Application of SEBAL approach and MODIS time-series to map vegetation water use patterns in the data scarce Krishna river basin of India.
Evapotranspiration (ET) from irrigated land is one of the most useful indicators to explain whether the water is used as "intended". In this study, the Surface Energy Balance Algorithm for Land (SEBAL) was used to compute actual ET from a Landsat7 image of December 29, 2000 for diverse land use in the Krishna Basin in India. SEBAL ETa varies between 0 to 4.7 mm per day over the image and was quantified for identified land use classes. Seasonal/annual comparison of ETa from different land uses requires time series images, processed by SEBAL. In this study, the Landsat-derived snapshot SEBAL ETa result was interpreted using the cropping calendar and time series analysis of MODIS imagery. The wastewater irrigated area in the basin has the highest ETa in the image, partly due to its advanced growth stage compared to groundwater-irrigated rice. Shrub and forests in the senescence phase have similar ETa to vegetable/cash crops, and ETa from grasslands is a low 0.8 mm per day after the end of the monsoon. The results indicate that wastewater irrigation of fodder and rice is sufficient to meet crop water demand but there appears to be deficit irrigation of rice using groundwater.


Expression profiling and integrative analysis of the CESA/CSL superfamily in rice.
The cellulose synthase and cellulose synthase-like gene superfamily (CESA/CSL) is proposed to encode enzymes for cellulose and non-cellulosic matrix polysaccharide synthesis in plants. Although the rice (Oryza sativa L.) genome has been sequenced for a few years, the global expression profiling patterns and functions of the OsCESA/CSL superfamily remain largely unknown. A total of 45 identified members of OsCESA/CSL were classified into two clusters based on phylogeny and motif constitution. Duplication events contributed largely to the expansion of this superfamily, with Cluster I and II mainly attributed to tandem and segmental duplication, respectively. With microarray data of 33 tissue samples covering the entire life cycle of rice, fairly high OsCESA gene expression and rather variable OsCSL expression were observed. While some members from each CSL family (A1, C9, D2, E1, F6 and H1) were expressed in all tissues examined, many of OsCSL genes were expressed in specific tissues (stamen and radicles). The expression pattern of OsCESA/CSL and OsBC1L which extensively co-expressed with OsCESA/CSL can be divided into three major groups with ten subgroups, each showing a distinct co-expression in tissues representing typically distinct cell wall constitutions. In particular, OsCESA1, -3 & -8 and OsCESA4, -7 & -9 were strongly co-expressed in tissues typical of primary and secondary cell walls, suggesting that they form as a cellulose synthase complex; these results are similar to the findings in Arabidopsis. OsCESA5/OsCESA6 is likely partially redundant with OsCESA3 for OsCESA complex organization in the specific tissues (plumule and radicle). Moreover, the phylogenetic comparison in rice, Arabidopsis and other species can provide clues for the prediction of orthologous gene expression patterns. The study characterized the CESA/CSL of rice using an integrated approach comprised of phylogeny, transcriptional profiling and co-expression analyses. These investigations revealed very useful clues on the major roles of CESA/CSL, their potentially functional complement and their associations for appropriate cell wall synthesis in higher plants.


Deranged bioenergetics and defective redox capacity in T lymphocytes and neutrophils are related to cellular dysfunction and increased oxidative stress in patients with active systemic lupus erythematosus.
Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyl)lysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE) than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox) capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T) and polymorphonuclear neutrophils (PMN) of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px) and γ-glutamyl-transpeptidase (GGT), was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.


AIDS pacient's long-term battle with multiply recurrent tuberculosis: reinfection or reactivation?
The advent of Mycobacterium tuberculosis strain genotyping has allowed differentiation between disease relapse and exogenous re-infection. We report here a remarkable case of multiply recurrent tuberculosis in a patient living with HIV. Between 1995 and 2009, a young HIV-infected intravenous drug user, who was reluctant to comply with anti-retroviral treatment, underwent at least five tuberculosis episodes caused by three distinct M. tuberculosis strains sharply differentiated by drug susceptibility profile, genotype and infectious source. Eventually, the patient died during a relapse of tuberculosis due to a notorious multidrug-resistant outbreak-strain, which infected him during a prolonged hospitalization in the epicentre of such outbreak. Whether recurrent tuberculosis is due to a new infection or to reactivation of a previous one is a century-long controversial question. In our patient, both conditions alternated throughout his 15 years of living with HIV. Cases such as this might not be exceptional in certain underprivileged suburban areas of Argentina and should raise concern over three pending issues in tuberculosis control policies, namely secondary preventing therapy, institutional infection control and patient follow-up throughout the health network system.


MicroRNAs play a critical role in tooth development.
MicroRNAs are known to regulate gene function in many tissues and organs, but their expression and function, if any, in tooth development are elusive. We sought to identify them by microRNA screening analyses and reveal their overall roles by inactivating Dicer1 in the dental epithelium and mesenchyme. Discrete sets of microRNAs are expressed in molars compared with incisors as well as epithelium compared with mesenchyme. Conditional knockout (cKO) of Dicer1 (mature microRNAs) in the dental epithelium of the Pitx2-Cre mouse results in multiple and branched enamel-free incisors and cuspless molars, and change in incisor patterning and in incisor and molar size and shape. Analyses of differentiating dental epithelial markers reveal a defect in ameloblast differentiation. Conversely, the cervical loop (stem cell niche) is expanded in Dicer1 cKO. These results demonstrate that tooth development is tightly controlled by microRNAs and that specific microRNAs regulate tooth epithelial stem cell differentiation.


Promoting equity in immunization coverage through supply chain design in Pakistan.
To improve equity in immunization coverage, potent immunization products must be available in the communities in which low coverage rates persist. Most supply side investments are focused on replacing or establishing new health facilities to improve access to immunization. However, supply chain design must be improved to ensure that potent vaccines are available at all facilities to promote immunization equity. We used the supply chain design process in Pakistan as an opportunity to conceptualize how supply chains could impact equity outcomes. This paper outlines our approach and key considerations for assessing supply chain design as a contributing factor in achieving equitable delivery of immunization services. We conducted a supply chain analysis based on sub-national supply chain and immunization coverage at district level. Supply chain metrics included cold chain coverage and distances between vaccination sites and storage locations. Immunization coverage metrics included the third-dose diphtheria- tetanus-pertussis (DTP3) vaccination rate and the disparity in DTP3 coverage between urban and rural areas. All metrics were analyzed at the district level. Despite data limitations, triangulation across these metrics provided useful insights into the potential contributions of supply chain to equitable program performance at the district level within each province. Overall, our analysis identified supply chain gaps, highlighted supply chain contributions to program performance and informed future health system investments to prioritize children unreached by immunization services.


Effect of oral melatonin administration on sex hormone, prolactin, and thyroid hormone concentrations in adult dogs.
To determine the effect of oral melatonin (MT) administration on serum concentrations of sex hormones, prolactin, and thyroxine in dogs. Prospective study. 8 male and 8 female adult sexually intact dogs. 5 male and 5 female dogs were treated with MT (1.0 to 1.3 mg/kg [0.45 to 0.59 mg/lb] of body weight), PO, every 12 hours for 28 days; the other 6 dogs were used as controls. Blood samples were collected on days 0, 14, and 28, and serum concentrations of estradiol-17 beta, progesterone, testosterone, androstenedione, 17-hydroxyprogesterone (17-HP), dihydroepiandrostenedione sulfate (DHEAS), prolactin, and thyroxine were determined. On day 5, serum MT concentrations were measured before and periodically for up to 8 hours after MT administration in 4 treated dogs. Female dogs treated with MT had significant decreases in serum estradiol, testosterone, and DHEAS concentrations between days 0 and 28. Male dogs treated with MT had significant decreases in serum estradiol and 17-HP concentrations between days 0 and 28. Serum MT concentrations increased significantly after MT administration and remained high for at least 8 hours. Prolactin and thyroxine concentrations were unaffected by treatment. Melatonin is well absorbed following oral administration and may alter serum sex hormone concentrations.


Effect of fibrate treatment on liver function tests in patients with the metabolic syndrome.
Fibrates are used especially in patients with hypertriglyceridaemia, a feature of the metabolic syndrome. Elevated LFTs are often observed in these patients perhaps related to fatty infiltration. We wished to study changes seen in LFTs (GGT, ALT and ALP) following fibrate therapy and then determine associated factors. This was a retrospective observational study in which data was collected from case notes of patients started on fibrates (n = 118, 2002-2008) in the lipid clinic at Good Hope Hospital and pre/post-fibrate lipid and LFT values were obtained. All biochemistry was performed on the Roche P-Unit using supplied reagents. Statistical analyses included t tests and regression analyses (factorised when quartiles were compared). Of the study population 106 patients were on fenofibrate; the remaining on bezafibrate. Significant lowering of GGT (p < 0.0001), ALT (p = 0.0014) and ALP (p < 0.0001) levels were observed following fibrate treatment. Baseline lipid (cholesterol, triglycerides and HDL) concentrations, alcohol intake, length of treatment, gender, concurrent statin treatment and diabetes did not correlate with these changes in LFT in a multiple regression analysis. Higher pre-fibrate GGT (p < 0.0001), ALT (p < 0.0001) and ALP (p < 0.0001) concentrations were associated with larger decreases in each of these tests respectively with the highest 2 quartiles (GGT > 57 IU/l, ALT > 34 IU/l and ALP > 94 IU/l) significantly different to the lowest quartile. The above associations remained significant even when the regression analyses were corrected for changes in lipid values (which did not show an association). Fibrate treatment led to improvements in LFT, the greatest benefit seen in patients with higher baseline LFT values. It appears that baseline and changes in lipid values post fibrate treatment were not associated with change in LFT.


Providing Value to New Health Technology: The Early Contribution of Entrepreneurs, Investors, and Regulatory Agencies.
New technologies constitute an important cost-driver in healthcare, but the dynamics that lead to their emergence remains poorly understood from a health policy standpoint. The goal of this paper is to clarify how entrepreneurs, investors, and regulatory agencies influence the value of emerging health technologies. Our 5-year qualitative research program examined the processes through which new health technologies were envisioned, financed, developed and commercialized by entrepreneurial clinical teams operating in Quebec's (Canada) publicly funded healthcare system. Entrepreneurs have a direct influence over a new technology's value proposition, but investors actively transform this value. Investors support a technology that can find a market, no matter its intrinsic value for clinical practice or healthcare systems. Regulatory agencies reinforce the "double" value of a new technology-as a health intervention and as an economic commodity-and provide economic worth to the venture that is bringing the technology to market. Policy-oriented initiatives such as early health technology assessment (HTA) and coverage with evidence may provide technology developers with useful input regarding the decisions they make at an early stage. But to foster technologies that bring more value to healthcare systems, policy-makers must actively support the consideration of health policy issues in innovation policy.


Coexistent gout and rheumatoid arthritis.
Gout and rheumatoid arthritis are relatively common entities individually; however, the coexistence of these two conditions has been reported rarely in the literature. The authors present a case that was followed for 20 years. The patient was seen by the acknowledged internist and podiatrist. Criteria for the evaluation and diagnosis of each disease entity are discussed and correlated to the case reported. Various theories and research attempting to explain the negative coexistence of gout and rheumatoid arthritis are presented.


Impact of an Electronic Medical Record Best Practice Alert on Expedited Partner Therapy for Chlamydia Infection and Reinfection.
Atrius Health implemented a best practice alert (BPA) to encourage clinicians to provide expedited partner therapy (EPT) in October 2014. We assessed (1) the impact of the BPA on EPT provision and chlamydial reinfection and (2) the impact of EPT on testing for chlamydia reinfection and reinfection rates. We included patients ≥15 years with ≥1 positive chlamydia test between January 2013 and March 2019. Tests-of-reinfection were defined as chlamydia tests 28-120 days after initial infection, and corresponding positive results were considered evidence of reinfection. We used interrupted time series analyses to identify changes in (1) frequency of EPT, (2) tests-of-reinfection, and (3) reinfections after the BPA was released. Log-binomial regression models, with generalized estimating equation methods, assessed associations between (1) EPT and tests-of-reinfection and (2) EPT and reinfection. Among 7267 chlamydia infections, EPT was given to 1475 (20%) patients. Expedited partner therapy frequency increased from 15% to 22% of infections between January 2013 and September 2014 (β = 0.003, P = .03). After the BPA was released, EPT frequency declined to 19% of infections by March 2019 (β = -0.004, P = .008). On average, 35% of chlamydia infections received a test-of-reinfection and 7% were reinfected; there were no significant changes in these percentages after BPA implementation. Patients given EPT were more likely to receive tests-of-reinfection (prevalence ratio [PR] 1.09; 95% confidence interval [CI], 1.01-1.16) but without change in reinfections (PR 0.88; 95% CI, 0.66-1.17). Best practice alerts in electronic medical record systems may not be effective at increasing EPT prescribing and decreasing chlamydial reinfection. However, patients given EPT were more likely to receive a test of chlamydia reinfection.


Impact of phenotype definition on genome-wide association signals: empirical evaluation in human immunodeficiency virus type 1 infection.
Discussion on improving the power of genome-wide association studies to identify candidate variants and genes is generally centered on issues of maximizing sample size; less attention is given to the role of phenotype definition and ascertainment. The authors used genome-wide data from patients infected with human immunodeficiency virus type 1 (HIV-1) to assess whether differences in type of population (622 seroconverters vs. 636 seroprevalent subjects) or the number of measurements available for defining the phenotype resulted in differences in the effect sizes of associations between single nucleotide polymorphisms and the phenotype, HIV-1 viral load at set point. The effect estimate for the top 100 single nucleotide polymorphisms was 0.092 (95% confidence interval: 0.074, 0.110) log(10) viral load (log(10) copies of HIV-1 per mL of blood) greater in seroconverters than in seroprevalent subjects. The difference was even larger when the authors focused on chromosome 6 variants (0.153 log(10) viral load) or on variants that achieved genome-wide significance (0.232 log(10) viral load). The estimates of the genetic effects tended to be slightly larger when more viral load measurements were available, particularly among seroconverters and for variants that achieved genome-wide significance. Differences in phenotype definition and ascertainment may affect the estimated magnitude of genetic effects and should be considered in optimizing power for discovering new associations.


Comparison of the movement behaviour of experienced and novice performers during the Cat exercise.
Two previous studies showed kinematic differences between novice and experienced performers during unchoreographed movements executed in standing position. However, no study explores if these kinematic differences holds during unchoreographed movements executed in quadrupedal position. The aim of this study is to compare the movement behaviour of experienced and novice performers during an exercise wherein they are challenged to use dynamic and largely unchoreographed movement patterns executed in quadrupedal position. The exercise studied was the Cat exercise, in which participants were asked to behave like a feline for 10 minutes. An inventory of the chosen movements and the assessment of their average and coefficient of variation of the ground contact temporal parameters, computed by analysing the tri-dimensional whole-body kinematics of 25 performers (n = 13 novices and n = 12 experienced), was compared according to their experience level. No significant difference was found between the groups for the number of chosen movements, and median or coefficient of variation of ground contact temporal parameters, except for a greater foot/ knee swing coefficient of variation in experienced performers. This suggests that biomechanical constraints induced by quadrupedal position "prevent" a different selection of motor strategies by experienced performers, although the latter can be more variable in their movements.


Serial analysis of gene expression (SAGE) in bovine trypanotolerance: preliminary results.
In Africa, trypanosomosis is a tsetse-transmitted disease which represents the most important constraint to livestock production. Several indigenous West African taurine Bos taurus) breeds, such as the Longhorn (N'Dama) cattle are well known to control trypanosome infections. This genetic ability named "trypanotolerance" results from various biological mechanisms under multigenic control. The methodologies used so far have not succeeded in identifying the complete pool of genes involved in trypanotolerance. New post genomic biotechnologies such as transcriptome analyses are efficient in characterising the pool of genes involved in the expression of specific biological functions. We used the serial analysis of gene expression (SAGE) technique to construct, from Peripheral Blood Mononuclear Cells of an N'Dama cow, 2 total mRNA transcript libraries, at day 0 of a Trypanosoma congolense experimental infection and at day 10 post-infection, corresponding to the peak of parasitaemia. Bioinformatic comparisons in the bovine genomic databases allowed the identification of 187 up- and down- regulated genes, EST and unknown functional genes. Identification of the genes involved in trypanotolerance will allow to set up specific microarray sets for further metabolic and pharmacological studies and to design field marker-assisted selection by introgression programmes.


Synchronous Double Primary Malignant Tumors and their Possible Shared Genes: A Rare Clinical Entity.
This study sought to analyze the 18F-FDG PET/CT and contrast-enhanced computed tomography (CT) images of synchronous colorectal cancer (CRC) and renal clear cell carcinoma (ccRCC) and identify the shared genes between these two types of cancer through bioinformatic analysis. A retrospective analysis was conducted on a patient with synchronous CRC and ccRCC who underwent 18F-FDG PET/CT and contrast-enhanced CT before treatment. Databases were analyzed to identify differentially expressed genes between CRC and ccRCC, and co-expression genes were extracted for RCC and CRC. 18F-FDG PET/CT revealed intense metabolic activity in the primary colorectal lesion (SUVmax 13.2), while a left renal mass (diameter = 35 mm) was observed with no significant uptake. Contrast-enhanced CT during the arterial phase showed heterogeneous intense enhancement of the renal lesion, and the lesion washed out earlier than in the renal cortex in the nephrographic and excretory phases, indicating ccRCC. The histopathological results confirmed synchronous double primary malignant tumors. Our bioinformatic analysis results showed that synchronous occurrence of CRC and ccRCC may correlate with simultaneous expression of Carbonic Anhydrase 9 (CA9), integrin-binding sialoprotein (IBSP), and Fibrinogen γ chain (FGG). 18F-FDG PET/CT combined with contrast-enhanced CT is an effective diagnostic tool in evaluating synchronous CRC and RCC. By analyzing this clinical case and conducting bioinformatic analysis, we improved our current understanding of the mechanisms underlying synchronous tumors.


Revisiting the pseudo-supercritical path method: An improved formulation for the alchemical calculation of solid-liquid coexistence.
Alchemical free energy calculations via molecular dynamics have been applied to obtain thermodynamic properties related to solid-liquid equilibrium conditions, such as melting points. In recent years, the pseudo-supercritical path (PSCP) method has proved to be an important approach to melting point prediction due to its flexibility and applicability. In the present work, we propose improvements to the PSCP alchemical cycle to make it more compact and efficient through a concerted evaluation of different potential energies. The multistate Bennett acceptance ratio (MBAR) estimator was applied at all stages of the new cycle to provide greater accuracy and uniformity, which is essential concerning uncertainty calculations. In particular, for the multistate expansion stage from solid to liquid, we employed the MBAR estimator with a reduced energy function that allows affine transformations of coordinates. Free energy and mean derivative profiles were calculated at different cycle stages for argon, triazole, propenal, and the ionic liquid 1-ethyl-3-methyl-imidazolium hexafluorophosphate. Comparisons showed a better performance of the proposed method than the original PSCP cycle for systems with higher complexity, especially the ionic liquid. A detailed study of the expansion stage revealed that remapping the centers of mass of the molecules or ions is preferable to remapping the coordinates of each atom, yielding better overlap between adjacent states and improving the accuracy of the methodology.


Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience.
The Japan Pancreas Society criteria for diagnosis of autoimmune pancreatitis (AIP) mandate presence of characteristic imaging (diffuse pancreatic enlargement with diffusely irregular, narrow pancreatic duct). AIP has unique histologic features associated with infiltration of tissues of affected organs with abundant IgG4-positive cells. We propose expanded diagnostic criteria for AIP with a cohort of histologically confirmed AIP. We reviewed the pancreatic imaging findings on computed tomography scans, serum IgG4 levels, other organ involvement, and response to steroids in 29 consecutive patients who met histologic criteria for AIP. Computed tomography scans (n = 22) showed diffuse pancreatic enlargement in 6 (27%) patients; the rest had focal enlargement, distinct mass, normal pancreas, or focal acute pancreatitis. Serum IgG4 level was elevated in 15 of 21 (71%) patients, and other organ involvement (eg, intrahepatic biliary strictures) was noted in 11 of 29 (38%) patients. All 17 patients treated with steroids exhibited resolution/marked improvement of pancreatic/extrapancreatic manifestation. On the basis of this experience we propose that diagnosis of AIP can be made in patients with > or =1 of these criteria: (1) diagnostic histology, (2) characteristic imaging on computed tomography and pancreatography with elevated serum IgG4 level, or (3) response to steroid therapy of pancreatic/extrapancreatic manifestations of AIP. Twenty additional patients met expanded diagnostic criteria for AIP, and their demographic and clinical profile was similar to that of the 29 patients meeting histologic criteria. AIP defined by histological criteria shows a wide spectrum of radiologic features, with characteristic imaging seen only in a minority. Incorporation of additional features into current diagnostic criteria can identify the full spectrum of clinical presentations of AIP.


Targeting NR1D1 in organ injury: challenges and prospects.
Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα) belongs to the nuclear receptor (NR) family, and is a heme-binding component of the circadian clock that consolidates circadian oscillators. In addition to repressing the transcription of multiple clock genes associated with circadian rhythms, NR1D1 has a wide range of downstream target genes that are intimately involved in many physiopathological processes, including autophagy, immunity, inflammation, metabolism and aging in multiple organs. This review focuses on the pivotal role of NR1D1 as a key transcription factor in the gene regulatory network, with particular emphasis on the milestones of the latest discoveries of NR1D1 ligands. NR1D1 is considered as a promising drug target for treating diverse diseases and may contribute to research on innovative biomarkers and therapeutic targets for organ injury-related diseases. Further research on NR1D1 ligands in prospective human trials may pave the way for their clinical application in many organ injury-related disorders.


Neurological disorders in HIV in Africa: a review.
Neurological disorders in HIV infection are a common cause of morbidity and mortality. The aim of this paper is to provide a narrative overview of up to date information concerning neurological disorders affecting HIV infected persons in Africa. Seminal research concerning neurological disorders among HIV-infected adults in sub-Saharan Africa from prior to 2000 was combined with an in-depth search of PubMed to identify literature published from 2000 to 2017. The following Mesh terms were used. "Nervous System Diseases" "HIV Infections" and "Africa South of the Sahara" and "Seizures" or "Spinal Cord Diseases" or "Peripheral Nervous System Diseases" or "AIDS Dementia Complex" or "Opportunistic Infections" or "Immune Reconstitution Inflammatory Syndrome" or "Stroke". Only those articles written in English were used. A total of 352 articles were identified, selected and reviewed and 180 were included in the study. These included case series, observational studies, interventional studies, guidelines and reviews with metanalyses. The author also included 15 publications on the subject covering the earlier phase of the HIV epidemic in Africa from 1987 to 1999 making a total of 195 references in the study. This was combined with extensive personal experience diagnosing and treating these neurological disorders. Neurological disorders were common, typically occurring in WHO stages III/IV. These were in three main categories: those arising from opportunistic processes mostly infections, direct HIV infection and autoimmunity. The most common were those arising from direct HIV infection occurring in >50%. These included HIV-associated neurocognitive dysfunction (HAND), neuropathy and myelopathy. Opportunistic infections occurred in >20% and frequently had a 6-9-month mortality rate of 60-70%. The main causes were cryptococcus, tuberculosis, toxoplasmosis and acute bacterial meningitis. Concurrent systemic tuberculosis occurred in almost 50%. Neurological disorders are common in HIV in Africa and the main CNS opportunistic infections result in high mortality rates. Strategies aimed at reducing their high burden, morbidity and mortality include early HIV diagnosis and anti-retroviral therapy (ART), screening and chemoprophylaxis of main opportunistic infections, improved clinical diagnosis and management and programme strengthening.


Broadband Spectrometer with Single-Photon Sensitivity Exploiting Tailored Disorder.
Harnessing tailored disorder for broadband light scattering enables high-resolution signal analysis in nanophotonic spectrometers with a small device footprint. Multiple scattering events in the disordered medium enhance the effective path length which leads to increased resolution. Here we demonstrate an on-chip random spectrometer cointegrated with superconducting single-photon detectors suitable for photon-scarce environments. We combine an efficient broadband fiber-to-chip coupling approach with a random scattering area and broadband transparent silicon nitride waveguides to operate the spectrometer in a diffusive regime. Superconducting nanowire single-photon detectors at each output waveguide are used to perform spectral-to-spatial mapping via the transmission matrix at the system, allowing us to reconstruct a given probe signal. We show operation over a wide spectral range with sensitivity down to powers of -111.5 dBm in the telecom band.


Loss of FOXA1 Drives Sexually Dimorphic Changes in Urothelial Differentiation and Is an Independent Predictor of Poor Prognosis in Bladder Cancer.
We previously found loss of forkhead box A1 (FOXA1) expression to be associated with aggressive urothelial carcinoma of the bladder, as well as increased tumor proliferation and invasion. These initial findings were substantiated by The Cancer Genome Atlas, which identified FOXA1 mutations in a subset of bladder cancers. However, the prognostic significance of FOXA1 inactivation and the effect of FOXA1 loss on urothelial differentiation remain unknown. Application of a univariate analysis (log-rank) and a multivariate Cox proportional hazards regression model revealed that loss of FOXA1 expression is an independent predictor of decreased overall survival. An ubiquitin Cre-driven system ablating Foxa1 expression in urothelium of adult mice resulted in sex-specific histologic alterations, with male mice developing urothelial hyperplasia and female mice developing keratinizing squamous metaplasia. Microarray analysis confirmed these findings and revealed a significant increase in cytokeratin 14 expression in the urothelium of the female Foxa1 knockout mouse and an increase in the expression of a number of genes normally associated with keratinocyte differentiation. IHC confirmed increased cytokeratin 14 expression in female bladders and additionally revealed enrichment of cytokeratin 14-positive basal cells in the hyperplastic urothelial mucosa in male Foxa1 knockout mice. Analysis of human tumor specimens confirmed a significant relationship between loss of FOXA1 and increased cytokeratin 14 expression.


CYP450-dependent biotransformation of the insecticide fipronil into fipronil sulfone can mediate fipronil-induced thyroid disruption in rats.
In rats, the widely used insecticide fipronil increases the clearance of thyroxine (T(4)). This effect is associated with a high plasma concentration of fipronil sulfone, the fipronil main metabolite in several species including rats and humans. In sheep, following fipronil treatment, fipronil sulfone plasma concentration and thyroid disruption are much lower than in rats. We postulated that fipronil biotransformation into fipronil sulfone by hepatic cytochromes P450 (CYP) could act as a potential thyroid disruptor. The aim of this study was to determine if fipronil sulfone treatment could reproduce the fipronil treatment effects on T(4) clearance and CYP induction in rats. Fipronil and fipronil sulfone treatments (3.4 μmol/kg/day per os, 14 days) increased total and free T(4) clearances to the same extent in THX + T(3), euthyroid-like rats. Both treatments induced a 2.5-fold increase in Ugt1a1 and Sult1b1 messenger RNA (mRNA) expressions and a twofold increase in UGT1A activity suggesting that T(4) elimination was mediated, at least in part, by hepatic uridine 5'-diphospho-glucuronosyltransferases (UGT) and/or sulfotransferases (SULT) induction. Both treatments induced a 10-fold increase in Cyp3a1 and Cyp2b2 mRNA expressions concomitant with a threefold increase in CYP3A immunoreactivity and a 1.7-fold increase in antipyrine clearance, a biomarker of CYP3A activity. All these results showed that fipronil sulfone treatment could reproduce the fipronil treatment effects on T(4) clearance and hepatic enzyme induction in rats. The potential of fipronil sulfone to act as a thyroid disruptor is all the more critical because it persists much longer in the organism than fipronil itself.


Characterization of transcriptional activation and DNA-binding functions in the hinge region of the vitamin D receptor.
The vitamin D receptor (VDR) is a ligand-responsive transcription factor that forms active, heterodimeric complexes with the 9-cis retinoic acid receptor (RXR) on vitamin D response elements (VDREs). Both proteins consist of an N-terminal DNA-binding domain, a C-terminal ligand-binding domain, and an intervening hinge region. The length requirements of the hinge for both transcriptional regulation and DNA binding have not been studied to date for any member of the steroid hormone superfamily. We have generated a series of internal deletion mutants of the VDR hinge and found that deletion of as few as five amino acids from the C-terminus of the hinge significantly reduces transcriptional activation in vivo. Replacing deleted residues in the C-terminus of the hinge with alanines restored activity, indicating that this section of the hinge acts as a sequence-independent spacer. The hinge region of VDR forms a long helix, and the geometric consequences of this structure may explain the requirement of the hinge region for transcriptional activity. Interestingly, all of the deletion mutants, even those that do not activate transcription, bind VDREs with equal and high affinity, indicating that the defect in these mutants is not their ability to bind VDREs. In contrast to VDR, constructs of RXR containing deletions of up to 14 amino acids in the hinge region exhibit near wild-type transcriptional activity. The ability to delete more of the RXR hinge may be related to the additional plasticity required by its role as the common heterodimer partner for nuclear receptors on differing DNA elements.


Development and Quantitation of Pseudomonas aeruginosa Biofilms after in vitro Cultivation in Flow-reactors.
Characterization of biofilm formation and metabolic activities is critical to investigating biofilm interactions with environmental factors and illustrating biofilm regulatory mechanisms. An appropriate in vitro model that mimics biofilm in vivo habitats therefore demands accurate quantitation and investigation of biofilm-associated activities. Current methodologies commonly involve static biofilm setups (such as biofilm assays in microplates, bead biofilms, or biofilms on glass-slides) and fluidic flow biofilm systems (such as drip-flow biofilm reactors, 3-channel biofilm reactors, or tubing biofilm reactors). Continuous flow systems take into consideration the contribution of hydrodynamic shear forces, nutrient supply, and physical transport of dispersed cells, which define the habitat for biofilm development in most natural and engineered systems. This protocol describes the assembly of 3 flow-system setups to cultivate Pseudomonas aeruginosa PAO1 and Shewanella oneidensis MR-1 model biofilms, including the respective quantitation and observation approaches. The standardized flow systems promise productive and reproducible biofilm experimental results, which can be further modified according to specific research projects.


Infant gut microbiota contributes to cognitive performance in mice.
Gut microbiota has been linked to infant neurodevelopment. Here, an association between infant composite cognition and gut microbiota composition is established as soon as 6 months. Higher diversity and evenness characterize microbial communities of infants with composite cognition above (Inf-aboveCC) versus below (Inf-belowCC) median values. Metaproteomic and metabolomic analyses establish an association between microbial histidine ammonia lyase and infant histidine metabolome with cognition. Fecal transplantation from Inf-aboveCC versus Inf-belowCC donors into germ-free mice shows that memory, assessed by a novel object recognition test, is a transmissible trait. Furthermore, Inf-aboveCC mice are enriched in species belonging to Phocaeicola, as well as Bacteroides and Bifidobacterium, previously linked to cognition. Finally, Inf-aboveCC mice show lower fecal histidine and urocanate:histidine and urocanate:glutamate ratios in the perirhinal cortex compared to Inf-belowCC mice. Overall, these findings reveal a causative role of gut microbiota on infant cognition, pointing at the modulation of histidine metabolite levels as a potential underlying mechanism.


Behavioral consequences of infections of the central nervous system: with emphasis on viral infections.
Infections of the central nervous system can damage the brain and cause abnormal behavior. In this article, the authors examine how behavior is affected by damage to different parts of the brain. They then focus on damage caused by specific infections of the brain and how these can result in abnormal behavior with legal consequences. Examples of such infections include neurosyphilis, encephalitis lethargica, herpes simplex encephalitis, and various other viral encephalitides, both acute and chronic. The AIDS dementia complex, which results from HIV infection of the brain, causes behavioral abnormalities in addition to motor and cognitive impairments. In some cases of violence and other criminal behavior, this can be a consequence of central nervous system infection, and the authors suggest that criminal sanctions in such events are inappropriate in the absence of volitional criminal intent.


Plasma adiponectin array in women with Alzheimer's disease.
Introduction Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Typical features of AD include memory loss, social dysfunction and physical impairment. Although the pathological findings in the central nervous system are well established, the etiological factors are poorly known. Recent studies suggested the role of metabolic disturbances in the development of AD neurodegeneration. Adiponectin, an anti-inflammatory and metabolism regulating factor, was linked to AD. Aim The aim was to examine whether adiponectin fractions combined with insulin/insulin resistance-associated metabolic parameters correlate with AD progression. Material and methods The study comprised 98 women: 27 with moderate to severe AD, 31 with AD at early stage and 40 healthy controls, matched for age and BMI. To evaluate memory impairment, the MMSE was performed. Plasma total adiponectin and its high-, medium- and low molecular weights were measured with ELISA. Anthropometric, clinical and metabolic parameters were assessed. Correlations between adiponectin array and measured parameters were evaluated. Results In comparison to the controls, enhanced levels of total and medium molecular weight adiponectin characterized AD individuals. In AD, we found correlations between adiponectin array, and anthropometric and biochemical parameters. After adjustment to BMI, a significant increase of the total adiponectin and high- and medium molecular weight fractions was observed. A negative correlation between low molecular weight adiponectin and MMSE was found. Conclusions Our results indicate a possible link between adiponectin variations and AD. We hypothesize that changes in adiponectin profile observed in AD result from compensatory mechanism against neuropathological processes, as well as from adiponectin homeostasis impairment.


Topography of the recurrent laryngeal nerve in relation to the thyroid artery, Zuckerkandl tubercle, and Berry ligament in Kenyans.
Injury to the recurrent laryngeal nerve (RLN) is an important but avoidable complication of thyroidectomy. This complication may be avoided by the identification of the nerve facilitated by important landmarks found along its course. The setting for this work is the Human Anatomy Laboratory of the University of Nairobi. The aim of this work is to determine the topographic relationship of the RLN with the inferior thyroid artery (ITA), the tubercle of Zuckerkandl (TZ), and the ligament of Berry (LB) in a Kenyan population. The relationship between the nerve and the above landmarks was determined during dissection of 146 right and left thyroid lobes. One right side of the neck had a nonrecurrent nerve. Of the specimens where relationship was determined, the nerve was anterior to the ITA in 37% of cases and posterior in 51.4%. In relation to the LB, 45.3% were superficial (dorsolateral). The TZ was clearly delineated in 86 of the 146 specimens. No nerve traversed the tubercle. The RLN exhibited variations similar to those in other populations. The TZ when present was a reliable landmark to the nerve.


Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats.
To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl(4)) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 microg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl(4) administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 microg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl(4) after 4 h of CCl(4) administration, respectively. Rats living over 96 h were considered as survivals. The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 microg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50 microg/kg pcDNA3-ALR DNA. The effect of intravenous injection of recombinant pcDNA3-ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid, the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P<0.01). The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level of AST and ALT in CCl(4)-intoxicated rats.


Development and Assessment of a Machine Learning Model to Help Predict Survival Among Patients With Oral Squamous Cell Carcinoma.
Predicting survival of oral squamous cell carcinoma through the use of prediction modeling has been underused, and the development of prediction models would augment clinicians' ability to provide absolute risk estimates for individual patients. To develop a prediction model using machine learning for 5-year overall survival among patients with oral squamous cell carcinoma and compare this model with a prediction model created from the TNM (Tumor, Node, Metastasis) clinical and pathologic stage. A retrospective cohort study was conducted of 33 065 patients with oral squamous cell carcinoma from the National Cancer Data Base between January 1, 2004, and December 31, 2011. Patients were excluded if the treatment was considered palliative, staging demonstrated T0 or Tis, or survival or staging data were missing. Patient, tumor, treatment, and outcome information were obtained from the National Cancer Data Base. The data were split into a distribution of 80% for training and 20% for testing. The model was created using 2-class decision forest architecture. Permutation feature importance scores were used to determine the variables that were used in the model's prediction and their order of significance. Statistical analysis was conducted from August 1, 2018, to January 10, 2019. Ability to predict 5-year overall survival assessed through area under the curve, accuracy, precision, and recall. Among the 33 065 patients in the study, the mean (SD) age was 64.6 (14.0) years, 19 791 were men (59.9%), 13 274 were women (40.1%), and 29 783 (90.1%) were white. At 60 months, there were 16 745 deaths (50.6%). The median time of follow-up was 56.8 months (range, 0-155.6 months). Age, pathologic T stage, positive margins at the time of surgery, lymph node size, and institutional identification were identified among the most significant variables. The calculated area under the curve for this machine learning model was 0.80 (95% CI, 0.79-0.81), accuracy was 71%, precision was 71%, and recall was 68%. In comparison, the calculated area under the curve of the TNM staging system was 0.68 (95% CI, 0.67-0.70), accuracy was 65%, precision was 69%, and recall was 52%. Using machine learning algorithms, a prediction model was created based on patient social, demographic, clinical, and pathologic features. The developed prediction model proved to be better than a prediction model that exclusively used TNM pathologic and clinical stage according to all performance metrics. This study highlights the role that machine learning may play in individual patient risk estimation in the era of big data.


Classification of anaemia on the basis of ferrokinetic parameters.
Quantitative information on abnormalities of erythropoiesis and mechanisms of anaemia has been obtained in 136 anaemic patients by means of ferrokinetic studies. To derive a functional classification of anaemia based on ferrokinetic parameters, agglomerative hierarchical cluster analysis and principal coordinate analysis were utilized as techniques for unsupervised classification. Two main clusters were found and named anaemia with low potential erythropoiesis and with high potential erythropoiesis, since the most discriminant parameter between them was total erythroid iron turnover, a measure of total erythropoietic activity. A value of total erythropoiesis equal to 4 times the normal was found to discriminate these two types of anaemia in 94% of cases. Within the group with low potential erythropoiesis, three clusters showing different qualitative disturbances of erythropoiesis were singled out. Among patients with high potential erythropoiesis, two clusters were found. A value of effective erythropoiesis equal to 2.5 times the normal was shown to have a high discriminant power between these clusters. This threshold level distinguished between patients having ineffective erythropoiesis or peripheral haemolysis as the major mechanism of anaemia. The present functional classification of anaemia provides a complete picture of the different pathogenetic mechanisms and may represent the basis for a more rational diagnostic approach to erythroid disorders.


Continuous-wave mid-infrared intra-cavity singly resonant PPLN-OPO under 880 nm in-band pumping.
We report herein a continuous-wave mid-infrared intra-cavity singly resonant optical parametric oscillator (ICSRO) which is the first example of ICSRO that utilize in-band pumped Nd-doped vanadate laser as pump source. A 1064 nm Nd:YVO₄ laser in-band pumped by 880 nm LD and a periodically poled lithium niobate (PPLN) crystal are employed as the parent pump laser and the nonlinear medium, respectively. The idler output wavelength tuning range is 3.66-4.22 µm. A maximum output power of 1.54 W at 3.66 µm is obtained at absorbed pump power of 21.9 W, with corresponding optical efficiency being 7.0%. The control experiment of ICSRO under 808 nm traditional pumping is also carried out. The results show that in-band pumped ICSRO has better performance in terms of threshold, power scaling, efficiency and power stability than ICSRO traditionally pumped at 808 nm.


Data Collection during the COVID-19 Pandemic: Learning from Experience, Resulting in a Bayesian Repertory.
A novel pandemic disease offered the opportunity to create new, disease-specific, symptom rubrics for the homeopathic repertory. The aim of this study was to discover the relationship between specific symptoms and specific medicines, especially of symptoms occurring frequently in this disease. Worldwide collection of data in all possible formats by various parties was coordinated by the Liga Medicorum Homeopathica Internationalis. As the data came in, more symptoms were assessed prospectively. Frequent analysis and feedback by electronic newsletters were used to improve the quality of the data. Likelihood ratios (LRs) of symptoms were calculated. An algorithm for combining symptom LRs was programmed and published in the form of an app. The app was tested against 18 well-described successful cases from Hong Kong. LRs of common symptoms such as 'Fatigue' and 'Headache' provided better differentiation between medicines than did existing repertory entries, which are based only on the narrow presence or absence of symptoms. A mini-repertory for COVID-19 symptoms was published and supported by a web-based algorithm. With a choice of 20 common symptoms, this algorithm produced the same outcome as a full homeopathic analysis based upon a larger number of symptoms, including some that are traditionally considered more specific to particular medicines. A repertory based on clinical data and LRs can differentiate between homeopathic medicines using a limited number of frequently occurring epidemic symptoms. A Bayesian computer algorithm to combine symptoms can complement a full homeopathic analysis of cases.


Hypoparathyroidism.
The regulation of plasma calcium levels is essential for the normal physiologic function of every cell. Parathyroid hormone (PTH) is the principal regulator of serum calcium and phosphate homeostasis. PTH is synthesized and secreted by the parathyroid chief cells in the parathyroid glands primarily in response to a decline in serum calcium levels. The causes of hypocalcemia can be broadly classified as inadequate PTH or vitamin D production, PTH resistance, or miscellaneous causes. The term "hypoparathyroidism" refers to a metabolic disorder in which hypocalcemia and hyperphosphatemia occur either from a failure of the parathyroid glands to secrete sufficient amounts of biologically active PTH, or from an inability of PTH to appropriately induce a biological response in its target tissues. The most common cause of acquired hypoparathyroidism is surgery, accounting for 75% of all cases. Nonsurgical causes of hypoparathyroidism include autoimmune, genetic variants, infiltrative, metastatic, radiation, mineral deposition, magnesium deficiency or excess or idiopathic. The objective of this chapter is to provide a comprehensive review of the physiology of calcium homeostasis, the causes of hypocalcemia, and the epidemiology of hypoparathyroidism. It is very important to determine the underlying cause of the hypoparathyroidism in order to effectively treat our patients and improve quality of life.


Decreased levels of the RNA splicing factor Prpf3 in mice and zebrafish do not cause photoreceptor degeneration.
Pre-mRNA processing factor 3 (PRPF3) is a spliceosomal component essential for pre-mRNA processing. Mutations in PRPF3 have been implicated in retinitis pigmentosa (RP) 18 through an unknown mechanism. The authors created and characterized Prpf3 knockout mice and zebrafish to determine whether RP18 is a result of haploinsufficiency. Mice were produced from a Prpf3 gene trap cell line, and parameters of retinal function, structure, and RNA splicing were analyzed. The retinas of prpf3 insertional mutant zebrafish were also analyzed histologically. Homozygous Prpf3 knockout mice do not survive to 14 days postfertilization (dpf), implying that this allele is required for early embryonic development. Homozygous Prpf3 knockout zebrafish die by 4dpf, well beyond the mid-blastula transition at which transcription activates. Zebrafish knockout embryos reveal abnormally high levels of cell death in the developing eye. Heterozygous Prpf3 knockout mice have less than the expected 50% reduction in Prpf3 at the mRNA and protein levels, implying compensatory expression from the wild-type allele. The heterozygous mice develop normally, with no changes in retinal function, no evidence for photoreceptor degeneration at up to 23 months of age, and no decrease in pre-mRNA splicing of transcripts mutated in other forms of RP in the retina. Similarly, heterozygous prpf3 knockout zebrafish develop normally and show no retinal degeneration up to 12 months of age. These models suggest that RP18 is not a result of haploinsufficiency but instead arises from a toxic gain of function caused by missense mutations in PRPF3.


Effect of tropospheric ozone on morphological characteristics of Nicotiana tabacum L., Phaseolus vulgaris L. and Petunia×Hybrida L. in ambient air conditions.
The cumulative ozone effect on morphological parameters (visible leaf injury, plant height and leaf growth, number of bean pods, petunia flowers and stalks) was examined in this study. Well-known ozonesensitive (Bel W3) and ozone-resistant (Bel B) tobacco cultivars as well as bean cv. Nerina and petunia cv. White cascade, both recognized as ozone sensitive, were used in the experiment. Investigations were carried out at two exposure sites varying in tropospheric ozone levels. Ozone negatively affected the leaf growth of both tobacco cultivars and bean. A negative relation was also found for ozone concentration and tobacco plant height. Number of petunia flowers and stalks and bean pods was positively correlated with ozone concentration. This could have been connected with earlier plant maturation due to faster generative development of plants in ozone-stress conditions.


A Modified Levator Resection to Improve Postoperative Lagophthalmos and Eyelid Lag.
To assess the effect of releasing the central attachment between the Whitnall's ligament (WL) and the levator palpebrae superioris muscle on the postoperative levator function (LF), eyelid lag, and degree of lagophthalmos. This retrospective case-control study included patients with moderate and severe simple congenital ptosis who underwent skin approach levator aponeurosis resection (LR) as a primary procedure with a minimum of 6-month follow up. Patients were divided into 2 groups; the first group underwent LR without WL release (control group) while the second group underwent LR with WL release. Preoperative demographics and clinical data were reviewed. Postoperative LF, eyelid lag, and degree of lagophthalmos as well as surgical outcomes were compared and analyzed in both groups. A total of 81 patients (88 eyelids) were included in this study. There were 50 males (61.7%). The mean age was ±SD 12.0 ± 9.5 years. The first group included 43 eyelids while the second had 45 eyelids. There was no statistical difference in demographics and preoperative data between both groups. The postoperative LF was higher in the second group (10.7 ± 2.1 mm) with less consecutive eyelid lag compared with the control group (7.8 ± 1.9 mm) (p < 0.001). The control group had acquired more postoperative lagophthalmos compared with the second group (p < 0.001). Complete surgical success was achieved in 82.2% in the second group compared with 60.5% in the control group (p = 0.024). Releasing the central attachment between WL and levator palpebrae superioris muscle has achieved an improvement in LF with minimal postoperative eyelid lag, lagophthalmos, and corneal complications.Releasing the central attachment between levator palpebrae superioris muscle and Whitnall's ligament during levator aponeurosis resection allows better levator excursion and minimizes postoperative lagophthalmos, eyelid lag, and corneal complications.


Regional Anaesthesia in Harris Platelet Syndrome for Transurethral Resection of Prostate-A Clinical Conundrum or Certitude?
Routine use of the autoanalyzer has helped uncover the increasing incidence of thrombocytopenia. Disorders associated with macrothrombocytes with thrombocytopenia necessitate a preoperative evaluation to assess the bleeding tendencies and the need for transfusion of blood products. Harris platelet syndrome is one such disorder where macrothrombocytes with thrombocytopenia are associated with no congenital abnormalities and low risk of bleeding intraoperatively. There are cases where Harris platelet syndrome has been treated with steroids or splenectomy, which is unwarranted. We report successful management of a patient with Harris platelet syndrome who underwent transurethral resection of the prostate under spinal anaesthesia with no complications.


Dental implant materials. II. Preparative procedures and surface spectroscopic studies.
The tissue response to an implant may involve both physical and chemical factors. There is little reliable information on the effects of these parameters and the associated ionic release on the cell-material interaction because the majority of studies have not fully characterized the implant material. In this work surface spectroscopy using ISS, ESCA, and SIMS was carried out on Ti6A14V, Co-Cr-Mo, A12O3, and hydroxyapatite dental implant materials that had been subjected to six commonly used preparative procedures. The results showed that each procedure generated an individualistic composition for the outermost surface of each material. These differences could be significant in cellular and tissue response. Improved understanding of these factors requires defined and reproducible surfaces.


Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes.
Myocyte hypertrophy antecedent to heart failure involves changes in global gene expression, although the preceding mechanisms to coordinate DNA accessibility on a genomic scale are unknown. Chromatin-associated proteins alter chromatin structure by changing their association with DNA, thereby altering the gene expression profile. Little is known about the global changes in chromatin subproteomes that accompany heart failure, and the mechanisms by which these proteins alter chromatin structure. The present study tests the fundamental hypothesis that cardiac growth and plasticity in the setting of disease recapitulates conserved developmental chromatin remodeling events. We used quantitative proteomics to identify chromatin-associated proteins extracted via detergent and to quantify changes in their abundance during disease. Our study identified 321 proteins in this subproteome, demonstrating it to have modest conservation (37%) with that revealed using strong acid. Of these proteins, 176 exhibited altered expression during cardiac hypertrophy and failure; we conducted extensive functional characterization of one of these proteins, Nucleolin. Morpholino-based knockdown of nucleolin nearly abolished protein expression but surprisingly had little impact on gross morphological development. However, hearts of fish lacking Nucleolin displayed severe developmental impairment, abnormal chamber patterning and functional deficits, ostensibly due to defects in cardiac looping and myocyte differentiation. The mechanisms underlying these defects involve perturbed bone morphogenetic protein 4 expression, decreased rRNA transcription, and a shift to more heterochromatic chromatin. This study reports the quantitative analysis of a new chromatin subproteome in the normal and diseased mouse heart. Validation studies in the complementary model system of zebrafish examine the role of Nucleolin to orchestrate genomic reprogramming events shared between development and disease.


Talking about Y generation.
Recruitment is often the key preoccupation of healthcare providers and governments in relation to workforce issues, but nurse retention is fast becoming a more pressing issue.


Simple models for phosphorus loss from manure during rainfall.
Mechanistic, predictive equations for phosphorus (P) transport in runoff from manure-applied fields constitute a critical knowledge gap for developing nonpoint-source pollution models. We derived two simple equations to describe the P release from animal manure during a rainfall event-one based on first-order P desorption kinetics and one based on second-order kinetics. The manure characteristics needed in the two kinetic equations are the maximum amount of water-extractable phosphorus (WEP) and a characteristic desorption time. Water-extractable P can be measured directly but currently the characteristic time can only be obtained by fitting experimental data. In addition, we evaluated two models usually used to estimate P loss from soil, the Elovitch equation and power function, both of which relate P loss to time. The models were tested against previously published data of P release from different manures under laboratory conditions. All equations fit the data well. Of the two kinetic equations, the second-order model showed better agreement with the data than the first-order model; for example, maximum relative differences between the model results and measured data were 2.6 and 4.7%, respectively. The characteristic times varied between 20 min for dairy manure and almost 100 min for poultry manure. The characteristic time did not appear to change with flow rate but decreased with smaller manure aggregates. The parameters for power-function relationships could not be related to measured manure characteristics. These results provide the first step to process-based approximations for predicting P release from manure with time during rainfall shortly after land application, when P losses are the greatest.


Compassion fade: affect and charity are greatest for a single child in need.
Charitable giving in 2013 exceeded $300 billion, but why do we respond to some life-saving causes while ignoring others? In our first two studies, we demonstrated that valuation of lives is associated with affective feelings (self-reported and psychophysiological) and that a decline in compassion may begin with the second endangered life. In Study 3, this fading of compassion was reversed by describing multiple lives in a more unitary fashion. Study 4 extended our findings to loss-frame scenarios. Our capacity to feel sympathy for people in need appears limited, and this form of compassion fatigue can lead to apathy and inaction, consistent with what is seen repeatedly in response to many large-scale human and environmental catastrophes.


Effects of activated macrophages on Nacardia asteroides.
The mechanism(s) of host resistance against Nocardia asteroides has not been well defined. Since disease due to N. asteroides frequently occurs in patients with impaired cell-mediated immunity, we studied the interaction of N. asteroides with activated and control mouse peritoneal macrophages. Activated macrophages were from mice infected with Toxoplasma gondii or injected with Corynebacterium parvum. N. asteroides in the early stationary phase (>99% in the coccobacillary form) was used for challenge of macrophage monolayers. Growth of two strains of N. asteroides was markedly inhibited in activated macrophages, whereas N. asteroides grew well in control macrophages. Quantitation of macrophage-associated N. asteroides indicated that activated macrophages killed 40 to 50% of N. asteroides within 6 h (P < 0.002). In control macrophage preparations, it appeared as if Nocardia filaments extended from within macrophages to the outside, and many of these filaments appeared to have extended to and then grown through neighboring macrophages. In activated macrophage preparations, Nocardia remained in the coccobacillary form in most macrophages. Control macrophage monolayers were almost completely overgrown with and destroyed by Nocardia 20 h after challenge, whereas activated macrophage monolayers remained intact. Nocardia that grew in control macrophages were not acid-alcohol fast or only weakly so, whereas the few Nocardia that grew in activated macrophages were strongly acid-alcohol fast. Our results indicate that activated macrophages may be important in host defense against N. asteroides.


Hepatitis C virus seroprevalence in pregnant women delivering live-born infants in North Thames, England in 2012.
To estimate HCV seroprevalence in subpopulations of women delivering live-born infants in the North Thames region in England in 2012, an unlinked anonymous (UA) cross-sectional survey of neonatal dried blood spot samples was conducted. Data were available from 31467 samples from live-born infants received by the North Thames screening laboratory. Thirty neonatal samples had HCV antibodies, corresponding to a maternal seroprevalence of 0·095% (95% confidence interval 0·067-0·136). Estimated HCV seroprevalences in women born in Eastern Europe, Southern Asia and the UK were 0·366%, 0·162% and 0·019%, respectively. For women born in Eastern Europe seroprevalence was highest in those aged around 27 years, while in women born in the UK and Asia-Pacific region, seroprevalence increased significantly with age. HCV seroprevalence in UK-born women whose infant's father was also UK-born was 0·016%. One of the 30 HCV-seropositive women was HIV-1 seropositive. Estimated HCV seroprevalence for women delivering live-born infants in North Thames in 2012 (0·095%) was significantly lower than that reported in an earlier UA survey in 1997-1998 (0·191%). Data indicate that the cohort of UK-born HCV-seropositive women is ageing and that, in this area of England, most perinatally HCV-exposed infants were born to women themselves born in Southern Asia or Eastern Europe.


Attention mediates the flexible allocation of visual working memory resources.
Though it is clear that it is impossible to store an unlimited amount of information in visual working memory (VWM), the limiting mechanisms remain elusive. While several models of VWM limitations exist, these typically characterize changes in performance as a function of the number of to-be-remembered items. Here, we examine whether changes in spatial attention could better account for VWM performance, independent of load. Across 2 experiments, performance was better predicted by the prioritization of memory items (i.e., attention) than by the number of items to be remembered (i.e., memory load). This relationship followed a power law, and held regardless of whether performance was assessed based on overall precision or any of 3 measures in a mixture model. Moreover, at large set sizes, even minimally attended items could receive a small proportion of resources, without any evidence for a discrete-capacity on the number of items that could be maintained in VWM. Finally, the observed data were best fit by a variable-precision model in which response error was related to the proportion of resources allocated to each item, consistent with a model of VWM in which performance is determined by the continuous allocation of attentional resources during encoding. (PsycINFO Database Record


NHS allergy services in the UK: proposals to improve allergy care.
Allergy is common and its prevalence has increased substantially in the last 2-3 decades. There has been a particular increase in severe allergic disease, including anaphylaxis and food, drug and latex rubber allergy. Provision of allergy services in the NHS is poor and there is a huge unmet need. Allergy is a full specialty, but there are few consultants and few trainees: only six centres in the UK offer a full-time specialist service. Most allergy services are provided by doctors--general practitioners and consultants in other specialties--with little or no training in allergy. Whilst specialists in other areas of medicine have a role in the management of allergy, it is no longer adequate to devolve most allergy care to them. The lack of special care leads to morbidity, mortality and substantial cost to the NHS, much of it avoidable. To ensure that adequate standards of care are satisfactory, allergy care must be led by allergy specialists. More consultant posts and training posts in allergy are urgently needed; this requires recognition by trust managers, regional commissioners and the Department of Health. As a first step, we propose the setting up of appropriately staffed regional allergy centres. This could be achieved with a central directive and (relatively minor) pump-priming of funding.


Early diagnosis and treatment of DDH: a sonographic approach.
This study reviews the data regarding clinical and ultrasound (US) examinations, collected during an 11-year period, in a DDH dedicated outpatient clinic. The material was analysed in order to verify the importance of US hip examination and Ortolani's test for early DDH diagnosis, to select dysplastic, unstable hips, to identify the role of the labrum in DDH, and to analyse the treatment strategy. Of the 21709 newborns (43418 hips) examined with US and Ortolani's manoeuvre for DDH diagnosis, 431 patients (356 F; 75 M; average age 42+/-33 days) had 574 unstable, dysplastic hips (1.32%). The hips identified according to Graf's classification were: 298 type D, 252 type IIIa, 4 type IIIb, 20 type IV. In 73.09% of the patients, no risk factors were identified; 18.56% had positive family history for DDH, 5.57% had breech presentation, 2.78% had both risk factors. Only 10.63% had a positive Ortolani's test. The diagnosis was made in 21.5% of cases by the 2nd week of life, in 52.9% between the 2nd-8th week, and in 25.5% after the 8th week. Unstable dislocated hips were treated, after reduction with or without sedation, by applying a cast; dysplastic hips were treated using a Gekeler splint. No open reductions or reconstruction surgery were needed. The labrum was always positioned on top of the femoral head, never inverted, and it was not an obstacle to closed reduction. Neither the Ortolani's sign, nor the risk factors are sure signs for the early diagnosis of DDH and its instability. Only US examination permits an early diagnosis of dysplasia and instability of the hip.


Mechanical forces and the 3D genome.
Traditionally, the field of genomics has been studied from a biochemical perspective. Besides chemical influences, cells are subject to a variety of mechanical signals from their surrounding tissue microenvironment. These mechanical signals can not only cause changes to a cell's physical structure but can also lead to alterations in their genomes and gene expression programs. Understanding the mechanical control of genome organization and expression may provide a new perspective on gene regulation.


Workload and its impact on community pharmacists' job satisfaction and stress: a review of the literature.
The objective was to identify, review and evaluate published literature on workloads of pharmacists in community pharmacy. It included identification of research involving the measurement of pharmacist workload and its impact on stress levels and job satisfaction. The review focused on literature relating to practice in the UK. Electronic databases were searched from 1995 to May 2011. In addition, manual searches were completed for documents not available electronically. The findings were analysed with specific focus on research methodology, workload and its impact on pharmacist job satisfaction and stress levels. Thirteen relevant studies relating to workload in community pharmacy alone or in conjunction with job satisfaction and stress were identified. One utilised both qualitative and quantitative methods to identify differences in pharmacist workload in retail pharmacy businesses before and after the implementation of the 2005 English and Welsh community pharmacy contractual framework. This indicated that pharmacists spend most of their working day dispensing. The majority of studies suggested community pharmacists generally perceived that workload levels were increasing. Several also stated that increased workload contributed to increasing job-related stress and decreasing job satisfaction. No studies reporting dispensing rates for community pharmacies in the UK were identified and there was limited evidence concerning time devoted to non-dispensing services. One study investigated the differences between self-estimated and actual workload. Whilst there is a clear perception that the type and amount of work output expected from individual community pharmacists has been changing and increasing over the last few decades, pharmacists are viewed as continuing to remain based in the dispensary. The impact of such changes to the practice of community pharmacy in the UK is poorly defined, although links have been made to increasing levels of pharmacist job dissatisfaction and stress.


Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma.
Somatic mutations in EGFR (exons 19 and 21) and KRAS (exon 2) are found in lung adenocarcinomas and have potential prognostic value in patients with advanced disease. These mutations also have therapeutic significance, as they predict for sensitivity and resistance, respectively, to EGFR tyrosine kinase inhibitor therapy. Whether EGFR and KRAS mutations also have an impact on survival in patients who undergo lung resection for curative intent in the absence of targeted therapy has not been established. We analyzed the clinical characteristics and outcomes data for 296 patients who underwent resection at our institution for stage I-III lung adenocarcinoma. Tumors were assessed for both EGFR and KRAS mutations by established methods. EGFR and KRAS mutations were found in tumors from 40 (14%) and 50 (17%) patients, respectively. Patients with EGFR mutant tumors were more likely to be never smokers (48%), present with stage I disease (88%), and had a 90% (95% confidence interval [CI] 70-97%) 3-year overall survival, whereas patients with KRAS mutant tumors were more likely to be former/current smokers (92%), present with locally advanced disease (40%), and had a 66% (95% CI 48-79%) 3-year overall survival. EGFR and KRAS mutations define distinct molecular subsets of resected lung adenocarcinoma. Because EGFR and KRAS mutations also predict whether tumors are sensitive or resistant, respectively, to EGFR tyrosine kinase inhibitors, they can readily be used in clinical trials to help guide the administration of specific types of adjuvant therapy.


Circulating lipoprotein-associated phospholipase A2 in high-grade carotid stenosis: a new biomarker for predicting unstable plaque.
To test plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with high-grade carotid stenosis according to plaque histology. This cross-sectional single-centre study included patients with ≥70% North American Symptomatic Carotid Endarterectomy Trial (NASCET) carotid stenosis, who were treated surgically. Serum Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) were determined on the day of surgery. Histopathological analysis classified carotid plaque as stable or unstable, according to AHA classification. Of the 42 patients (mean age 70.4 ± 10.5 years; 67% men), neurological symptoms were present in 16 (38%). Unstable plaques were found in 23 (55%). Median plasma level of Lp-PLA2 was significantly higher in patients with unstable plaque compared to those with stable plaque (222.4 (174.9-437.5) interquartile range (IQR) 63.5 vs. 211.1 (174.9-270.6) IQR 37.2 ng ml(-1); p = 0.02). Moreover, median Lp-PLA2 level were higher in asymptomatic patients with unstable plaque (226.8 ng ml(-1) (174.9-437.5) IQR 76.8) vs. stable plaque (206.9 ng ml(-1) (174.9-270.6) IQR 33.7; p = 0.16). Logistic regression showed that only the neurological symptoms (OR = 30.9 (3.7-244.6); p < 0.001) and the plasma Lp-PLA2 level (OR = 1.7 (1.1-12.3); p = 0.03) were independently associated with unstable carotid plaque as defined by histology. This study showed that circulating Lp-PLA2 was increased in patients with high-grade carotid stenosis and unstable plaque. Lp-PLA2 may be a relevant biomarker to guide for invasive therapy in asymptomatic patients with carotid artery disease.


From narcissistic personality disorder to frontotemporal dementia: a case report.
Premorbid personality characteristics could have a pathoplastic effect on behavioral symptoms and personality changes related to neurodegenerative diseases. Patients with personality disorders, in particular of the dramatic cluster, may present functional frontolimbic abnormalities. May these neurobiological vulnerabilities linked to a premorbid personality disorder predispose or represent a risk factor to subsequently develop a neurodegenerative disorder? Are subjects with personality disorders more at risk to develop a dementia than mentally healthy subjects? This topic is discussed presenting the clinical case of a patient who suffered of a probable Narcissistic Personality Disorder and subsequently developed a clinically diagnosed Frontotemporal Dementia.


Digital measurements of air leak flow and intrapleural pressures in the immediate postoperative period predict risk of prolonged air leak after pulmonary lobectomy.
The objective of this prospective observational study was to evaluate the association between the airflow and intrapleural pressures digitally recorded during the immediate postoperative period after lobectomy and their ability to predict the risk of subsequent prolonged air leak (PAL). A total of 145 consecutive patients underwent pulmonary lobectomy in two centers. All patients were managed with the chest tube placed on suction (-20 cm H(2)O) until the morning of the first postoperative day. Measurement of airflow and maximum and minimum intrapleural pressures were recorded during the 6th postoperative hour using a digital chest drainage device. Logistic regression analysis validated by bootstrap was used to test independent association of variables with PAL (air leak>72 h). The mean air leak flow at the 6th postoperative hour was 86 ml min(-1) (0-1100 ml min(-1)). The mean maximum and minimum pleural pressures at the 6th postoperative hour were -11.4 cm H(2)O and -21.9 cm H(2)O, respectively. Logistic regression and bootstrap showed that the mean air leak flow (p=0.007) and the mean differential pleural pressure (ΔP: maximum-minimum intrapleural pressure) (p=0.02) at the 6th postoperative hour were reliably associated with PAL, independent of the effect of age, forced expiratory volume 1 (FEV1), chronic obstructive pulmonary disease (COPD) status, diffusing capacity of the lung for carbon monoxide (DLCO), side, and site of lobectomy. According to best cutoffs derived by receiver operating characteristic (ROC) analysis the following combinations showed incremental risk of PAL: ΔP<10+Flow<50: 4% (3/73); ΔP>10+Flow<50: 15% (5/33); ΔP<10+Flow>50: 36% (5/14); ΔP>10+Flow>50: 52% (13/25). The levels of both air leak flow and pleural pressure measured at the 6th postoperative hour are associated to a different extent with the duration of air leak. Interpretation of the data measured at an early time point by digital chest drainage systems allows estimation of the risk of subsequent PAL. In this way, digital devices may help to plan postoperative management to allow both safe and more accurate implementation of fast-tracking strategies.


Dietary diversities score and anthropometric characteristics in Iranian elementary school children.
Dietary diversity scoring is a good method to assess quality of individual's diet. The study aimed to investigate the association between dietary diversity and body mass index among elementary school students in the south of Tehran, Iran. This cross-sectional study was conducted on elementary school students, age range of 7-12 years old, in 2015. Data were collected using a personal information questionnaire and three 24-h recall questionnaires. Dietary diversity score was calculated from the number of food groups in these questionnaires. A total of 536 students, 258 (48.1%) female and 278 (51.9%) male, were recruited in the study. The mean age of the students was 9.43 ± 1.73 years. Seafood consumption was more frequent and beans was lower frequent in students at higher BMI (≥95th percentile) than the other children (34% vs 25% and 71% vs 83%, respectively, p<0.05). However, the statistical analysis failed to find significant relationships between children's body mass index (BMI) with consumption of diary, vegetable, fruits, protein, fat, and junk food intake. The association between children's BMI with seafood and beans consumption confirmed in multivariate analysis (OR= 1.50 and 0.52, respectively, p<0.05). The study finding showed that seafood and beans consumption may influence on elementary student BMI.


Increased oxidative burst potential exhibited by macrophages during graft-versus-host reactions in mice.
Graft versus host reactions (GVHR) in mice are accompanied by macrophage activation. Since macrophage oxidative burst (OB) was found to increase in activated macrophages (MPs), we examined the OB of peritoneal and spleen MPs from mice during GVHR. Parental spleen lymphocytes, were injected i.p. into F1 hybrids (BALB/cXC57Bl/6) and at different intervals following injection we monitored the number of peritoneal exudate cells (PEC), spleen enlargement, and the OB of both peritoneal and spleen adherent MPs. Macrophage OB was assessed by measuring O-2 and H2O2 production, following stimulation with the phorbol ester TPA. The spleen-to-body weight ratio increased by 40-70% in mice with GVHR during the period of 6-20 days post-injection and decreased to almost normal levels after 27 days. In such mice with GVHR the number of PEC returned to normal (approximately equal to 6 X 10(6) cells/animal) after 20 days compared with 5 days in control mice (injected with F1 spleen cells). Adherent peritoneal MPs from control mice and mice with GVHR exhibited increased OB activity 3 days following treatment. However, in the control mice the OB response returned to normal within 6 days, while in the experimental mice it showed a slight decrease after 6 days, increased again within 9-17 days, and finally decreased 20-27 days after treatment. Adherent spleen MPs from mice with GVHR generated a high response 6 days posttreatment, which gradually returned to the basal level after 17 days. These findings suggest that during GVHR in mice, macrophage OB was potentiated, giving rise to cytotoxic products such as O2- and H2O2, which may contribute to tissue damage during GVHR.


Stressful environments can indirectly select for increased longevity.
Longevity is modulated by a range of conserved genes in eukaryotes, but it is unclear how variation in these genes contributes to the evolution of longevity in nature. Mutations that increase life span in model organisms typically induce trade-offs which lead to a net reduction in fitness, suggesting that such mutations are unlikely to become established in natural populations. However, the fitness consequences of manipulating longevity have rarely been assessed in heterogeneous environments, in which stressful conditions are encountered. Using laboratory selection experiments, we demonstrate that long-lived, stress-resistant Caenorhabditis elegans age-1(hx546) mutants have higher fitness than the wild-type genotype if mixed genotype populations are periodically exposed to high temperatures when food is not limited. We further establish, using stochastic population projection models, that the age-1(hx546) mutant allele can confer a selective advantage if temperature stress is encountered when food availability also varies over time. Our results indicate that heterogeneity in environmental stress may lead to altered allele frequencies over ecological timescales and indirectly drive the evolution of longevity. This has important implications for understanding the evolution of life-history strategies.


Molecular mechanism of selectivity among G protein-coupled receptor kinase 2 inhibitors.
G protein-coupled receptors (GPCRs) are key regulators of cell physiology and control processes ranging from glucose homeostasis to contractility of the heart. A major mechanism for the desensitization of activated GPCRs is their phosphorylation by GPCR kinases (GRKs). Overexpression of GRK2 is strongly linked to heart failure, and GRK2 has long been considered a pharmaceutical target for the treatment of cardiovascular disease. Several lead compounds developed by Takeda Pharmaceuticals show high selectivity for GRK2 and therapeutic potential for the treatment of heart failure. To understand how these drugs achieve their selectivity, we determined crystal structures of the bovine GRK2-Gβγ complex in the presence of two of these inhibitors. Comparison with the apoGRK2-Gβγ structure demonstrates that the compounds bind in the kinase active site in a manner similar to that of the AGC kinase inhibitor balanol. Both balanol and the Takeda compounds induce a slight closure of the kinase domain, the degree of which correlates with the potencies of the inhibitors. Based on our crystal structures and homology modeling, we identified five amino acids surrounding the inhibitor binding site that we hypothesized could contribute to inhibitor selectivity. However, our results indicate that these residues are not major determinants of selectivity among GRK subfamilies. Rather, selectivity is achieved by the stabilization of a unique inactive conformation of the GRK2 kinase domain.


Allergenicity evaluation of quinoa proteins - A study in Brown Norway rats.
The popularity of quinoa seeds has increased in the last decade due to their high nutritional value and natural gluten-free composition. Consumption of new proteins may pose a risk of introducing new allergies. In the present study the immunogenicity and sensitising capacity of quinoa proteins were assessed in a dose-response experiment in Brown Norway rats in comparison to proteins from spinach and peanut. Cross-reactivity between quinoa proteins and known allergens was evaluated by in silico analyses followed by analyses with 11 selected protein extracts and their anti-sera by means of ELISAs and immunoblotting. Further, an in vitro simulated gastro-duodenal digestion was performed. Quinoa proteins were found to have an inherent medium to high immunogenicity and sensitising capacity, being able to induce specific IgG1 and IgE levels higher than spinach but lower than peanut and elicit reactions of clinical relevance similar to peanut. Quinoa proteins were generally shown to resist digestion and retain capacity to bind quinoa-specific antibodies. Quinoa proteins were shown to be cross-reactive with peanut and tree nut allergens as high sequence homology and antibody cross-binding were demonstrated. Present study suggests that quinoa pose a medium to high level of allergenicity that should be further investigated in human studies.


Does antimicrobial use increase the rate of antimicrobial resistance? A one year experience.
Antimicrobial resistance has been a challenge in all countries. The aim of this study is to ascertain the risk factors that predispose patients to infections with extended spectrum beta lactamase (ESBL)-producing gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA). Patients who were treated in the secondary care hospital due to infections in 2009 and their isolates were evaluated retrospectively. In total, 174 patients and their 189 isolates, which contained 36 ESBL-producing gram-negative bacteria, 112 non-ESBL-producing gram-negative bacteria, and 41 gram-positive bacteria were evaluated retrospectively. Hospitalisation in the previous 3 months, comorbidity, and usage of amoxicillin-clavulanate in the previous 3 months were determined to be the risk factors associated with infections by the ESBL-producing gram-negative bacteria. Hospitalisation was found to be a risk factor for infection with MRSA. Hospitalisation and underlying conditions increase the colonisation with resistant bacteria and resistance rates in the patients, hospitals and communities. An infection control programme should be contemplated not only for hospitals, but also for the greater community.


Mental Health Clinician and Community Clergy Collaboration to Address Moral Injury in Veterans and the Role of the Veterans Affairs Chaplain.
Moral injury in veterans with posttraumatic stress disorder includes symptoms of guilt and shame, and these symptoms are often not responsive to evidence-based mental health treatments. Clergy provide a pathway for relieving the guilt and shame. However, there is a long history of mistrust between clergy and mental health clinicians and not enough Veterans Health Administration chaplains to meet this need. The goal of this study was to gather qualitative interview data from relevant stakeholders regarding whether and how Veterans Affairs (VA) mental health clinicians and community clergy could collaborate to address moral injury issues such as guilt and shame in veterans being treated for posttraumatic stress disorder. The stakeholders for this study were veterans, mental health clinicians, and clergy. Qualitative data were organized into three domains: barriers, facilitators, and intervention suggestions. These data were used to develop a new intervention for moral injury that includes a central role for the Veterans Affairs chaplain.


Functional capacity evaluations for the prevention of occupational re-injuries in injured workers.
Functional capacity evaluation (FCE) has been widely used to assess workers' physical state of readiness to return to work (RTW) after an injury and to make recommendations for the time and capacity in which they might return. FCEs are also used to prevent re-injury after RTW. Despite being a commonly used tool, little is known about how effective FCE is in preventing occupational injuries. To assess the effectiveness of FCE-based return to work recommendations in preventing occupational re-injuries of injured workers compared with no intervention or alternative interventions. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 4), MEDLINE (1966 to December 2009), EMBASE (1980 to December 2009), CINAHL (1980 to December 2009), PsycINFO (1983 to December 2009) and PEDro (1929 to December 2009). The searches were not restricted by date, language or type of publication. We included randomised controlled trials (RCTs) of FCE-based return to work recommendations for preventing occupational re-injuries in injured workers. Four authors (NM, ES, JV, ML), in pairs, independently selected studies for inclusion, extracted data and assessed risk of bias. We found no studies that compared FCE to no intervention. We found one RCT with 372 participants in which a short-form of one FCE was compared to the standard long-form FCE (Isernhagen Work Systems). Outcomes were recurrence rates of re-injuries. There was no significant difference between the two forms of FCE.We rated the overall quality of the evidence as low. There is no evidence for or against the effectiveness of FCE compared to no intervention. A short version of FCE showed similar effectiveness to a long version in preventing re-injury. More RCTs are needed.


Amphibious hearing in a diving bird, the great cormorant (Phalacrocorax carbo sinensis).
Diving birds can spend several minutes underwater during pursuit-dive foraging. To find and capture prey, such as fish and squid, they probably need several senses in addition to vision. Cormorants, very efficient predators of fish, have unexpectedly low visual acuity underwater. So, underwater hearing may be an important sense, as for other diving animals. We measured auditory thresholds and eardrum vibrations in air and underwater of the great cormorant (Phalacrocorax carbo sinensis). Wild-caught cormorant fledglings were anaesthetized, and their auditory brainstem response (ABR) and eardrum vibrations to clicks and tone bursts were measured, first in an anechoic box in air and then in a large water-filled tank, with their head and ears submerged 10 cm below the surface. Both the ABR waveshape and latency, as well as the ABR threshold, measured in units of sound pressure, were similar in air and water. The best average sound pressure sensitivity was found at 1 kHz, both in air (53 dB re. 20 µPa) and underwater (58 dB re. 20 µPa). When thresholds were compared in units of intensity, however, the sensitivity underwater was higher than in air. Eardrum vibration amplitude in both media reflected the ABR threshold curves. These results suggest that cormorants have in-air hearing abilities comparable to those of similar-sized diving birds, and that their underwater hearing sensitivity is at least as good as their aerial sensitivity. This, together with the morphology of the outer ear (collapsible meatus) and middle ear (thickened eardrum), suggests that cormorants may have anatomical and physiological adaptations for amphibious hearing.


Virological Surveillance of Influenza in the eight epidemic seasons after the 2009 pandemic in Emilia-Romagna (Northern Italy).
Influenza virological surveillance is essential for monitoring the evolution of influenza viruses (IVs) as well as for annual updating of the vaccine composition. The aim of this study is to analyse IVs circulation in Emilia-Romagna during the eight epidemic seasons after the 2009 pandemic and to evaluate their match with seasonal vaccine strains. A total of 7882 respiratory specimens from patients with influenza-like illness (ILI), were collected by regional sentinel practitioners and hospital physicians. Viral investigations were conducted by rRT-PCR assay. Genetic characterization was performed for a spatial-temporal representative number of influenza laboratory-confirmed specimens. Influenza-positive samples per season ranged between 28.9% (2013-2014) and 66.8% (2012-2013). Co-circulation of IVs type A and type B was observed in all seasons, although with a different intensity. In all seasons, the highest number of positive samples was recorded in younger patients aged 5-14 years with relative frequencies ranging from 40% in the 2013-2014 season and 78% in the 2012-2013 season. Since the 2009 pandemic, A/H1N1pdm09 IVs circulating were closely related to the vaccine strain A/California/7/2009. Antigenic mismatch between vaccine strain and A/H3N2 IVs was observed in the 2011-2012 and 2014-2015 seasons. During 2015-2016, 2016-2017 and 2017-2018 seasons a complete or nearly complete mismatch between the predominant influenza B lineage of IVs type B circulating and vaccine B lineage occurred. This analysis confirms the importance of the virological surveillance and highlights the need of a continuous monitoring of IVs circulation, to improve the most appropriate vaccination strategies. (www.actabiomedica.it).