophin by miR-206. The assay has a Z' of 0.7, indicating robust performance in high-throughput format. This assay can be used to study utrophin regulatory mechanisms or to screen chemical libraries for compounds that upregulate utrophin posttranscriptionally via its UTRs. Compounds identified via this assay, used alone or in a synergistic combination with utrophin promoter-targeting molecules, would be predicted to have therapeutic potential for DMD.


miR-375 maintains normal pancreatic alpha- and beta-cell mass.
Altered growth and development of the endocrine pancreas is a frequent cause of the hyperglycemia associated with diabetes. Here we show that microRNA-375 (miR-375), which is highly expressed in pancreatic islets, is required for normal glucose homeostasis. Mice lacking miR-375 (375KO) are hyperglycemic, exhibit increased total pancreatic alpha-cell numbers, fasting and fed plasma glucagon levels, and increased gluconeogenesis and hepatic glucose output. Furthermore, pancreatic beta-cell mass is decreased in 375KO mice as a result of impaired proliferation. In contrast, pancreatic islets of obese mice (ob/ob), a model of increased beta-cell mass, exhibit increased expression of miR-375. Genetic deletion of miR-375 from these animals (375/ob) profoundly diminished the proliferative capacity of the endocrine pancreas and resulted in a severely diabetic state. Bioinformatic analysis of transcript data from 375KO islets revealed that miR-375 regulates a cluster of genes controlling cellular growth and proliferation. These data provide evidence that miR-375 is essential for normal glucose homeostasis, alpha- and beta-cell turnover, and adaptive beta-cell expansion in response to increasing insulin demand in insulin resistance.


Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column.
To evaluate the efficacy of tiludronate for the treatment of horses with signs of pain associated with lesions of the thoracolumbar vertebral column. 29 horses with clinical manifestations of pain associated with lesions of the thoracolumbar vertebral column and abnormal radiographic findings indicative of osteoarthritis of the articular processes-synovial intervertebral joints. Horses were initially examined in accordance with a standardized protocol, which included radiographic, ultrasonographic, and scintigraphic examinations. Fifteen horses were randomly assigned to receive tiludronate (1 mg/kg, IV, as a slow-rate infusion), and 14 horses received a control substance (day 0). Horses were monitored for the subsequent 120 days. Clinical evaluations were performed on days 60 and 120. Horses that had no evidence of clinical improvement on day 60 were administered tiludronate. Statistical analyses were performed to compare efficacy at day 60, improvement of dorsal flexibility at day 120, and dorsal flexibility before and 60 days after administration of tiludronate. Horses treated with tiludronate had significant improvement in dorsal flexibility between days 0 and 60, compared with control horses. Clinical improvement in dorsal flexibility was still evident at day 120. The percentage of positive responses was higher in the tiludronate group at 60 days. Tiludronate had efficacy in the treatment of horses with signs of pain induced by osteoarticular lesions of the thoracolumbar vertebral column, causing a significant improvement in dorsal flexibility. Tiludronate may offer a treatment option for the management of horses with intervertebral lesions and the associated pain.


High spatial resolution (1.1 μm and 20 nm) FTIR polarization contrast imaging reveals pre-rupture disorder in damaged tendon.
Collagen is a major constituent in many life forms; in mammals, collagen appears as a component of skin, bone, tendon and cartilage, where it performs critical functions. Vibrational spectroscopy methods are excellent for studying the structure and function of collagen-containing tissues, as they provide molecular insight into composition and organization. The latter is particularly important for collagenous materials, given that a key feature is their hierarchical, oriented structure, organized from molecular to macroscopic length scales. Here, we present the first results of high-resolution FTIR polarization contrast imaging, at 1.1 μm and 20 nm scales, on control and mechanically damaged tendon. The spectroscopic data are supported with parallel SEM and correlated AFM imaging. Our goal is to explore the changes induced in tendon after the application of damaging mechanical stress, and the consequences for the healing processes. The results and possibilities for the application of these high-spatial-resolution FTIR techniques in spectral pathology, and eventually in clinical applications, are discussed.


Hempseed Lignanamides Rich-Fraction: Chemical Investigation and Cytotoxicity towards U-87 Glioblastoma Cells.
The weak but noteworthy presence of (poly)phenols in hemp seeds has been long overshadowed by the essential polyunsaturated fatty acids and digestible proteins, considered responsible for their high nutritional benefits. Instead, lignanamides and their biosynthetic precursors, phenylamides, seem to display interesting and diverse biological activities only partially clarified in the last decades. Herein, negative mode HR-MS/MS techniques were applied to the chemical investigation of a (poly)phenol-rich fraction, obtained from hemp seeds after extraction/fractionation steps. This extract contained phenylpropanoid amides and their random oxidative coupling derivatives, lignanamides, which were the most abundant compounds and showed a high chemical diversity, deeply unraveled through high resolution tandem mass spectrometry (HR-MS/MS) tools. The effect of different doses of the lignanamides-rich extract (LnHS) on U-87 glioblastoma cell line and non-tumorigenic human fibroblasts was evaluated. Thus, cell proliferation, genomic DNA damage, colony forming and wound repair capabilities were assessed, as well as LnHS outcome on the expression levels of pro-inflammatory cytokines. LnHS significantly inhibited U-87 cancer cell proliferation, but not that of fibroblasts, and was able to reduce U-87 cell migration, inducing further DNA damage. No modification in cytokines' expression level was found. Data acquired suggested that LnHS acted in U-87 cells by inducing the apoptosis machinery and suppressing the autophagic cell death.


Planned neck dissection following chemoradiotherapy for advanced head and neck cancer: is it necessary for all?
In the absence of large-scale randomized trials evaluating dissection versus observation of the involved neck after neoadjuvant chemoradiotherapy, there is a need to collect data that will either support or ultimately refute a role for planned posttreatment neck dissection. A significant percentage of patients with extensive (N2 or N3) neck disease who demonstrate a complete response to chemoradiation therapy may harbor residual occult metastases, and identification of this subset of patients remains a clinical challenge. Because surgical salvage rates are greatly diminished when occult nodal disease becomes clinically manifest, planned posttreatment neck dissection is advocated but may not be necessary in all patients. The role of positron emission tomography chemoradiotherapy (PET-CT) in this scenario remains unproven but holds promise in being able to identify which patients may be harboring residual disease in the neck after chemoradiotherapy. The implementation of as yet unidentified molecular tumor markers in combination with PET-CT may ultimately prove to be effective in identifying patients who will best benefit from posttherapy neck dissection. Correlation of imaging results and pathologic node status will be important in determining the accuracy and, therefore, the value of this imaging modality for predicting the presence or absence of residual disease.


Prevalence of obstructive sleep apnea in Asian adults: a systematic review of the literature.
Obstructive sleep apnea (OSA) is a common disease, affecting approximately 2% of women and 4% of men residing in Western communities. No systematically reviewed data are available about the prevalence of this disease in Asia, the most heavily populated continent. PubMed/Medline, Scopus and Google Scholar were searched for articles published from 1993 to May 2012 that reported the prevalence of OSA diagnosed via sleep monitoring and the prevalence of patients at risk for OSA as assessed by symptomatology and/or sleep questionnaires. We have also searched abstract database of major pulmonary and sleep scientific societies for relevant abstracts presented from 2010 to 2012. The following inclusion criteria were used: articles published in English, age ≥ 18 years, ≥ 100 participants in studies using sleep monitoring for the diagnosis of OSA, ≥ 300 participants in studies using questionnaires to detect patients at high risk for OSA. duplicate publications, studies reporting the prevalence of central sleep apnea only, hospital based studies as well as studies assessing OSA prevalence among patients with resistant arterial hypertension, chronic kidney disease, heart failure and in patients with concomitant neurological disease. Twenty four articles were found to meet the inclusion criteria, covering 47,957 subjects (26,042 men and 21,915 women) and four relevant abstracts were noted. OSA prevalence ranged from 3.7% to 97.3%. Male gender, older age, a higher BMI and waist to hip ratio, greater neck circumference, arterial hypertension, smoking, snoring and daytime sleepiness were associated with OSA. Sample size, difference between the populations studied and the fact that some works included patients with a high pre-test probability of OSA explain the difference in prevalence rates. This systematic review highlights the lack of data regarding the prevalence of OSA in Asians. Only a few studies provide an approximate estimate of the OSA burden in some Asian communities.


Blood pressure change in Africa: case study from Nigeria.
Studies of migrants and comparisons of rural versus urban communities are potentially informative study designs because they allow examination of genetically similar population subgroups exposed to diverse environmental conditions. These designs have been underused in Africa, where recent urbanization has created many situations in which nearby communities of common ethnicity and culture live under different social and economic circumstances. The International Study of Hypertension in Blacks (ICSHIB) conducted several overlapping surveys in Nigeria starting in 1993. These surveys were based primarily in the rural village of Idere and the urban community of Idikan, both inhabited by people defined ethnically as Oyo Yoruba and sharing a common language and culture. Survey teams collected standardized blood pressure and anthropometric measurements, and some study participants provided 24-hr urine samples and questionnaire data on psychosocial stress and social integration. Rural and urban groups differed substantially in blood pressure and related characteristics. Age-adjusted prevalence of hypertension (blood pressure > or = 140/90 mm Hg) for participants aged 25 years and older was 7-8% in Idere and 24-27% in Idikan. The distributions of overweight, sodium/potassium ratio, perceived stress, and social integration scores all contributed to lower hypertension risk in Idere. The effects and interactions of these identified risk factors remain poorly understood, even among people who share a common genetic background, similar diet, and many other lifestyle features. Nonetheless, the rural-urban distinction is sufficiently salient to engender a nearly threefold difference in hypertension prevalence. This disparity in disease prevalence demonstrates the sensitivity of human beings to the environmental determinants of disease and provides a sobering example of the difficulty in identifying subtle genetic effects, which can be easily overwhelmed by small differences in environmental exposures.


Tailoring the coupling between localized and propagating surface plasmons: realizing Fano-like interference and high-performance sensor.
Surface plasmon modes originated from various metallic nanostructures possess unique features of strong nanoscale light confinement and enhancement with tunable energy, which make them attractive and promising for a variety of applications such as sensing, solar cell, and lasing. Here, we have investigated the interaction between localized and propagating surface plasmons in a structure consisting of a gold nanobar array and a thick gold film, separated by a silica dielectric spacer layer. It is found that the reflection spectrum of the designed plasmonic structure can be readily tailored by changing the gold nanobar size, array period and the spacer layer thickness. Moreover, the strong coupling between the localized and propagating modes can result in an anticrossing behavior and even induce a Fano-like asymmetric lineshape. Importantly, the sensitivity and the figure of merit (FoM) of this plasmonic system can reach as high as 936 nm/RIU and 112, respectively. Our study offers a new, simple, efficient and controllable way to design the plasmonic systems with desired modes coupling and spectral lineshapes for different applications.


Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: adrenocortical and pituitary glucocorticoid responsiveness.
Long-term ingestion of alcohol produces marked alterations in hypothalamic-pituitary-adrenal axis activity. The authors engaged in a series of studies to determine the distinct role of the hypothalamus and the pituitary and adrenal glands in the disturbances observed in abstinent alcohol-dependent subjects. In this first of a two-part study, the authors report on (1) the basal secretory profile of corticotropin and cortisol from 2000 to 0800 hrs, (2) adrenocortical sensitivity in both the presence and absence of endogenous pituitary activation, and (3) pituitary glucocorticoid sensitivity to dexamethasone. Eleven male, 4 to 6 weeks abstinent, alcohol-only-dependent subjects and 10 age-matched male healthy controls were studied. Basal circulating concentrations of corticotropin and cortisol were obtained from 2000 to 0800 hr. A submaximal dose of cosyntropin (0.01 microg/kg), a corticotropin analogue was then administered to assess adrenocortical sensitivity. In a separate session, cosyntropin was administered following high-dose dexamethasone (8 mg iv) to assess adrenocortical sensitivity in the relative absence of endogenous corticotropin. In addition, the corticotropin response to dexamethasone was measured to determine pituitary glucocorticoid responsiveness. Cortisol, but not corticotropin, pulse amplitude (p < 0.05) and mean concentration (p= 0.05) was significantly lower in alcohol-dependent subjects compared with controls. The cortisol response to cosyntropin was lower in alcohol-dependent subjects following endogenous corticotropin suppression by high-dose dexamethasone (p <0.04) but not without dexamethasone pretreatment. Mean corticotropin (p <0.004) and cortisol (p <0.05) concentrations in response to dexamethasone were attenuated in the patients compared to controls. Basal concentrations of 11-deoxycortisol, the precursor to cortisol, were also decreased in alcohol-dependent subjects (p <0.05). Attenuated basal and stimulated adrenocortical concentrations in abstinent alcohol-dependent men are coupled with a nonhomeostatic increase in pituitary glucocorticoid inhibition. A decrease in stress-axis responsivity in alcohol dependence may have implications for treatment outcome.


Development and representation of a fall-injury risk assessment instrument in a clinical information system.
The potential for informatics solutions to address inpatient safety issues is significant; however, several challenges are associated with the development of patient safety related informatics applications. These challenges include: 1) the identification and/or development of valid and reliable instruments; 2) adequate representation of key safety concepts, constructs, and associated concepts in the clinical information system; and 3) identification of data sources for instrument pre-population. As part of a larger project aimed at identifying and addressing the information needs of clinicians while using a clinical information system, an electronic fall and injury risk assessment instrument is in development to address a hospital-based fall and injury prevention initiative. The concepts contained in the instrument are well represented by Clinical LOINC and the UMLS. Associated concepts have been identified in the existing clinical information system data dictionary for pre-population of the instrument.


Effect of metformin on ovulation and reproductive outcomes in women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials.
To evaluate the effect of MET on ovulation and reproductive outcomes in patients with polycystic ovary syndrome. Meta-analysis of available data from randomized controlled trials that examined the ovulation, pregnancy and live birth rate after the administration of clomiphene citrate (CC) or MET alone or combined. The ovulation rate was found to be higher in the group treated with MET combined with clomiphene citrate (CC) than only with CC, odds ratio (OR): 1.27, 95 % confidence interval (95 % CI) (1.03-1.56), while the pregnancy and live birth rate showed no significant difference between the two groups, OR: 1.19, 95 % CI (0.99-1.42) and OR: 0.99, 95 % CI (0.84-1.17), respectively. The MET + CC group produced a higher ovulation and pregnancy rate than MET group, OR: 2.10, 95 % CI (1.89-2.34) and OR: 2.08, 95 % CI (1.55-2.80), respectively, while between two groups the live birth rate showed no significant difference, OR: 1.50, 95 % CI (0.75-3.00). The ovulation rate was lower in MET than in CC group, OR: 0.65, 95 % CI (0.43-0.995), while between the two groups the pregnancy and live birth rate showed no significant difference, OR: 0.86, 95 % CI (0.42-1.74) and OR: 0.89, 95 % CI (0.71-1.13). The current study indicated that combination of MET and CC could gain advantage over a single administration in the ovulation induction and pregnancy rate.


Liver Metastases in Prostate Carcinoma Represent a Relatively Aggressive Subtype Refractory to Hormonal Therapy and Short-Duration Response to Docetaxel Monotherapy.
We report a single institution's experience from a small series of patients suggesting that liver metastasis in metastatic castration-refractory prostate cancer (mCRPC) represents a relatively aggressive subtype that is refractory to hormonal manipulation treatment, including luteinizing hormone-releasing hormone agonist (LA) and abiraterone (Ab) therapy, although docetaxel is briefly effective. Between 2007 and 2013, six patients with prostate cancer with liver metastases were analyzed. Biochemical response was defined as > 50% decrease in prostate-specific antigen (PSA) value. Two patients who presented with liver metastases died in less than 3 months after LA therapy. Two out of three patients (one died while receiving chemotherapy) received Ab after chemotherapy did not show any response and died while on therapy. One patient who presented with lung metastases initially received LA therapy and progressed on it with liver metastases in < 6 months. Thus, five of six patients did not respond to hormone therapy including LA and Ab. Three patients who received docetaxel after LA therapy had more than 50% objective PSA response with a mean survival of 4 months. No literature addresses the response to hormone treatment in hepatic metastasis in prostate carcinoma. This small series suggests that liver metastases in prostate carcinoma represent a relatively aggressive subset against which hormonal therapy, including the LA and Ab, appears to be ineffective. Although our patients responded to docetaxel chemotherapy, their responses were of short duration. A further clinical trial involving more patients will be necessary to substantiate our findings.


Cytosolic DNA Sensing Promotes Macrophage Transformation and Governs Myocardial Ischemic Injury.
Myocardium irreversibly injured by ischemic stress must be efficiently repaired to maintain tissue integrity and contractile performance. Macrophages play critical roles in this process. These cells transform across a spectrum of phenotypes to accomplish diverse functions ranging from mediating the initial inflammatory responses that clear damaged tissue to subsequent reparative functions that help rebuild replacement tissue. Although macrophage transformation is crucial to myocardial repair, events governing this transformation are poorly understood. Here, we set out to determine whether innate immune responses triggered by cytoplasmic DNA play a role. We report that ischemic myocardial injury, along with the resulting release of nucleic acids, activates the recently described cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Animals lacking cyclic GMP-AMP synthase display significantly improved early survival after myocardial infarction and diminished pathological remodeling, including ventricular rupture, enhanced angiogenesis, and preserved ventricular contractile function. Furthermore, cyclic GMP-AMP synthase loss of function abolishes the induction of key inflammatory programs such as inducible nitric oxide synthase and promotes the transformation of macrophages to a reparative phenotype, which results in enhanced repair and improved hemodynamic performance. These results reveal, for the first time, that the cytosolic DNA receptor cyclic GMP-AMP synthase functions during cardiac ischemia as a pattern recognition receptor in the sterile immune response. Furthermore, we report that this pathway governs macrophage transformation, thereby regulating postinjury cardiac repair. Because modulators of this pathway are currently in clinical use, our findings raise the prospect of new treatment options to combat ischemic heart disease and its progression to heart failure.


Psychotherapy research, the recovery movement and practice-based evidence in psychiatric rehabilitation.
This article reviews the literature on psychotherapy outcome research and discusses the relationship between those findings and the tenets of the consumer-driven recovery model. The research provides compelling evidence for practitioners to abandon the current emphasis on diagnosis and theory, model, and technique in favor of a partnership with clients that leverages the common factors and places emphasis on the alliance. Empirical support of the shortcomings of evidence-based practices is provided. Use of outcome and alliance feedback to inform the work and shift to practice-based evidence is offered as a practice that is informed by the research and honors the recovery model's call for consumer-driven mental health services.


Concurrent analysis of white matter bundles and grey matter networks in the chimpanzee.
Understanding the phylogeny of the human brain requires an appreciation of brain organization of our closest animal relatives. Neuroimaging tools such as magnetic resonance imaging (MRI) allow us to study whole-brain organization in species which can otherwise not be studied. Here, we used diffusion MRI to reconstruct the connections of the cortical hemispheres of the chimpanzee. This allowed us to perform an exploratory analysis of the grey matter structures of the chimpanzee cerebral cortex and their underlying white matter connectivity profiles. We identified a number of networks that strongly resemble those found in other primates, including the corticospinal system, limbic connections through the cingulum bundle and fornix, and occipital-temporal and temporal-frontal systems. Notably, chimpanzee temporal cortex showed a strong resemblance to that of the human brain, providing some insight into the specialization of the two species' shared lineage.


Gender Effects in a Multischool Alcohol Media Literacy Study With Preadolescents.
Alcohol media literacy (AML) programs have achieved positive results for alcohol prevention; however, gender may moderate program effectiveness. This study investigated gender differences for an Australian AML intervention. Fifth and sixth graders ( N = 165), allocated to an intervention or wait-list control group, participated in an AML program. Student questionnaires were administered at three time points. The intervention resulted in significantly higher media deconstruction skills but did not lead to less preference for branded merchandise or greater understanding of persuasive intent, and these effects did not differ by gender. Gender differences were present in social norms for drinking and alcohol expectancies. AML education likely has appeal and benefit to both genders as it connects with students' lifeworlds. Social norms may be more difficult to shift for males due to a more ingrained drinking culture. Future research could explore contextual factors responsible for gender differences.


The lupus susceptibility locus Sle1 facilitates the peripheral development and selection of anti-DNA B cells through impaired receptor editing.
Systemic lupus erythematosus is characterized by the spontaneous production of IgG autoantibodies in patients and lupus-prone mice. In this study, we investigated the effect of the Sle1 lupus susceptibility locus on the peripheral development of 56R(+) anti-DNA transgenic B cells by tracking 56R(+) B cells in mice without (B6.56R) or with (B6.Sle1.56R) the Sle1 locus. Compared with B6.56R mice, B6.Sle1.56R mice exhibited increased class-switched IgG2a anti-DNA Abs in their serum, encoded by the transgene. Interestingly, within the spleen, Sle1 facilitated the development of these cells into clusters of IgG2a class-switched B cells juxtaposed to CD4(+) T cells within extrafollicular sites. Through sequence analysis of B cell hybridomas, we also found that B cells from B6.Sle1.56R mice are inefficient at Ig H and L chain editing. Thus, the Ig H chains in Sle1.56R(+) B cells are partnered more often with cationic L chains that facilitate DNA binding. Taken together, these findings indicate that the Sle1 lupus-susceptibility locus may facilitate the emergence of anti-DNA B cells by subduing BCR revision and possibly by shaping the extrafollicular development of effector B cells, although the precise molecular mechanisms await further study.


Awareness and practice of contraception among female students at the Institute of Management and Technology (IMT), Enugu.
A study of the knowledge, attitudes to and practice of contraception among the female students at the Institute of Management and Technology (IMT), Enugu, was carried out, involving 266 female students out of a total female student population of 1,510. The mean age of the population sample was 19.1 years and 254 (95%) were single. Ninety-six percent were aware of the availability of contraceptives. Knowledge relating to the practice of contraception was superficial since as many as 61% of the objectors believed that contraception subsequently led to infertility. One hundred and thirty (49%) of the studied population had used one form of contraception or another sometime in their lives. Seventy-six percent had not used any contraception for initial intercourse. The rhythm method followed by the barrier method were the most popular forms of contraception. Practice of contraception by the studied population was inconsistent as 21% of the students eventually had an unwanted pregnancy and 18% had an induced abortion. Health education is strongly recommended to our women folk in order to reduce the high incidence of unwanted pregnancy and its associated medical and social complications.


Structural insights into drug development strategy targeting EGFR T790M/C797S.
Treatment of non-small-cell lung cancers (NSCLCs) harboring primary EGFR oncogenic mutations such as L858R and exon 19 deletion delE746_A750 (Del-19) using gefitinib/erlotinib ultimately fails due to the emergence of T790M mutation. Though WZ4002/CO-1686/AZD9291 are effective in overcoming EGFR T790M by targeting Cys797 via covalent bonding, their efficacy is again limited due to the emergence of C797S mutation. New agents effectively inhibiting EGFR T790M without covalent linkage through Cys 797 may solve this problem. We presented here crystal structures of EGFR activating/drug-resistant mutants in complex with a panel of reversible inhibitors along with mutagenesis and enzyme kinetic data. These data revealed a previously un-described hydrophobic clamp structure in the EGFR kinase which may be exploited to facilitate development of next generation drugs targeting EGFR T790M with or without concomitant C797S. Interestingly, mutations in the hydrophobic clamp that hinder drug binding often also weaken ATP binding and/or abolish kinase activity, thus do not readily result in resistance to the drugs.


Functional genomics of stromal cells in chronic inflammatory diseases.
Stroma is a broad term referring to the connective tissue matrix in which other cells reside. It is composed of diverse cell types with functions such as extracellular matrix maintenance, blood and lymph vessel development, and effector cell recruitment. The tissue microenvironment is determined by the molecular characteristics and relative abundances of different stromal cells such as fibroblasts, endothelial cells, pericytes, and mesenchymal precursor cells. Stromal cell heterogeneity is explained by embryonic developmental lineage, stages of differentiation to other cell types, and activation states. Interaction between immune and stromal cell types is critical to wound healing, cancer, and a wide range of inflammatory diseases. Here, we review recent studies of inflammatory diseases that use functional genomics and single-cell technologies to identify and characterize stromal cell types associated with pathogenesis. High dimensional strategies using mRNA sequencing, mass cytometry, and fluorescence activated cell-sorting with fresh primary tissue samples are producing detailed views of what is happening in diseased tissue in rheumatoid arthritis, inflammatory bowel disease, and cancer. Fibroblasts positive for CD90 (Thy-1) are enriched in the synovium of rheumatoid arthritis patients. Single-cell RNA-seq studies will lead to more discoveries about the stroma in the near future. Stromal cells form the microenvironment of inflamed and diseased tissues. Functional genomics is producing an increasingly detailed view of subsets of stromal cells with pathogenic functions in rheumatic diseases and cancer. Future genomics studies will discover disease mechanisms by perturbing molecular pathways with chemokines and therapies known to affect patient outcomes. Functional genomics studies with large sample sizes of patient tissues will identify patient subsets with different disease phenotypes or treatment responses.


Temporal Variation in Sindbis Virus Antibody Prevalence in Bird Hosts in an Endemic Area in Sweden.
Sindbis virus (SINV) is a mosquito-borne bird virus that occasionally causes human disease in Fennoscandia, suggested to have cyclic 7-year intervals between outbreaks. Reliable data on human infections in Sweden is however lacking. Here we investigated the SINV antibody prevalence among birds in a Swedish area endemic to SINV to scrutinize if a cyclic variation in antibody prevalence is present in the natural host of SINV. Serum from birds were sampled in the summers of 2002-2004 and 2009 in the floodplains of the River Dalälven in central Sweden, with 2002 and 2009 representing hypothesized years of SINV outbreaks. A total of 963 birds from 52 species (mainly passerines) were tested for the presence of SINV antibodies using a plaque reduction neutralization test. The highest SINV antibody prevalence was found in Turdidae species, specifically Fieldfare, Redwing and Song thrush in which more than 70% of sampled individuals had antibodies to SINV in 2009. The SINV antibody prevalence significantly varied between years with 2% in 2002, 8% in 2003, 14% in 2004 and 37% in 2009. Antibodies were found equally often in hatchlings and in adults and increased from early to late in the season. Clearly, the SINV antibody prevalence was not elevated in the bird hosts in the predicted outbreak year 2002, thus solid evidence of a cyclic occurrence of SINV in Sweden is still lacking.


Development and validation of a triplex assay to study an antibody cocktail against Ebola virus in cynomolgus serum.
Background: To support the rapid development of an antibody cocktail against Ebola virus and avoid unnecessary exposure to infectious environments, an automatic and fast turnover triplex assay was developed using Simoa® (Quanterix Corporation, MA, USA). Materials & methods: A robust triplex assay was developed and validated for simultaneous quantification of the antibody cocktail against Ebola virus in cynomolgus serum. Results: The assay had a quantitation range of 78.1-5000 ng/ml. The intra- and interassay precisions (%CV) were within 11.4 and 13.9%, and the accuracies (%RE) were within -10.8 to 6.8%, respectively. Cross-reactivity was evaluated, and the results met the acceptance criteria. Conclusion: The assay was successfully applied to a pharmacokinetics study following a single-dose intravenous administration of 10 mg/kg the antibody cocktail against Ebola virus to cynomolgus monkeys.


Mannitol promotes adherence of an outbreak strain of Burkholderia multivorans via an exopolysaccharide-independent mechanism that is associated with upregulation of newly identified fimbrial and afimbrial adhesins.
Burkholderia multivorans, a member of the Burkholderia cepacia complex (Bcc), is an important pathogen of the cystic fibrosis (CF) lung. Mannitol, approved as an inhaled osmolyte therapy for use in CF patients, promotes exopolysaccharide (EPS) production by the Bcc. In the present study, we investigated the role of mannitol-induced EPS in the adherence of B. multivorans. We report that mannitol promoted adherence of two representative B. multivorans strains. However, whilst this enhanced adherence was largely EPS-dependent in an environmental isolate, it was EPS-independent within a CF outbreak strain, suggesting strain-to-strain variation in adhesins. Genome sequencing of the outbreak strain enabled the identification of two distinct loci encoding putative fimbrial and afimbrial adhesins. The putative fimbriae-encoding locus was found to be widely distributed amongst clinical and environmental B. multivorans. In contrast, the locus encoding the putative afimbrial adhesin (of the filamentous haemagglutinin family, FHA) was restricted to clinical isolates. Both loci contributed to biofilm formation and mucin adherence. Furthermore, we report that mannitol promoted expression of both loci, and that the locus encoding the putative FHA-family adhesin is a key determinant of the enhanced adherence observed following growth in mannitol. Our studies provide the first characterization, to our knowledge, of B. multivorans adhesins, and in so doing highlight the strain-dependent role of EPS in the Bcc and the difficulties in assigning phenotypic traits to Bcc EPS due to the wider response to mannitol. Our observations also highlight the need to monitor the microbiological effects of inhaled mannitol therapy in Bcc-infected CF patients.


Rapid Virological Response After Early Treatment with a Combined Therapy of Ledipasvir and Sofosbuvir in HCV Genotype 4 After Living Donor Liver Transplantation in a HCC Downstaged Patient: Case Report and Review of the Literature.
BACKGROUND Hepatitis C virus (HCV) genotype 4 (GT-4) is widespread in the Middle East, where it is responsible for the majority of HCV infections. It shows moderate treatment response rates when compared to other genotypes in the current era of interferon-based regimens. However, in the era of direct acting antiviral (DAA) drugs, its response is at least as good as observed for HCV genotypes 1-3. CASE REPORT We present a case of a 44-year-old patient with HCV cirrhosis. Since 2007, he has been treated for HCV infection with multiple ineffective regimens of interferon (INF) and ribavirin. A liver biopsy in 2010 revealed stage 5-6/6 indicating cirrhosis, which was later complicated by the occurrence of portal vein thrombosis and a large hepatocellular carcinoma (HCC) (maximum diameter 9 cm). The patient was successfully treated with sorafenib, transcatheter arterial chemoembolization (TACE), and radiofrequency ablation. After four TACE procedures, the patient's AFP (alpha-fetoprotein) decreased remarkably and almost normalized. The HCC disappeared radiologically as shown by triple phase CT, MRI with contrast, and PET-CT. He successfully underwent a living donor liver transplantation. Four weeks post liver transplantation he started treatment with sorafenib, and switched from tacrolimus to Rapamune (sirolimus) as immunosuppressant therapy. Ten weeks after liver transplantation, HCV treatment was introduced along with ledipasvir and sofosbuvir due to his increasing liver enzyme levels. A rapid viral response was achieved after 14 days. In total, the patient received 12 weeks of this treatment. CONCLUSIONS This case study might be of significance in informing early management and personalized treatment of patients with recurrent HCV GT-4 infections after liver transplantation, even in complex clinical surroundings.


Complex Formation via Hydrogen bonding between Rhodamine B and Montmorillonite in Aqueous Solution.
This study investigates the adsorption mechanism differences among four nitrogenous dyes, sulforhodamine G (SRG), uncharged/deprotonated rhodamine B (RhB), orange II (Or II) and methyl blue (MB) by montmorillonite (MMT). MMT adsorption capacity for cationic MB was three times that of uncharged RhB and anionic SRG, while anionic Or II was not absorbed. Colloidal MMT particles have two types of surfaces, basal and edge, that interact with nitrogenous dyes very differently. The surface acidity of MMT was characterized with the pyridine adsorption method using in-situ diffuse reflectance infrared Fourier transform spectroscopy (in-situ DRIFTS). Adsorption of cationic MB was compared with the adsorption of RhB. In-situ attenuated total reflectance Fourier transform infrared (in-situ ATR-FTIR) spectroscopy indicated that a nitrogen atom on RhB complexes with a metal hydroxyl on an MMT edge through a water bridge. The highly polar edge hydroxyl is important to hydrogen bond formation. Cation ion exchange and washing experiments, as well as studies on the effect of temperature, pH and ionic strength on adsorption further clarified the adsorption mechanism. Our results provide insights into the effects of molecular structure on the adsorption of nitrogenous dyes by clay and the role of edge surfaces in the adsorption process.


Expression of ecotropic murine leukemia virus in the brains of C58/M, DBA2/J, and in utero-infected CE/J mice.
In C58 and AKR mice, endogenous N-tropic, ecotropic murine leukemia virus (MuLV) proviruses become activated in rare cells during embryogenesis. Resultant replication-competent progeny viruses then actively infect a large number of cells throughout the fetus, including cells in the developing central nervous system. By in situ hybridization analyses, we have assessed the presence of ecotropic MuLV RNA in the brains of C58 mice as a function of age. Only a few ecotropic MuLV-positive cells were observed in weanling mice, but the number of positive cells in the brain increased progressively with increasing age of the mice. Throughout the lives of the mice, the ecotropic MuLV RNA-positive cells were primarily located in well-defined white-matter tracts of the brain (commissura anterior, corpus callosum, fimbria hippocampi, optical tract, and striatum) and of the spinal cord. Cells of the subventricular zone also expressed ecotropic MuLV RNA, and in older mice a small number of positive cells were present in the grey matter. Infection of endogenous ecotropic MuLV provirus-less CE/J mice in utero with ecotropic MuLV clone AKR-623 resulted in the extensive infection of brain cells. The regional distribution of ecotropic MuLV RNA-containing cells was the same as observed in the brains of C58 mice, in which cells became infected by endogenously activated virus, but the number of positive cells was higher.


Cytoplasmic delayed neuronal death in the myenteric plexus of the rat small intestine after ischemia.
The present study demonstrates light and electron microscopic changes in neurons in the myenteric plexus of the rat ileum following four-hour ischemia. Macroscopically, an intestinal constriction occurred at the damaged portion at three weeks after ischemia; the segment oral to the constriction markedly swelled at four weeks. In light microscopy, at three weeks after ischemia, the myenteric neurons appeared spongy or foamy, containing many vacuoles in their somatic cytoplasm. At four weeks, the neuronal cytoplasm and nerve fiber bundles had disintegrated to form vacant spaces in the myenteric plexus. The neuronal nucleus of the damaged plexus did not show positive nick-end labeling. In electron microscopy, neuronal cytoplasm revealed degenerative signs already at one week after ischemia: a distended endoplasmic reticulum and swollen mitochondria with fragmentary cristae. The nerve fibers also showed destruction of the mitochondria, and degenerative changes in the postsynaptic sites appeared earlier than the presynaptic terminals. The results suggest that intestinal ischemia causes delayed neuronal death, which differs from the apoptotic process previously demonstrated in the ischemia-damaged brain.


Crystallization and preliminary X-ray diffraction analysis of 5,10- methylenetetrahydrofolate dehydrogenase/cyclohydrolase from Thermoplasma acidophilum DSM 1728.
The methylenetetrahydrofolate dehydrogenase/ cyclohydrolase (MTHFDC) from the thermoacidophilic archaeon Thermoplasma acidophilum is a 30.6 kDa molecular-mass enzyme that sequentially catalyzes the conversion of formyltetrahydrofolate to methylenetetrahydrofolate, with a preference for NADP as a cofactor, rather than NAD. In order to elucidate the functional and structural features of MTHFDC from archaeons at a molecular level, it was overexpressed in Escherichia coli and crystallized in the presence of its cofactor, NADP, at 295 K using polyethylene glycol (PEG) 4000 as a precipitant. The crystal is a member of the monoclinic space group P21, with the following unit cell parameters: a=66.333 A, b=52.868 A, c=86.099 A, and beta= 97.570o, and diffracts to a resolution of at least 2.40 A at the synchrotron. Assuming a dimer in the crystallographic asymmetric unit, the calculated Matthews parameter (VM) was 2.44 A3/Da and the solvent content was 49.7%.


First Report of Fig mosaic virus Infecting Common Fig (Ficus carica) in China.
The common fig (Ficus carica) is one of the earliest plants domesticated by humans. It has been cultivated in China ever since the early seventh century. Fig fruit is an important traditional Chinese medicine and a fine health food, featuring a unique flavor and rich nutrients. In addition to its great medicinal values, its abundant availability in the Xinjiang province of China has made the fig one of the most popular fruits in the country. One of the major diseases that affect figs is the fig mosaic disease (FMD) (1,4), which was reported in China in 1935 (3). A causal agent of this disease is associated with the Fig mosaic virus (FMV), a negative-strand RNA virus with six RNA segments (2). In 2013, and later during a survey in 2014, fig plants in several orchards in Xinjiang displayed symptoms of a virus-like disease, which was characterized as FMD. These symptoms included chlorotic clearing as well as banding of leaf veins along with various patterns of discoloration, severely distorted leaves, and deformed fruits. Total RNA extracts (TRIzol reagent, Ambion) from 18 symptomatic and four asymptomatic leaf samples were subjected to reverse reaction (RT) assays using M-MLV reverse transcriptase (Promega, Fitchburg, WI) with primer FMV-GP-R (TATTACCTGGATCAACGCAG). PCR analysis of the synthesized cDNA was performed using FMV-specific primers FMV-GP-F (ACTTGCAAAGGCAGATGATA) and FMV-GP-R. Amplicons of 706 bp produced by RT-PCR assays were obtained from most (15 out of 18) of the symptomatic samples; however, none was obtained from the four asymptomatic leaves. The purified amplicons were cloned and sequenced. BLAST analysis of these sequences revealed more than 94% nucleotide identity with glycoprotein precursor (GP) genes of an FMV-Serbia isolate (SB1). One sequence was deposited in NCBI databases, and one sequence was submitted to GenBank (Accession No. KM034915). RNA segments 2 to 6 of FMV were also amplified by RT-PCR and sequenced. These sequences showed 94 to 96% identity with FMV sequences deposited in the NCBI databases. The collected samples were further detected by Northern-blot hybridization with a digoxigenin-labeled RNA probe, which targets the RNA1 genome of the FMV. The result was in line with RT-PCR detection. To our knowledge, this is the first report of FMV in fig trees in China. Considering the economic importance of fig plants and the noxious nature of FMV, this virus poses a great threat to the economy of the fig industry of Xinjiang. Thus, it is important to develop immediate effective quarantine and management of this virus to reduce any further predictable loss. References: (1) T. Elbeaino et al. J. Gen. Virol. 90:1281, 2009. (2) K. Ishikawa et al. J. Gen. Virol. 93:1612, 2012. (3) H. A. Pittman. J. West Aust. Dept. Agric. 12:196, 1935. (4) J. J. Walia et al. Plant Dis. 93:4, 2009.


[Quality of life in menopause. Experimental research].
Psychophysiological relationship in menopausal women was explored by the comparison of stress level and resistance to stress and related symptoms: socio-economic and cultural variables and willingness to participate into a specific therapeutic program were taken into account. One hundred women, aged 44-59 years (54.2 +/- 5.64), that consecutively were referred to an out-patient menopausal Clinic, were studied by a questionnaire that evaluates quality of life (qol) derived and adapted from the Sickness Impact Profile and the Functional Living Test; moreover the test MSP (psychological stress measurement), translated from the original and adapted to Italy, was used. Psychological complaints of women examined are minimal: adaptation tests are substantially normal, and stress index measurements are even lower in comparison with a gender and age matched population group. Our results suggest that after a short period of psychological tension at the onset of climaterium, women acquire a positive, stable status, well different from stereotypes and prejudices around psychological disturbance associated with menopause. Minimal relevance of perceived disturbance seems the reason that limits the women's need and request for a specific therapy. Menopausal depression seems more related to life changes than to hormonal alterations. Reduced physical fitness, increased risk of parental death, difficulty to cope with new roles, apart the care of adult sons or daughters. A critical point is socio-economic level and the possibility to maintain a satisfying work. Contextual conditions, and specially degree of instruction, type of role change inside the family and number of sons, appears the most evident and relevant variables that mediate psychophysical conditions and perceived quality of life.


Does the Pulmonary Embolism Severity Index accurately identify low risk patients eligible for outpatient treatment?
The pulmonary embolism severity index (PESI) and the recently derived simplified PESI prognostic model have been developed to estimate the risk of 30-day mortality in patients with acute PE. We sought to assess if the PESI and simplified PESI prognostic models can accurately identify adverse events and to determine the rates of events in patients treated as outpatients. A retrospective cohort study of patients with acute pulmonary embolism (PE) presenting at the Ottawa Hospital (Canada) was conducted between 1 January 2007 and 31 December 2008. Two hundred and forty three patients were included. A total of 118 (48.6%) and 81 (33.3%) were classified as low risk patients using the original and simplified PESI prognostic models respectively. None of the low risk patients died within the 3months of follow-up. One hundred and fifteen (47.3%) patients were safely treated as outpatients with no deaths or bleeding episodes and only 1 recurrent event within the first 14days or after 30days of follow-up. Thirty four (29.6%) of these outpatients were classified as high risk patients according to the original PESI and 54 (47.0%) to the simplified PESI prognostic model. Both PESI strategies accurately identify patients with acute PE who are at low risk and high risk for short-term adverse events. However, 30 to 47% of patients with acute PE and a high risk PESI score were safely managed as outpatients. Future research should be directed at developing tools that predict which patients would benefit from inpatient management.


Marginal Bone Level Evaluation after Functional Loading Around Two Different Dental Implant Designs.
Purpose. To investigate peri-implant alveolar bone changes using periapical radiographs before and after prosthetic delivery in submerged and nonsubmerged dental implants. Methods. Digital periapical films of 60 ITI Straumann nonsubmerged dental implants and 60 Xive Dentsply submerged dental implants were taken before, immediately after, and 12 and 24 weeks after the prosthetic restoration was delivered. Results. The 60-nonsubmerged dental implant group showed mean marginal bone resorption at baseline of 0.10 ± 0.23 mm and 24 weeks later, marginal bone resorption was 0.16 ± 0.25 mm. The submerged dental implant group showed a significantly higher distal marginal bone resorption over the mesial side. Mean marginal bone resorption at baseline was 0.16 ± 0.32 on the mesial and 0.41 ± 0.56 on the distal side. Twenty-four weeks later, it was 0.69 ± 0.69 mm on the mesial and 0.99 ± 0.90 mm on the distal side. Conclusion. First, it was possible to determine that submerged implants had a higher mean marginal bone resorption and less bone-to-implant contact than nonsubmerged implants. And second, the distal side of submerged dental implants presented higher marginal bone loss than the mesial side.


Bile and plasma lipid composition in non-obese normolipidemic subjects with and without cholesterol gallstones.
A two-stage study was carried out to characterize the bile and plasma lipid composition in normolipidemic non-obese patients with and without cholesterol gallstones. The first stage involved 11 patients with cholesterol gallstones admitted for elective cholecystectomy and a control group of 16 patients without cholesterol gallstones undergoing elective laparotomy. Bile samples were obtained intraoperatively by aspiration from the gallbladder. The bile of all the gallstone patients was supersaturated with cholesterol and its nucleation time was much shorter than that of bile in the control group (2.5 days vs 22.5 days, respectively, P < 0.001). The biliary fatty acid profile of phosphatidylcholine (PC) and free fatty acids (FFA) of gallstone patients was similar to that of the control group. C-22 fatty acids were found in a higher concentration in the FFA than in the PC fatty acids (P < 0.05) in both groups of patients. Plasma triglyceride levels in the gallstone patients were significantly higher than those in the control group and the biliary cholesterol level correlated with that of plasma triglycerides. In the second stage of the study, plasma lipid profiles were obtained in two additional groups of patients, 20 patients with and 24 patients without cholesterol gallstones, for an in-depth characterization of the differences in plasma lipid profiles. The gallstone patients were found to have not only significantly higher concentrations of plasma triglycerides but increased cholesterol and phospholipid level as well. These differences were essentially due to a higher lipid content of the plasma VLDL fraction, similar to the pattern of patients with type IV hyperlipoproteinemia.


Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.
The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) predicts mortality and morbidity after cardiac resynchronization therapy (CRT). Growth differentiation factor-15, a transforming growth factor-beta-related cytokine which is up-regulated in cardiomyocytes via multiple stress pathways, predicts mortality in patients with heart failure treated pharmacologically. Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 +/- 11 years (mean +/- SD), left ventricular ejection fraction (LVEF) 23.1 +/- 9.8%, New York Class Association (NYHA) class III (n = 117) or IV (n = 41), and QRS 153.9 +/- 28.2 ms] undergoing CRT and followed up for a maximum of 5.4 years for events. In a stepwise Cox proportional hazards model with bootstrapping, adopting log GDF-15, log NT pro-BNP, LVEF, and NYHA class as independent variables, only log GDF-15 [hazard ratio (HR), 3.76; P = 0.0049] and log NT pro-BNP (HR, 2.12; P = 0.0171) remained in the final model. In the latter, the bias-corrected slope was 0.85, the optimism (O) was -0.06, and the c-statistic was 0.74, indicating excellent internal validity. In univariate analyses, log GDF-15 [HR, 5.31; 95% confidence interval (CI), 2.31-11.9; likelihood ratio (LR) chi(2) = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55-5.26; LR chi(2) = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91-17.5; LR chi(2) = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR chi(2) for all endpoints. Pre-implant GDF-15 is a strong predictor of mortality and morbidity after CRT, independent of NT pro-BNP. The predictive value of these analytes is enhanced by combined measurement.


Estimating daily evaporation from poorly-monitored lakes using limited meteorological data: A case study within Qaraoun dam - Lebanon.
Open water evaporation is influenced by several meteorological parameters such as: irradiance, soil temperature, relative humidity, atmospheric pressure and wind speed. However, dealing with that matter, in a case of measurements scarcity, is a challenging task. To overcome this problem, the authors sought a less-dimensional method to estimate lake evaporation. This technique takes into account only three weather variables: temperature, relative Humidity and dew point. In fact, the approach is summarized as follows: 1- using Levenberg-Marquardt algorithm, a Nonlinear Regression model based on Magnus formula is trained and tested to estimate the dew point. 2- a simplified Penman formula provides an estimate for the lake evaporation rate. To test the approach effectiveness, the suggested method was applied on Qaraoun Lake - Lebanon. Upon testing, the regression model exhibited high accuracy with a goodness of fit value equal to 0.99. Afterwards, the evaporation rates were estimated using Penman formula. Unfortunately, evaporation measurements are not available on site to carry the testing procedures. Instead, outcomes were investigated and compared with the monthly evaporation average retrieved from the nearest region to the lake. Estimated rates were reasonably good with a correlation coefficient equal to 0.89 and mean absolute percentage error around 9.8%. At the final stage of this study, sensitivity analysis is performed to quantify the impact of temperature and relative humidity change on evaporation. Overall, the achieved results were reliable enough to carry out a further assessment of the economic impact of evaporation losses from Qaraoun reservoir on the hydropower generation and on the irrigation sector.


Thrombin does not alter vascular hyporeactivity in models of endotoxin-induced septic shock in rats.
1. Hypotension and vascular hyporesponsiveness to vasoconstrictors are observed during endotoxic shock, and are associated with increased production of nitric oxide in the vascular wall. Disseminated intravascular coagulation is another feature of septicaemia. We hypothesized that thrombin generated during disseminated intravascular coagulation might modulate the changes in vascular tone induced by endotoxin. 2. Incubation of rat aortic rings for 4 h with alpha-thrombin (0.003-3.0 NIH units/ml) did not change their reactivity to noradrenaline. Incubation for 4 h with lipopolysaccharide increased the EC50 for noradrenaline, whereas co-incubation of thrombin (0.5 NIH units/ml) with lipopolysaccharide did not alter this hyporeactivity to noradrenaline. 3. In vivo in rats, lipopolysaccharide caused early (1 h) and late (4-6 h) hyporeactivity to noradrenaline. In rats infused with lipopolysaccharide and heparin (1 U min-1 kg-1, 0.4 ml/h) or hirudin (2.2 mg ml-1 kg-1, 0.8 ml/h), vasopressor responses to noradrenaline were not different from those after infusion of lipopolysaccharide alone. Aortic rings taken from rats receiving both anticoagulant treatment and lipopolysaccharide had the same sensitivity to noradrenaline as those obtained from rats receiving lipopolysaccharide alone. 4. Our results suggest that, in vivo, disseminated intravascular coagulation does not modify the early and late effects of lipopolysaccharide on arterial pressure and that, in vitro, thrombin neither induces hyporeactivity to noradrenaline nor modifies lipopolysaccharide-induced hyporeactivity. We propose that thrombin generated during disseminated intravascular coagulation in rats does not play a major role in the alterations of vascular tone observed during endotoxic shock.


[Objectives, tools and methods for an epidemiological use of electronic health archives in various areas of Italy].
The availability of Electronic Health Archives (EHA) has increased remarkably over the last twenty years. As part of a joint project of the Italian Association of Epidemiology (AIE) and the Italian Association of Medical Statistics and Clinical Epidemiology (SISMEC), a workgroup of experts was set up in 2005 with the aim of comparing various experiences and of standardizing the procedures by which electronic sources can be integrated. In particular, the workgroup's aim was to estimate the frequency of certain major diseases using standard algorithms applied to EHA. This volume is published with the purpose of making available in a common publication the methods and the results obtained. The results from a multicentre study using a standard approach to probabilistic record-linkage procedures are also included in a specific chapter. Eleven Italian centres from five Italian regions with an overall population of 11,932,026 collected and treated more than 21,374,426 records (year 2003) from five electronic information sources: death certificates, hospital discharge records (including outpatient discharges), drug prescriptions, tax- exemptions, and pathology records in order to estimate the frequency of the following diseases: diabetes, ischemic heart diseases, acute myocardial infarction, stroke, asthma, chronic obstructive pulmonary disease, obstructive lung diseases. For each pathology a specific algorithm was developed and used by all centres for the identification of the prevalent/incident cases of the selected diseases. Standardized methods were used to estimate the rates. The results confirm the need for a common standard approach to produce estimates based on EHA, considering the variability of the quality and of the completeness of the archives, and the difficulties of standardizing record-linkage operations in the various centres. The main achievement of this work was the elimination of the variability due to the use of different algorithms to identify cases using EHA.


Epidemiology and Healthcare Resource Utilization Associated With Children With Short Bowel Syndrome in the United States.
There is a lack of large database research relating to the epidemiology and health resource utilization associated with short bowel syndrome (SBS) in the United States. We analyzed the Kids' Inpatient Database for the year 2012 and utilized International Classification of Diseases, Ninth Revision, and Clinical Modification ( ICD-9-CM) diagnosis codes to identify patients 0-3 years of age with SBS, who were matched by age and sex to children without SBS. The study variables included patient and hospital demographics, All Patient Refined Diagnosis Related Groups, in-hospital mortality, hospital length of stay, and hospitalization costs. We also determined the most frequent ICD-9-CM diagnostic and procedural codes associated with SBS. Children with SBS demonstrated a higher rate of mortality than that of children without SBS (1.6% vs 0.7%; P < .001). Children with SBS also experienced a longer length of stay (median days [interquartile range]: 8 [15] vs 2 [3]; P < .001) and higher hospital costs ($17,000 [$34,000] vs $3000 [$5000]; P < .001). The most frequent medical diagnoses associated with SBS were infection (62%), anemia (29%), and liver disease (17%). Children with SBS also demonstrated more severe illness as assessed by an All Patient Refined Diagnosis Related Group score of 3 or 4 (94.30% vs 16.20%; P < .001). Children hospitalized with SBS have a high severity of illness and experience complicated inpatient courses related to their disease. Our study represents the first use of national U.S. data to study the epidemiology and health resource utilization associated with SBS.


Prebiotic synthesis of aminooxazoline-5'-phosphates in water by oxidative phosphorylation.
RNA is essential to all life on Earth and is the leading candidate for the first biopolymer of life. Aminooxazolines have recently emerged as key prebiotic ribonucleotide precursors, and here we develop a novel strategy for aminooxazoline-5'-phosphate synthesis in water from prebiotic feedstocks. Oxidation of acrolein delivers glycidaldehyde (90%), which directs a regioselective phosphorylation in water and specifically affords 5'-phosphorylated nucleotide precursors in upto 36% yield. We also demonstrated a generational link between proteinogenic amino acids (Met, Glu, Gln) and nucleotide synthesis.