Use of antiretroviral therapy in pregnancy and association with birth outcome among women living with HIV in Denmark: A nationwide, population-based cohort study.
To describe antiretroviral therapy (ART) regimens during pregnancy among women living with HIV (WLWH) in Denmark and to examine the association between ART use in pregnancy and adverse birth outcomes. A population-based cohort study including all pregnancies among WLWH in Denmark between 2000 and 2019. Data were collected through national registries. Temporal trends of ART use in pregnancy were evaluated. Logistic regression models were used to examine the association of ART use in pregnancy and other risk factors with adverse birth outcomes. In total, 589 pregnancies were included. Combination treatment with a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor (PI) was the most common ART regimen (96%). ART regimen, PI use in pregnancy and timing of ART initiation were not significantly associated with increased odds of preterm birth, small for gestational age or low birth weight. First-trimester initiation of ART was significantly associated with increased odds of intrauterine growth restriction in the multivariate analysis [adjusted odds ratio (aOR) = 3.78, 95% confidence interval (CI): 1.23-11.59], while first trimester PI use was associated with increased odds of IUGR in the univariate analysis only [OR = 3.24, 95% CI: 1.13-9.30]. Smoking, comorbidity, and maternal HIV RNA ≥ 50 copies/mL were independently associated with increased odds of adverse birth outcomes. Pregnant WLWH living in Denmark are generally well treated with HIV RNA < 50 copies/mL at delivery and NRTI + PI as the most common ART regimen used in pregnancy. Initiation of ART in the first trimester may be associated with poor fetal growth. The association between ART use in pregnancy and adverse birth outcomes may partly be explained by maternal risk factors.


Replacement lipomatosis related to renal tuberculosis: imaging findings in one case.
Replacement lipomatosis of the kidney in a case of long-standing renal tuberculosis is reported. The radiologic and pathologic findings are described and the differential diagnosis is discussed. A hypothesis is given to explain the association of renal tuberculosis and replacement lipomatosis of the kidney.


Quantitation of 13 azole fungicides in wine samples by liquid chromatography-tandem mass spectrometry.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the direct quantitation of residues of 13 azole fungicides in wine and has been successfully applied to 103 wine samples. The method utilizing 25 transitions is highly sensitive and specific with centrifugation as the only sample work-up step. Precision was better than 14% and accuracy ranged between 80 and 120%. Quantitation limits (LOQs) ranged between 0.25 (penconazole) and 7.5 ng/mL (triadimefon). Since the LOQs achieved are at least four times lower than the maximum residue levels for azole-fungicides in wine prescribed, the method presented here can be conveniently used as a screening assay for azole-residues in wine samples.


A pilot study of peripheral blood DNA methylation models as predictors of knee osteoarthritis radiographic progression: data from the Osteoarthritis Initiative (OAI).
Knee osteoarthritis (OA) is a leading cause of chronic disability worldwide, but no diagnostic or prognostic biomarkers are available. Increasing evidence supports epigenetic dysregulation as a contributor to OA pathogenesis. In this pilot study, we investigated epigenetic patterns in peripheral blood mononuclear cells (PBMCs) as models to predict future radiographic progression in OA patients enrolled in the longitudinal Osteoarthritis Initiative (OAI) study. PBMC DNA was analyzed from baseline OAI visits in 58 future radiographic progressors (joint space narrowing at 24 months, sustained at 48 months) compared to 58 non-progressors. DNA methylation was quantified via Illumina microarrays and beta- and M-values were used to generate linear classification models. Data were randomly split into a 60% development and 40% validation subsets, models developed and tested, and cross-validated in a total of 40 cycles. M-value based models outperformed beta-value based models (ROC-AUC 0.81 ± 0.01 vs. 0.73 ± 0.02, mean ± SEM, comparison p = 0.002), with a mean classification accuracy of 73 ± 1% (mean ± SEM) for M- and 69 ± 1% for beta-based models. Adjusting for covariates did not significantly alter model performance. Our findings suggest that PBMC DNA methylation-based models may be useful as biomarkers of OA progression and warrant additional evaluation in larger patient cohorts.


Responses to concurrent radiotherapy and hormone-therapy and outcome for large breast cancers in post-menopausal women.
This study aimed to evaluate responses and outcome of hormone-therapy (HT) and radiotherapy (RT) given concurrently for large breast cancers in post-menopausal women. Forty-two breast carcinomas in 41 women were treated with HT and concurrent RT to the breast +/- lymph node bearing areas. For 30 tumours this was followed by breast surgery (with axillary lymph node dissection when the axilla had not been irradiated). RT delivered a median dose to the tumour of 50 Gy (48-66) and 75 Gy (65-84) for, respectively, preoperative and exclusive RT-HT. Median follow-up was 64 months. Out of 42 clinically assessable tumours (after a mean dose of 50 Gy), 9 tumours (21%) had complete clinical responses, 24 (57%) partial responses, 9 (21%) stable disease. Breast-conserving surgery or exclusive RT-HT was possible in 74% of tumours. For 29 patients who underwent breast surgery, the rate of pathological complete responses was 17%. At 50 Gy no skin toxicity higher than grade 2 occurred. Five year OS, RFS and local control were, respectively, 85%, 84% and 97%. Lymphoedema occurred in one patient. Concurrent association of RT-HT demonstrated good efficacy, both in terms of clinical and pathological complete responses. It allowed breast conservation with acceptable tolerance and good 5-year local control.


Initial experience with hyperoxemic reperfusion after primary angioplasty for acute myocardial infarction: results of a pilot study utilizing intracoronary aqueous oxygen therapy.
The purpose of this study was to evaluate the feasibility and safety of intracoronary hyperoxemic reperfusion after primary angioplasty for acute myocardial infarction (MI). Hyperoxemic therapy with aqueous oxygen (AO) attenuates reperfusion injury and preserves left ventricular (LV) function in experimental models of MI. In a multi-center study of patients with acute MI undergoing primary angioplasty (PTCA), hyperoxemic blood (pO(2): 600 to 800 mm Hg) was infused into the infarct-related artery for 60 to 90 min after intervention. The primary end points were clinical, electrical and hemodynamic stability during hyperoxemic reperfusion and in-hospital major adverse cardiac events. Global and regional LV function was evaluated by serial echocardiography after PTCA, after AO infusion, at 24 h and at one and three months. Twenty-nine patients were enrolled (mean age: 58.9+/-12.6 years). Hyperoxemic reperfusion was performed successfully in all cases (mean infusion time: 80.8+/-18.2 min; mean coronary perfusate pO(2): 631+/-235 mm Hg). There were no adverse events during hyperoxemic reperfusion or the in-hospital period. Compared with baseline, a significant improvement in global wall motion score index was observed at 24 h (1.68+/-0.24 vs. 1.48+/-0.24, p < 0.001) with a trend toward an increase in ejection fraction (48.6+/-7.3% vs. 51.8+/-6.8%, p = 0.08). Progressive improvement in LV function was observed at one and three months, primarily due to recovery of infarct zone function. Intracoronary hyperoxemic reperfusion is safe and well tolerated after primary PTCA. These preliminary data support the need for a randomized controlled trial to determine if hyperoxemic reperfusion enhances myocardial salvage or improves long-term outcome.


Entrepreneurial treatment activism for undone science: mannitol and Parkinson's disease.
This paper describes CliniCrowd, a patient-designed, entrepreneurial, crowd-sourced citizen-science approach to evaluating mannitol-essentially, an orphan drug-as a Parkinson's disease treatment. As such, CliniCrowd addresses 'undone science', and our paper contributes to the sociological literature thereon. Based on 38 qualitative interviews, fieldwork, and content analyses (2017-2020), we trace CliniCrowd's background and rationale. We: discuss undone science and its wider contexts; present earlier iterations of citizen-science and treatment activism; examine CliniCrowd's application of crowd-sourced citizen-science to address undone science around 'orphan drug' treatment for Parkinson's disease; explore how CliniCrowd has evolved, and re-framed its work, since its founding; ponder its future; and consider whether their approach can guide future citizen-science treatment research. Our paper contributes to the existing literature in four ways. First, we focus on medical treatment issues, an under-studied area of undone science. Second, we highlight orphan drugs as both major source of, and fruitful area for research on, undone science. Third, we describe CliniCrowd's pragmatic, entrepreneurial-rather than the more common activist-citizen-science approach to addressing undone treatment science. Finally, from our data on CliniCrowd we distil a preliminary model for future treatment activism around undone science.


Dinosaur locomotion from a new trackway.
Ardley Quarry in Oxfordshire, UK, contains one of the most extensive dinosaur-trackway sites in the world, with individual trackways extending for up to 180 metres. We have discovered a unique dual-gauge trackway from a bipedal theropod dinosaur from the Middle Jurassic in this locality, which indicates that these large theropods were able to run and that they used different hindlimb postures for walking and running. Our findings have implications for the biomechanics and evolution of theropod locomotion.


Maternal and Cord Anti-SARS-CoV-2-Spike IgG following COVID-19 Vaccination versus Infection during Pregnancy: A Prospective Study, Israel October 2021-March 2022.
Defining how pregnant women respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination is critical to optimize vaccination strategies that protect mother and infant at the epidemic. This study aimed to compare anti-SARS-CoV-2-spike immunoglobulin G (IgG) of vaccinated versus infected women and to determine the optimal timing of maternal vaccination during pregnancy at the time of epidemic. We collected maternal/cord blood at delivery (October 2021-March 2022) and measured anti-SARS-CoV-2-spike IgG geometric mean concentrations (IgG-GMCs) using a quantitative immunoassay. We compared groups according to timing and number of doses and correlated maternal and fetal IgG levels. We described the proportion of women with IgG levels above the 150 AU/mL positivity threshold according to the timing of infection/vaccination and performed a subanalysis for maternal IgG-GMC levels pre- and during the Omicron wave. We included 238 vaccinated women, 125 who received two doses and 113 three doses, and 48 unvaccinated infected women. All groups infected/vaccinated in the second or third trimester had an IgG-GMC above the positivity threshold. Third-trimester vaccination (second/third dose) resulted in higher maternal and cord-blood IgG-GMC compared to the second trimester (maternal-IgG: 102,32 vs. 4,325 AU/mL, p < 0.001; cord-IgG: 12,113 vs. 8,112 AU/mL, p < 0.001). Compared with infected-only women, a higher proportion of vaccinated women with ≥2 doses and their newborns had IgG levels above the positivity threshold at all time points. In vaccinated women, there were higher maternal IgG-GMC levels during the Omicron wave than pre-Omicron. At the time of epidemic, receiving an additional COVID-19 vaccine dose in the third trimester resulted in a higher IgG-GMC compared to the second trimester. Relatively higher levels of maternal and cord IgG-GMC were achieved following vaccination than infection. Women infected during or before the first trimester might benefit from an additional third-trimester dose to prevent peripartum infection and to passively immunize their newborn. The higher levels of maternal IgG-GMC in the Omicron period are suggestive of hybrid immunity. · Higher maternal anti-SARS-IgGs in vaccinated → infected.. · Higher cord anti-SARS-IgGs in vaccinated → infected.. · Third-trimester vaccine resulted in high-cord IgG levels..


Combining remaining life expectancy and time to death as a measure of old-age dependency related to health care needs.
Public concern about the rising number of older dependent citizens is still based mainly on standard population aging indicators. This includes the old-age dependency ratio (OADR), which divides the state pension age population by the working age population. However, the OADR counts neither the dependent elderly nor those who provide for them. This paper builds on previous research to propose several alternative indicators, including the health care (HC) need-adjusted real elderly dependency ratio and the HC need-adjusted dependent population-to-tax rate. These indicators consider improvements in old-age survival and time to death in order to better define the health care needs of the dependent old-age population and to better approximate their financial burden. We define the old-age population dependent on health care as those above the age at which remaining life expectancy is 15 years or less and are expected to die within 5 years. We use data from the US to illustrate differences between the proposed new and standard measures. Results show that, as a share of the total population, the old-age population dependent on health care has virtually not changed since 1950. Moreover, increases in GDP and state tax revenue have outstripped population aging almost continuously since 1970, irrespective of the indicator used, and they are expected to continue to do so during the coming decade. The demand for health care services is therefore not being fueled by population aging but instead by other factors such as progress in medical knowledge and technology, costs of hospitalization, and the increasing use of long-term care facilities.


Omarigliptin/galangin combination mitigates lipopolysaccharide-induced neuroinflammation in rats: Involvement of glucagon-like peptide-1, toll-like receptor-4, apoptosis and Akt/GSK-3β signaling.
The objectives of this work were to assess the possibility of administration of omarigliptin and/or galangin to combat lipopolysaccharide (LPS)-induced neuroinflammation in rats and to explore the possible mechanisms that might contribute to their actions. In a rat model of LPS-induced neuroinflammation, the changes in the behavioral tests, biochemical parameters, and the histopathological picture were assessed. Administration of either omarigliptin or galangin to LPS-injected rats was able to significantly improve the behavioral changes with restoration of the oxidant/antioxidant balance, decrement of toll-like receptor-4 levels, and amelioration of the neuroinflammation associated with inhibition of apoptosis and restoration of glucagon-like peptide-1 levels in the cerebral tissues. In addition, omarigliptin and/or galangin significantly reduced the levels of phospho-Akt and glycogen synthase kinase 3 beta (GSK-3β) and significantly increased the expression of beclin-1 in the cerebral tissues compared versus the group treated with LPS alone. As a result, these changes were positively reflected on the histopathological and the electron microscopic picture of the cerebral tissues. These beneficial effects were maximally evidenced in rats treated with omarigliptin/galangin combination relative to the use of either omarigliptin or galangin alone. Omarigliptin/galangin combination might be proposed as a promising therapeutic line for mitigation of the pathophysiologic events of LPS-induced neuroinflammation.


Patterns of secondary succession in a mangrove forest of Southern Florida.
Successional patterns were studied in mangrove forests which had developed recently in response to salinization of areas formerly supporting freshwater marshes along Biscayne Bay in North Miami, Florida. The population structures of these Induced Forests were compared with an adjacent Historical Forest which consisted of a nearly pure stand ofRhizophora mangle. A mixed forest ofRhizophora andLaguncularia racemosa had developed in intertidal areas, while areas above the mean high water elevation supported a scrub community dominated byLaguncularia. Maximum growth of bothRhizophora andLaguncularia occurred in intertidal areas, while both species were stunted and had sparse, poorly formed canopies in drier environments above the mean high water level. Analysis of population structure suggests that Induced Forests in intertidal areas are undergoing succession to a stand ofRhizophora. Laguncularia is unable to compete effectively withRhizophora in these areas and it is suggested that it eventually will be limited to the drier areas, where competition fromRhizophora will be reduced or absent.


Methods of tracing hydrogen in polyketide biosynthesis: High field NMR spectroscopy of citrinin produced in a D2O based medium.
Penicillium citrinum cultures have been germinated on an H2O-based medium, resuspended on a D2O-based medium and treated with [l,2-(13)C2] acetate. The resulting citrinin (1) has been analysed by(2)H and(13)C nuclear magnetic resonance spectroscopy and information about the metabolism of hydrogen in citrinin biosynthesis has been deduced.


Cortical silent period in two patients with meningioma and preoperative seizures: a pre- and postsurgical follow-up study.
Prolongation of the cortical silent period (CSP) following transcranial magnetic stimulation has been reported in patients with partial epilepsy involving the primary motor cortex (M1). This study aimed to investigate the relationship between the expected intraindividual variations in risk factors for seizures and CSP duration. We studied a 59-year-old woman with a rolandic meningioma and simple motor partial seizures and a 71-year-old woman with a parietal/occipital meningioma and complex partial seizures. Both patients had seizure as their initial symptom with complete postsurgical remission. Repeated pre- and postoperative CSP recordings were made from both first dorsal interosseous muscles. We compared the results to those obtained in 13 normals. In the patient with simple motor partial seizures, the CSP was significantly prolonged in preoperative recordings and 3 weeks after surgery. This CSP lengthening partly subsided 3 months after surgery. Finally, the CSP was normal 6, 8, and 18 months after surgery. In the patient with complex partial seizures, no CSP change was observed. In our patient with a rolandic meningioma, CSP prolongation was observed when the risk of seizure relapse was supposed to be higher (preoperative and early postoperative periods). This supports the view that CSP changes reflect compensatory mechanisms in M1 epilepsy.


Patterns of growth in executive functioning during school years: Contributions of early mother-child attachment security and maternal autonomy support.
Executive functioning (EF) undergoes marked developmental improvements during the early school years. Given the crucial role of EF in learning and school adjustment, it is important to document the factors that bolster the development of executive competence, especially during a period of growth. Although substantial evidence suggests that parent-child relationships relate to EF, few longitudinal studies have examined the parental antecedents of EF developmental trajectories during the school years. Accordingly, this multiyear longitudinal study (N = 102) explored the respective roles of early mother-child attachment security and maternal autonomy support in the prediction of patterns of growth in working memory, cognitive flexibility, and planning skills across Grades 2 to 4. Multilevel growth curve analyses revealed a unique positive relation between attachment security and all EF skills, whereas autonomy support was mainly independently associated with initial planning performance. These findings provide further suggestion for a global contribution of secure attachment relationships to children's executive competence and highlight the importance of supporting children's autonomy to foster the emergence of more complex EF abilities such as planning. This study also supports the relevance of considering multiple aspects of parent-child relationships to delineate how early caregiving experiences contribute to children's EF development.


Retracted: Effects of the Wnt/β-Catenin Signaling Pathway on Proliferation and Apoptosis of Gastric Cancer Cells.
[This retracts the article DOI: 10.1155/2022/5132691.].


A sparkle in the eye: Illumination cues and lightness constancy in the perception of eye contact.
In social interactions, our sense of when we have eye contact with another person relies on the distribution of luminance across their eye region, reflecting the position of the darker iris within the lighter sclera of the human eye. This distribution of luminance can be distorted by the lighting conditions, consistent with the fundamental challenge that the visual system faces in distinguishing the nature of a surface from the pattern of light falling upon it. Here we perform a set of psychophysics experiments in human observers to investigate how illumination impacts on the perception of eye contact. First, we find that simple changes in the direction of illumination can produce systematic biases in our sense of when we have eye contact with another person. Second, we find that the visual system uses information about the lighting conditions to partially discount or 'explain away' the effects of illumination in this context, leading to a significantly more robust sense of when we have eye contact with another person. Third, we find that perceived eye contact is affected by specular reflections from the eye surface in addition to shading patterns, implicating eye glint as a potential cue to gaze direction. Overall, this illustrates how our interpretation of social signals relies on visual mechanisms that both compensate for the effects of illumination on retinal input and potentially exploit novel cues that illumination can produce.


Ingestible transiently anchoring electronics for microstimulation and conductive signaling.
Ingestible electronic devices enable noninvasive evaluation and diagnosis of pathologies in the gastrointestinal (GI) tract but generally cannot therapeutically interact with the tissue wall. Here, we report the development of an orally administered electrical stimulation device characterized in ex vivo human tissue and in in vivo swine models, which transiently anchored itself to the stomach by autonomously inserting electrically conductive, hooked probes. The probes provided stimulation to the tissue via timed electrical pulses that could be used as a treatment for gastric motility disorders. To demonstrate interaction with stomach muscle tissue, we used the electrical stimulation to induce acute muscular contractions. Pulses conductively signaled the probes' successful anchoring and detachment events to a parenterally placed device. The ability to anchor into and electrically interact with targeted GI tissues controlled by the enteric nervous system introduces opportunities to treat a multitude of associated pathologies.


Human leukocyte antigen-DQ beta 1 chain (DQB1) gene polymorphisms are associated with dilated cardiomyopathy: a systematic review and meta-analysis.
Previous studies reported an association between the human leukocyte antigen (HLA)-DQ antigen beta 1 chain (DQB1) alleles and dilated cardiomyopathy (DCM). However, the results of those studies have been inconsistent. To clarify the association between HLA-DQB1 and DCM, we performed a systematic review and meta-analysis of case-control studies. Searches were performed using the PubMed database, the Excerpta Medica Database (EMBASE), the Cochrane Central Register of Controlled Trials database, the Science Citation Index database, the China Biology Medicine disc, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search terms included "dilated cardiomyopathy" and "DQB1." Ten case-controlled studies were included in the systematic review to assess the association between DCM and the HLA-DQB1*0201, *0302, *0504, *0301, and *0602 alleles. In total, 8 studies were included in the meta-analysis of the HLA-DQB1 *0201 allele. The pooled odds risk (OR) for this allele was .47, with a 95% confidence interval (CI) of .28 to .77 (P < .01). With respect to the HLA-DQB1 *0504 allele, only 3 studies were included in our meta-analysis. The pooled OR was .36 (95% CI, .15 to .84; P < .05). Nine, 8, and 7 studies of the HLA-DQB1 *0301, *0302, and *0602 alleles, respectively, were included in our meta-analysis. No statistically significant difference was evident in the frequency of these 3 alleles between the DCM and normal control groups. The HLA-DQB1 *0201 and *0504 alleles may be protective against DCM.


Hepatocyte Growth Factor in Blood and Gastric Cancer Risk: A Nested Case-Control Study.
Potential of hepatocyte growth factor (HGF)-stimulating signaling pathways related to cytotoxin-associated gene A (CagA) to predict gastric cancer development has not been fully investigated. We conducted a nested case-control study consisting of 238 gastric cancer cases and 238 matched controls within the Korean Multicenter Cancer Cohort. Plasma HGF concentrations were measured with a human HGF ELISA. Odds ratios (OR) and 95% confidence intervals (CI) for gastric cancer development according to HGF level were calculated using conditional logistic regression model. Sequential elevation of gastric cancer risk according to HGF level increase was observed (OR, 10.99; 95% CI, 4.91-24.62) for highest quartile HGF (≥364 pg/mL) versus lowest quartile HGF (<167 pg/mL). A significantly increased gastric cancer risk associated with high HGF level measured even 6 or more years prior to cancer diagnosis was also found. The group with both high risk of HGF and CagA-related genetic variants was associated with highest gastric cancer risk compared with the group with both low risk of HGF and genetic variants (P interaction = 0.05). Model performance using HGF and CagA-related genetic variants to discriminate gastric cancer was fair [area under the curve of receiver operating characteristic (AUC-ROC), 0.71; 95% CI, 0.64-0.78] and significantly higher than that of model not including those biomarkers. Our results suggest HGF as a potential biomarker to predict gastric cancer development. These findings suggest HGF as a useful biomarker to predict gastric cancer risk. Further research to assess gastric cancer risk based on useful biomarkers, including HGF, may contribute to primary prevention of gastric cancer.


Dangerous Entrapment for NRF2.
Progerin, a mutated lamin A, causes the severe premature-aging syndrome Hutchinson-Gilford progeria (HGPS). Kubben et al. present a driving mechanism for HGPS involving trapping of NRF2 at the nuclear periphery by progerin. This local restriction results in impaired NRF2 signaling and chronic oxidative stress.


Evidence for a single species of DNA ligase localized in nuclei of rat liver.
DNA ligase activity was distributed mainly in the extract of nuclei rapidly isolated from rat liver and about 20% of the nuclear activity in the cytoplasmic fraction. The DNA ligases of nuclear extract and cytoplasmic fraction showed similar gel-filtration patterns and the same sedimentation coefficient of 5.5 S. The appearance of 4-S enzyme from nuclei or nuclear extract was partly inhibited by phenylmethylsulfonyl fluoride. These results suggest that the major activity of DNA ligase in rat liver is due to a single species of the enzyme localized in nuclei and that 4-S nuclear DNA ligase reported previously is an artifact arising from 5.5-S enzyme during the isolation procedure.


Quantitation of proteins on Coomassie blue-stained polyacrylamide gels based on spectrophotometric determination of electroeluted dye.
A procedure for quantitating proteins on Coomassie blue-stained polyacrylamide gels is presented. The method is based on the observations that the dye is rapidly eluted electrophoretically from stained protein bands or spots in the presence of sodium dodecyl sulfate, and that the eluted dye is nondialyzable. Protein may therefore be assayed indirectly by measuring the dye in electroeluents spectrophotometrically. Moreover, the stain elutes more rapidly than the protein, allowing separate recovery of the protein for further analysis. The assay is independent of band or spot size, and does not involve physical disruption of the gel piece or any chemical treatment harsher than the staining process itself. The technique has been applied to the contractile proteins myosin, actin, and commercially obtained standards resolved by one-dimensional electrophoresis, and to proteins in nuclear extracts of HeLa cells on two-dimensional gels.


Non-invasive intraventricular pressure differences estimated with cardiac MRI in subjects without heart failure and with heart failure with reduced and preserved ejection fraction.
Non-invasive assessment of left ventricular (LV) diastolic and systolic function is important to better understand physiological abnormalities in heart failure (HF). The spatiotemporal pattern of LV blood flow velocities during systole and diastole can be used to estimate intraventricular pressure differences (IVPDs). We aimed to demonstrate the feasibility of an MRI-based method to calculate systolic and diastolic IVPDs in subjects without heart failure (No-HF), and with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). We studied 159 subjects without HF, 47 subjects with HFrEF and 32 subjects with HFpEF. Diastolic and systolic intraventricular flow was measured using two-dimensional in-plane phase-contrast MRI. The Euler equation was solved to compute IVPDs in diastole (mitral base to apex) and systole (apex to LV outflow tract). Subjects with HFpEF demonstrated a higher magnitude of the early diastolic reversal of IVPDs (-1.30 mm Hg) compared with the No-HF group (-0.78 mm Hg) and the HFrEF group (-0.75 mm Hg; analysis of variance p=0.01). These differences persisted after adjustment for clinical variables, Doppler-echocardiographic parameters of diastolic filling and measures of LV structure (No-HF=-0.72; HFrEF=-0.87; HFpEF=-1.52 mm Hg; p=0.006). No significant differences in systolic IVPDs were found in adjusted models. IVPD parameters demonstrated only weak correlations with standard Doppler-echocardiographic parameters. Our findings suggest distinct patterns of systolic and diastolic IVPDs in HFpEF and HFrEF, implying differences in the nature of diastolic dysfunction between the HF subtypes.


Cellular automata imbedded memristor-based recirculated logic in-memory computing.
Memristor-based circuits offer low hardware costs and in-memory computing, but full-memristive circuit integration for different algorithm remains limited. Cellular automata (CA) has been noticed for its well-known parallel, bio-inspired, computational characteristics. Running CA on conventional chips suffers from low parallelism and high hardware costs. Establishing dedicated hardware for CA remains elusive. We propose a recirculated logic operation scheme (RLOS) using memristive hardware and 2D transistors for CA evolution, significantly reducing hardware complexity. RLOS's versatility supports multiple CA algorithms on a single circuit, including elementary CA rules and more complex majority classification and edge detection algorithms. Results demonstrate up to a 79-fold reduction in hardware costs compared to FPGA-based approaches. RLOS-based reservoir computing is proposed for edge computing development, boasting the lowest hardware cost (6 components/per cell) among existing implementations. This work advances efficient, low-cost CA hardware and encourages edge computing hardware exploration.


Effect of renal clearance on vancomycin area under the concentration-time curve deviations in critically ill patients.
Augmented renal clearance (ARC) increases vancomycin (VCM) clearance. Therefore, higher VCM doses are recommended in patients with ARC; however, impacts of ARC on the area under the concentration-time curve (AUC) discrepancies between initial dosing design and therapeutic drug monitoring (TDM) period remains unclear. We retrospectively collected data from critically ill patients treated with VCM. The primary endpoint was the association between ARC and AUC24-48h deviations. ARC and AUC deviation were defined as a serum creatinine clearance (CCr) ≥130 mL/min/1.73 m2 and an AUC at TDM 30% or more higher than the AUC at the initial dosing design, respectively. The pharmacokinetic profiles of VCM were analyzed with the trough levels or peak/trough levels using the Bayesian estimation software Practical AUC-guided TDM (PAT). Among 141 patients (median [IQR]; 66 [58-74] years old; 30% women), 35 (25%) had ARC. AUC deviations were significantly more frequent in the ARC group than in the non-ARC group (20/35 [57.1%] and 17/106 [16.0%] patients, respectively, p < 0.001). Age- and sex-adjusted multivariate analyses revealed that the number of VCM doses before TDM ≥5 (odds ratio, 2.56; 95% confidence interval [CI]: 1.01-6.44, p = 0.047) and CCr ≥130 mL/min/1.73 m2 were significantly associated with AUC deviations (odds ratio, 7.86; 95%CI: 2.91-21.19, p < 0.001). Our study clarifies that the AUC of VCM in patients with ARC is higher at the time of TDM than at the time of dosage design.


Central Serous Chorioretinopathy: Signal to Reduce Corticoid in Renal Transplant Recipients?
The aim of this work was to report the treatment effectiveness of central serous chorioretinopathy (CSCR) in a renal transplant recipient who received conventional therapy with little effect, and then reducing corticoid successively and with a better outcome later. We performed a retrospective comparison of best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) of a 57-year-old renal transplant recipient who received conventional therapy and reducing corticoid successively after he was diagnosed as CSCR in the left eye. The BCVA of the left eye stayed at 20/200 after 3 months' conventional therapy, but rapidly improved to 20/25 after reducing corticoid by one-half. At the same time, SD-OCT showed much more obvious absorption of retinal liquid in the left eye from reducing corticoid than from conventional therapy. Despite the reducing of corticoid by one-half, the patient did not show any signs of rejection of the renal transplant. CSCR may be a sign in renal transplant recipients for reducing corticoid, and reducing corticoid might be a more reliable and safer treatment for such patients.


Multiple N-cadherin enhancers identified by systematic functional screening indicate its Group B1 SOX-dependent regulation in neural and placodal development.
Neural plate and sensory placodes share the expression of N-cadherin and Group B1 Sox genes, represented by Sox2. A 219-kb region of the chicken genome centered by the N-cadherin gene was scanned for neural and placodal enhancers. Random subfragments of 4.5 kb average length were prepared and inserted into tkEGFP reporter vector to construct a library with threefold coverage of the region. Each clone was then transfected into N-cadherin-positive (lens, retina and forebrain) or -negative embryonic cells, or electroporated into early chicken embryos to examine enhancer activity. Enhancers 1-4 active in the CNS/placode derivatives and non-specific Enhancer 5 were identified by transfection, while electroporation of early embryos confirmed enhancers 2-4 as having activity in the early CNS and/or sensory placodes but with unique spatiotemporal specificities. Enhancers 2-4 are dependent on SOX-binding sites, and misexpression of Group B1 Sox genes in the head ectoderm caused ectopic development of placodes expressing N-cadherin, indicating the involvement of Group B1 Sox functions in N-cadherin regulation. Enhancers 1, 2 and 4 correspond to sequence blocks conserved between the chicken and mammalian genomes, but enhancers 3 and 5 are unique to the chicken.


Compact parallel optical modified-signed-digit arithmetic-logic array processor with electron-trapping device.
A compact two-step modified-signed-digit arithmetic-logic array processor is proposed. When the reference digits are programmed, both addition and subtraction can be performed by the same binary logic operations regardless of the sign of the input digits. The optical implementation and experimental demonstration with an electron-trapping device are shown. Each digit is encoded by a single pixel, and no polarization is included. Any combinational logic can be easily performed without optoelectronic and electro-optic conversions of the intermediate results. The system is compact, general purpose, simple to align, and has a high signal-to-noise ratio.


Technical considerations in using DNA microarrays to define regulons.
Transcription is the major regulatory target of gene expression in bacteria, and is controlled by many regulatory proteins and RNAs. Microarrays are a powerful tool to study the regulation of transcription on a genomic scale. Here we describe the use of transcription profiling and ChIP-chip to study transcriptional regulation in bacteria. Transcription profiling determines the outcome of regulatory events whereas ChIP-chip identifies the protein-DNA interactions that determine these events. Together they can provide detailed information on transcriptional regulatory systems.


Mechanisms of disease: ion channel remodeling in the failing ventricle.
In an attempt to compensate for compromised hemodynamics in heart failure, neurohumoral mechanisms are activated that trigger fundamental changes in gene expression and in protein processing, trafficking and post-translational regulation, resulting in myocyte hypertrophy. Unfortunately, over time these changes become maladaptive, predisposing to myocyte loss, chamber dilatation, interstitial hyperplasia and intercellular uncoupling. Intrinsic and peripheral responses to mechanical dysfunction alter the expression and function of key ion channels and calcium-handling proteins, thereby remodeling the cellular action potential and the intracellular calcium transient. This electrophysiological remodeling renders the heart more vulnerable to ventricular arrhythmias that underlie sudden cardiac death. In this Review, we consider key ventricular ionic changes that are associated with heart failure, with the intention of identifying molecular targets for antiarrhythmic therapy.


Tissue resident cell processes determine organ damage in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects almost any organ. Multiple immunological abnormalities involving every domain of the immune system contribute to the expression of the disease. It is now recognized that elements of the immune system instigate processes in tissue resident cells which execute organ damage. Although correction of ongoing immune aberrations is important in the control of disease activity, targeting tissue specific injurious processes may prove desirable in limiting organ damage.


Novobiocin inhibits the self-splicing of the primary transcripts of T4 phage thymidylate synthase gene.
Effects of the antibiotic novobiocin on the self-splicing of primary transcripts of the phage T4 thymidylate synthase gene (td) have been investigated. Novobiocin at 10 mM concentration inhibited the splicing by about 5% but at 40 mM concentration the splicing rate was inhibited by about 50%. The novobiocin inhibition of the self-splicing reaction was not reversed even at a high concentration (200 microM) of guanosine. However, increasing the Mg(2+) ion concentrations up to 20 mM almost fully restored the splicing activity to the normal splicing level. The double reciprocal plot analysis demonstrated that novobiocin acts as a mixed noncompetitive inhibitor for the td intron RNA with a K (i) of 90 mM. The splicing inhibition by novobiocin was strongly dependent on Mg(2+) ion concentration, indicating electrostatic interactions with the td intron RNA. It is likely that the antibiotic novobiocin may interfere with the catalytic actions of Mg(2+) ion in the splicing reaction of the td intron RNA.


Stepped Care Versus Direct Face-to-Face Cognitive Behavior Therapy for Social Anxiety Disorder and Panic Disorder: A Randomized Effectiveness Trial.
The aim of this study was to assess the effectiveness of a cognitive behavioral therapy (CBT) stepped care model (psychoeducation, guided Internet treatment, and face-to-face CBT) compared with direct face-to-face (FtF) CBT. Patients with panic disorder or social anxiety disorder were randomized to either stepped care (n=85) or direct FtF CBT (n=88). Recovery was defined as meeting two of the following three criteria: loss of diagnosis, below cut-off for self-reported symptoms, and functional improvement. No significant differences in intention-to-treat recovery rates were identified between stepped care (40.0%) and direct FtF CBT (43.2%). The majority of the patients who recovered in the stepped care did so at the less therapist-demanding steps (26/34, 76.5%). Moderate to large within-groups effect sizes were identified at posttreatment and 1-year follow-up. The attrition rates were high: 41.2% in the stepped care condition and 27.3% in the direct FtF CBT condition. These findings indicate that the outcome of a stepped care model for anxiety disorders is comparable to that of direct FtF CBT. The rates of improvement at the two less therapist-demanding steps indicate that stepped care models might be useful for increasing patients' access to evidence-based psychological treatments for anxiety disorders. However, attrition in the stepped care condition was high, and research regarding the factors that can improve adherence should be prioritized.


Structure of water-soluble polysaccharides in spore of Ganoderma lucidum and their anti-inflammatory activity.
Ganoderma lucidum spore is widely accepted as functional food. Polysaccharides are the predominant bioactive components in G. lucidum spore and contribute much to its health benefits. However, their structural characteristics remain unclear. In this work, water-soluble polysaccharides (GLSP) were obtained by hot water extraction. Three monosaccharides, including arabinose (Ara), glucose (Glc) and galactose (Gal), were presented in GLSP. 1D and 2D NMR data revealed that GLSP were composed mainly by two polysaccharides, β-glucan and arabinogalactan. The arabinogalactan had a backbone of galactan with Araf in the side chain. β-Glucan was the dominant polysaccharide in G. lucidum spore. The molecular weight was measured. GLSP could induce IEC-6 cells proliferation in a concentration-dependent manner. Moreover, GLSP possessed a strong anti-inflammatory activity through inhibiting the overproduction of NO and pro-inflammatory cytokines, like interleukin-6 (IL-6) and interleukin-1β (IL-1β) induced by LPS. These results implied the potential of GLSP on gut barrier protection.


Peptide inhibition of cytokine-stimulated aromatase activity in breast tissue fibroblasts.
The cytokine interleukin-6 (IL-6) and its soluble receptor (IL-6sR) can act synergistically to stimulate aromatase activity in cultured stromal fibroblasts derived from breast tissues. In this study, a 16 amino acid peptide, AROHIB, has been used in an attempt to block the ability of IL-6 plus IL-6sR to stimulate aromatase activity in stromal fibroblasts. Pre-incubation of cells with AROHIB for a 3-h period before the addition of IL-6 and IL-6sR resulted in a marked (67%) reduction in the ability of these factors to stimulate aromatase activity. AROHIB was found to be rapidly degraded when exposed to MCF-7 breast cancer cells or fibroblasts. Analysis by FAB-MS was used to identify the site of peptide cleavage. Subsequently, a series of 10 amino acid peptides, DP1-DP4, were designed, synthesised and tested for their ability to resist proteolytic degradation and to inhibit IL-6 plus IL-6sR-stimulated aromatase activity. Peptide DP2, a modified version of the active fragment of AROHIB, had N-acetyl and C-amino terminal protection and an internal D-amino acid (instead of L form) at the site of proteolytic cleavage. Using cells cultured in the presence of 2% stripped foetal calf serum, peptide DP2 resulted in a 74% reduction in cytokine-stimulated aromatase activity. Under serum-free conditions, peptides DP1-DP3 showed modest inhibitory properties. Results from this study suggest that it may be possible to develop small peptides to inhibit cytokine-stimulated aromatase activity in a tissue-specific manner.


The Royal Marsden NHS Trust manual of clinical nursing procedures (fourth edition) The Royal Marsden NHS Trust manual of clinical nursing procedures (fourth edition) Jane Mallett and Christopher Bailey (Editors) Blackwell Science 662pp £15.99 0632-04068-8 0632040688.
Those who are familiar with earlier editions of this book will understand why it has become the definitive manual of clinical nursing procedures. It is because of its high quality, and common-sense approach, combined with a rigorous attention to detail.


Left upper lobe torsion following lower lobe resection. Early recognition of a rare complication.
Left upper lobe torsion occurred in a woman during the first 24 hours following left lower lobectomy for bronchogenic carcinoma resection. To our knowledge, this is the first report of left upper lobe torsion. When atypical chest pain or opacification of the remaining lung develops following resectional surgery, torsion of the remaining lung must be suspected. Prompt diagnosis and treatment may prevent the morbidity and mortality associated with pulmonary infarction from torsion.


Role of green fluorescent proteins and their variants in development of FRET-based sensors.
Since the last decade, a lot of advancement has been made to understand biological processes involving complex intracellular pathways. The major challenge faced was monitoring and trafficking of metabolites in real time. Although a range of quantitative and imaging techniques have been developed so far, the discovery of green fluorescent proteins (GFPs) has revolutionized the advancement in the field of metabolomics. GFPs and their variants have enabled researchers to 'paint' a wide range of biological molecules. Fluorescence resonance energy transfer (FRET)-based genetically encoded sensors is a promising technology to decipher the real-time monitoring of the cellular events inside living cells. GFPs and their variants, due to their intrinsic fluorescence properties, are extensively being used nowadays in cell-based assays. This review focuses on structure and function of GFP and its derivatives, mechanism emission and their use in the development of FRET-based sensors for metabolites.


The first records of Leishmania (Leishmania) amazonensis in dogs (Canis familiaris) diagnosed clinically as having canine visceral leishmaniasis from Araçatuba County, São Paulo State, Brazil.
Two cases of Leishmania (Leishmania) amazonensis are reported in the domestic dog (Canis familiaris). These are the first records of this parasite in this species. The animals lived in the endemic visceral leishmaniasis area of Araçatuba, São Paulo State, Brazil and were initially diagnosed, on clinical grounds, as having visceral leishmaniasis. Attempted parasite isolation from inguinal lymph node aspirates was unsuccessful and the indirect immunofluorescent test for visceral leishmaniasis was negative in both cases. Parasites were seen in cytological preparations of their lymph nodes and the DNA obtained from these same tissues produced the expected fragment in a Leishmania specific rDNA based PCR assay. The products only hybridized with the L. (L.) amazonensis specific probe S8. No human cases of L. (L.) amazonensis have been reported in this region. These results suggest that L. (L.) amazonensis is being transmitted in the peridomestic habitat and that this parasite is responsible for a clinical condition that is similar to visceral leishmaniasis caused by L. (L.) i. chagasi that is present in the same area.


Musical murmurs: an echo-phonocardiographic study.
Five patients with muscial murmurs were studied noninvasively with simultaneous echocardiography and phonocardiograpy and phonocardiography. Three patients had aortic regurgitation, one mitral regurgitation and one tricuspid regurgitation. The frequency of the muscial murmurs ranged from 40 to 158 cycles/sec. The patient with tricuspid regurgitation manifested an inspiratory honk. Simultaneous echo-phonocardiography revealed regular valve leaflet flutter (aortic, mitral or tricuspid) at a frequency identical to that of the simultaneously recorded muscial murmur. This study demonstrates that echocardiography is a useful noninvasive tool in identifying the site of origin of musical murmurs.


Production of 2-keto-L-gulonic acid by metabolically engineered Escherichia coli.
The 2-keto-L-gulonic acid (2-KLG) is the direct precursor for industrial vitamin C production. The main biosynthetic method for 2-KLG production is the classical two-step fermentation route. However, disadvantages of this method are emerging, including high consumption of energy, difficulties in strain screening, complex operation, and poor stability. In this study, five recombinant Escherichia coli strains overexpressing different sorbose/sorbosone dehydrogenases were constructed and used for 2-KLG production. By optimizing catalytic conditions and further expressing pyrroloquinoline quinone in the recombinant strain, the titer of 2-KLG reached 72.4 g/L, with a conversion ratio from L-sorbose of 71.2% in a 5-L bioreactor. To achieve direct biosynthesis of 2-KLG from D-sorbitol, a co-culture system consisting of Gluconobacter oxydans and recombinant E. coli was designed. With this co-culture system, 16.8 g/L of 2-KLG was harvested, with a conversion ratio from D-sorbitol of 33.6%. The approaches developed here provide alternative routes for the efficient biosynthesis of 2-KLG.


Development and validation of a multivariable risk prediction model for identifying ketosis-prone type 2 diabetes.
To develop and validate a multivariable risk prediction model for ketosis-prone type 2 diabetes mellitus (T2DM) based on clinical characteristics. A total of 964 participants newly diagnosed with T2DM were enrolled in the modeling and validation cohort. Baseline clinical data were collected and analyzed. Multivariable logistic regression analysis was performed to select independent risk factors, develop the prediction model, and construct the nomogram. The model's reliability and validity were checked using the receiver operating characteristic curve and the calibration curve. A high morbidity of ketosis-prone T2DM was observed (20.2%), who presented as lower age and fasting C-peptide, and higher free fatty acids, glycated hemoglobin A1c and urinary protein. Based on these five independent influence factors, we developed a risk prediction model for ketosis-prone T2DM and constructed the nomogram. Areas under the curve of the modeling and validation cohorts were 0.806 (95% confidence interval [CI]: 0.760-0.851) and 0.856 (95% CI: 0.803-0.908). The calibration curves that were both internally and externally checked indicated that the projected results were reasonably close to the actual values. Our study provided an effective clinical risk prediction model for ketosis-prone T2DM, which could help for precise classification and management.


[Ocular injuries in children aged 0-15 years: epidemiological and clinical aspects at the Bangui National Teaching Hospital].
Ocular injuries in children are frequent and are an ophthalmological emergency. If not managed sufficiently early, these lesions may cause definitive partial loss of vision or blindness. In this survey, the authors analyze different epidemiological and clinical aspects of ocular injuries at the Bangui National Teaching Hospital in the Central African Republic to increase the awareness of children's parents, guardians, and care-takers. A prospective study was conducted on 194 cases in the ophthalmology department over a period of 3 years, and included children aged 0-15 years. A total of 197 eyes were examined by the same practitioner, comprising 191 unilateral ocular injuries and three bilateral injuries. Of the children examined, 59% were males and 41% were females, with a sex ratio of 1.3. The age group with the highest exposure (39.3%) was between 5 and 10 years. Punishments (25.9%), accidents during games (19.3%) and fights (18.8%) were the main sources of these ocular injuries. Consultation most often occurred long after the incident. Only 2.0% were seen before the 6th hour and 43.7% between 48 hours and 1 week. The clinical picture was dominated by bruises posing a therapeutic problem: 25 hyphemas (12.7%), 19 conjunctival injuries (9.6%), 19 lens dislocations with or without vitreous loss (9.6%), 18 trauma-induced cataracts (9.4%), and 15 eye lid injuries with or without lachrymal duct ruptures (7.6%). The most serious injuries were cornea injuries with or without hernia of the iris (19.8%) and nine globe dislocations (4.5%). The frequency and gravity of the lesions identified, the severity of the injuries and the delay in treating these injuries show that the public authorities, parents and child care-takers need more information in order to reduce the frequency of these accidents.


Improved catalysts for the iridium-catalyzed asymmetric isomerization of primary allylic alcohols based on Charton analysis.
An improved generation of chiral cationic iridium catalysts for the asymmetric isomerization of primary allylic alcohols is disclosed. The design of these air-stable complexes relied on the preliminary mechanistic information available, and on Charton analyses using two preceding generations of iridium catalysts developed for this highly challenging transformation. Sterically unbiased chiral aldehydes that were not accessible previously have been obtained with high levels of enantioselectivity, thus validating the initial hypothesis regarding the selected ligand-design elements. A rationale for the high enantioselectivities achieved in most cases is also presented.


Physiological effects of sleeping with the head of the bed elevated 18 in. in young healthy volunteers.
Sleeping with the head of bed tilted upwards (SHU) is recommended as a treatment of orthostatic hypotension though the supporting evidence is weak. To investigate the physiological effects of SHU amongst a group of young healthy volunteers. Twenty-nine volunteers, mean age 22 years, underwent 1-week of SHU at 18-in. elevation. Before and after hemodynamic and non-haemodynamic parameters were recorded. After SHU, there were reductions in the systolic blood pressure drop on standing, upright total peripheral resistance, haemoglobin, nocturnal urinary volume, orthostatic dizziness and increases in weight, standing cardiac output and ankle circumference. There were no differences in heart rate, stroke volume, renin, aldosterone, pro-atrial natriuretic peptide or 24-h blood pressure. In these healthy subjects, SHU for 1 week had a nocturnal antidiuretic effect with both intra- and extra-vascular accumulation of fluid and was associated with reduced postural drop in SBP and improved orthostatic tolerance.


On the coordination of La3+ by phosphatidylserine.
In a recent study by Bentz, J., D. Alford, J. Cohen, and N. Düzgünes (1988. Biophys. J. 53:593-607), La3+ was found to be more effective than Ca2+ in causing nonleaky fusion of phosphatidylserine vesicles. It was proposed that this difference in fusion efficiency may be due, in part, to a difference in coordination of the two cations. That is, Ca2+ was presumed to bind to the lipid phosphate, whereas La3+ was proposed to be coordinated by the serine carboxylate and amine. 31P and 13C NMR results presented here demonstrate that the lanthanides, Tb3+ and La3+, are coordinated by the phosphodiester and carboxylate moieties of phosphatidylserine. Tb3+-Phosphatidylserine optical experiments suggest that the serine amine does not coordinate the lanthanide below pH 10, at least not while the membrane has a net negative surface charge. Although these observations disagree with the structural details proposed by Bentz et al. (1988), they are not in conflict with their general fusion mechanism. The work presented here also demonstrates that La3+ affects the inner surface phosphodiesters differently than those on the outer surface of phosphatidylserine vesicles. The vesicles studied are of an intermediate size, having diameters on the order of 150-200 nm. The cation appears to have a more immediate effect on the packing of the crowded headgroups on the inner surface. Higher levels of bound La3+ on the outer surface may be required to induce the same changes in headgroup conformation.


A comparison of skin storage methods for oculoplastic surgery.
To assess the level of contamination of full-thickness skin grafts stored with or without an antibiotic cover. Full-thickness skin grafts were harvested from 40 bilateral upper lid blepharoplasties. Before surgery the face was sterilised, the head of the patient was packed with sterile, single-use surgical drapes and the whole face was left exposed. The harvested full-thickness skin grafts were conserved in sterile containers at 4 degrees C for 6 days, rolled in gauze moistened with either 4 ml of sterile saline solution (group I) or with 4 ml of gentamicin solution (2 mg/ml) (group II). The degree of contamination, expressed in colony forming units (CFU), was evaluated on days 2, 3, 4, 5 and 6. Identification of the microorganisms was done to species level following standard procedures and commercial methods. In group I 2 grafts (5%) were negative during the whole observation period while the other 38 grafts (95%) presented a degree of contamination ranging from 10(2) to 10(4) CFU. Microorganisms isolated were: Staphylococcus epidermidis (24 cases), Staphylococcus aureus (5 cases), Staphylococcus saprophyticus (2 cases), Pseudomonas aeruginosa (4 cases), Serratia liquefaciens (1 case) and Klebsiella oxytoca (2 cases). In group II, 26 grafts (65%) were negative during the whole observation time while in 14 cases (35%) a few colonies (3 to 6) of Candida albicans were isolated on day 2 and remained constant in number for the whole observation time. The storage of full-thickness skin graft with an antibiotic cover is more reliable than the storage of full-thickness skin graft without an antibiotic cover.


Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials.
Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) levels and CK-related adverse events (AEs) in tofacitinib-treated patients with UC were evaluated. Data were analyzed for three UC cohorts: Induction (phase 2 and 3 induction studies); Maintenance (phase 3 maintenance study); Overall [patients who received tofacitinib 5 or 10 mg twice daily (b.d.) in phase 2, phase 3, or open-label, long-term extension studies; data at November 2017]. Clinical trial data for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis are presented for contextualization. Week 8 mean change from baseline CK with tofacitinib 10 mg b.d. induction therapy was 91.1 U/L (95% CI, 48.1-134.1) versus 19.2 U/L (8.5-29.9) with placebo. Among patients completing induction with 10 mg b.d. and re-randomized to 52 weeks of maintenance therapy, mean increases from induction baseline to the end of maintenance were 35.9 (8.1-63.7), 90.3 (51.9-128.7), and 115.6 U/L (91.6-139.7), with placebo, 5 and 10 mg b.d., respectively. The incidence rate (unique patients with events per 100 patient-years) for AEs of CK elevation in the tofacitinib-treated UC Overall cohort was 6.6 versus 2.2, 6.5, and 3.7 for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, respectively. No serious AEs of CK elevation or AEs of myopathy occurred in UC studies. In patients with UC, CK elevations with tofacitinib appeared reversible and not associated with clinically significant AEs. UC findings were consistent with tofacitinib use in other inflammatory diseases. NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01059864; NCT01164579; NCT00976599; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661; NCT01710046; NCT00678210; NCT01276639; NCT01309737; NCT01241591; NCT01186744; NCT01163253; NCT01877668; NCT01882439; NCT01976364.


Discovery of novel PDE10 inhibitors by a robust homogeneous screening assay.
To develop a homogeneous assay for high-throughput screening (HTS) of inhibitors of phosphodiesterase 10 (PDE10). Purified human PDE10 enzyme derived from E coli, [(3)H]-cAMP and yttrium silicate microbeads were used to develop an HTS assay based on the scintillation proximity assay (SPA) technology. This method was applied to a large-scale screening campaign against a diverse compound library and subsequent confirmation studies. Preliminary structure-activity relationship (SAR) studies were initiated through limited structural modifications of the hits. The IC50 value of the control compound (papaverine) assessed with the SPA approach was comparable and consistent with that reported in the literature. Signal to background (S/B) ratio and Z' factor of the assay system were evaluated to be 5.24 and 0.71, respectively. In an HTS campaign of 71 360 synthetic and natural compounds, 67 hits displayed reproducible PDE10 inhibition, of which, 8 were chosen as the scaffold for structural modifications and subsequent SAR analysis. The homogeneous PDE10 SPA assay is an efficient and robust tool to screen potential PDE10 inhibitors. Preliminary SAR studies suggest that potent PDE10 inhibitors could be identified and developed through this strategy.


Long-term changes in endemic threshold populations for pertussis in England and Wales: A spatiotemporal analysis of Lancashire and South Wales, 1940-69.
Metapopulation dynamics play a critical role in driving endemic persistence and transmission of childhood infections. The endemic threshold concept, also referred to as critical community size (CCS), is a key example and is defined as the minimum population size required to sustain a continuous chain of infection transmission. The concept is fundamental to the implementation of effective vaccine-based disease control programmes. Vaccination serves to increase endemic threshold population size, promoting disease fadeout and eventual elimination of infection. To date, empirical investigations of the relationship between vaccination and endemic threshold population size have tended to focus on isolated populations in island communities. Very few studies have examined endemic threshold dynamics in 'mainland' regional populations with complex hierarchical spatial structures and varying levels of connectivity between subpopulations. The present paper provides the first spatially explicit analysis of the temporal changes in endemic threshold populations for one vaccine-preventable childhood infection (pertussis) in two dynamic regions of England and Wales: Lancashire and South Wales. Drawing upon weekly disease records of the Registrar-General of England and Wales over a 30-year period (January 1940-December 1969) regression techniques were used to estimate the endemic threshold size for pertussis in the two study regions. Survival analyses were performed to compare disease fadeout duration and probability for both regions in the pre-vaccine and vaccine eras, respectively. Our findings reveal the introduction of mass vaccination led to a considerable increase in threshold size for both Lancashire (~387,333) and South Wales (~1,460,667). Significant growth in fadeout duration was observed in the vaccine era for pertussis non-hotspots in both regions, consistent with geographical synchronisation of epidemic activity. Regional differences in endemic threshold populations reflect significant regional variations in spatial connectivity, population dispersion and level of geographical isolation.


On not reinventing the wheel.
An alphabet soup of organizations and initiatives across the world are concerned with identifying, collecting and evaluating disease-causing human gene variants and using them to diagnose and treat rare diseases. Despite increasing standardization of nomenclature and technology, our efforts still need coordination to produce a pipeline leading from discovery to delivery.


Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington's disease.
Huntington's disease (HD) is a chronic neurodegenerative disorder characterized by a late clinical onset despite ubiquitous expression of the mutant Huntingtin gene (HTT) from birth. Transcriptional dysregulation is a pivotal feature of HD. Yet, the genes that are altered in the prodromal period and their regulators, which present opportunities for therapeutic intervention, remain to be elucidated. Using transcriptional and chromatin profiling, we found aberrant transcription and changes in histone H3K27acetylation in the striatum of R6/1 mice during the presymptomatic disease stages. Integrating these data, we identified the Elk-1 transcription factor as a candidate regulator of prodromal changes in HD. Exogenous expression of Elk-1 exerted beneficial effects in a primary striatal cell culture model of HD, and adeno-associated virus-mediated Elk-1 overexpression alleviated transcriptional dysregulation in R6/1 mice. Collectively, our work demonstrates that aberrant gene expression precedes overt disease onset in HD, identifies the Elk-1 transcription factor as a key regulator linked to early epigenetic and transcriptional changes in HD, and presents evidence for Elk-1 as a target for alleviating molecular pathology in HD.


Peranal coloanal anastomosis following low anterior resection for rectal carcinoma.
Since 1978, 41 patients (12 percent of all restorative operations) have undergone peranal coloanal reconstruction following anterior resection (LAR) for cancers of the midrectum. Twenty-seven patients (66 percent) were men and 14 patients (34 percent) were women (mean, 58.8 years). The mean distance of the primary tumor from the anal verge was 6.7 cm and 50 percent of the primary tumors were considered highly mobile. In 29 patients, a hand-sewn anastomosis was performed between the colon and the dentate line. In the 12 most recent patients, the anastomosis was performed using a circular stapling instrument. A diverting colostomy should be employed in all cases and is closed approximately three months later. There has been no operative mortality. Morbidity included anastomotic separation (two patients), minor anastomotic defects (three patients), pelvic sepsis (two patients), and bacteremia of unknown origin (two patients). Where fecal diversion was employed, there were no instances of anastomotic leak. Two patients with hemorrhage were returned to the operating room. Thirty-seven of the 41 patients underwent curative resections. Thirty-three percent of the patients had Dukes' C lesions. With a median follow-up of 31 months for the curative resections, 73 percent remain free of disease. Sixty-four percent of evaluable patients have either excellent or good anorectal function nine to 12 months after colostomy closure. Of 26 operations performed by one surgeon, 22 patients (85 percent) are currently evaluable. Nineteen (86 percent) of the 22 have normal or near-normal bowel function. Four guidelines for performing a functionally successful operation are presented. Coloanal reconstruction following LAR, were pull-through operations were previously required, is an excellent sphincter-preserving operation. The functional results one year after the operation are gratifying, with the majority of patients leading an active life with normal bowel function.


Deviants violating higher-order auditory regularities can become predictive and facilitate behaviour.
The human auditory system is believed to represent regularities inherent in auditory information in internal models. Sounds not matching the standard regularity (deviants) elicit prediction error, alerting the system to information not explainable within currently active models. Here, we examine the widely neglected characteristic of deviants bearing predictive information themselves. In a modified version of the oddball paradigm, using higher-order regularities, we set up different expectations regarding the sound following a deviant. Higher-order regularities were defined by the relation of pitch within tone pairs (rather than absolute pitch of individual tones). In a deviant detection task participants listened to oddball sequences including two deviant types following diametrically opposed rules: one occurred mostly in succession (high repetition probability) and the other mostly in isolation (low repetition probability). Participants in Experiment 1 were not informed (naïve), whereas in Experiment 2 they were made aware of the repetition rules. Response times significantly decreased from first to second deviant when repetition probability was high-albeit more in the presence of explicit rule knowledge. There was no evidence of a facilitation effect when repetition probability was low. Significantly more false alarms occurred in response to standards following high compared with low repetition probability deviants, but only in participants aware of the repetition rules. These findings provide evidence that not only deviants violating lower- but also higher-order regularities can inform predictions about auditory events. More generally, they confirm the utility of this new paradigm to gather further insights into the predictive properties of the human brain.


The impact of early environmental rearing condition on the discriminative stimulus effects and Fos expression induced by cocaine in adult male and female rats.
A number of environmental manipulations, including maternal separation (MS), have been shown to alter behavioral responses to drugs of abuse. This study assessed if MS affected the stimulus and Fos-inducing effects of cocaine. In experiment 1, male and female Sprague-Dawley rats were exposed to brief maternal separations (BMS), long maternal separations (LMS), or animal facility rearing (AFR) and then trained as adults to discriminate cocaine (10 mg/kg, intraperitoneally) from saline. Following training, generalization tests to novel doses of cocaine and other dopaminergic compounds were performed. Assessments of variations in training dose pretreatment times were also made. In experiment 2, male and female rats exposed to MS conditions were administered cocaine or saline for 14 days, and Fos expression in the mesolimbic system was measured. In males, BMS retarded the acquisition of the cocaine discrimination. Generalization to novel doses of cocaine did not differ among rearing conditions, but the training dose cue lasted longer in LMS. Distinct generalization and ED(50) profiles were found between male rearing conditions for all dopamine compounds. While BMS females had higher cocaine ED(50) estimates, no other differences were found in females. LMS males and females, as well as AFR females, had significant increases in Fos expression after cocaine in a region-specific manner. No differences were found with other rearing groups. Early environmental variables altered the stimulus effects (in a sex-dependent manner) as well as the neuronal responsiveness to cocaine, which may be mediated by the dopamine system.


Long Noncoding RNA MALAT1 Promotes the Development of Colon Cancer by Regulating miR-101-3p/STC1 Axis [Retraction].
[This retracts the article DOI: 10.2147/OTT.S242300.].


Subacute combined degeneration of the spinal cord and the vitamin B12 metabolism, a clinical study.
In 28 patients suffering from subacute combined degeneration of the spinal cord, vitamin B12 metabolism was investigated. Two postulates, proving vitamin B12 deficiency and excluding another cause for the clinical symptoms, have to be fulfilled. Two patients had no disturbance in their vitamin B12 metabolism. Seven patients had a distinct vitamin B12 deficiency. In the remaining 19 patients we found a mild vitamin B12 deficiency. Of these patients, 5 had had a subtotal gastrectomy, one had had a low absorption of vitamin B12, and 13 patients we could not find a distinct cause for the vitamin B12 deficiency. It is not impossible that nutritional habits can be hold responsible for this deficiency. The question whether these 13 patients should be treated with vitamin B12 for the rest of their lives is difficult to answer. It is a conditio sine qua non that in the patients with S.C.D. the vitamin B12 metabolism is examined circumstantially. By so doing, it may be possible to detect, in cases with minor clinical signs and symptoms of S.C.D., the cause of their illness.


An analysis of 'looked but failed to see' accidents involving parked police vehicles.
Drivers who collide with a vehicle that is parked on the hard shoulder of a motorway or dual-carriageway sometimes claim not to have seen it before the collision. Previous research into vehicle conspicuity has taken such 'looked but failed to see' claims at face value, and concentrated on attempting to remedy the problem by making vehicles more conspicuous in sensory terms. However, the present study describes investigations into accidents of this kind which have involved stationary police cars, vehicles which are objectively highly conspicuous. Two laboratory studies showed that experienced drivers viewing a film of dual-carriageway driving were slower to respond to a parked police car as a 'hazard' if it was parked directly in the direction of travel than if it was parked at an angle; this effect was more pronounced when the driver's attention was distracted with a secondary reasoning task. Taken together with the accident reports, these results suggest that 'looked but failed to see' accidents may arise not because the parked vehicle is difficult to see, but for more cognitive reasons, such as vigilance failure, or possession by the driver of a 'false hypothesis' about the road conditions ahead. An emergency vehicle parked in the direction of travel, with only its blue lights flashing, may encourage drivers to believe that the vehicle is moving rather than stationary. Parking at an angle in the road, and avoiding the use of blue lights alone while parked, are two steps that drivers of parked emergency vehicles should consider taking in order to alert approaching drivers to the fact that a stationary vehicle is ahead.


Hot-spots of HIV infection in Cameroon: a spatial analysis based on Demographic and Health Surveys data.
The Human Immunodeficiency Virus(HIV) infection prevalence in Cameroon has decreased from [Formula: see text] in 2004 to [Formula: see text] in 2018. However, this decrease in prevalence does not show disparities especially in terms of spatial or geographical pattern. Efficient control and fight against HIV infection may require targeting hotspot areas. This study aims at presenting a cartography of HIV infection situation in Cameroon using the 2004, 2011 and 2018 Demographic and Health Survey data, and investigating whether there exist spatial patterns of the disease, may help to detect hot-spots. HIV biomarkers data and Global Positioning System (GPS) location data were obtained from the Cameroon 2004, 2011, and 2018 Demographic and Health Survey (DHS) after an approved request from the MEASURES Demographic and Health Survey Program. HIV prevalence was estimated for each sampled area. The Moran's I (MI) test was used to assess spatial autocorrelation. Spatial interpolation was further performed to estimate the prevalence in all surface points. Hot-spots were identified based on Getis-Ord (Gi*) spatial statistics. Data analyses were done in the R software(version 4.1.2), while Arcgis Pro software tools' were used for all spatial analyses. Generally, spatial autocorrelation of HIV infection in Cameroon was observed across the three time periods of 2004 ([Formula: see text], [Formula: see text]), 2011 ([Formula: see text], [Formula: see text]) and 2018 ([Formula: see text], [Formula: see text]). Subdivisions in which one could find persistent hot-spots for at least two periods including the last period 2018 included: Mbéré, Lom et Djerem, Kadey, Boumba et Ngoko, Haute Sanaga, Nyong et Mfoumou, Nyong et So'o Haut Nyong, Dja et Lobo, Mvila, Vallée du Ntem, Océan, Nyong et Kellé, Sanaga Maritime, Menchum, Dounga Mantung, Boyo, Mezam and Momo. However, Faro et Déo emerged only in 2018 as a subdivision with HIV infection hot-spots. Despite the decrease in HIV epidemiology in Cameroon, this study has shown that there are spatial patterns for HIV infection in Cameroon and possible hot-spots have been identified. In its effort to eliminate HIV infection by 2030 in Cameroon, the public health policies may consider these detected HIV hot-spots, while maintaining effective control in other parts of the country.


Monsplasty for women after massive weight loss.
Ptosis with excess skin in the pubic area is a very common deformity in patients after massive weight loss. This deformity requires adequate surgical treatment whether combined with abdominoplasty or not. The enlarged pubogenital area may lead to psychosocial distress and impaired quality of life. A series of 23 women with a mean age of 39.5 years who previously underwent bariatric surgeries and later presented with pubogenital ptosis underwent monsplasty. The preoperative surgical markings and the surgical technique presented are easily reproducible. In this prospective study, the surgical outcomes were assessed by questionnaires applied to the patients, who scored the following parameters: movement dynamics, aesthetic appearance, sexual performance, improved hygiene, and use of clothing items. Four of the parameters assessed (movement dynamics, aesthetic appearance, hygiene, and use of clothing items) showed clear improvement, with scores ranging from good to very good. A small percentage of the patients (13%) reported fair improvement in sexual performance. The findings showed monsplasty to be a simple and reproducible technique with favorable outcomes and low morbidity rates. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.


Mycorrhizal symbiosis increases growth, reproduction and recruitment of Abutilon theophrasti Medic. in the field.
We examined in the field the effect of the vesicular-arbuscular (VA) mycorhizal symbiosis on the reproductive success of Abutilon theophrasti Medic., an early successional annual member of the Malvaceae. Mycorrhizal infection greatly enhanced vegetative growth, and flower, fruit and seed production, resulting in significantly greater recruitment the following year. In addition, the seeds produced by mycorrhizal plants were significantly larger and contained significantly more phosphorus than seeds from non-mycorrhizal plants, an effect which may improve offspring vigor. Infection by mycorrhizal fungi may thus contribute to the overall fitness of a host plant and strongly influence long-term plant population dynamics.


Netrin-1 pretreatment protects rat kidney against ischemia/reperfusion injury via suppression of oxidative stress and neuropeptide Y expression.
Netrin-1 has been found to protect kidneys from ischemia/reperfusion injury. In this study, we aimed to address whether the protective effects were mediated through suppression of oxidative stress and neuropeptide Y. Compared to sham-operated animals, animals after ischemia/reperfusion showed marked kidney damage and significantly increased levels of serum creatinine, blood urea nitrogen, malondialdehyde, and neuropeptide Y. Renal myeloperoxidase activity was elevated in animals with ischemia/reperfusion relative to sham-operated animals, whereas renal superoxide dismutase activity was reduced. Netrin-1 pretreatment attenuated ischemia/reperfusion-induced functional and pathological changes in the kidney. Moreover, the ischemia/reperfusion-induced changes in the oxidative stress biomarkers and neuropeptide Y were significantly counteracted by prior administration of netrin-1. Taken together, our data showed that netrin-1 pretreatment prevented renal ischemia/reperfusion injury, at least partially through reduction of oxidative stress and neuropeptide Y expression.


Ferroelectric switching in ferroelastic materials with rough surfaces.
Electric switching of non-polar bulk crystals is shown to occur when domain walls are polar in ferroelastic materials and when rough surfaces with steps on an atomic scale promote domain switching. All domains emerging from surface nuclei possess polar domain walls. The progression of domains is then driven by the interaction of the electric field with the polarity of domain boundaries. In contrast, smooth surfaces with higher activation barriers prohibit effective domain nucleation. We demonstrate the existence of an electrically driven ferroelectric hysteresis loop in a non-ferroelectric, ferroelastic bulk material.


Monoclonal antibodies produced by in vitro immunization with sera of human-xenotransplant-bearing mice.
In vitro immunization procedures, using sera of athymic mice bearing human WOC ovarian tumors or CM III mammary tumors as immunizing antigen, induced a highly efficient formation of mABs (44% of antibody-producing clones) reacting with human ovarian and/or mammary tumor cells. More than half of these mABs showed cross-reactivity with mouse cell lines. Immunogenicity of normal mouse components in the sera from tumor bearers can be excluded since control immunization with sera of normal athymic mice yielded no mABs reacting with mouse or human cell lines. Furthermore, immunization with sera from tumor bearers did not induce mABs only reacting with mouse cells since 20% of the antibody-producing clones showed an exclusive specificity for the human tumor cells. On the basis of these results we concluded that the human-mouse cross-reacting mABs were induced by circulating human TAA with epitopes shared by mouse cellular components.


Diagnosis and Treatment of Testicular Cancer: A Clinician's Perspective.
Testicular germ cell tumors (GCTs) include seminoma and nonseminoma. Chance of cure is excellent for clinical stage I disease regardless of whether adjuvant treatment or a surveillance strategy with treatment only for those who relapse is used. Risk of recurrence is greater in nonseminoma with evidence of lymphovascular invasion, but most can be salvaged with chemotherapy and survival rates remain high. This article outlines key pathologic and clinical considerations in clinical stage I seminoma, nonseminoma, advanced disease, and assessment of cancer of unknown primary as a potential GCT.


Protective effect of compression socks in a marathon runner with a genetic predisposition to thrombophilia due to Factor V Leiden.
The present case study is an analysis of the effect of compression socks on hemostatic activation following a marathon in a female endurance athlete found to be heterozygous for the coagulation factor V (F5 1691 G>A [Arg>Gln rs6025/560]) risk allele that predisposes one to a genetically inherited disorder of blood clotting, Factor V Leiden. Markers for coagulation and fibrinolysis were obtained 24 h prior to (PRE), immediately after (FINISH) and 24 h after (POST) completion of two marathons: the first in which the runner was not wearing compression socks, and the second in which the runner wore compression socks throughout the race. Compression socks worn during a marathon appeared to lower the overall impact on hemostasis as well as clot formation in this particular athlete as evidenced by lower t-PA (-56%), TAT (-63%) and D-dimer (-30%). Hemostatic activation may be lower with the use of compression socks, and thus may be effective for preserving hemostasis in endurance athletes at risk.


Clinical results of shoulder manipulation under ultrasound-guided cervical nerve root block for frozen shoulder in patients with diabetes.
We investigated clinical results of manipulation under ultrasound-guided cervical nerveroot block (MUC) in frozen shoulder (FS). FS was defined refractory to conservative treatment and ≦100° in passive forward flexion. 15 shoulders were diabetes mellitus (DM) group and 81 were non-DM group. We evaluated ROM, JOA scores, Constant Shoulder Score, and UCLA scores pre and post-MUC. Although there were significantly improved the forward flexion, internal rotation, JOA scores, Constant Shoulder Score, and UCLA scores between pre and post-MUC in both groups, external rotation after MUC in DM group were significantly inferior to those in non-DM group.


CYBER-AIDD: A novel approach to implementing improved cyber security resilience for large Australian healthcare providers using a Unified Modelling Language ontology.
This paper proposes a novel cyber security risk governance framework and ontology for large Australian healthcare providers, using the structure and simplicity of the Unified Modelling Language (UML). This framework is intended to mitigate impacts from the risk areas of: (1) cyber-attacks, (2) incidents, (3) data breaches, and (4) data disclosures. Using a mixed-methods approach comprised of empirical evidence discovery and phenomenological review, existing literature is sourced to confirm baseline ontological definitions. These are supplemented with Australian government reports, professional standards publications and legislation covering cyber security, data breach reporting and healthcare governance. Historical examples of healthcare cyber security incidents are reviewed, and a cyber risk governance UML presented to manage the defined problem areas via a single, simplified ontological diagram. A clear definition of 'cyber security' is generated, along with the 'CYBER-AIDD' risk model. Specific examples of cyber security incidents impacting Australian healthcare are confirmed as N = 929 over 5 years, with human factors the largest contributor. The CYBER-AIDD UML model presents a workflow across four defined classes, providing a clear approach to implementing the controls required to mitigate risks against verified threats. The governance of cyber security in healthcare is complex, in part due to a lack of clarity around key terms and risks, and this is contributing to consistently poor operational outcomes. A focus on the most essential avenues of risk, using a simple UML model, is beneficial in describing these risks and designing governance controls around them.


Expiry of veterinary medicines in supply outlets in Central Uganda: prevalence, management and associated factors.
Animal diseases are a danger to livestock, businesses, and public health. This is why the public and private sectors in Africa have invested immensely in the manufacture and distribution of veterinary drugs. However, veterinary drug supply chain actors still suffer losses as a result of expiration. Besides, the way expired products are managed might pose risks to human, animal, and environmental health. This study investigated the prevalence, management of, and factors associated with the expiry of veterinary medicines in supply outlets in Central Uganda. A cross-sectional study was conducted among owners and caretakers of veterinary drug supply outlets. Data were collected using self-administered, semi-structured questionnaires. The level of expiry was computed as "acceptable" (for levels reported as ≤ 5%) and "unacceptable" (for levels reported as ˃5%). Logistic regression was used to assess associations between the level of drug expiry and predictor variables. A total of 168 owners/caretakers of veterinary drug supply outlets were included in this study. The majority (148/168, 88.1%) of respondents reported having experienced expiries in their outlets. Unacceptable levels of expiry were reported in 38/168 (22.6%) of the outlets. Retail outlets accounted for the majority (34/38, 89.5%) of the unacceptable levels. Powdered drugs accounted for most expiries (106/148, 71.6%). Most expiries were for drugs supplied to outlets on credit (58/124, 46.8%) and those used to treat rare diseases (26/124, 21%). Major reasons for expiry included irrational prescription, inaccurate forecasts, overstocking, dry seasons, and stocking without considering stock-at-hand. Methods of disposal of expired drugs included throwing at pits (74/168, 44.1%); returning drugs to suppliers (51/168, 30.4%); and incineration (33/168, 19.6%). Factors associated with acceptable levels of expiry included the caretaker being female [adjusted OR = 2.9, 95% CI = 1.22-5.08]; having a procurement policy [adjusted OR = 3.9, 95% CI = 1.29-4.81] and practicing first expiry, first out [adjusted OR = 6.07, 95% CI = 4.71-8.70]. Veterinary drug expiries are common in Uganda, and environmentally unfriendly methods of disposal are widely used. Acquisition and use of inventory tracking technologies that support First-Expiry-First-Out principles as well as proper disposal of expired medicines are recommended.


[Mid-long term complications of endovascular repair in aortic diseases and its secondary interventional strategies].
To investigate the methods and effects of secondary intervention for mid-long term complications of endovascular repair (EVR) in aortic diseases. From May 1999 to Jun 2007, 21 patients with mid-long term complications after EVR were treated in our center. Of these cases, 15 cases received first EVR for abdominal aortic aneurysm (AAA), 3 cases for thoracic aortic aneurysm (TAA) and 3 cases for aortic dissection (TAD). The mid-long term complications included 11 cases of type I endoleak, 4 cases of type II endoleak, 2 cases of type III endoleak and 4 cases of migration of stent grafts. Proximal or distal extensions were used for type I and III endoleak in 9 cases. Fenestrated, scallop and bifurcated stent grafts were used to reconstruct the aortic arch in 3 cases. Emboli technique was used in treating type II endoleak. Thrombectomy and bypass technique were used in 4 cases with stent graft limb occlusion. One ruptured AAA accepted open surgery. Secondary endovascular technique were undergone in 20 (95.2%) cases. One case died in 30 days after the secondary intervention and endoleak remained after the secondary operation in 5 cases. Three cases died of the secondary intervention. Endoleak and limb occlusion were the chief mid-long complications after EVR. Secondary endovascular technique can be used in most cases and carries great challenges in aortic arch lesions.


24-2 SITA Standard versus 24-2 SITA Faster in Perimetry-Naive Normal Subjects.
To compare the Swedish Interactive Thresholding Algorithm (SITA) Standard (SS) and SITA Faster (SFR) strategies in normal individuals undergoing standard automated perimetry (SAP) for the first time. Randomized, comparative, observational case series. Seventy-four perimetry-naive healthy individuals. All individuals underwent SAP 24-2 testing with the Humphrey Field Analyzer III (model 850 Zeiss) using the SS and SFR strategies. One eye of each individual was tested. Test order between strategies was randomized, and an interval of 15 minutes was allowed between the tests. The following variables were compared: test time, foveal threshold, false-positive errors, number of unreliable tests, mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), glaucoma hemifield test (GHT), and number of depressed points deviating at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total and pattern deviation probability maps. Specificity of the SS and SFR strategies were compared using Anderson's criteria for abnormal visual fields. The SFR tests were 60.4% shorter in time compared with SS (P < 0.001) and were associated with a significantly lower PSD (1.75 ± 0.80 decibel [dB] vs. 2.15 ± 1.25 dB; P = 0.016). There were no significant differences regarding the MD, VFI, foveal threshold, GHT, and number of points depressed at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total deviation and pattern deviation probability maps between SS and SFR. When all exams were analyzed and any of Anderson's criteria was applied, the specificity was 68% with SFR and 61% with SS (P = 0.250). The specificities observed with SFR and SS when only the first or second exams were analyzed were also similar (63% vs. 64% and 72% vs. 58%, respectively, P > 0.05). The SS and SFR were associated with similar specificities in perimetry-naive individuals. The SFR did not increase the number of depressed points in the total and pattern deviation probability maps. Ophthalmologists should be aware that both strategies are associated with disturbingly high false-positive rates in perimetry-naive individuals. Proprietary or commercial disclosure may be found after the references.


Is fertilization the dominant source of ammonia in the urban atmosphere?
It was previously believed that ammonia (NH3) has a short residence time in the atmosphere and cannot be transported far from its sources. In late March, however, this study observed a severe NH3 episode in urban Beijing when fertilizer was intensively applied on the North China Plain, with the highest hourly concentrations of 66.9 μg m-3 throughout the year. The stable nitrogen isotopic composition of NH3 (δ15N-NH3) during this episode (-37.0 to -20.0‰) fell in the range of endmembers of fertilizer and livestock, suggesting the long-range transport of NH3 from agricultural to urban regions. Based on a Bayesian isotope mixing model, the contribution of agriculture (fertilization) to urban NH3 concentrations was apportioned as 43.5% (26.0%) on polluted days. However, these contributions were reduced to 29.1% (12.8%) when nitrogen isotope fractionation between NH3 and ammonium was considered. In contrast to the limited contribution of agricultural sources, we found that nonagricultural emissions, particularly vehicles, dominate the source of NH3 in urban Beijing, even during the fertilization period. This finding indicated that nonagricultural sources should be considered when designing a control strategy for NH3 to reduce haze pollution in the urban atmosphere.


Small Amounts of Archaic Admixture Provide Big Insights into Human History.
Modern humans overlapped in time and space with other hominins, such as Neanderthals and Denisovans, and limited amounts of hybridization occurred. Here, we review recent work that has identified archaic hominin sequence that survives in modern human genomes and what these genomic excavations reveal about human evolutionary history.


Bioaccumulation as a method of removing psychoactive compounds from wastewater using aquatic plants.
Since WWTPs are not able to eliminate all psychoactive pharmaceuticals, these compounds become a part of the aquatic ecosystem. Our results indicate that compounds such as codeine or citalopram are eliminated with low efficiency (<38%), and compounds such as venlafaxine, oxazepam, or tramadol even with almost no efficiency. Lower elimination efficiency may be caused by the accumulation of these compounds in the wastewater treatment process. This study is focused on the possibility to remove problematic psychoactive compounds using aquatic plants. HPLC-MS analysis of the leaf extract obtained from studied plants showed that the amount of accumulated methamphetamine was highest in Pistia stratiotes and lower in the leaves of Limnophila sessiliflora and Cabomba caroliniana. However, tramadol and venlafaxine were accumulated considerably only in Cabomba caroliniana. Our study demonstrates that especially these three compounds - tramadol, venlafaxine, and methamphetamine, are accumulated in aquatic plants and can be removed from the aquatic environment. In our study was also observed that helophytic aquatic plants show a higher ability to remove psychoactive compounds from wastewater. Iris pseudacorus showed the best results in selected pharmaceuticals removal with no bioaccumulation effect in leaves or roots.