Sibling accounts of attention deficit hyperactivity disorder (ADHD).
The goal of this research was to generate a description of how siblings in families with attention deficit hyperactivity disorder (ADHD) children experienced and lived with this chronic behavioral disorder. Interview and diary data from 11 families (N = 43) were analyzed using the constant comparative method. Data analysis revealed that siblings felt victimized by their ADHD sibling and that their experience of victimization was often minimized or overlooked in the family. Findings suggest that there is a need for increased social and mental health services for all members of the family over the course of the disorder, and that the effects on siblings, in particular, can be potentially quite deleterious to their health and well-being.


Reduced sensitivity of cholinesterase as a factor of resistance in leptophos selected strain in the Egyptian cotton leafworm.
Larvae of a leptophos resistant strain of the Egyptian cotton leafworm Spodoptera littoralis (Boisd) showed varying levels of cross resistance to several organophosphorus insecticides and to the carbamate matacil. Enzymatic determinations revealed that levels of cholinesterase activity were almost identical in larvae of susceptible and resistant strains. Resistant larvae, which remained susceptible to the carbamate methomyl possessed cholinesterase of nearly normal sensitivity to this compound. On the other hand, there was a considerable degree of insensitivity of cholinesterase to inhibition by leptophos-oxon, methyl paraoxon, cyolane, cytrolane, monocrotophos, and matacil in larvae of the resistant strain. It was concluded that reduced sensitivity of cholinesterase enzyme could be considered as an important factor which complements other variables contributing to the mechanism of resistance in larvae of the Egyptian cotton leafworm.


Investigating the Accuracy of Wheelchair Push Counts Measured by Fitness Watches: A Systematic Review.
Wheelchair users face an elevated risk of metabolic syndromes due to their sedentary lifestyles. One of the methods to prevent and treat various metabolic syndromes is regular physical activity, which varies among individuals based on their abilities. Monitoring physical activity among them can be performed by using wearable physical activity monitors (WPAMs), which utilize accelerometers and algorithms to track wheelchair push counts. However, the accuracy of push count detection varies among the devices due to technological limitations. The objective of this literature review was to evaluate the accuracy of WPAMs, specifically smartwatches, in measuring physical activity in the wheelchair population. This systematic literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in November 2022 for relevant articles. The initial search yielded 447 articles, seven of which were selected based on the inclusion criteria, which were as follows: participant ability to maneuver a wheelchair, arm- or wrist-worn WPAMs, and articles published after 2017. Among the devices studied, the Apple Watch was determined to be the most accurate calibration system for wheelchair users, with the lowest mean absolute percentage error (MAPE). Each succeeding generation of the Apple Watch (first to fourth) studied was more accurate than the previous. The review demonstrates that research on wheelchair fitness tracking remains scarce and further studies are required to address this issue.


Interception of a Rautenstrauch intermediate by alkynes for [5+2] cycloaddition: rhodium-catalyzed cycloisomerization of 3-acyloxy-4-ene-1,9-diynes to bicyclo[5.3.0]decatrienes.
Rholling in the bicycles: a rhodium(I)-catalyzed cycloisomerization for the synthesis of bicyclic compounds containing a cycloheptatriene ring from linear alkenynes (see scheme; cod=1,5-cyclooctadiene) is proposed to proceed through 1,2-acyloxy migration, 6 π electrocyclization, migratory insertion, and reductive elimination. The overall process can be viewed as a novel intramolecular [5+2] cycloaddition with concomitant 1,2-acyloxy migration.


Does Timing of Antenatal Care Initiation and the Contents of Care Have Effect on Caesarean Delivery in Ethiopia? Findings from Demographic and Health Survey.
Antenatal care (ANC) is an important preventive set of core healthcare services through pregnancy. Caesarean deliveries are significantly increasing in many low-, middle-, and high-income countries. However, overuse of the caesarean section service interferes with the quality and cost of the procedure. Hence, this study aimed to assess the effect of timing of first antenatal care initiation and the contents of care on caesarean delivery. A population level cross-sectional study was conducted with a total of 4757 study participants. The multivariable analysis was computed using the setup of 3 models. The rate of caesarean section among women who initiated antenatal care in the first trimester was 1.32% (95% CI = 0.91-4.21). Women initiated antenatal care in the first trimester (AOR = 2.74; 95% CI = 1.49-6.2) and received contents of care (AOR = 1.98; 95% CI = 1.24-3.78])were more likely to have caesarean section delivery as compared to their counterparts. Caesarean section among women who initiated ANC in the first trimester is low. The finding suggests ANC initiated early (within 16 weeks) can have a positive impact on caesarean section delivery. In addition, being urban residents, primipara women, initiating antenatal care before 16 weeks, received contents of care, and having antenatal care visits three and more increase the odds of having caesarean section. As a result, different obstetric, medical, and surgical complications are detected and managed as early as possible.


Hypolipidaemic and haematological evaluation of the hydromethanolic extract of Ficus glumosa stem bark in alloxan-induced diabetic rats.
Diabetes mellitus is associated with dyslipidaemia and haematological disorders which lead to cardiovascular complications and anaemia respectively. In this study, hydromethanolic extract of Ficus glumosa was evaluated for its hypolipidaemic and haematological effects in alloxan-induced diabetic rats. Treatment was done orally using 62.5, 125 and 250 mg/kg of F. glumosa extract (FGE) with glibenclamide (2 mg/kg) as standard reference drug for 21 days. At the end of the treatment, blood collected through direct heart puncture was used for evaluation of serum lipid profile and determination of haematological parameters. Organosomatic index evaluation of the liver, spleen and kidney was also done using standard procedures. All doses of the extract and glibenclamide (2 mg/kg) caused dose-dependent and significant (p<0.05) reduction in serum levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) of the treated rats when compared with the control group. The extract and glibenclamide produced significant (p<0.05) increase in the serum levels of high-density lipoprotein cholesterol (HDL-C) in the treated rats. The extract (62.5 mg/kg) and glibenclamide (2 mg/kg) caused a significant (p<0.05) increase in red blood cell (RBC), haemoglobin (Hb), packed cell volume (PCV) and mean corpuscular haemoglobin concentration (MCHC) in the treated rats when compared to the negative control group. However, FGE (62.5 mg/kg) and glibenclamide (2 mg/kg) produced a significant (p<0.05) decrease in mean corpuscular volume (MCV) value of the treated rats. FGE (125 and 250 mg/kg) produced a significant (p<0.05) increase in the organosomatic index of kidney in treated rats. The results suggest that F. glumosa may be of help in diabetes-induced anaemia and dyslipidaemia associated with diabetes mellitus.


LIFE-CYCLE COMPONENTS OF SELECTION IN ERIGERON ANNUUS: I. PHENOTYPIC SELECTION.
The magnitude and direction of phenotypic selection on emergence date and seedling size in Erigeron annuus was measured to determine the heterogeneity of selection among sites and the proportion of fitness variance explained by seedling size and emergence date. Three disturbance treatments (open, annual vegetation, perennial vegetation) were imposed to test the hypothesis of stronger selection on seedlings in competitive environments. Selection was most heterogeneous early in the life cycle, with significant spatial heterogeneity in the magnitude of selection on a local scale. The disturbance treatments affected only fecundity selection gradients and selection was strongest in open plots. Significant variation in the sign of selection differentials on emergence date was observed for establishment and fall viability selection episodes; at later stages selection varied in magnitude but not direction. Seedlings in the earliest cohort experienced high mortality during establishment, but increased size and fecundity later in the life cycle. Both stabilizing and disruptive selection on emergence date were observed during establishment, but in general selection was purely directional. At Stony Brook most selection on emergence date operated indirectly through seedling size, whereas at the Weld Preserve direct selection was stronger. There were persistent effects of both seedling emergence date and rosette diameter on adult fitness components, and October rosette diameter explained 18% of the total phenotypic variance in fecundity. Overall, viability fitness components were much more important than fecundity selection. Winter survivorship was the single most important episode of selection.


Male-female genotype interactions maintain variation in traits important for sexual interactions and reproductive isolation.
Prezygotic reproductive isolation can evolve quickly when sexual selection drives divergence in traits important for sexual interactions between populations. It has been hypothesized that standing variation for male/female traits and preferences facilitates this rapid evolution and that variation in these traits is maintained by male-female genotype interactions in which specific female genotypes prefer specific male traits. This hypothesis can also explain patterns of speciation when ecological divergence is lacking, but this remains untested because it requires information about sexual interactions in ancestral lineages. Using a set of ancestral genotypes that previously had been identified as evolving reproductive isolation, we specifically asked whether there is segregating variation in female preference and whether segregating variation in sexual interactions is a product of male-female genotype interactions. Our results provide evidence for segregating variation in female preference and further that male-female genotype interactions are important for maintaining variation that selection can act on and that can lead to reproductive isolation.


Comprehensive transcriptomics and proteomics analyses of pollinated and parthenocarpic litchi (Litchi chinensis Sonn.) fruits during early development.
Litchi (Litchi chinensis Sonn.) is an important fruit that is widely cultivated in tropical and subtropical areas. In this study, we used RNA-Seq and iTRAQ technologies to compare the transcriptomes and proteomes of pollinated (polLFs) and parthenocarpic (parLFs) litchi fruits during early development (1 day, 2 days, 4 days and 6 days). We identified 4,864 DEGs in polLFs and 3,672 in parLFs, of which 2,835 were shared and 1,051 were specifically identified in parLFs. Compared to po1LFs, 768 DEGs were identified in parLFs. iTRAQ analysis identified 551 DEPs in polLFs and 1,021 in parLFs, of which 305 were shared and 526 were exclusively identified in parLFs. We found 1,127 DEPs in parLFs compared to polLFs at different stages. Further analysis revealed some DEGs/DEPs associated with abscisic acid, auxin, ethylene, gibberellin, heat shock protein (HSP), histone, ribosomal protein, transcription factor and zinc finger protein (ZFP). WGCNA identified a large set of co-expressed genes/proteins in polLFs and parLFs. In addition, a cross-comparison of transcriptomic and proteomic data identified 357 consistent DEGs/DEPs in polLFs and parLFs. This is the first time that protein/gene changes have been studied in polLFs and parLFs, and the findings improve our understanding of litchi parthenocarpy.


[Evaluation of the effectiveness of a program of detection of asymptomatic Chlamydia trachomatis infection in women].
Chlamydia Trachomatis is at present the most prevalent pathogenic agent among the causes of sexually transmitted diseases in developed countries, and has reached epidemic proportions in some of them. These infections can give rise to a considerable number of complications, many with very serious consequences. Given that, in addition, a great number of cases are asymptomatic, a general consensus exists about the convenience of carrying out screening programmes. The aim of this study is to accomplish the first stage of the screening programme of asymptomatic infection by C. trachomatis in women who seek help at a family planning centre. A descriptive study to determine the prevalence each year of the period studied, an analysis of its temporal tendency and the assessment of the programme effectiveness in terms of a proportional reduction in prevalence. A total number of 6.746 women were included, who attended the family planning centre for a regular checkup or contraceptive advice between January 1991 and December 1993. The programme showed a global effectiveness rate of 80%, with a reduction in prevalence from 5.1% in 1990 to 1.0% in 1993. A significant fall was observed in all the categories analyzed, except for women using prophylactics and those with higher education. The programme achieves its objectives very effectively. Nevertheless, it would be advisable to evaluate its efficiency together with a cost-analysis, since by reducing prevalence, the positive estimated value of the test considerably decreases, which raises the cost of a single case detection.


Letter to the editor comments on Groparu-Cojocaru and Doray (2013).
Although estimating the five parameters of an unknown Generalized Normal Laplace (GNL) density by minimizing the distance between the empirical and true characteristic functions seems appealing, the approach cannot be advocated in practice. This conclusion is based on extensive numerical simulations in which a fast minimization procedure delivers deceiving estimators with values that are quite far away from the truth. These findings can be predicted by the very large values obtained for the true asymptotic variances of the estimators of the five parameters of the true GNL density.


Can modifications of the MDRD formula improve the estimation of glomerular filtration rate in renal allograft recipients?
Two modifications of the MDRD equation [the Mayo Clinic (MC) equation and Rule's refitted (RR) MDRD formula] were proposed to overcome disadvantages of the original MDRD formula to calculate glomerular filtration rate (GFR). Additionally, a correction factor for the original MDRD formula has been introduced to adapt this formula to creatinine values measured by the isotope-dilution mass spectrometry (IDMS) method. Although precise determination of GFR is of central importance in renal transplant recipients, these equations have not been tested in these patients so far. Considering the impact of different creatinine calibrations, we analysed the MC equation and the RR-MDRD formula in comparison with the old as well as the re-expressed (IDMS traceable) MDRD equation and the Cockcroft-Gault (C-G) formula in 126 consecutive patients after kidney transplantation with respect to correlation, bias, precision, accuracy and ROC analysis. GFR was determined as technetium-diethylenetriamine pentaacetic acid ((99m)Tc-DTPA-clearance). After adjustment to IDMS creatinine determination, the performance of the re-expressed MDRD formula improved considerably in comparison to the original MDRD equation. In comparison with the re-expressed MDRD formula bias of the MC formula and the RR-MDRD formula were significantly smaller (2.31 and -0.35 vs 3.82 ml/min/1.73 m(2)). However, precision and correlation of these formulae did not differ significantly from one another, but all equations showed a higher precision than the C-G formula (P < or = 0.006 each). The accuracies within 30% of true GFR of the MC (79.4%) and the RR-MDRD equation (84.9%) were significantly higher than those of the re-expressed MDRD formula (72.2%; P < 0.03). In comparison to the original and the re-expressed MDRD formula, calculation of GFR by the MC equation and the RR-MDRD formula led to improved diagnostic performance in renal transplant recipients after adjustment of creatinine. In quotidian work both formulae can be applied to these patients. Nonetheless, to determine GFR exactly, gold standard techniques are mandatory.


Apremilast for the management of moderate to severe plaque psoriasis.
Psoriasis is a chronic inflammatory skin disease characterized by erythematous plaques on extensor surfaces, scalp, and back. Current therapies for psoriasis are limited by route of administration, side effects, and cost. Apremilast is the first oral phosphodiesterase inhibitor approved for moderate-to-severe plaque psoriasis. It is a small molecule inhibitor of phosphodiesterase-4, and decreases the inflammatory activity associated with psoriasis. Areas covered: This review will discuss the pharmacology of apremilast, mechanism of action, results from key clinical trials, and its use in managing psoriasis. Currently approved treatments are also discussed. Expert commentary: The advantages of apremilast include convenient oral administration and dosing, a favorable safety and tolerability profile, and significant efficacy in moderate-to-severe plaque psoriasis.


Keratinocyte and epidermal leukocyte expression of CD36 (OKM5) in benign and malignant skin diseases.
CD36 recognizes a 88 Kd glycoprotein, found on different cell populations involved in immunoregulation and are induced on keratinocytes by in vitro treatment with gamma-interferon. Therefore, we obtained skin biopsies from 48 patients with various dermatological diseases and from 5 healthy volunteers and stained these with monoclonal antibodies OKM5 (CD36), anti-HLA-DR and OKT6 (CD1a) using a three stage immunoperoxidase method. In normal skin, CD36 expression was not observed. In contrast, keratinocytes in diseased skin were CD36+. In most cases, the staining was restricted to the stratum granulosum and the stratum spinosum, but in psoriasis, squamous cell carcinoma and lymphomatoid papulosis, more extensive staining of keratinocytes was seen. In addition, CD36+ epidermal leukocytes were found in allergic patch-test infiltrates and in mycosis fungoides. The findings of CD36 expression by epidermal cells within a broad spectrum of dermatological diseases indicate a role for these cells in the regulation of immune reactions in the skin.


Age-Dependent Systemic Effects of a Systemic Intermittent Hypoxic Therapy In Vivo.
Introduction: The adaptive response to systemic intermittent hypoxic therapy (SIHT) may be used for therapeutic advances due to the activation of multiple pathways involved in angiogenesis, immunomodulation, and tissue homeostasis. The aim of this study was to investigate the early age-dependent systemic response of different exposures of SIHT in mice. Materials and Methods: Sixty-four C57BL/6NRj female mice in three different age groups, young (4-5 weeks), adolescent (8-10 weeks), and adults (23-32 weeks), were exposed to SIHT. Different algorithms for equal hypoxic challenges (oxygen-decrease*time) were investigated to allow examination of the role of absolute hypoxia (oxygen-decrease) compared with relative hypoxia (total oxygen depletion over time). The systemic effects of angiogenetic regulation were investigated using blood samples analyzed by ELISA, proteome profiles, and proximity extension immunoassay. One-way analysis of variance with post hoc Bonferroni analyses was performed. Results: The early systemic response to SIHT was dependent on the absolute hypoxia rather than relative hypoxia over time. Serum erythropoietin (EPO) levels were increased significantly in young mice receiving low-oxygen SIHT treatments (10% and 15% oxygen). The expression of angiogenic proteins differed between the different age groups indicating an age-dependent response to SIHT. Focusing on hypoxia-inducible factor-1 (HIF-1) signaling, there was a trend toward upregulated angiogenetic response with younger age. Furthermore, clustering of protein expression in low-oxygen SIHT algorithms were found between young and adolescent mice. In adult mice, the majority of the proteins were downregulated as a response to SIHT. The systemic response of metabolites expressions was most pronounced in young mice. Systemic levels of cardiac troponin I (Tnni3) was unaffected by SIHT independent of age groups. Conclusions: The systemic response to SIHT is dependent on the absolute hypoxic exposure rather than the relative hypoxic depletion over time. Age-dependent effects of a short-term SIHT were associated with an increase in EPO, upregulation of angiogenetic pathways, and select metabolic and cell-surface proteins.


Second-line therapy for non-small cell lung cancer in clinical practice: final results and treatment pathways from the SELECTTION observational study.
SELECTTION was a multinational, prospective observational study to assess the choice of and the time from initiation of second-line treatment to treatment discontinuation for any reason in patients with non-small cell lung cancer. Treatment cohorts were constructed based on prescribed second-line treatments that were at the discretion of the treating physicians, for 1013 patients enrolled in 11 countries. Propensity score analysis was conducted to assess whether the cohorts were comparable. Time from initiation of second-line treatment to treatment discontinuation was the primary endpoint. Reasons for treatment discontinuation, overall survival, progression-free survival and choice of second-line treatment were secondary endpoints. The treatment cohorts were pemetrexed (46.2%), docetaxel (22.9%), erlotinib (20.4%) and other treatments (10.5%). Analyses of baseline data and propensity scores showed that the erlotinib cohort comprised substantially different patients compared with the pemetrexed and docetaxel cohorts: patients in the erlotinib cohort were more likely to be women, never-smokers, have adenocarcinoma and worse performance status. Therefore, comparisons of outcomes between cohorts were not appropriate. Although disease progression was the most common reason for treatment discontinuation in all cohorts, erlotinib patients tended to continue treatment after disease progression, whereas in the docetaxel and pemetrexed cohorts, discontinuation occurred soon after disease progression. In real-world clinical practice the profiles of patients assigned to erlotinib were distinctly different from those assigned to pemetrexed or docetaxel. The most common reason for treatment discontinuation was progressive disease, reflecting adherence to clinical recommendations. It is difficult to extrapolate these findings to the present, as both clinical practice and the approved indications for NSCLC treatments have evolved substantially.


Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice.
Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation. Acox2 knockout (-/-) mice spontaneously developed liver cancer with marked lymphocytic infiltrate. Tandem-affinity purification coupled with mass spectrometry analysis revealed that Acox2 interacted with methylcrotonoyl-CoA carboxylase followed by co-immunoprecipitation confirmation. Here we reported that non-histone lysine crotonylation (Kcr) levels were downregulated in Acox2-/- mice livers. Interestingly, Kcr signals were concentrated in the nucleus of tumor cells but mostly located in the cytoplasm of adjacent normal liver cells of Acox2-/- mice. Quantitative analysis of the global crotonylome further revealed that 54% (27/50) of downregulated non-histone Kcr sites were located in mitochondrial (11/50) and peroxisomal (17/50) enzymes including Ehhadh, Scp2, Hsd17b4, Crot, Etfa, Cpt1a, Eci1/2, Hadha, Etfdh, and Idh2. Subsequent site-directed mutagenesis and transcriptome analysis revealed that Ehhadh K572cr might have site-specific regulatory roles by downregulating TOP3B expression that lead to increased DNA damage in vitro. Our findings suggested Acox2 is a regulator of Kcr that might play critical role on hepatic metabolic homeostasis.


The Mitrofanoff procedure in paediatric urinary tract reconstruction.
Urinary tract reconstruction is required in many congenital and some acquired urological conditions in childhood. The majority are managed by clean intermittent catheterization (CIC), for which purpose the appendix or other tubular structure may be used to provide a continent catheterizable abdominal stoma. Between 1991 and 1996, 23 children underwent urinary tract reconstruction of varying complexity together with a continent diversion according to the Mitrofanoff principle. The appendix was used in 14 patients and the ureter in seven. Two patients had previously had an appendicectomy and the ureters were not suitable. One had a catheterizable channel made from an isolated segment of colon and the other had a detrusor tube constructed. Twelve patients with an appendix conduit, six with a ureteric conduit, and one with a colonic tube are continent, although the latter has had some problems with stomal stenosis. All manage CIC with comfort, the older children doing the procedure themselves. One appendix conduit has stomal incontinence and another was inadvertently divided during renal transplantation. The detrusor tube strictured and was removed. A continent abdominal stoma using the Mitrofanoff principle gives reliable results in children and is well tolerated. It should be considered in the management of children undergoing urinary tract reconstruction when CIC is necessary. The appendix is eminently suitable for this purpose but the ureter provides a satisfactory alternative in selected cases. When neither is available, alternative techniques for constructing a catheterizable continent channel may be considered.


Spin-labeled stearic acid behavior and perturbations on the structure of a gel-phase-lipid bilayer in water: 5-, 12- and 16-SASL.
We have studied the effect of the insertion of spin-labeled molecules n-doxyl-stearic acid (n-SASL, n = 5, 12, 16) on the structure and dynamics of a model lipid bilayer in gel-like phases using molecular dynamics simulations. We have studied the atomic density depth profiles and configurations of the labeled molecules in a host hydrated stearic acid bilayer system. We have found that the 5-SASL label positions its paramagnetic group at the water-lipid interface, and its polar head builds H bonds to neighboring lipids and to the solvent. 16-SASL positions its paramagnetic group at the lipid-lipid interface. The 12-SASL label presents two configurations at high lateral pressure. In one configuration, the doxyl ring lays at the lipid-lipid interface, shifting its polar head toward the bilayer center. The other equilibrium configuration of 12-SASL presents its paramagnetic group laying in the center of the compact hydrophobic region of the layer (erected configuration). It was determined that the coexistence of these two configurations is governed by the polar head-water interaction. We have found that the insertion of the labeled molecules at the concentrations used in the present work (0.36 mol %) do not perturb global properties like area per lipid, tilt angle, or order parameters. Nevertheless, there are local perturbations of the host system that are confined to a 10 angstroms neighboring shell around the spin label molecule. To study the interactions that determine the position of the labeled molecules in the bilayer, we performed simulations at different lateral pressures, which allowed us to extract important conclusions.


On-axis three-dimensional meta-holography enabled with continuous-amplitude modulation of light.
Conventional three-dimensional (3D) holography based on recording interference fringes on a photosensitive material usually has unavoidable zero-order light, which merges with the holographic image and blurs it. Off-axis design is an effective approach to avoid this problem; however, it in turn leads to the waste of at least half of the imaging space for holographic reconstruction. Herein, we propose an on-axis 3D holography based on Malus-assisted metasurfaces, which can eliminate the zero-order light and project the holographic image in the full transmission space. Specifically, each nanostructure in the metasurface acts as a nano-polarizer, which can modulate the polarization-assisted amplitude of incident light continuously, governed by Malus law. By carefully choosing the orientation angles of nano-polarizers, the amplitude can be both positive and negative, which can be employed to extinct zero-order light without affecting the intensity modulation for holographic recording. We experimentally demonstrate this concept by projecting an on-axis 3-layer holographic images in the imaging space and all experimental results agree well with our prediction. Our proposed metasurface carries unique characteristics such as ultracompactness, on-axis reconstruction, extinction of zero-order light and broadband response, which can find its market in ultracompact and high-density holographic recording for 3D objects.


Mechanical thrombectomy in ischemic stroke: Parameters affecting the TICI outcome.
Mechanical thrombectomy (MT) is a standard stroke treatment for patients with large vessel occlusions (LVOs). A decisive factor for a successful outcome is, among other things, timely treatment. The objective was to analyze several time points in relation to outcomes and/or surrogate parameters. Furthermore, our data was placed in the context of other clinical trial data. We retrospectively evaluated 133 data sets from patients who underwent MT. The correlation of various time periods with parameters, such as the ASPECTS, NIHSS, mRS, and, particularly, the TICI score, was investigated. A correlation was found for both the NIHSS score at discharge and the TICI score with the time periods of arrival and/or start to groin puncture as well as with arrival to the end of the intervention and the duration of the intervention. This retrospective study is consistent with large randomized clinical trials investigating stroke management and provides data from daily clinical practice.


Deciphering the origin of variation in the spin ground state and oxidation state of a {Mn19} cluster on a Au(111) surface: is the Au(111) surface innocent?
Periodic DFT calculations on a {Mn19} cluster possessing S = 83/2 ground state and its reduced variant on a Au(111) surface unravel the importance of structural distortions that triggered drastic variations in the J values leading to a large reduction in the spin ground state. Reduction of MnIII ions leads to antiferromagnetic Js with a very small spin ground state manifesting the non-innocent behavior of the Au(111) surface.


Bullous diseases caused by KRT1 gene mutations: from epidermolytic hyperkeratosis to a novel variant of epidermolysis bullosa simplex.
Mutations in the KRT1 gene encoding keratin 1 cause epidermolytic hyperkeratosis characterized by blistering in the neonatal period followed by ichthyotic hyperkeratosis in childhood and adolescent life. We observed a spectrum of clinical manifestations of blistering disorders caused by different mutations in the same KRT1 gene. To analyse the phenotypic spectrum of blistering disorders caused by the KRT1 mutations. Four patients with an epidermal barrier defect manifesting as blistering with the KRT1 mutations were included to the study. The clinical course of the disease was analysed, histology, immunofluorescence and electron microscopic examinations were performed. An adult patient with severe ichthyosis with p.Asn188Lys mutation in exon 1 of KRT1 who occasionally develops blisters in adolescence represents epidermolytic hyperkeratosis, a newborn child who died 4 days after birth due to disruption of the epidermal barrier (extensive blister and erosions) with mutation p.Ser193Pro in the KTR1 gene and two adult sisters harbouring heterozygous mutation c.591+1A>G in the KRT1 gene who present superficial blisters induced by mild trauma from the birth up to adolescent life without ichthyosis suggesting the diagnosis of epidermolysis bullosa simplex. Histopathology in all adult patients showed cytoplasm disruption in keratinocytes of the stratum spinosum with keratohyalin granule-like structures and, on the ultrastructural level, the presence of keratin clumping confirming the pathology of keratin intermediate filaments. This study extends the knowledge of the clinical spectrum for the KRT1 gene mutations. This is the first description of familial dominant epidermolysis bullosa simplex linked to the KRT1 mutation.


Biofilm formation capability of enterococcal strains causing urinary tract infection vis-a-vis colonisation and correlation with enterococcal surface protein gene.
Data regarding differences in biofilm formation among urinary isolates of enterococci causing nosocomial infection versus asymptomatic colonisation is lacking. Conflicting data are available for the role of enterococcal surface protein (esp) gene in the development of enterococcal biofilms. A total of 50 (25 each of asymptomatic bacteriuria and urinary tract infection (UTI) isolates were collected from admitted patients who had nosocomial acquisition of enterococci in urine culture (≥105 cfu/ml). Biofilm assay was done by the quantitative adherence assay. Screening for esp gene was carried out by polymerase chain reaction, and confocal laser scanning microscopy was used to examine biofilms. Out of 25 enterococcal isolates from asymptomatic patients, 9 (36%) isolates were found to be biofilm producers (6 weak [optical densities [OD]595 0.2] and three medium [OD595≥0.2 to595>0.5]). The esp gene was present in 30 (12 biofilm+, 18 biofilm-) isolates. Seventeen esp positive isolates were from asymptomatic cases whereas 13 were from UTI. However, we found that 100% of medium and strong biofilm producers were esp positive (P < 0.001). On comparing Enterococcus faecalis (n = 10) and E. faecium (n = 40) isolates, 70% of E. faecalis isolates were biofilm producers as compared to only 35% of E. faecium isolates (P > 0.05). The esp positivity was observed more in E. faecium isolates (65%) as compared to 40% in E. faecalis. Vancomycin-sensitive enterococcal and vancomycin-resistant enterococcal isolates and catheter-related and unrelated isolates showed similarity in biofilm production and esp positivity. The esp gene is not compulsorily required to produce biofilm but when present may enhance the biofilm formation. We did not find any correlation between biofilm formation and the ability of the strain to cause symptomatic UTI be associated with catheters or vancomycin resistance.


The HEXACO Model of Personality and Risky Driving Behavior.
This research tested the association between the HEXACO personality model and risky driving behavior as well as the predictive power of the HEXACO model in explaining risky driving behavior compared with the Big Five model. In Sample 1, 227 undergraduate students completed measures of the HEXACO personality model, the Big Five model, and driving aggression. In Sample 2, 244 community respondents completed measures of the HEXACO personality model, the Big Five model, and driving styles. Results showed that the Honesty-Humility factor is an important addition to personality models that aim to explain risky driving behavior as being related to all forms of driving aggression as well as to maladaptive and adaptive driving styles and having incremental validity in predicting verbally aggressive expression, risky driving, high-velocity driving, and careful driving. Moreover, compared with the Big Five model, the HEXACO model had better predictive power of aggressive driving.


TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota.
Inflammatory bowel disease (IBD) is defined as chronic intestinal inflammation, and includes ulcerative colitis and Crohn's disease. Multiple factors are involved in the pathogenesis of IBD, and the condition is characterized by aberrant mucosal immune reactions to intestinal microbes in genetically susceptible hosts. Transforming growth factor-β (TGF-β) is an immune-suppressive cytokine produced by many cell types and activated by integrins. Active TGF-β binds to its receptor and regulates mucosal immune reactions through the TGF-β signaling pathway. Dysregulated TGF-β signaling is observed in the intestines of IBD patients. TGF-β signal impairment in specific cell types, such as T-cells and dendritic cells, results in spontaneous colitis in mouse models. In addition, specific intestinal microbes contribute to immune homeostasis by modulating TGF-β production. In this review, we describe the role of TGF-β in intestinal immunity, focusing on immune cells, epithelium, and intestinal microbes. In addition, we present potential therapeutic strategies for IBD that target TGF-β.


Diagnosis of recurrent venous thromboembolism.
The diagnostic management of suspected recurrent venous thromboembolism (VTE) is challenging for four main reasons. First, clinical decision rules are less useful to identity patients with a low pre-test probability. Second, the diagnostic performance of D-dimer tests is decreased. Together, these two point lead to a clearly lower proportion of patients in whom recurrent VTE can be ruled out without performing imaging tests. Third, recurrent thrombi may be difficult to differentiate from residual thrombi, which may be often identified in patients with a history of VTE. Fourth and lastly, the prevalence of VTE in patients with suspected recurrent disease is higher than in patients with suspected first VTE. As a consequence, the failure rates of the algorithms in patients with suspected recurrent VTE are higher as well, underling the relevance of accurate diagnostic management of this specific patient population. There is a lack of large well designed diagnostic studies that focus mainly on patients with prior VTE. Even so, available evidence suggests that diagnostic algorithms validated for first VTE are also largely applicable to suspected recurrent VTE. Emerging imaging techniques such as magnetic resonance direct thrombus imaging (MRDTI) are likely to improve the accuracy of the algorithms in the near future.


Sign Switch of Gaussian Bending Modulus for Microemulsions: A Self-Consistent Field Analysis Exploring Scale Invariant Curvature Energies.
Bending rigidities of tensionless balanced liquid-liquid interfaces as occurring in microemulsions are predicted using self-consistent field theory for molecularly inhomogeneous systems. Considering geometries with scale invariant curvature energies gives unambiguous bending rigidities for systems with fixed chemical potentials: the minimal surface Im3m cubic phase is used to find the Gaussian bending rigidity κ[over ¯], and a torus with Willmore energy W=2π^{2} allows for direct evaluation of the mean bending modulus κ. Consistent with this, the spherical droplet gives access to 2κ+κ[over ¯]. We observe that κ[over ¯] tends to be negative for strong segregation and positive for weak segregation, a finding which is instrumental for understanding phase transitions from a lamellar to a spongelike microemulsion. Invariably, κ remains positive and increases with increasing strength of segregation.


Uncoupling response inhibition.
The ability to prevent unwanted movement is fundamental to human behavior. When healthy adults must prevent a subset of prepared actions, execution of the remaining response is markedly delayed. We hypothesized that the delay may be sensitive to the degree of similarity between the prevented and continued actions. Fifteen healthy participants performed an anticipatory response inhibition task that required bilateral index finger extension or thumb abduction with homogeneous digit pairings, or a heterogeneous pairing of a combination of the two movements. We expected that the uncoupling of responses required for selective movement prevention would be more difficult with homogeneous (same digit, homologous muscles) than heterogeneous pairings (different digits, nonhomologous muscles). Measures of response times (and asynchrony between digits) during action execution, stopping performance, and electromyography from EIP (index finger extension) and APB (thumb abduction) were analyzed. As expected, selective trials produced a delay in the remaining movement compared with execution trials. Successful performance in the selective condition occurred via suppression of the entire prepared response and subsequent selective reinitiation of the remaining component. Importantly, the delayed reinitiation of motor output was sensitive to the degree of similarity between responses, occurring later but at a faster rate with homogeneous digits. There were persistent aftereffects from the selective condition on the motor system, which indicated greater levels of inhibition and a higher gain were necessary to successfully perform selective trials with homogeneous pairings. Overall, the results support a model of inhibition of a unitary response and selective reinitiation, rather than selective inhibition.


Use of Anecdotal Occurrence Data in Species Distribution Models: An Example Based on the White-Nosed Coati (Nasua narica) in the American Southwest.
Species distributions are usually inferred from occurrence records. However, these records are prone to errors in spatial precision and reliability. Although influence of spatial errors has been fairly well studied, there is little information on impacts of poor reliability. Reliability of an occurrence record can be influenced by characteristics of the species, conditions during the observation, and observer's knowledge. Some studies have advocated use of anecdotal data, while others have advocated more stringent evidentiary standards such as only accepting records verified by physical evidence, at least for rare or elusive species. Our goal was to evaluate the influence of occurrence records with different reliability on species distribution models (SDMs) of a unique mammal, the white-nosed coati (Nasua narica) in the American Southwest. We compared SDMs developed using maximum entropy analysis of combined bioclimatic and biophysical variables and based on seven subsets of occurrence records that varied in reliability and spatial precision. We found that the predicted distribution of the coati based on datasets that included anecdotal occurrence records were similar to those based on datasets that only included physical evidence. Coati distribution in the American Southwest was predicted to occur in southwestern New Mexico and southeastern Arizona and was defined primarily by evenness of climate and Madrean woodland and chaparral land-cover types. Coati distribution patterns in this region suggest a good model for understanding the biogeographic structure of range margins. We concluded that occurrence datasets that include anecdotal records can be used to infer species distributions, providing such data are used only for easily-identifiable species and based on robust modeling methods such as maximum entropy. Use of a reliability rating system is critical for using anecdotal data.


Responsiveness of isolated dog veins to bradykinin and other bioactive peptides: distribution of sensitivity to bradykinin and possible correlation with genesis of the venous system.
Contractile responses of isolated dog veins to bradykinin were studied. Responses to norepinephrine were taken as standards. According to their sensitivity to bradykinin, the veins obtained from 14 sites of the venous system were divided into two groups, while all the veins were almost uniform in their sensitivity to norepinephrine. One group has high sensitivity to bradykinin and the other has low sensitivity. The former includes the pulmonary, hepatic, splenic, and portal veins, the anterior vena cava, and the upper and the middle divisions of the posterior vena cava. The latter includes the external jugular, cephalic, azygos, femoral, and saphenous veins, and the lower division of the posterior vena cava. The responses of the renal vein were intermediate. A striking correlation was noted between the distribution of bradykinin sensitivity and the genesis of the venous system. Five bioactive peptides other than bradykinin were also studied. Only angiotensin induced contraction in some preparation, but, as a whole, caerulein, eledoisin-related peptide, oxytocin and vasopressin rarely showed contractile activity.


Building accountability into the Internet of Things: the IoT Databox model.
This paper outlines the IoT Databox model as a means of making the Internet of Things (IoT) accountable to individuals. Accountability is a key to building consumer trust and is mandated by the European Union's general data protection regulation (GDPR). We focus here on the 'external' data subject accountability requirement specified by GDPR and how meeting this requirement turns on surfacing the invisible actions and interactions of connected devices and the social arrangements in which they are embedded. The IoT Databox model is proposed as an in principle means of enabling accountability and providing individuals with the mechanisms needed to build trust into the IoT.


Study of the area affected by onchocerciasis in Brazil: survey of local residents.
An epidemiologic survey encompassing most of Brazil's Federal Territory of Roraima and the northern tip of Amazonas State has been carried out in an effort to define the boundaries and the epidemiologic characteristics of onchocerciasis in Brazil. This article describes results relating to human infections--including discovery of a new focus at Auaris in northern Roraima and analysis of data from tests conducted there and at various other locations. These findings lead the authors to conclude that the three known Brazilian foci represent independent influxes of the disease from neighboring Venezuela, that groups of both Yanomama and Makiritare Indians have been infected, and that various factors (including proximity of these foci and the route for Brazil's Northern Perimeter Highway) indicate the disease could pose a potential danger for other areas of Brazil.


Resistance in long-term cancer support groups.
This article describes the common resistance patterns that occur in ongoing cancer support groups. These resistances, which can often go unrecognized, are a normal part of group development and group life in such groups, rather than the result of a few "problem" group members. The thesis of this article posits that the identification and working through of these resistances creates openings to deeper engagement among members and to overall greater group cohesion. Technical guidelines are offered for working with these resistances in the group-as-a-whole, in members, and also in the therapist.


The Detection of Date Shifting in Real-World Data.
Analysis of health care real-world data (RWD) provides an opportunity to observe the actual patient diagnostic, treatment, and outcome events. However, researchers should understand the possible limitations of RWD. In particular, the dates in these data may be shifted from their actual values, which might affect the validity of study conclusions. A methodology for detecting the presence of shifted dates in RWD was developed by considering various approaches to confirm the expected occurrences of medical events, including unique temporal occurrences as well as recurring seasonal or weekday patterns in diagnoses or procedures. Diagnosis and procedure data was obtained from 71 U.S. health care data provider organizations (HCOs), members of the TriNetX global research network. Synthetic data was generated for various degrees of date shifting corresponding to the diagnoses and procedures studied, yielding the resulting patterns when various degrees of shifting (including no shift) were applied. These patterns were compared with those produced for each HCO to predict the presence and degree of date shifting. These predictions were compared with statements of date shifting by the originating HCOs to determine the predictive accuracy of the methods studied. Twenty-eight of the 71 HCOs analyzed were predicted by methodology and confirmed by their data providers to have shifted data. Likewise, 39 were predicted and confirmed to not have shifted data. With four HCOs, agreement between predicted and stated date shifting status was not obtained. The occurrence of routine medical exams, only happening during weekdays, for these U.S. HCOs was most predictive (0.92 correlation coefficient) of the presence or absence of date shifting. The presence of date shifting for U.S. HCOs may be reliably detected assessing whether the routine exams should always occur on weekdays.


QTAIM analysis of the bonding in Mo-Mo bonded dimolybdenum complexes.
A number of local and integral topological parameters of the electron density of relevant bonding interactions in the binuclear molybdenum complexes [Mo(2)Cl(8)](4-), [Mo(2)(μ-CH(3)CO(2))(4)], [Mo(2)(μ-CF(3)CO(2))(4)], [Mo(2)(μ-CH(3)CO(2))(4)Br(2)](2-), [Mo(2)(μ-CF(3)CO(2))(4)Br(2)](2-), [Mo(2)(μ-CH(3)CO(2))(2)Cl(4)](2-), [Mo(2)(μ-CH(3)CO(2))(2)(μ-Cl)(2)Cl(4)](2-), and [Mo(2)(μ-Cl)(3)Cl(6)](3-) have been calculated and interpreted under the perspective of the quantum theory of atoms in molecules (QTAIM). These data have allowed a comparison between related but different atom-atom interactions, such as different Mo-Mo formal bond orders, ligand-unbridged versus Cl-bridged, CH(3)CO(2)-bridged, and CF(3)CO(2)-bridged Mo-Mo interactions, and Mo-Cl(terminal) and Mo-Cl(bridge) versus Mo-Br and Mo-O interactions. Calculations carried out using nonrelativistic and relativistic approaches afforded similar results.


Dynamic Kinetic Resolution of Axially Chiral Naphthamides via Atroposelective Allylic Alkylation Reaction.
Axially chiral amides are usually found in many biologically active compounds and are useful ligands in asymmetric catalysis. Herein, by using the dynamic kinetic resolution approach, an asymmetric allylic alkylation reaction of racemic amide naphthols is disclosed, which leads to generation of the axially chiral naphthamides in good to excellent yields (up to 97%) and enantioselectivities (up to 96:4 e.r.). Density functional theory was used to gain a theoretical understanding of the enantioselectivities in this reaction.


Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis.
ABT-494 is a potent and selective Janus kinase (JAK) 1 inhibitor being developed for the treatment of several autoimmune disorders, with potential for an improved safety profile compared with non-selective JAK inhibitors. This work characterized the pharmacokinetics, safety, and tolerability of ABT-494 following single and multiple dosing of the immediate-release formulation. ABT-494 single (1-48 mg or placebo; n = 56) and multiple (3-24 mg or placebo twice daily for 14 days; n = 44) doses in healthy subjects, as well as multiple doses (3-24 mg or placebo twice daily for 27 days; n = 14) in subjects with rheumatoid arthritis (RA) on a background of methotrexate were evaluated. Pharmacokinetic samples were collected and safety and tolerability were assessed. ABT-494 followed bi-exponential disposition, with a terminal elimination half-life of 6-16 h and a functional half-life, calculated from maximum observed plasma concentration (C max) to trough plasma concentration (C trough) ratio at steady state, of 3-4 h. ABT-494 exposure was approximately dose proportional over the 3-36 mg dose range, with no significant accumulation with repeated dosing. In subjects with RA, no pharmacokinetic interaction between ABT-494 and methotrexate was observed. The fraction of ABT-494 dose eliminated in urine as unchanged ABT-494 was 14-25 %. All treatment-emergent adverse events (TEAEs) were mild or moderate in severity, with headache being the most frequently observed TEAE (15.6 % for ABT-494 vs. 16.7 % for placebo) after multiple twice-daily administration to healthy subjects. No clinically significant changes in laboratory parameters, vital signs, or electrocardiogram findings in healthy or RA subjects were observed. The favorable pharmacokinetics, safety, and tolerability results from these studies supported further evaluations of ABT-494 in phase IIb dose-ranging trials in RA and Crohn's disease. ClinicalTrials.gov ( https://clinicaltrials.gov/ ) identifier: NCT01741493.


Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Indomethacin Disposition in Pregnancy.
Findings of a recent clinical study showed indomethacin has lower plasma levels and higher steady-state apparent clearance in pregnant subjects when compared to those in non-pregnant subjects reported in separate studies. Thus, in the current work we developed a pregnancy physiological based pharmacokinetic/pharmacodynamic (PBPK/PD) model for indomethacin to explain the differences in indomethacin pharmacokinetics between pregnancy and non-pregnancy. A whole-body PBPK model with key pregnancy-related physiological changes was developed to characterize indomethacin PK in pregnant women and compare these parameters to those in non-pregnant subjects. Data related to maternal physiological and biological changes were obtained from literature and incorporated into the structural PBPK model that describes non-pregnant PK data. Changes in indomethacin area under the curve (AUC), maximum concentration (Cmax) and average steady-state concentration (Cave) in pregnant women were predicted. Model-simulated PK profiles were in agreement with observed data. The predicted mean ratio (non-pregnant:second trimester (T2)) of indomethacin Cave was 1.6 compared to the observed value of 1.59. In addition, the predicted steady-state apparent clearance (CL/Fss) ratio was almost similar to the observed value (0.46 vs. 0.42). Sensitivity analysis suggested changes in CYP2C9 activity, and to a lesser extent UGT2B7, as the primary factor contributing to differences in indomethacin disposition between pregnancy and non-pregnancy. The developed PBPK model which integrates prior physiological knowledge, in vitro and in vivo data, allowed the successful prediction of indomethacin disposition during T2. Our PBPK/PD model suggested a higher indomethacin dosing requirement during pregnancy.


Acidemia versus hypercapnia and risk for severe intraventricular hemorrhage.
In extremely low birth weight (ELBW) infants, levels of hypercapnia (Paco 2) > 60 mm Hg are considered a risk factor for severe intraventricular hemorrhage (IVH). Since cerebral vasoreactivity depends on arterial pH (apH) rather than Paco 2, we hypothesize that the role of mild-to-moderate hypercapnia (45-60 mm Hg) in the occurrence of severe IVH is modulated by the metabolic component of acid-base status. ELBW infants (n = 580, born < 28 wk gestation, and BW < 1,000 g) were separated into "high-base deficit (BD)" (n = 291) and "low-BD" (n = 289) groups if infants' median BD were > 4 mEq/L or ≤4 mEq/L, respectively. Rates of severe IVH were higher in "high-BD" (16%) than "low-BD" (9%) group. Although adjusted risk for severe IVH increased with higher Paco 2 and higher BD, apH was the sole predictor of severe IVH. In ELBW infants, higher degree of acidemia, rather than hypercapnia per se, during the first 48 hours of life, is associated with higher occurrences of severe IVH.


Design of an enzyme cocktail consisting of different fungal platforms for efficient hydrolysis of sugarcane bagasse: Optimization and synergism studies.
Lignocellulosic materials represent a very important and promising source of renewable biomass. In order to turn them into fermentable sugars, synergism among the different enzymes that carry out bioconversion of these materials is one of the main factors that should be considered. Experimental mixture design was performed to optimize the proportion of enzymes produced by native strains of Trichoderma harzianum IOC 3844, Penicillium funiculosum ATCC 11797, and Aspergillus niger ATCC 1004, resulting in a proportion of 15, 50, and 35%, respectively. This mixture was able to hydrolyze 25 g/L of pretreated sugarcane bagasse with 91% of yield after 48 h of enzymatic reaction. Synergism along the hydrolysis process, besides the influence of lignin, hemicellulose, and solids loading, were also studied. Response surface methodology (RSM) based on Central Composite Rotatable Design was used to optimize solids and protein loadings to increase glucose release and enzymatic hydrolysis yield. The optimum solid and protein loadings established with RSM were 196 g/L and 24 mg/g cellulose, respectively, and under these conditions (94.1 ± 8) g/L of glucose were obtained, corresponding to a hydrolysis yield of 64%. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1222-1229, 2016.


The Parkinson's Disease Protein LRRK2 Interacts with the GARP Complex to Promote Retrograde Transport to the trans-Golgi Network.
Mutations in Leucine-rich repeat kinase 2 (LRRK2) cause Parkinson's disease (PD). However, the precise function of LRRK2 remains unclear. We report an interaction between LRRK2 and VPS52, a subunit of the Golgi-associated retrograde protein (GARP) complex that identifies a function of LRRK2 in regulating membrane fusion at the trans-Golgi network (TGN). At the TGN, LRRK2 further interacts with the Golgi SNAREs VAMP4 and Syntaxin-6 and acts as a scaffolding platform that stabilizes the GARP-SNAREs complex formation. Therefore, LRRK2 influences both retrograde and post-Golgi trafficking pathways in a manner dependent on its GTP binding and kinase activity. This action is exaggerated by mutations associated with Parkinson's disease and can be blocked by kinase inhibitors. Disruption of GARP sensitizes dopamine neurons to mutant LRRK2 toxicity in C. elegans, showing that these pathways are interlinked in vivo and suggesting a link in PD.


Helices on Interdomain Interface Couple Catalysis in the ATPPase Domain with Allostery in Plasmodium falciparum GMP Synthetase.
GMP synthetase catalyses the conversion of XMP to GMP through a series of reactions that include hydrolysis of Gln to generate ammonia in the glutamine amidotransferase (GATase) domain, activation of XMP to adenyl-XMP intermediate in the ATP pyrophosphatase (ATPPase) domain and reaction of ammonia with the intermediate to generate GMP. The functioning of GMP synthetases entails bidirectional domain crosstalk, which leads to allosteric activation of the GATase domain, synchronization of catalytic events and tunnelling of ammonia. Herein, we have taken recourse to the analysis of structures of GMP synthetases, site-directed mutagenesis and steady-state and transient kinetics on the Plasmodium falciparum enzyme to decipher the molecular basis of catalysis in the ATPPase domain and domain crosstalk. Our results suggest an arrangement at the interdomain interface, of helices with residues that play roles in ATPPase catalysis as well as domain crosstalk enabling the coupling of ATPPase catalysis with GATase activation. Overall, the study enhances our understanding of GMP synthetases, which are drug targets in many infectious pathogens.


Studies on the encapsulation of diclofenac in small unilamellar liposomes of soya phosphatidylcholine.
The encapsulation of acid (AD) and sodium diclofenac (SD) in small unilamellar liposomes (SUV) as well as the interactions of the drug with the bilayer was studied. SUV was prepared by sonication from multilamellar liposomes containing soya phosphatidylcholine and diclofenac at various proportions. The size distribution obtained from dynamic light scattering showed that the incorporation of SD decreases significantly the size of the liposomes suggesting that the drug interacts with the bilayer of the liposomes. This size decrease is related with the phase transition of liposomes to mixed micelar solution. The encapsulation of the hydrophilic dye indocyanine green in the aqueous compartment of liposomes showed that the rate of captured dye decreases with SD concentration suggesting the transition of liposomes to mixed micelles. The (31)P NMR analysis indicates that SD interacts with the phosphate of phosphatidylcholine head groups. A schematic model for interaction of SD with phosphatidylcholine of the liposomes in which the diclofenac anion interacts with the ammonium group of the phospholipid and the dichlorophenyl ring occupies a more internal site of bilayer near phosphate group was proposed.


MicroRNAs as regulatory elements in psoriasis.
Psoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.


Neural variability, or lack thereof.
We do not claim that the brain is completely deterministic, and we agree that noise may be beneficial in some cases. But we suggest that neuronal variability may be often overestimated, due to uncontrolled internal variables, and/or the use of inappropriate reference times. These ideas are not new, but should be re-examined in the light of recent experimental findings: trial-to-trial variability is often correlated across neurons, across trials, greater for higher-order neurons, and reduced by attention, suggesting that "intrinsic" sources of noise can only account for a minimal part of it. While it is obviously difficult to control for all internal variables, the problem of reference time can be largely avoided by recording multiple neurons at the same time, and looking at statistical structures in relative latencies. These relative latencies have another major advantage: they are insensitive to the variability that is shared across neurons, which is often a significant part of the total variability. Thus, we suggest that signal-to-noise ratios in the brain may be much higher than usually thought, leading to reactive systems, economic in terms of number of neurons, and energy efficient.


Analysis of the Molecular Mechanisms of Reepithelialization in Drosophila Embryos.
Significance: The epidermis provides the main barrier function of skin, and therefore its repair following wounding is an essential component of wound healing. Repair of the epidermis, also known as reepithelialization, occurs by collective migration of epithelial cells from around the wound edge across the wound until the advancing edges meet and fuse. Therapeutic manipulation of this process could potentially be used to accelerate wound healing. Recent Advances: It is difficult to analyze the cellular and molecular mechanisms of reepithelialization in human tissue, so a variety of model organisms have been used to improve our understanding of the process. One model system that has been especially useful is the embryo of the fruit fly Drosophila, which provides a simple, accessible model of the epidermis and can be manipulated genetically, allowing detailed analysis of reepithelialization at the molecular level. This review will highlight the key insights that have been gained from studying reepithelialization in Drosophila embryos. Critical Issues: Slow reepithelialization increases the risk of wounds becoming infected and ulcerous; therefore, the development of therapies to accelerate or enhance the process would be a great clinical advance. Improving our understanding of the molecular mechanisms that underlie reepithelialization will help in the development of such therapies. Future Directions: Research in Drosophila embryos has identified a variety of genes and proteins involved in triggering and driving reepithelialization, many of which are conserved in humans. These novel reepithelialization proteins are potential therapeutic targets and therefore findings obtained in Drosophila may ultimately lead to significant clinical advances.


M and N specific hemagglutinins of human erythrocytes stored in glucose solutions.
Alloagglutinins of M and N specificites with unique characteristics found in normal sera are described. Specific M or N agglutination by these sera occurred only when erythrocytes had been exposed to glucose-containing solutions. Conversion to the form of MN recognized by these sera required incubation of the cells in 1 to 2% glucose buffered to physiological or alkaline pH and was dependent on time and temperature of exposure, occurring in hours at 37 C and in days at 4 C. The sera appeared to be detecting an antigenic structure in which interaction between glucose and the amino group of the N-terminal amino acid of the MN receptor has produced a new specificity, analogous to the action of formaldehyde on N receptors and the resulting N-like structure detected by sera from hemodialysis patients.


"Currently flying blind" Stakeholders' perceptions of implementing statewide population-based cancer staging at diagnosis into the Western Australian Cancer Registry: a rapid qualitative process evaluation of the WA Cancer Staging Project.
Cancer stage at diagnosis is essential for understanding cancer outcomes, guiding cancer control activities and healthcare services, and enabling benchmarking nationally and internationally. Yet, most cancer registries in Australia do not routinely collect this data. This study explored key stakeholders' perceptions of implementing cancer staging utilising Natural Language Processing and Machine Learning algorithms within the Western Australian Cancer Registry. Perceptions of key breast and colorectal cancer stakeholders, including registry staff, clinicians, consumers, data scientists, biostatisticians, data management, healthcare staff, and health researchers, were collected. Prospective and retrospective qualitative proformas at two-time points of the Western Australian Cancer Staging Project were employed. The Consolidated Framework for Implementation Research was used to guide data collection, analysis and interpretation embedded in a Participatory Action Research approach. Data analysis also incorporated Framework Analysis and an adapted version of grading qualitative data using a visual traffic light labelling system to highlight the levels of positivity, negativity, and implementation concern. Twenty-nine pre-proformas and 18 post-proformas were completed online via REDCap. The grading and visual presentation of barriers and enablers aided interpretation and reviewing predicted intervention outcomes. Of the selected constructs, complexity (the perceived difficulty of the intervention) was the strongest barrier and tension for change (the situation needing change) was the strongest enabler. Implementing cancer staging into the Western Australian Cancer Registry was considered vital. Benefits included improved knowledge and understanding of various outcomes (e.g., treatment received as per Optimum Care Pathways) and benchmarking. Barriers included compatibility issues with current systems/workflows, departmental/higher managerial support, and future sustainment. The findings aid further review of data gaps, additional cancer streams, standardising cancer staging and future improvements. The study offers an adapted version of a rapid qualitative data collection and analytic approach for establishing barriers and enablers. The findings may also assist other population-based cancer registries considering collecting cancer stage at diagnosis.


Noninvasive gene delivery to the liver by mechanical massage.
With the recent completion of the human genome project and the tremendous growth of biotechnology, the desire to extract information concerning gene expression, protein level, subcellular localization, and functionality in the liver will demand the development of efficient gene transfer to this organ with minimal toxicity. In this report, we show that significant gene expression in the liver could be achieved by simple mechanical massage after intravenous injection of naked plasmid DNA into mice. This method is simple, highly reproducible, repeatable, and, more importantly, free of toxicity. Hepatic gene transfer with hepatocyte growth factor (HGF) plasmid DNA prevented endotoxin-induced lethal fulminant hepatic failure, leading to dramatically enhanced survival in mice.


Evaluation strategies and uncertainty calculation of isotope amount ratios measured by MC ICP-MS on the example of Sr.
This paper critically reviews the state-of-the-art of isotope amount ratio measurements by solution-based multi-collector inductively coupled plasma mass spectrometry (MC ICP-MS) and presents guidelines for corresponding data reduction strategies and uncertainty assessments based on the example of n((87)Sr)/n((86)Sr) isotope ratios. This ratio shows variation attributable to natural radiogenic processes and mass-dependent fractionation. The applied calibration strategies can display these differences. In addition, a proper statement of uncertainty of measurement, including all relevant influence quantities, is a metrological prerequisite. A detailed instructive procedure for the calculation of combined uncertainties is presented for Sr isotope amount ratios using three different strategies of correction for instrumental isotopic fractionation (IIF): traditional internal correction, standard-sample bracketing, and a combination of both, using Zr as internal standard. Uncertainties are quantified by means of a Kragten spreadsheet approach, including the consideration of correlations between individual input parameters to the model equation. The resulting uncertainties are compared with uncertainties obtained from the partial derivatives approach and Monte Carlo propagation of distributions. We obtain relative expanded uncertainties (U rel; k = 2) of n((87)Sr)/n((86)Sr) of < 0.03 %, when normalization values are not propagated. A comprehensive propagation, including certified values and the internal normalization ratio in nature, increases relative expanded uncertainties by about factor two and the correction for IIF becomes the major contributor.


Post-traumatic stress disorder in nurses: An integrative review.
To synthesise literature regarding PTSD among nurses. Two objectives guided this review: (a) describe the prevalence of PTSD in registered nurses and (b) identify factors associated with nursing work-related PTSD. Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can occur from direct or indirect exposure to traumatic events. Nurses are at risk of developing PTSD due to their indirect and/or direct exposure to traumatic situations while providing care to vulnerable patient populations. An integrative review. A literature search was conducted in PubMed and the Cumulative Index of Nursing and Allied Health Literature (CINAHL). Data extraction and quality assessment were independently performed by two reviewers. Data analysis procedures consisted of four concurrent activities: data reduction, data display, data comparison and conclusion drawing and verification. Conclusions were narratively synthesised and thematically presented by review objective using PRISMA guidelines. Twenty-four articles met criteria for review. One theme emerged from the synthesis of literature describing the prevalence of PTSD in nurses: All Over the Board. Authors reported vastly different PTSD prevalence rates across studies likely due to variability in measurement. Four themes emerged from the synthesis of factors that influence PTSD among nurses: The Workplace Matters, Relationships Matter, It Hurts to Care and Interpersonal Strengths. These overarching themes captured a multitude of factors that occur across three levels of influence: organisational, interpersonal and intrapersonal. This integrative review highlights PTSD as a growing concern in the nursing profession. The thematic analysis and associated subthemes provide a framework for the design of interventions to reduce the risk of PTSD symptom development among nurses working in inpatient settings. Multitargeted efforts directed at the organisational, interpersonal and intrapersonal factors identified in this review may help mitigate the harmful impact of PTSD and promote nurse well-being.


Direct Growth of MoS2 Nanowalls on Carbon Nanofibers for Use in Supercapacitor.
Direct growth of MoS2 nanowalls on vapor grown carbon nanofibers (VGCNFs) has been achieved using a microwave-assisted hydrothermal (MAH) method under an acidic condition. The acidic condition was obtained through the addition of an HCl aqueous solution. We demonstrate that the HCl not only modifies the pH value for limiting the growth rate but also leads to the formation of NaCl, which is the key for the direct and unique growth of MoS2 on the VGCNF surface. A growth mechanism is therefore proposed. The growth of MoS2 onto the high electrically conducting VGCNF creates a unique structure that not only reduces the aggregation of MoS2 but also improves the electrical conductivity of the resulting composite electrode. The MoS2 nanowall/VGCNF composite shows Csp as high as 248 F g-1 at 5 mV s-1 and excellent electrochemical stability with a retention of 96% after 1,000 cycles at a high charge rate of 200 mV s-1. The ease of composite fabrication and electrochemical stability suggest that the MoS2 nanowall/VGCNF composite is a promising candidate electrode material for supercapacitor.


All-Inkjet-Printed Flexible Nanobio-Devices with Efficient Electrochemical Coupling Using Amphiphilic Biomaterials.
Nanostructured flexible electrodes with biological compatibility and intimate electrochemical coupling provide attractive solutions for various emerging bioelectronics and biosensor applications. Here, we develop all-inkjet-printed flexible nanobio-devices with excellent electrochemical coupling by employing amphiphilic biomaterial, an M13 phage, numerical simulation of single-drop formulation, and rational formulations of nanobio-ink. Inkjet-printed nanonetwork-structured electrodes of single-walled carbon nanotubes and M13 phage show efficient electrochemical coupling and hydrostability. Additive printing of the nanobio-inks also allows for systematic control of the physical and chemical properties of patterned electrodes and devices. All-inkjet-printed electrochemical field-effect transistors successfully exhibit pH-sensitive electrical current modulation. Moreover, all-inkjet-printed electrochemical biosensors fabricated via sequential inkjet-printing of the nanobio-ink, electrolytes, and enzyme solutions enable direct electrical coupling within the printed electrodes and detect glucose concentrations at as low as 20 μM. Glucose levels in sweat are successfully measured, and the change in sweat glucose levels is shown to be highly correlated with blood glucose levels. Synergistic combination of additive fabrication by inkjet-printing with directed assembly of nanostructured electrodes by functional biomaterials could provide an efficient means of developing bioelectronic devices for personalized medicine, digital healthcare, and emerging biomimetic devices.


Is ovarian relaxin a stimulus to placental protein 14 secretion in pregnancy?
The objective of this study was to investigate whether relaxin might be involved in placental protein 14 (PP14) secretion by measuring serum levels of PP14 during labour and post partum in normal women with a term pregnancy given vaginal human recombinant relaxin (rhRlx) gel for induction of labour. A randomized double-blind controlled trial was conducted on 11 women with a singleton pregnancy at term admitted for induction of labour. Comparison of serum PP14 and relaxin concentrations in the control and treated groups of subjects revealed that there was an increase in serum relaxin concentrations in women receiving 3 mg or 6 mg relaxin. There was no difference in serum PP14 levels between the control and treatment groups. These findings do not support the hypothesis that relaxin is involved in the control of PP14 secretion. However, the failure of any response might be a consequence of the very small increase in systemic levels of relaxin produced by topical vaginal administration of rhRlx. Furthermore, these measurements were made in late pregnancy and hence may not relate to the events in early pregnancy, when serum levels of PP14 are maximal.


Dynamic thermal expansivity of liquids near the glass transition.
Based on previous works on polymers by Bauer et al. [Phys. Rev. E 61, 1755 (2000)], this paper describes a capacitative method for measuring the dynamical expansion coefficient of a viscous liquid. Data are presented for the glass-forming liquid tetramethyl tetraphenyl trisiloxane (DC704) in the ultraviscous regime. Compared to the method of Bauer et al., the dynamical range has been extended by making time-domain experiments and by making very small and fast temperature steps. The modeling of the experiment presented in this paper includes the situation in which the capacitor is not full because the liquid contracts when cooling from room temperature down to around the glass-transition temperature, which is relevant when measuring on a molecular liquid rather than a polymer.


Small-subunit rRNA Phylogenies Suggest That Epalxella antiquorum (penard, 1922) corliss, 1960 (ciliophora, odontostomatida) is a member of the plagyopylea.
The odontostomatid ciliates have remained a homogeneous order of ciliates since the 1930s when they were recognized as a monophyletic assemblage. Since that time they have been placed with the heterotrich ciliates, and more recently transferred as incertae sedis to the new "riboclass" class Armophorea. We were able to obtain the small subunit rRNA gene sequence of the odontostomatid Epalxella antiquorum (Penard, 1922) Corliss, 1960, collected from the meromictic alpine Lake Alat in Germany, in July 2005. An alignment with representatives of all 11 classes of ciliates unambiguously places the Epalxella sequence with other representatives of the class Plagiopylea with 100% support in both maximum likelihood and Bayesian analyses. Epalxella is the basal lineage with trimyemid and plagiopylid ciliates forming the two terminal sister clades. While this molecular support is strong and unambiguous, there are no obvious morphological features to unite these three clades. Thus, the class Plagiopylea must continue to be referred to as a "riboclass." Using the Epalxella sequence as a basal marker, we tentatively identified 20 environmental sequences to the terminal plagiopylean clades: eight to the genus Trimyema; four to the genus Plagiopyla; and eight to two new species, one of which might represent a new plagiopylean genus.


Impact of the human immunodeficiency virus epidemic on detection of Mycobacterium isolates in a general hospital.
The number of human samples processed in our mycobacteriology laboratory ranged from 148 per 1,000 admissions in 1988 to 263 per 1,000 admissions in 1995 (5.2% were positive). The human immunodeficiency virus (HIV)-positive population contributed 33.3% of all samples, 43.3% of all isolates, and 36% of all new patients. Given that the ratios of the total number of samples to the number of Mycobacterium-positive samples were 18.3:1 in HIV-positive patients and 28:1 in HIV-negative patients, efforts to reduce the laboratory workload should begin with the HIV-negative population.


Tailoring magnetic nanoparticle for transformers application.
In this study photoacoustic spectroscopy was used to investigate the effect of dilution of an oil-based magnetic fluid sample on the magnetic nanoparticle surface-coating. Changes of the photoacoustic signal intensity on the band-L region (640 to 830 nm) upon dilution of the stock magnetic fluid sample were discussed in terms of molecular surface desorption. The model proposed here assumes that the driving force taking the molecules out from the nanoparticle surface into the bulk solvent is the gradient of osmotic pressure. This gradient of osmotic pressure is established between the nanoparticle surface and the bulk suspension. It is further assumed that the photoacoustic signal intensity (area under the photoacoustic spectra) scales linearly with the number of coating molecules (surface grafting) at the nanoparticle surface. This model picture provides a non-linear analytical description for the reduction of the surface grafting coefficient upon dilution, which was successfully-used to curve-fit the photoacoustic experimental data.


Effect of tactile stimulation on serum lactate in the newborn rat.
Maturation of the CNS in neonatal animals is dependent upon both sensory input and the constant availability of metabolic fuel. Previous reports indicate that the preferred metabolic substrate for the developing rat brain is lactate. In this study, we used the neonatal Sprague-Dawley rat to investigate a possible interactive role between touch and the regulation of serum lactate. Two hundred and fifty rats (postnatal d 0-7) were exposed to a standard tactile stimulation (TS) regimen to mimic nonspecific maternal stimulation. This regimen consisted of stroking the dorsum with a soft camel hair brush for 30 s every minute for 10 min. Serum lactate and glucose levels were measured after TS. In newborn (d 0) rats, lactate levels were increased by 207% in stroked pups versus controls. This elevation of serum lactate persisted for 30 min after cessation of TS. On d 7, TS increased lactate only 11%. Glucose levels were unaffected at all ages. In neonatal pups, pretreatment with pentobarbital blocked the effect of TS, whereas epidermal growth factor evoked a synergistic response. Capsaicin pretreatment had no effect. Mixed arteriovenous blood gases revealed a mild increase in pH and a decrease in Pco2 after TS. We conclude that TS in newborn rats is a regulator of circulating lactate. This response is maximal in the immediate postnatal period and wanes over the 1st wk of life. We speculate that the transduction of sensory signals by the skin is a mechanism regulating the availability of cerebral energy substrates in the newborn mammal.


Vasopressors for shock.
Besides reversing the underlying cause, the first line treatment for the symptoms of shock is usually the administration of intravenous fluids. If this method is not successful, vasopressors such as dopamine, dobutamine, adrenaline, noradrenaline and vasopressin are recommended. It is unclear if there is a vasopressor of choice, either for the treatment of particular forms of shock or for the treatment of shock in general. To assess the efficacy of vasopressors for circulatory shock in critically ill patients. Our main aim was to assess whether particular vasopressors reduce overall mortality. We also intended to identify whether the choice of vasopressor influences outcomes such as length-of-stay in the intensive care unit and health-related quality of life. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, PASCAL BioMed, CINAHL, BIOSIS, and PsychINFO:all from inception to November 2003; for randomized controlled trials. We also asked experts in the field and searched meta-registries for ongoing trials. We included randomized controlled trials comparing various vasopressors, vasopressors with placebo or vasopressors with intravenous fluids for the treatment of any kind of circulatory failure (shock). Mortality was the main outcome. Two reviewers abstracted data independently. Disagreement between two reviewers was discussed and resolved with a third reviewer. We used random effects models for combining quantitative data. We identified eight randomized controlled trials. Reporting of methodological details was for many items not satisfactory: only two studies reported allocation concealment, and two that the outcome assessor was blind to the intervention. Two studies compared norepinephrine plus dobutamine with epinephrine alone in patients with septic shock (52 patients, relative risk of death 0.98, 95% confidence interval 0.57 to 1.67). Three studies compared norepinephrine with dopamine in patients with septic shock (62 patients, relative risk 0.88, 0.57 to 1.36). Two studies compared vasopressin with placebo in patients with septic shock (58 patients, relative risk 1.04, 0.06 to 19.33). One study compared terlipressin with norepinephrine in patients with refractory hypotension after general anaesthesia but there were no deaths (20 patients). The current available evidence is not suited to inform clinical practice. We were unable to determine whether a particular vasopressor is superior to other agents in the treatment of states of shock.


Postembryonic development of the bone-eating worm Osedax japonicus.
Bone-eating worms of the genus Osedax exclusively inhabit sunken vertebrate bones on the seafloor. The unique lifestyle and morphology of Osedax spp. have received much scientific attention, but the whole process of their development has not been observed. We herein report the postembryonic development and settlement of Osedax japonicus Fujikura et al. (Zool Sci 23:733-740, 2006). Fertilised eggs were spawned into the mucus of a female, and the larvae swam out from the mucus at the trochophore stage. Larvae survived for 10 days under laboratory conditions. The larvae settled on bones, elongated their bodies and crawled around on the bones. Then they secreted mucus to create a tube and the palps started to develop. The palps of O. japonicus arose from the prostomium, whereas the anterior appendages of other siboglinids arose from the peristomium. The recruitment of dwarf males was induced by rearing larvae with adult females. Females started to spawn eggs 6 weeks after settlement.


Expected consequences of convenience euthanasia perceived by veterinarians in Quebec.
In companion animal practice, convenience euthanasia (euthanasia of a physically and psychologically healthy animal) is recognized as one of the most difficult situations. There is little published on veterinary perceptions of the consequences of convenience euthanasia. A qualitative study on the subject based on interviews with 14 veterinarians was undertaken. The animal's interests in the dilemma of convenience euthanasia was taken into consideration, strictly from the point of view of the physical suffering and stress related to the procedure. The veterinarian's goal was to respect the animal's interests by controlling physical pain. Most often, veterinarians made their own interests and those of the owners a priority when considering the consequences of their decision to perform or refuse convenience euthanasia.


Immunological properties of the beta-subunit of human chorionic gonadotropin. I. Effect of chemical and enzymatic modifications.
The beta-subunit of hCG (hCG beta) displays immunological cross-reactivity with human LH (hLH). A detailed study was undertaken to investigate the effect of chemical and enzymatic modifications on the immunological behavior of hCG beta, particularly on its cross-reactivity with hLH, with a view to obtaining a highly hCG-specific antigen. hCG beta was modified in both the carbohydrate and protein parts of the molecule. The carbohydrate part was modified enzymatically by sequential cleavage of monosaccharides by specific glycosidases, and the protein portion was modified chemically in the amino and carboxyl groups and in the cystinyl, tyrosyl, histidyl, and arginyl residues. These derivatives were immunologically evaluated by RIAs; their hCG beta activities were measured in the [125I]hCG beta-anti-hCG beta system, and the hLH cross-reactivity in the [125I]hLH-anti-hLH system. The present studies have led to the following conclusions. 1) The carbohydrate does not play a significant role in the immunological activity of hCG beta. 2) The antigenic determinants of hCG beta reside primarily in the polypeptide chain and are conformational rather than sequential in nature. 3) hCG beta has two types of antigenic determinants, those which are unique to hCG and those which are common to both hCG and hLH. 4) Finally, it is possible to destroy preferentially one or the other type of determinants. The controlled reduction and alkylation of hCG beta yielded derivatives which retain significant immunological activity in the hCG beta system, but have no or reduced cross-reactivity in the hLH system. These derivatives are much more specific antigens than hCG beta and, therefore, are of potential importance for the development of a specific RIA for hCG and possibly for use as contraceptive agents.


The Enduring Power of Magnet®.
More than 3 decades have passed since an enterprising team of nurse researchers unearthed groundbreaking findings that led to the creation of the American Nurses Credentialing Center's Magnet Recognition Program®. Over time, the program has grown bigger and broader than anyone could predict, making a significant impact on nurses, the nursing profession, and healthcare delivery around the world. After the recent upheavals caused by the COVID-19 pandemic, is Magnet® still relevant today? This month's Magnet Perspectives column examines the program's enduring significance and proven value in supporting nurses and helping healthcare organizations navigate the financial, labor, and regulatory challenges of the post-COVID era.


Expression of granzymes A and B in synovial tissue from patients with rheumatoid arthritis and osteoarthritis.
Granzymes A and B are serine proteinases which are stored in the granules of activated cytotoxic T cells and NK cells. Expression of these granzymes by cytotoxic cells in tissues can be used as an activation marker for these cells. To investigate a possible role of cytotoxic lymphocytes in rheumatoid arthritis (RA) and osteoarthritis (OA), we assessed the expression of granzymes A and B by cytotoxic lymphocytes in synovial biopsies from five RA and five OA patients using mAb specific for these serine proteinases. In three of the five RA patients but also in two of the five OA patients granzyme A- and B-expressing lymphocytes were observed in the synovium. Double-labeling immunohistochemical techniques revealed that up to 75% of the granzyme-positive synovial lymphocytes had the CD16+ or CD56+ natural killer cell phenotype. Less than 5% were CD3+, CD8+ cytotoxic T cells, whereas in some patients the phenotype of up to 50% of these cells could not be identified. The presence of granzymes A and B in the synovium of both RA as well as OA patients was confirmed on the molecular level in a second group of 11 RA and 5 OA patients using the polymerase chain reaction. Thus, expression of granzymes A and B occurs in the synovium in patients with RA as well as those with OA. These proteins are mainly expressed by NK cells that may therefore play a role in the pathogenesis of these diseases.


An assessment of drug and substance abuse prevalence: a cross-sectional study among undergraduates in selected southwestern universities in Nigeria.
This cross-sectional study aimed to assess the prevalence and awareness of drug and substance abuse among undergraduates in four southwestern universities in Nigeria. The sample of 400 students included 100 male and female students in the 15- to 29-year age range from each of the four selected universities in southwest Nigeria between December 2019 and June 2020. Descriptive statistics and Pearson chi-square tests were used for data analysis using the statistical package for social sciences (SPSS). Four hundred students satisfied the inclusion criteria and suitably completed the questionnaire. Most respondents were in the 15- to 19-year and 20- to 24-year age groups and were female (68%). Drug and substance abuse prevalence was 45.7%; one in every four students abused substances despite an aggregate risk awareness level of 94.6%. Alcohol and cigarettes-legally and socially accepted substances-were the most abused (61.5% and 54.5%, respectively). Codeine-containing syrup and tramadol topped the list of drugs, ranking higher than cannabis. The major motive was to 'get high' and numb emotional problems caused by predominantly socioeconomic and societal factors. The study showed a notable prevalence of drug and substance abuse across the selected universities in southwest Nigeria.


Cognitive Changes in the Spinocerebellar Ataxias Due to Expanded Polyglutamine Tracts: A Survey of the Literature.
The dominantly-inherited ataxias characterised by expanded polyglutamine tracts-spinocere bellar ataxias (SCAs) 1, 2, 3, 6, 7, 17, dentatorubral pallidoluysian atrophy (DRPLA) and, in part, SCA 8-have all been shown to result in various degrees of cognitive impairment. We survey the literature on the cognitive consequences of each disorder, attempting correlation with their published neuropathological, magnetic resonance imaging (MRI) and clinical features. We suggest several psychometric instruments for assessment of executive function, whose results are unlikely to be confounded by visual, articulatory or upper limb motor difficulties. Finally, and with acknowledgement of the inadequacies of the literature to date, we advance a tentative classification of these disorders into three groups, based on the reported severity of their cognitive impairments, and correlated with their neuropathological topography and MRI findings: group 1-SCAs 6 and 8-mild dysexecutive syndrome based on disruption of cerebello-cortical circuitry; group 2-SCAs 1, 2, 3, and 7-more extensive deficits based largely on disruption of striatocortical in addition to cerebello-cerebral circuitry; and group 3-SCA 17 and DRPLA-in which cognitive impairment severe enough to cause a dementia syndrome is a frequent feature.


Treatment of acute respiratory tract infections with doxycycline in general practice.
A multi-centre general practitioner trial was carried out in the Netherlands during the winter of 1973/1974. This trial was part of a larger pan-European study. There were 13- cases studied in the Netherlands who were only treated with doxycycline, by 17 physicians. All patients included in the trial had an acute infection of either the upper or lower respiratory tract. tthere were 64 females and 66 males. The results were excellent at 100 patients (76.9%) had a very good result, 21 patients (16.2%) had moderate or fair results, and only 7 patients (5.4%) had poor or negative results. Doxycycline was well tolerated as no side-effects were noted in 122 of the patients (93.8%). In the 8 patients who experienced side-effects they were mild and self-limiting.


Effect of Lemon Essential Oil Microemulsion on the Cariogenic Virulence Factor of Streptococcus mutans via the Glycolytic Pathway.
To investigate the effects and mechanisms of lemon essential oil products on dental caries prevention. Lemon essential oil microemulsions (LEOM) with concentrations of 1/8 minimum inhibitory concentration (MIC), 1/4 MIC, and 1/2 MIC were applied to S. mutans at concentrations of 0.2%, 1%, and 5% glucose, respectively. Changes in acid production capacity of S. mutans were measured based on changes in pH. The effect of the reductive coenzyme I oxidation method on LDH activity was examined. The effect of lemon essential oil microemulsion on the expression of the lactate dehydrogenase gene (ldh) was detected by a quantitative real-time polymerase chain reaction. Lemon essential oil microemulsion at 1/2 MIC concentration reduced the environmental pH value at different glucose concentrations, compared to those observed in the control group (p < 0.05). LDH activity of S. mutans was decreased at three subinhibitory concentrations of lemon essential oil microemulsions (p < 0.05). The effect of lemon essential oil microemulsions on S. mutans LDH activity and bacterial acid production were positively correlated (r = 0.825, p < 0.05). Lemon essential oil microemulsion at 1/2 MIC concentration downregulated the expression of the ldh gene of S. mutans at different glucose concentrations (p < 0.05). In different glucose environments, lemon essential oil microemulsions at subminimum inhibitory concentrations can inhibit the acid production of S. mutans by reducing ldh expression and LDH activity in the glycolytic pathway, proving its anti-caries potential. LEOM can effectively prevent dental caries and maintain the microecological balance of the oral environment.