Adrenomedullin optimises mortality prediction in COPD patients.
Current multicomponent scores that predict mortality in COPD patients might underestimate the systemic component of COPD. Therefore, we evaluated the accuracy of circulating levels of proadrenomedullin (MR-proADM) alone or combined with the ADO (Age, Dyspnoea, airflow Obstruction), updated ADO or BOD (Body mass index, airflow Obstruction, Dyspnoea) index to predict all-cause mortality in stable COPD patients. This study pooled data of 1285 patients from the COMIC and PROMISE-COPD study. Patients with high MR-proADM levels (≥0.87 nmol/l) had a 2.1 fold higher risk of dying than those with lower levels (p < 0.001). Based on the C-statistic, the ADOA index (ADO plus MR-proADM) (C = 0.72) was the most accurate predictor followed by the BODA (BOD plus MR-proADM) (C = 0.71) and the updated ADOA index (updated ADO plus MR-proADM) (C = 0.70). Adding MR-proADM to ADO and BOD was superior in forecasting 1- and 2-year mortality. The net percentages of persons with events correctly reclassified (NRI+) within respectively 1-year and 2-year was 31% and 20% for ADO, 31% and 20% for updated ADO and 25% and 19% for BOD. The net percentages of persons without events correctly reclassified (NRI-) within respectively 1-year and 2-year was 26% and 27% for ADO, 27% and 28% for updated ADO and 34% and 34% for BOD. Adding MR-proADM increased the predictive power of BOD, ADO and updated ADO index.


The effect of aminophylline on gastrointestinal blood flow and oxygen metabolism in the conscious newborn lamb.
Aminophylline, widely used in the neonatal period, has been reported to be associated with necrotizing enterocolitis. We hypothesized that aminophylline might alter gastrointestinal blood flow and oxygen delivery. The effects of this drug on gastrointestinal (GI) blood flow and oxygen delivery, consumption, and extraction were examined using the radioactive microsphere method in ten chronically catheterized, unanesthetized lambs aged 5-12 days. While cardiac output and systemic oxygen consumption did not change, we found statistically significant increases (p less than 0.05) in small intestinal blood flow as a function of lamb weight and as a percentage of cardiac output. Splanchnic oxygen consumption also increased significantly. The oxygen reserve available to the GI tract can be compromised by aminophylline at levels similar to those used in the human neonate for treatment of apnea.


Reciprocal pre- and postsynaptic actions of cocaine at a central noradrenergic synapse.
Single-unit microelectrode studies were conducted to test the effects of systemic cocaine HCl on spontaneously firing single noradrenergic locus ceruleus (presynaptic) and cerebellar Purkinje (postsynaptic) neurons in rats in vivo. The spontaneous neuronal activity of all locus ceruleus neurons was inhibited by cocaine in a dose-dependent manner (0.5 to 2 mg/kg). These doses of cocaine elicited a predominant activation of postsynaptic Purkinje neurons. No effect of cocaine on neuronal action potential amplitude or slope was observed. Similar doses of the local anesthetic agent, procaine, did not affect action potential amplitudes or slopes of either locus ceruleus or Purkinje neurons. In addition, although cocaine elicited a significantly greater absolute change in the discharge rate of locus ceruleus neurons than of Purkinje neurons, the effects of procaine on those neurons were not significantly different from each other. The inhibition of locus ceruleus neurons by cocaine was significantly attenuated by pretreatment either with the alpha 2-adrenoceptor antagonist, yohimbine, or with reserpine. The activation of Purkinje neurons by cocaine was also significantly attenuated by reserpine pretreatment. Systemic cocaine administration (1 mg/kg, i.v.) did not potentiate the inhibitory effects of either locus ceruleus stimulation or local iontophoretic application of norepinephrine on Purkinje neuron discharge rate. We conclude that cocaine potently inhibits locus ceruleus neurons and this effect probably elicits Purkinje cell activation through disinhibition.


Burden, Severity and Characteristic Pattern of Coronary Artery Disease using 160-Slice Computed Tomographic Angiography: Earliest Report from Northern Nigeria.
Coronary computed tomography angiography (CCTA) allows for non-invasive visualization of the coronary arteries which is promising in diagnosing coronary artery disease. To determine the prevalence, morphology, anatomic distribution pattern and correlates of CAD in our environment. This cross-sectional study was conducted on the first cohort of patients referred for CCTA in our hospital. The patients were examined with 160-slice Toshiba® CT scanner. Their demographic data, relevant clinical information as well as the findings on CCTA were extracted and documented. The data were analysed using the R programming software version 4.0.4. Out of a total of 153 patients who presented for CCTA within the study period, 133 (84.7%) were eligible for analysis. Their age ranged from 22-78 years with a mean ± SD of 55.8 ± 11.7 years. A total of 33 (24.8%) had normal CCTA, while 100 (75.2%) had either stenosis or total occlusion. There was a significantly higher (p-value of 0.00001) calcium score among those with stenosis compared to those with normal CCTA. The severity of the stenotic lesion was associated with the calcium score. The logistic regression analyses showed a statistically significant (P = 0.0415, OR = 1.0569, 97.5% CI =1.078152-1.123240) association between age and the presence of coronary stenosis. In addition, most of the stenotic lesions were in the left anterior descending artery (LAD). Majority of the patients had coronary artery disease of variable severity and the LAD was the most involved artery. There was no significant association between sex and severity of the disease; however, old age and higher number of lesions were associated with severe disease.


A BLADE-ON-PETIOLE orthologue regulates corolla differentiation in the proximal region in Torenia fournieri.
The three-dimensional shape of a flower is integrated by morphogenesis along different axes. Differentiation along the petal proximodistal axis is tightly linked to the specification of pollinators; however, it is still unclear how a petal patterns this axis. The corolla of Torenia fournieri exhibits strong differentiation along the proximodistal axis, and we previously found a proximal regulator, TfALOG3, controlling corolla neck differentiation. Here, we report another gene, TfBOP2, which is predominantly expressed in the proximal region of the corolla. TfBOP2 mutants have shorter proximal corolla tubes and longer distal lobe, demonstrating its function as a proximal regulator. Arabidopsis BOPs mutant shows similar defects, favouring a shared role of BOPs homologues. Genetic analysis demonstrates the interaction between TfBOP2 and TfALOG3, and we further found that TfALOG3 physically interacts with TfBOP2 and can recruit TfBOP2 to the nuclear region. Our study favours a hypothetical shared BOP-ALOG complex that is recruited to regulate corolla differentiation in the proximal region axis of T. fournieri.


Association of 5-HTTLPR polymorphism with smoking behaviors: A meta-analysis.
Published articles reported controversial results about the association of 5-HTTLPR polymorphism with the risk of smoking behaviors. A meta-analysis was performed to assess the association between 5-HTTLPR polymorphism and smoking behaviors. A comprehensive search was conducted to identify studies (from January, 1990 to December, 2014) of the aforementioned association. The Q test and the I(2) statistic were used to examine between-study heterogeneity. Fixed or random effect model was selected based on heterogeneity test among studies. Meta-regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using funnel plots and Harbord test. Twenty-one published articles were included. Overall, we didn't find any significant association of 5-HTTLPR polymorphism with smoking initiation and smoking cessation in any of allele, dominant and recessive models. In the subgroup analysis stratified by ethnicity (Caucasian and Asian) or by whether smokers accepted the treatment for smoking cessation or not (Yes/No), there were still no significant associations detected in all genetic models. In conclusion, this meta-analysis suggested that there might be no association of 5-HTTLPR polymorphism with the risk of smoking behaviors. Further studies are needed to confirm these conclusions.


Metabolic stimulation of polymorphonuclear leucocytes: effects of tetravalent and divalent concanavalin A.
Polymorphonuclear leucocytes (PMNL) undergo a marked activation of their oxidative metabolism upon interaction with surface-reactive soluble stimuli as well as with phagocytosable objects. To get some insight into the mechanism of this stimulation, we have compared the stimulatory activity of the tetravalent lectin concanavalin A (Con A) with that of the divalent derivative succinyl-Con A (S-Con A). Both lectins bind to the PMNL surface to the same extent. S-Con A, however, is much less efficient in stimulating the PMNL metabolism. When S-Con A-treated PMNL are further reacted with antiserum to Con A, a potentiation of the metabolic stimulation is observed. Normal serum or addition to PMNL of antiserum to Con A in the absence of lectin has no effect. Furthermore, if S-Con A is displaced from its receptors on the cell membrane with alpha-methyl mannopyranoside, the addition of antiserum fails to cause a respiratory stimulation. These results suggest that the initial triggering of the metabolic stimulation of PMNL is in part accomplished through cross-linkage of membrane constituents.


Topiramate treatment of bipolar spectrum disorders: a retrospective chart review.
The objective of this paper was to determine if topiramate is effective as treatment for bipolar spectrum disorders in a naturalistic setting. All charts of outpatients treated with topiramate (n = 76) were reviewed, and clinical response was assessed retrospectively using the Clinical Global Impressions Scale for Improvement. Mild improvement was seen in 47% (n = 36) and moderate-to-marked improvement in 13% (n = 10). Responders received a higher mean dose (180 mg/day) than did nonresponders (83.2 mg/day, p = 0.002). Topiramate dose was also higher in those who lost weight (138.3 mg/day) than in those who did not (70 mg/day, p = 0.007). Weight loss was experienced by 50% of the sample, with a mean loss of 14.2 lbs. Side effects were reported by 82% (n = 62) of the population, including cognitive effects, sedation, parasthesias, nausea, insomnia, headache, and dizziness. Adverse effects led 36% (n = 27) of the total sample to discontinue treatment with topiramate. Topiramate led to significant weight loss in about half of this bipolar population, while also improving mood symptoms at least mildly in most patients. Topiramate response and weight loss were both dose-related, with efficacy, in particular, associated with higher doses (mean = 180 mg/day) than frequently used in current clinical practice.


Anti-hyperalgesic activity of corilagin, a tannin isolated from Phyllanthus niruri L. (Euphorbiaceae).
Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-glucose) is a tannin isolated from Phyllanthus niruri (Euphorbiaceae). This plant is well known for their therapeutic purposes to treat several diseases associated with dolorous process and are used in several ethno-medicines in tropical and subtropical countries. This study was designed to evaluate the anti-hyperalgesic activity of corilagin using chemically and thermally based nociception models in mice. Corilagin was isolated from Phyllanthus niruri (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hyperalgesic activity was evaluated by using writhing, formalin, capsaicin, glutamate and hot plate tests in mice. Corilagin presented activity in acetic acid model with the ID50 calculated value of 6.46 (3.09-13.51) being about 20.6 fold more potent than acetylsalicylic acid. It also exhibited activity against the first phase of formalin test with ID50 value of 18.38 (15.15-22.59) μmol/kg. In the capsaicin and glutamate models, corilagin demonstrated significant activity at the 3 mg/kg. The experimental data demonstrated that corilagin exhibits anti-hyperalgesic activity that may be due to interaction with the glutamatergic system.


Key Stakeholder Perceptions of Standard vs. Total Cost of Ownership: A Procurement Analysis for Orthopaedic-Powered Instruments.
This study compares standard procurement methodology (SPM) with total cost of ownership (TCO) methodology for the procurement of orthopaedic-powered instruments. The authors conducted semi-structured standardized interviews with key hospital procurement stakeholders following consolidated criteria for reporting qualitative research. Of the 33 hospital procurement stakeholders interviewed, all (100%) reported that SPM would be easier to use than TCO. However, only six (18%) preferred SPM over TCO. Barriers to the adoption of TCO emerged as a theme. Creating TCO frameworks can help to simplify the process for procurement agents and facilitate its adoption in the healthcare sector.


Neuromorphological changes in mouse olfactory bulb after neonatal exposure to phenobarbital.
Heterogeneous Sabra mice pups were injected daily with 50 mg/kg phenobarbital (B50) or 40 mg/kg (B40) from postnatal day 2 (P2) to P21. Control litter mates (C) received vehicle injections. All animals were killed on P50 and their brains removed for histological analysis. The volumetric growth of the main olfactory bulb (MOB) was assessed in hematoxylin and eosin-stained serial sections cut in the sagittal plane. The volume of MOB was reduced 20 to 25% in barbiturate-treated mice. The greatest reductions in volume were seen in the external layers of the bulb (20 to 28%). There were moderate reductions in the internal granular layer (IGL, 6 to 20%) and no reductions in the subependymal layer that contains the migrating and immature cells. The number of prenatally-formed mitral cell neurons was unaffected by the treatment while the number of the pre- and postnatally generated granule cells was significantly reduced in the B40 group. There were no treatment effects on the sizes or packing densities of the mitral or granule cells. Like the hippocampus and the cerebellum, the developing MOB is vulnerable to barbiturate-exposure.


Mycotoxin production in a carbendazim-resistant strain of fusarium sporotrichioides.
Mycelial yield and production of three trichothecenes, namely T-2 toxin, diacetoxyscirpenol (DAS) and neosolaniol (NEO) were compared in control (CS) and carbendazim-resistant strains (RS) ofFusarium sporotrichioides. Each strain was exposed to graded concentrations of carbendazim (0, 1, 2, and 4 μg/ml media) for 2, 5 and 7 days under shake-culture conditions at an incubation temperature of 25°C. Mycelial yield was significantly (P<0.001) affected by strain, carbendazim concentration and incubation time. The strain differences in mycelial mass at 2 days (P<0.05) became more pronounced at 5 and 7 days of incubation (P<0.001). However, mycelial growth differences between the two strains were greatest following exposure to carbendazim, with the effects becoming more divergent with time. Combined results for the three incubation times showed dose related effects in carbendazim inhibition of T-2 toxin production by CS isolates. In contrast, RS cultures exposed to the 2 μg/ml addition of carbendazim significantly increased T-2 toxin production (P<0.05 or better). At 1 and 4 μg/ml additions, T-2 toxin inhibition occurred but the effect was less marked than in the CS series. RS yielded more DAS than CS at 5 days (P<0.05) and at 7 days (P<0.01) of incubation. The major component of this strain difference arose from the effects of the 2 μg/ml addition of carbendazim (P<0.01). NEO production was also higher in RS than in CS, with the difference becoming progressively more pronounced from day 5 (P<0.05) to day 7 (P<0.01) of incubation. However, these differences reflected enhanced NEO output with carbendazim addition of 4 μg/ml (P<0.05) in day 5 extracts and of both 2 μg/ml (P<0.01) and 4 μg/ml additions (P<0.05) in day 7 samples. Moreover, the ratio of NEO to T-2 toxin production was affected by an interaction involving incubation time, strain and carbendazim dose (P<0.05 or better). On day 5, this ratio was greater in CS exposed to 2 μg/ml, but at 4 μg/ml, the ratio was higher in RS. It is concluded that carbendazim resistance induced genuine differences in the synthesis of T-2 toxin and NEO. It is suggested that the strain difference may reside in the conversion of NEO to T-2 toxin which may be sensitive to fungicide concentration. This would imply that carbendazim resistance induces changes in the terminal rather than initial phases of trichothecene biosynthesis.


Urinary Cotinine Is as Good a Biomarker as Serum Cotinine for Cigarette Smoking Exposure and Lung Cancer Risk Prediction.
Cotinine is a metabolite of nicotine. Serum and urinary cotinine are validated biomarkers for cigarette exposure. Their performance for lung cancer risk prediction has not been simultaneously examined in epidemiologic studies. A nested case-control study, including 452 incident lung cancer cases and 452 smoking-matched controls in the Shanghai cohort study, was conducted. Mass spectrometry-based methods were used to quantify cotinine in serum and urine samples collected from current smokers at baseline, on average 10 years before cancer diagnosis of cases. Logistic regression was used to estimate ORs, 95% confidence intervals (CI), and AUC ROC for lung cancer associated with higher levels of cotinine. Serum and urinary cotinine levels were significantly higher in lung cancer cases than controls. Compared with the lowest quartile serum cotinine (≤0.40 nmol/mL), the OR of lung cancer for smokers in the highest quartiles (>1.39 nmol/mL) was 5.46 (95% CI, 3.38-8.81). Similarly, the OR was 5.49 (95% CI, 3.39-8.87) for highest (>16.38 nmol/mg creatinine) relative to the lowest quartile of urinary total cotinine (≤4.11 nmol/mg creatinine). A risk prediction model yielded an AUC of 0.72 (95% CI, 0.69-0.75) for serum cotinine and 0.72 (95% CI, 0.69-0.75) for urinary total cotinine combined with smoking history. Urinary and serum cotinine have the same performance in prediction of lung cancer risk for current smokers. Urinary cotinine is a noninvasive biomarker that can replace serum cotinine in risk prediction of future lung cancer risk for current smokers.


Novel Cyclic Dextrins, Cycloisomaltooligosaccharides, from Bacillus sp. T-3040 Culture.
Three kinds of novel cyclic isomaltooligosaccharides were isolated from the culture broth of a strain of Bacillus sp. T-3040, which had been isolated from soil. They were identified as cycloisomalto-heptaose, -octaose, and -nonaose, respectively, on the basis of their mass spectra, proton nuclear magnetic resonance spectra, carbon nuclear magnetic resonance spectra, infrared spectra, reducing power, and results of enzymatic analysis using endo-dextranase and exo-dextranase. They also showed features similar to cyclodextrins upon high-pressure liquid chromatography analysis using an ODS column.


Harnessing insect olfactory neural circuits for detecting and discriminating human cancers.
There is overwhelming evidence that presence of cancer alters cellular metabolic processes, and these changes are manifested in emitted volatile organic compound (VOC) compositions of cancer cells. Here, we take a novel forward engineering approach by developing an insect olfactory neural circuit-based VOC sensor for cancer detection. We obtained oral cancer cell culture VOC-evoked extracellular neural responses from in vivo insect (locust) antennal lobe neurons. We employed biological neural computations of the antennal lobe circuitry for generating spatiotemporal neuronal response templates corresponding to each cell culture VOC mixture, and employed these neuronal templates to distinguish oral cancer cell lines (SAS, Ca9-22, and HSC-3) vs. a non-cancer cell line (HaCaT). Our results demonstrate that three different human oral cancers can be robustly distinguished from each other and from a non-cancer oral cell line. By using high-dimensional population neuronal response analysis and leave-one-trial-out methodology, our approach yielded high classification success for each cell line tested. Our analyses achieved 76-100% success in identifying cell lines by using the population neural response (n = 194) collected for the entire duration of the cell culture study. We also demonstrate this cancer detection technique can distinguish between different types of oral cancers and non-cancer at different time-matched points of growth. This brain-based cancer detection approach is fast as it can differentiate between VOC mixtures within 250 ms of stimulus onset. Our brain-based cancer detection system comprises a novel VOC sensing methodology that incorporates entire biological chemosensory arrays, biological signal transduction, and neuronal computations in a form of a forward-engineered technology for cancer VOC detection.


Disparities in survival of hematologic malignancies in the context of social determinants of health: a systematic review.
Social determinants of health (SDHs) have been reported as relevant factors responsible for health inequity. We sought to assess clinical data from observational studies conducted in the United States evaluating the impact of SDHs on the outcomes of patients with hematologic malignancies. Thus, we performed a systematic review in 6 databases on 1 September 2021, in which paired reviewers independently screened studies and included data from 41 studies. We assessed the risk of bias using the Joanna Briggs Institute appraisal tools and analyzed the data using a descriptive synthesis. The most common SDH domains explored were health care access and quality (54.3%) and economic stability (25.6%); others investigated were education (19%) and social and community context (7.8%). We identified strong evidence of 5 variables significantly affecting survival: lack of health insurance coverage or having Medicare or Medicaid insurance, receiving cancer treatment at a nonacademic facility, low household income, low education level, and being unmarried. In contrast, the reports on the effect of distance traveled to the treatment center are contradictory. Other SDHs examined were facility volume, provider expertise, poverty, and employment rates. We identified a lack of data in the literature in terms of transportation, debt, higher education, diet, social integration, environmental factors, or stress. Our results underscore the complex nature of social, financial, and health care barriers as intercorrelated variables. Therefore, the management of hematologic malignancies needs concerted efforts to incorporate SDHs into clinical care, research, and public health policies, identifying and addressing the barriers at a patient-based level to enhance outcome equity (PROSPERO CRD42022346854).


Two-year follow-up of bioresorbable vascular scaffolds in severe infra-popliteal arterial disease.
To assess the safety, efficacy, and durability of the Absorb bioresorbable vascular scaffold in predominantly complex, infra-popliteal lesions for the management of chronic limb ischemia at two-year clinical follow-up. Bioresorbable vascular scaffold are biodegradable scaffolds that provide short-term vascular support before undergoing intravascular degradation. A recent trial reported excellent 36-month vessel patency rates in simple infrapopliteal arterial lesions treated with Absorb bioresorbable vascular scaffold. This single-center, retrospective study evaluated the use of the Absorb bioresorbable vascular scaffold (everolimus impregnated poly-L-lactic scaffold) in patients with infra-popliteal peripheral arterial disease (PAD) with respect to safety (thrombosis and TIMI bleeding), technical success, and freedom from clinically driven target vessel failure at 24 months. 31 patients (51.6% male) with a median age of 67 years with predominantly advanced infra-popliteal disease were treated with 49 bioresorbable vascular scaffold in 41 vessels. The mean stenosis was 94% (80-100), with 49% of lesions being chronic thrombotic occlusions. No scaffold thrombosis or peri-procedural bleeding was observed. Procedural success was achieved in all patients; 93.5% of patients experienced freedom from clinically driven target vessel failure at 24 months, driven by one revascularization and one amputation. Primary patency was 96.7% at 12 months and 87.1% at 24 months. All patients were alive at 12 and 24 months. At 24 months, our study found that patients with predominantly advanced infra-popliteal PAD who were treated with Absorb bioresorbable vascular scaffold reported improved clinical status and a low and durable rate of clinically driven target vessel failure extending out to 24 months.


Multiple mycotoxin exposure during pregnancy and risks of adverse birth outcomes: a prospective cohort study in rural Ethiopia.
Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes in low- and middle-income countries. The evidence, however, is inconsistent and mainly limited to the assessment of a single mycotoxin. We assessed biomarkers of exposure to multiple mycotoxins during pregnancy and their associations with adverse birth outcomes in rural Ethiopia. We analyzed data from 579 pregnant women between 8 and 24 weeks of completed gestation enrolled in a prospective cohort study. Serum mycotoxin concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. Multivariable linear probability models, adjusted for potential confounding factors and multiple comparisons, were fitted to assess the associations between mycotoxin exposure and small for gestational age and preterm birth. We applied principal component analysis to reduce the dimensionality of biomarker data from several taxonomic mycotoxin groups. All pregnant women were co-exposed to at least five mycotoxins, and one pregnant woman was co-exposed to 27 mycotoxins. Fumonisins (FB), i.e., FB2, FB3, FB1, and tenuazonic acid were the most frequently identified mycotoxins in 98.8, 95.3, 93.3, and 81.4% of the samples respectively. Deoxynivalenol was detected in 38.7%, nivalenol in 50.1%, ochratoxin α in 67.9%, and zearalenone in 50.9% of the serum samples. After adjustment, we found no statistically significant (all P ≥ 0.05) associations between mycotoxin exposures and birth outcomes. Despite our study providing no evidence for relationships between mycotoxin biomarkers and adverse birth outcomes, our findings do indicate an extensive presence of multiple mycotoxin exposure among pregnant women. Public health policies and nutrition-sensitive interventions must ensure exposure to mycotoxins is reduced in rural Ethiopia.


Risk factors of female HIV-seropositive patients attending the clinic for sexually transmitted diseases at St Mary's Hospital, London.
Of 3450 women tested for antibodies to human immunodeficiency virus HIV-1 and HIV-2 between September 1985 and July 1989, 61 were positive (1.8%). Twenty-seven of these (44%) were presumed to have acquired their HIV infection by heterosexual contact and 23 (38%) were intravenous drug addicts. In geographical origin, 23 (38%) of the patients were from the UK and 19 (31%) from Africa. Amongst these 61 women, 2 (3%) have since died, one committed suicide and one was suspected of committing suicide.


Yeast Vps13 promotes mitochondrial function and is localized at membrane contact sites.
The Vps13 protein family is highly conserved in eukaryotic cells. Mutations in human VPS13 genes result in a variety of diseases, such as chorea acanthocytosis (ChAc), but the cellular functions of Vps13 proteins are not well defined. In yeast, there is a single VPS13 orthologue, which is required for at least two different processes: protein sorting to the vacuole and sporulation. This study demonstrates that VPS13 is also important for mitochondrial integrity. In addition to preventing transfer of DNA from the mitochondrion to the nucleus, VPS13 suppresses mitophagy and functions in parallel with the endoplasmic reticulum-mitochondrion encounter structure (ERMES). In different growth conditions, Vps13 localizes to endosome-mitochondrion contacts and to the nuclear-vacuole junctions, indicating that Vps13 may function at membrane contact sites. The ability of VPS13 to compensate for the absence of ERMES correlates with its intracellular distribution. We propose that Vps13 is present at multiple membrane contact sites and that separation-of-function mutants are due to loss of Vps13 at specific junctions. Introduction of VPS13A mutations identified in ChAc patients at cognate sites in yeast VPS13 are specifically defective in compensating for the lack of ERMES, suggesting that mitochondrial dysfunction might be the basis for ChAc.


Determination of beef tenderness based on airflow pressure combined with structural light three-dimensional (3D) vision technology.
The main factor affecting beef quality, consumer satisfaction, and purchase decisions is beef tenderness. In this study, a rapid nondestructive testing method for beef tenderness based on airflow pressure combined with structural light 3D vision technology was proposed. The structural light 3D camera was used to scan the 3D point cloud deformation information of the beef surface after the airflow acted on it for 1.8 s. Six deformation characteristics and three point cloud characteristics of the beef surface depression region were obtained by using denoising, point cloud rotation, point cloud segmentation, point cloud descending sampling, alphaShape, and other algorithms. A total of nine characteristics were mainly concentrated in the first five principal components (PCs). Therefore, the first five PCs were put into three different models. The results showed that the Extreme Learning Machine (ELM) model had a comparatively higher prediction effect for the prediction of beef shear force, with a root mean square error of prediction (RMSEP) of 11.1389 and a correlation coefficient (R) of 0.8356. In addition, the correct classification accuracy of the ELM model for tender beef achieved 92.96%. The overall classification accuracy reached 93.33%. Consequently, the proposed methods and technology can be applied for beef tenderness detection.


Taking stock of population-level interventions targeting risk factors for hypertension and diabetes in Rwanda and South Africa: methodological reflections and lessons learnt from conducting a multi-component situational analysis.
Hypertension and diabetes are on the rise both in Rwanda and South Africa. The responsibility for NCD risk factors cut across different sectors, which makes it complex to effectively manage. Policy-relevant intervention research is thus critical for addressing the NCD challenge. We conducted a situational analysis in both countries to identify and describe current population-level interventions targeting risk factors for diabetes and hypertension. This paper presents this methodology and shares challenges encountered, and lessons learnt in applying the methodology. We describe a multi-component methodology for conducting a situational analysis, which included a desk review, stakeholder mapping, survey, key informant interviews, and a consultative workshop. This methodology was applied in a standardized manner in two African countries. Following the analysis, the authors held iterative team consultations to reflect on challenges and lessons learnt during this process. Key challenges and lessons learnt relate to i) stakeholder recruitment, engagement and retainment; ii) utilization and triangulation of multiple sources of data; and iii) evolving circumstances, particularly related to the Covid-19 pandemic. It proved challenging to recruit stakeholders outside the health sector and in the private sector, as they often do not consider themselves as making or influencing policies and thus were reluctant to engage. The difficulties with responsiveness were often overcome through face-to-face visits, an opportunity to explain the relevance of their participation. With regards to health sector stakeholders and all other stakeholders, continued engagement over prolonged periods of time also turned out to be challenging. Covid-19 restrictions were preserved to be an impediment throughout the conduct of the situational analysis, specifically in South Africa. The use of multi-stage mixed methods was found to be appropriate for addressing the study objectives, as each step yielded unique data, concepts, and perspectives that complemented the other data. Conducting a situational analysis is crucial for understanding the current state of interventions and identifying opportunities for new interventions. The multi-component methodology used in two African countries was found to be feasible, appropriate, and informative. Others planning to conduct situational analysis may follow, adapt and improve upon our approach, reacting to the challenges encountered.


Methoxy substituent facilitated wide solvatofluorochromism, white light emission, polymorphism and stimuli-responsive fluorescence switching in donor-π-acceptor.
Introducing methoxy substituent into triphenylamine-acetophenone based donor-π-acceptor fluorophore, 3-(4-(diphenylamino)phenyl)-1-phenylprop-2-en-1-one (1), produced strong solvatofluorochromism including white light emission, fluorescent polymorphs and mechano-responsive fluorescence switching. The unsubstituted and methoxy substituted compounds displayed strong solvent polarity mediated tunable emission in the solution. Interestingly, 3-(4-(diphenylamino)phenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (2) and 3-(4-(diphenylamino)-2-methoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (3) showed single molecule white light emission in DMSO and ethanol, respectively. 1-3 exhibited strong green/yellow fluorescence in the solid-state (Quantum yield (Φf) = 10 to 23%). 2 produced fluorescent polymorphs (green (2-G) and yellow (2-Y). Single crystal structural analysis revealed that donor and acceptor phenyl units adopted coplanar conformation in 2-G and 3 whereas twisted molecular conformation in 1 and 2-Y. Further, 2-G exhibited π…π interactions facilitated isolated dimers whereas 2-Y showed well separated molecules in the crystal lattice. Aggregation induced emission (AIE) studies showed morphological transformation induced fluorescence tuning for 2. The intramolecular charge transfer (ICT) from TPA to acetophenone was confirmed by computational studies. Mechanofluorochromic (MFC) studies of 1 showed only slight reduction of intensity without modulating fluorescence wavelength significantly but 2 and 3 exhibited visible emissive colour change from yellow to green and vice versa by crushing and heating. Both 2 and 3 also exhibited self-reversible fluorescence switching that was confirmed by PXRD pattern. Thus, methoxy group introduction resulted in obtaining white light emitting fluorescence molecules in the solution state and self-reversible fluorescence switching materials.


Pleomorphic rhabdomyosarcoma of the liver in an adult: An extremely rare case report and review of literature.
Primary hepatic sarcomas are one of the extremely rare malignant tumors representing less than 0.1 % of all primary malignant neoplasms. A known compensated cirrhotic HCV 60-year-old female lady MELD score 8 with a medical history of controlled diabetes and hypertension presented to our hepatobiliary clinic experiencing a chronic right hypochondrial pain that radiate to her right shoulder of 3 months duration. O/E there was right hypochondrial and epigastric tenderness. Pelvi-abdominal US was done then PET CT which revealed a large exophytic focal lesion measuring about 8 × 7 × 6 cm and achieving 12.4 SUV max on FDG uptake. Pre-operative US guided true-cut biopsy showed small oval rounded cells with focal spindling and the neoplastic cells showed hyperchromatic pleomorphic nuclei with little cytoplasm with a positive reaction of tumor cells stained with Desmin and Myogenin with a diagnosis of pleomorphic rhabdomyosarcoma. The patient was scheduled for neoadjuvant chemotherapy and then elective Right hemihepatectomy. Although many challenges were encountered during the resection of the tumor as the tumor was attached to the under surface of the diaphragm, the tumor was resected with a safety margin of 1 cm with frozen histopathological examination being negative for any malignant cells. The patient's postoperative course was uneventful apart from wound infection and was discharged on the postoperative sixth day. The percutaneous liver biopsy plays an important role in the diagnosis of liver's rhabdomyosarcomas. Neoadjuvant chemotherapy addresses the behavior of the tumor, together with early surgical intervention can lead to favorable outcomes and reduce the recurrence.


Emergence of the Synucleins.
This study establishes the origin and evolutionary history of the synuclein genes. A combination of phylogenetic analyses of the synucleins from twenty-two model species, characterization of local synteny similarities among humans, sharks and lampreys, and statistical comparisons among lamprey and human chromosomes, provides conclusive evidence for the current diversity of synuclein genes arising from the whole-genome duplications (WGDs) that occurred in vertebrates. An ancestral synuclein gene was duplicated in a first WGD, predating the diversification of all living vertebrates. The two resulting genes are still present in agnathan vertebrates. The second WGD, specific to the gnathostome lineage, led to the emergence of the three classical synuclein genes, SNCA, SNCB and SNCG, which are present in all jawed vertebrate lineages. Additional WGDs have added new genes in both agnathans and gnathostomes, while some gene losses have occurred in particular species. The emergence of synucleins through WGDs prevented these genes from experiencing dosage effects, thus avoiding the potential detrimental effects associated with individual duplications of genes that encode proteins prone to aggregation. Additional insights into the structural and functional features of synucleins are gained through the analysis of the highly divergent synuclein proteins present in chondrichthyans and agnathans.


Topographical representation of odor hedonics in the olfactory bulb.
Hedonic value is a dominant aspect of olfactory perception. Using optogenetic manipulation in freely behaving mice paired with immediate early gene mapping, we demonstrate that hedonic information is represented along the antero-posterior axis of the ventral olfactory bulb. Using this representation, we show that the degree of attractiveness of odors can be bidirectionally modulated by local manipulation of the olfactory bulb's neural networks in freely behaving mice.


Occurrence of a barbiturate-inducible catalytically self-sufficient 119,000 dalton cytochrome P-450 monooxygenase in bacilli.
In a recent publication (Narhi, L.O. and Fulco, A.J.[1986] J. Biol. Chem. 261, 7160-7169) we described the characterization of a catalytically self-sufficient 119,000 Dalton cytochrome P-450 fatty acid monooxygenase (P-450BM-3) induced by barbiturates in Bacillus megaterium ATCC 14581. We have now examined cell-free preparations from 12 distinct strains of B. megaterium and from one or two strains each of B. alvei, B. brevis, B. cereus, B. licheniformis, B. macerans, B. pumilis and B. subtilis for the presence of this inducible enzyme. Using Western blot analyses in combination with assays for fatty acid hydroxylase activity and cytochrome P-450, we were able to show that 11 of the 12 B. megaterium strains contained not only a strongly pentobarbital-inducible fatty acid monooxygenase identical to or polymorphic with P-450BM-3 but also significant levels of two smaller P-450 cytochromes that were the same as or similar to cytochromes P-450BM-1 and P-450BM-2 originally found in ATCC 14581. Unlike the 119,000 Dalton P-450, however, the two smaller P-450s were generally easily detectable in cultures grown to stationary phase in the absence of barbiturates and, with some exceptions, were not strongly induced by pentobarbital. None of the non-megaterium species of Bacillus tested exhibited significant levels of either fatty acid monooxygenase activity or cytochrome P-450. The one strain of B. megaterium that lacked inducible P-450BM-3 was also negative for BM-1 and BM-2. However, this strain (ATCC 13368) did contain a small but significant level of another P-450 cytochrome that others have identified as the oxygenase component of a steroid 15-beta-hydroxylase system. Our evidence suggests that the BM series of P-450 cytochromes is encoded by chromosomal (rather than by plasmid) DNA.


Pneumolabyrinth as an Early Computed Tomographic Finding After Cochlear Implantation and its Clinical Significance.
To determine the incidence and volume of pneumolabyrinth using early temporal bone computed tomography (TBCT) findings and evaluate the correlation between pneumolabyrinth and various clinical variables. Retrospective case review. Tertiary academic center. Fifty-three consecutive adult cochlear implantation (CI) recipients (53 ears) with normal inner ears who underwent high-resolution TBCT within 3 days after CI were included. Axial TBCT images were used for detection and measurement of pneumolabyrinth. Incidence and volume of pneumolabyrinth were evaluated. In addition, the following clinical variables were analyzed to evaluate the correlation with pneumolabyrinth volume: demographics, implant type, surgical approach, postoperative dizziness, and preservation of functional residual hearing. Pneumolabyrinth was present in all patients, and the average volume was 8.496 mm3. Pneumolabyrinth was confined to the cochlea (pneumocochlea) in all patients except for one who also had pneumovestibule. The pneumolabyrinth volume in patients with postoperative dizziness was significantly larger than that in patients without postoperative dizziness (10.435 mm3 vs. 8.016 mm3; p = 0.029). Multivariate analysis showed that a larger volume of pneumolabyrinth was significantly associated with postoperative dizziness (odds ratio, 1.420; 95% confidence interval, 1.114-1.808; p = 0.005). A certain volume of pneumolabyrinth was always present in the early stage after CI, and the volume of pneumolabyrinth measured using early TBCT findings was significantly associated with the occurrence of postoperative dizziness.


A Novel Dual Antibody Staining Assay to Measure Estrogen Receptor Transcriptional Activity.
Activity of the canonical estrogen receptor (ER) pathway is equivalent to functional activity of the nuclear ER transcription factor. Monoclonal antibodies (MoAbs) that identify nuclear ER in cells and tissue samples are frequently used to assess ER transcriptional activity, however, it remains unclear if this approach is sufficiently predictive of ER pathway activity. This study uses ER-positive breast cancer cell lines (MCF7 and T47D) in which ER transcriptional activity was quantified using an mRNA-based ER pathway activity assay. The relationship between ER activity and nuclear ER staining with ER MoAbs was then investigated. Confirming earlier findings, the results show that while the presence of ER in the cell nucleus is a prerequisite for ER activity, it is not predictive of ER transcriptional activity. There were remarkable differences in the behaviours of the antibodies used in the study. EP1 and 1D5 showed reduced nuclear staining when ER was transcriptionally active, while staining with H4624 was independent of ER activity. To improve discrimination between active and inactive nuclear ER based on ER staining, a method was developed which consists of dual ER MoAb immunofluorescent staining, followed by generation of a digital image with a standard digital pathology scanner. Then a cell nucleus detection algorithm and per cell calculation of the nuclear H4624/EP1 fluorescence intensity ratio was applied, where a high H4624/EP1 ratio predicts an active ER pathway. With this method, the EP1 and 1D5 antibodies are interchangeable. We hypothesize that the transcriptional activation of ER hides the epitope recognized by MoAbs EP1 and 1D5, while H4624 binds an ER epitope that remains accessible during ER pathway activation. The method described in this study should add substantial value to the assessment of ER pathway activity for biomedical research and diagnostics.


Thermal influences on the habitat preference and the diurnal activity in three European Rana species.
The diurnal behaviour of frogs was recorded quantitatively in a habitatlike experimental environment by a new method of automatic registration via thermocouples. Three species with different habitat preferences during their summer activity period were chosen: the terrestrial common frog Rana temporaria LINNÈ and the semiaquatic water frog Rana lessonae CAMERANO and Rana ridibunda PALLAS. The activity, the location and the skin temperatures of these frogs were recorded continuously in four different temperature ranges (8.1° C-31.0° C) within the temperature span of the summer activity period. The thermal requirements and behavioural adaptations to the habitat of each species were analysed. The experimental results coincided with field observations and showed some details not yet known. The northern species R. temporaria exhibited a distinctive behavioural thermoregulation including cooling behaviour at high temperatures and warming behaviour at low temperatures during the day. In all temperatures tested these frogs remained on land changing their preferred location from the open area to the hiding places. The main activity period shifted from night to day with decreasing temperatures. The more southern species R. lessonae preferred higher temperatures than the other species showing basking behaviour during the day independent of the ambient temperature. With decreasing temperatures the preferred location changed from the shore to the water and the activity during the night almost disappeared. The closely related R. ridibunda tolerated high temperatures too, but only rarely basked. This species, however, reacted contrarily to decreasing temperatures: it changed its preference from the water to the land. This behavioural differenciation between the water frog species may be of importance for the actual habitat preference of these central european water frogs.


Composite materials with enhanced dimensionless Young's modulus and desired Poisson's ratio.
We have designed a new type of composite materials which not only has a Young's modulus much larger than the Voigt limit, but also is always nearly isotropic. Moreover, its Poisson's ratio can be designed at a desired value, e.g. positive, or negative, or zero. We have also demonstrated that structural hierarchy can help to enhance the stiffness of this type of composite materials. The results obtained in this paper provide a very useful insight into the development of new functional materials and structures.


CRISPR-Cas-Mediated Tethering Recruits the Yeast HMR Mating-Type Locus to the Nuclear Periphery but Fails to Silence Gene Expression.
To investigate the relationship between genome structure and function, we have developed a programmable CRISPR-Cas system for nuclear peripheral recruitment in yeast. We benchmarked this system at the HMR and GAL2 loci, both of which are well-characterized model systems for localization to the nuclear periphery. Using microscopy and gene silencing assays, we demonstrate that CRISPR-Cas-mediated tethering can recruit the HMR locus but does not detectably silence reporter gene expression. A previously reported Gal4-mediated tethering system does silence gene expression, and we demonstrate that the silencing effect has an unexpected dependence on the properties of the protein tether. The CRISPR-Cas system was unable to recruit GAL2 to the nuclear periphery. Our results reveal potential challenges for synthetic genome structure perturbations and suggest that distinct functional effects can arise from subtle structural differences in how genes are recruited to the periphery.


Retinol-binding protein 4 levels are associated with measures of liver and renal function and oxidant/antioxidant status in obese children.
Serum retinol-binding protein 4 (RBP4) has been proposed as a metabolic risk factor in obesity. We found that RBP4 levels also were associated with liver enzymes and cystatin C. Oxidant stress is a significant feature in obese children with greater values of RBP4 that can mediate the development of comorbidities.


[Transfer of genetic information from T to B human lymphocytes during an immune response to herpes simplex virus].
Human blood lymphocytes carrying different allotypes were divided into B and T subpopulations and cultured in presence or in absence of ultraviolet inactivated Herpes Simplex Virus. Isolated B or T cells did not produce any antiherpetic activity. The B lymphocytes cultured in presence of 1 or 50% of the supernatant collected from virus exposed T cells synthesized on antiherpetic antibody with some allotypic markers of the T cell donor.


Target-Based Care: An Intervention to Reduce Variation in Postoperative Length of Stay.
To derive care targets and evaluate the impact of displaying them at the point of care on postoperative length of stay (LOS). A prospective cohort study using 2 years of historical controls within a freestanding, academic children's hospital. Patients undergoing benchmark cardiac surgery between May 4, 2014, and August 15, 2016 (preintervention) and September 6, 2016, to September 30, 2018 (postintervention) were included. The intervention consisted of displaying at the point of care targets for the timing of extubation, transfer from the intensive care unit (ICU), and hospital discharge. Family satisfaction, reintubation, and readmission rates were tracked. The postintervention cohort consisted of 219 consecutive patients. There was a reduction in variation for ICU (difference in SD -2.56, P < .01) and total LOS (difference in SD -2.84, P < .001). Patients stayed on average 0.97 fewer days (P < .001) in the ICU (median -1.01 [IQR -2.15, -0.39]), 0.7 fewer days (P < .001) on mechanical ventilation (median -0.54 [IQR -0.77, -0.50]), and 1.18 fewer days (P < .001) for the total LOS (median -2.25 [IQR -3.69, -0.15]). Log-transformed multivariable linear regression demonstrated the intervention to be associated with shorter ICU LOS (β coefficient -0.19, SE 0.059, P < .001), total postoperative LOS (β coefficient -0.12, SE 0.052, P = .02), and ventilator duration (β coefficient -0.21, SE 0.048, P < .001). Balancing metrics did not differ after the intervention. Target-based care is a simple, novel intervention associated with reduced variation in LOS and absolute LOS across a diverse spectrum of complex cardiac surgeries.


Use of enoyl coenzyme A hydratase of Mycobacterium avium subsp. paratuberculosis for the serological diagnosis of Johne's disease.
Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), remains difficult to control because of the lack of specific and sensitive diagnostic tests. In order to improve the specificity of sero-diagnosis for JD, the phage display library derived from genomic DNA of MAP was immunoscreened to identify novel antigenic targets. We selected a clone using antibodies from MAP experimentally infected cattle, and annotated its coding sequence as MAP1197 in the MAP genome, which encoded "echA12_2" in the MAP protein (Map-echA) belonging to Enoyl-CoA hydratase, known as a crotonase enzyme. The Map-echA was expressed in Esherichia coli and purified as a histidine-tag recombinant protein (rMap-echA), and the diagnostic potential of the protein was further evaluated by enzyme-linked immunosorbent assays (ELISA). Antibody responses to rMap-echA were higher in MAP-infected cattle than in uninfected cattle. The specificity of the Map-echA ELISA was also confirmed by evaluation with hyper-immune sera against various kinds of Mycobacterium species. Furthermore, in all experimentally infected cattle the antibody against rMap-echA was detected 2-7months earlier than by a commercially available ELISA kit. These results suggested that Map-echA can be used as a specific and sensitive serological diagnostic antigen for the detection of MAP infection.


Immunolocalization of multidrug resistance protein 5 in the human genitourinary system.
The intracellular messenger cyclic guanosine monophosphate (cGMP) has an important role in regulating smooth muscle tone. An increase in intracellular cGMP levels is a prerequisite for penile erection. Inhibition of cGMP degradation by cGMP specific phosphodiesterase 5 has been used for treating erectile dysfunction. In addition to degradation by phosphodiesterase, cGMP is exported from cells by multidrug resistance protein 5 (MRP5), also called ABCC5, which we recently identified as an adenosine triphosphate dependent export pump for cGMP. MRP5 is potently inhibited by substances known as phosphodiesterase inhibitors, including sildenafil and trequinsin. Therefore, we analyzed whether MRP5 is expressed in tissues of the human genitourinary system and whether MRP5 and phosphodiesterase 5 proteins are localized in the same cell types. Localization of MRP5 and phosphodiesterase 5 was analyzed by immunofluorescence microscopy in cryosections of various tissues of the human genitourinary system. MRP5 and phosphodiesterase 5 were co-expressed in smooth muscle cells of the corpus cavernosum, ureter, urethra and bladder. In addition, MRP5 and phosphodiesterase 5 were localized in epithelial cells of the mucosa in the ureter and urethra, and in blood vessels of the lamina propria. The co-expression of MRP5 and phosphodiesterase 5 in smooth muscle cells of the genitourinary system indicates 2 distinct pathways for cGMP removal. Thus, MRP5 inhibition represents a new approach for enhancing cGMP levels in smooth muscle cells and developing drugs for erectile dysfunction.


[Analysis of the Luciani-Wenckebach phenomenon in the A-V node. II. Relationship between conduction and recovery times].
We have studied 20 cases Wenckebach A-V block by atrial pacing. The relationships between conduction time and recovery time of N. AV Wenckebach point, basal A-H time and A-H time of first cycle beat were analysed. No correlation was found between W point, basal A-H and A-H of the first beat by analysing the A-H = f (H-A) we found different curves which occur when the first A-H is longer or shorter than 110. These data were discussed on the basis of modern hypotheses of electrophysiological mechanism of Wenckebach periodism.


Establishing the relationship between FGF/MV and FI/FD, and determining the saturation state of sevoflurane anaesthesia during the induction phase and factors affecting nonrespiratory tract ejection volume.
To investigate (i) the relationship between the ratio of fresh gas flow to min volume (FGF/MV) and the ratio of the fraction of inspired sevoflurane to the delivered concentration of sevoflurane (FI/FD); (ii) to establish the saturation state of sevoflurane anaesthesia and factors affecting the volume of ejected sevoflurane through the nonrespiratory tract route (nVERT) during the saturation state. Two studies were undertaken in patients with cancer, scheduled to undergo surgery. All patients received tracheal intubation and inhaled sevoflurane. In study 1, anaesthesia parameters were fixed, the initial FD of sevoflurane was 2.2% vol and the FGF/MV was set to 0.2, 0.3, 0.4 and 1.0 in groups A, B, C and D, respectively. In study 2, FGF = MV and the initial FD of sevoflurane was 2.2% vol, but the tidal volume (TV) was set to 6, 8 or 10 ml/kg in groups I, II and III, respectively. Study 1 (n = 60) showed a positive relationship between FI/FD and FGF/MV. In study 2 (n = 60), when TV was fixed, nVERT increased during the saturation state as FD increased; when FD was fixed, nVERT remained stable, despite increased TV. FI/FD is positively associated with FGF/MV; nVERT is affected by FD but not TV.


Genetically proxied gut microbiota, gut metabolites with risk of epilepsy and the subtypes: A bi-directional Mendelian randomization study.
An increasing number of observational studies have revealed an association among the gut microbiota, gut metabolites, and epilepsy. However, this association is easily influenced by confounders such as diet, and the causality of this association remains obscure. Aiming to explore the causal relationship and ascertain specific gut microbe taxa for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on the genome-wide association study (GWAS) data of epilepsy from the International League Against Epilepsy, with the gut microbiota GWAS results from MiBioGen, and summary-level GWAS data of gut microbiota-dependent metabolites trimethylamine N-oxide and its predecessors. Nine phyla, 15 classes, 19 orders, 30 families, and 96 genera were analyzed. A suggestive association of host-genetic-driven increase in family Veillonellaceae with a higher risk of childhood absence epilepsy (odds ratio [OR]: 1.033, confidential interval [CI]: 1.015-1.051, P IVW = 0.0003), class Melainabacteria with a lower risk of generalized epilepsy with tonic-clonic seizures (OR = 0.986, CI = 0.979-0.994, P IVW = 0.0002), class Betaproteobacteria (OR = 0.958, CI = 0.937-0.979, P IVW = 0.0001), and order Burkholderiales (OR = 0.960, CI = 0.937-0.984, P IVW = 0.0010) with a lower risk of juvenile myoclonic epilepsy were identified after multiple-testing correction. Our sensitivity analysis revealed no evidence of pleiotropy, reverse causality, weak instrument bias, or heterogeneity. This is the first MR analysis to explore the potential causal relationship among the gut microbiota, metabolites, and epilepsy. Four gut microbiota features (two class levels, one order level, and one family level) were identified as potential interventional targets for patients with childhood absence epilepsy, generalized epilepsy with tonic-clonic seizures, and juvenile myoclonic epilepsy. Previous associations in numerous observational studies may had been interfered by confounders. More rigorous studies were needed to ascertain the relationship among the gut microbiota, metabolites, and epilepsy.


The impact of stress experience on heart rate and task performance in the presence of a novel stressor.
The impact of prior stress experience on heart rate and task performance in the presence of a novel stressor was studied. During a training phase 42 female students were required to solve arithmetical problems under conditions of either no stressor, delayed auditory feedback, or distraction. Subsequently in a testing phase all subjects performed the same task in the presence of delayed auditory feedback. Training in the presence of stress resulted in decreased heart rate and better performance in the testing phase. These data were interpreted as supporting the hypothesis that training under stress-inducing conditions increases stress resistance which generalizes to a novel stressor and which leads subjects to experience the novel stressor as being less stressful.


Cyclosporine for omalizumab-refractory chronic urticaria: a report of five cases.
While both the AAAAI/ACAAI and the EAACI/GA2LEN/EuroGuiDerm/APAAACI guidelines recommend starting cyclosporine for patients with chronic urticaria who have had an inadequate response to omalizumab, many clinicians are hesitant to initiate cyclosporine due to paucity of clinical data. The objective of this study was to report real-life clinical outcomes in adult patients with chronic urticaria who had an inadequate response to omalizumab and were switched from omalizumab to cyclosporine. Medical records of adult patients with chronic urticaria who had an inadequate response with omalizumab and were later treated with cyclosporine were reviewed retrospectively. Data pertaining to treatment method, clinical response, and adverse effects were recorded. Five patients with omalizumab-refractory chronic urticaria, three of whom also had angioedema and one with an inducible urticaria, were treated with low doses of oral cyclosporine (1-3 mg/kg/d). Four of five patients in this case series had complete resolution of symptoms with oral cyclosporine, while continuing other standard therapies. Systemic side effects occurred in three patients which prompted drug discontinuation in two patients. Cyclosporine alone was effective in inducing urticaria control in adult patients with chronic urticaria who had an inadequate response to omalizumab, though the impact of cyclosporine was limited by reversible adverse effects. Adverse effects were associated with pre-existing medical conditions. As novel chronic urticaria therapies are being investigated, this experience highlights the importance of uncovering chronic urticaria subtypes which tend to respond to cyclosporine, while providing alternative treatments with better tolerability.


Synthesis and water-swelling of thermo-responsive poly(ester urethane)s containing poly(epsilon-caprolactone), poly(ethylene glycol) and poly(propylene glycol).
Thermo-responsive multiblock poly(ester urethane)s comprising poly(epsilon-caprolactone) (PCL), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments were synthesized. The copolymers were characterized by GPC, NMR, FTIR, XRD, DSC and TGA. Water-swelling analysis carried out at different temperatures revealed that the bulk hydrophilicity of the copolymers could be controlled either by adjusting the composition of the copolymer or by changing the temperature of the environment. These thermo-responsive copolymer films formed highly swollen hydrogel-like materials when soaked in cold water and shrank when soaked in warm water. The changes are reversible. The mechanical properties of the copolymer films were assessed by tensile strength measurement. These copolymers were ductile when compared to PCL homopolymers. Young's modulus and the stress at break increased with increasing PCL content, whereas the strain at break increased with increasing PEG content. The results of the cytotoxicity tests based on the ISO 10993-5 protocol demonstrated that the copolymers were non-cytotoxic and could be potentially used in biomedical applications.


Editorial: Publishing in the Time of Pandemic: Editorial Policy of a Dermatology Journal During COVID-19.
[This corrects the article DOI: 10.4103/ijdvl.IJDVL_704_20].


Assessment of Low LDL Cholesterol in Patients Treated by PCSK9 Inhibition: Comparison of Martin/Hopkins and Friedewald Estimations.
Recent guidelines recommend further reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk populations. The use of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) enables many patients to achieve profound reduction in LDL-C. However, in patients with low cholesterol, the commonly used Friedewald equation tends to underestimate LDL-C, which may result in undertreatment. We aimed to compare Friedewald LDL-C estimation with the more novel Martin/Hopkins method in PCSK9i-treated patients achieving low LDL-C. We investigated high-risk patients treated by PCSK9i in whom Friedewald LDL-C levels were < 70 mg/dL and triglycerides ≤ 300 mg/dL. LDL-C was additionally assessed by the Martin/Hopkins method. The compatibility between estimations was evaluated using methods of concordance and reclassification between LDL-C categories (< 25, 25-40, 40-55, 55-70 mg/dL) and according to triglyceride strata. Mean age was 65 ± 10 years. The correlation coefficient between LDL-C estimations was r = 0.898. Martin/Hopkins reclassified 269 of the 608 patients (44%) to a higher LDL-C category, with 14% of the patients reaching LDL-C > 70 mg/dL. Of the 390 patients achieving Friedewald LDL-C < 55 mg/dL, 113 (29%) were estimated to have LDL-C ≥ 55 mg/dL by the Martin/Hopkins equation. The magnitude of discordance between LDL-C estimates was more pronounced in hypertriglyceridemic patients in whom LDL-C reclassification from < 55 to ≥ 55 mg/dL was observed in 48%. In real-world practice of high-risk patients achieving low LDL-C under PCSK9i, Martin/Hopkins algorithm displayed significant proportion of LDL-C upward discordance compared to the Friedewald equation, particularly observed in patients with elevated triglycerides, identifying patients that may need treatment intensification.


Projections from auditory cortex contact cells in the cochlear nucleus that project to the inferior colliculus.
Anterograde and retrograde tracing techniques were combined to determine whether auditory cortical axons contact cells in the cochlear nucleus that project to the inferior colliculus. FluoroRuby or fluorescein dextran was injected into auditory cortex to label cortical axons by anterograde transport. Different fluorescent tracers (Fast Blue, FluoroGold, FluoroRuby or fluorescein dextran) were injected into one or both inferior colliculi to label cells in the cochlear nucleus. After 12-15 days, the brain was processed for fluorescence microscopy and the cochlear nuclei were examined for apparent contacts between cortical axons and retrogradely labeled cochlear nucleus cells. The results suggest that axons from the ipsilateral or contralateral cortex contact fusiform and giant cells in the dorsal cochlear nucleus and multipolar cells in the ventral cochlear nucleus that project directly to the inferior colliculus. The contacts occur on cell bodies and dendrites. The target cells in the cochlear nucleus include cells that project ipsilaterally, contralaterally or bilaterally to the inferior colliculus. The results suggest that auditory cortex is in a position to exert direct effects on the monaural pathways that ascend from the cochlear nucleus.


A phylogeny of cycads (Cycadales) inferred from chloroplast matK gene, trnK intron, and nuclear rDNA ITS region.
Phylogenetic relationships among the three families and 12 living genera of cycads were reconstructed by distance and parsimony criteria using three markers: the chloroplast matK gene, the chloroplast trnK intron and the nuclear ITS/5.8S rDNA sequence. All datasets indicate that Cycadaceae (including only the genus Cycas) is remotely related to other cycads, in which Dioon was resolved as the basal-most clade, followed by Bowenia and a clade containing the remaining nine genera. Encephalartos and Lepidozamia are closer to each other than to Macrozamia. The African genus Stangeria is embedded within the New World subfamily Zamiodeae. Therefore, Bowenia is an unlikely sister to Stangeria, contrary to the view that they form the Stangeriaceae. The generic status of Dyerocycas and Chigua is unsupportable as they are paraphyletic with Cycas and the Zamia, respectively. Nonsense mutations in the matK gene and indels in the other two datasets lend evidence to reinforce the above conclusions. According to the phylogenies, the past geography of the genera of cycads and the evolution of character states are hypothesized and discussed. Within the suborder Zamiieae, Stangeria, and the tribe Zamieae evolved significantly faster than other genera. The matK gene and ITS/5.8S region contain more useful information than the trnK intron in addressing phylogeny. Redelimitations of Zamiaceae, Stangeriaceae, subfamily Encephalartoideae and subtribe Macrozamiineae are necessary.


Egocentric disorientation following bilateral parietal lobe damage.
Aguirre and D'Esposito (1999) suggested a taxonomy and theoretical framework for understanding topographical disorders. One of the problems they described involved egocentric disorientation, in which deficits are not strictly confined to the topographical sphere but are seen on a wide variety of visuo-spatial paradigms. Here, we report a neuropsychological investigation of MU, a person with egocentric disorientation. To test the usefulness of Aguirre and D'Esposito's framework, we administered tests which were predicted to be easy or difficult for people with egocentric disorientation to show that MU was impaired on tasks sensitive to egocentric disorientation and that he showed adequate performance on tests sensitive to other types of topographical representation. Thus MU showed normal performance on a test of recognition of famous landmarks and he could identify photographs of personally familiar places in his home town, yet he could not say how to get from a recognised building to another place in his environment. His performance fulfils the criteria for egocentric disorientation and fits the predictions derived from Aguirre and D'Esposito's views.


PASS-A course in Pediatric Acute Surgical Support to build pediatric surgical emergencies capacity in developing countries.
The burden of pediatric trauma and emergency, including pediatric surgical emergencies in low middle income countries (LMIC) is high. The goal of Pediatric Acute Surgical Support (PASS) course is to prepare caregivers in LMIC for the acute management of life-threatening pediatric surgical emergencies. We aim to show the feasibility of its initial deployment. PASS was developed in 2016 with LMIC faculty from a teaching children hospital CH. The course contents consisted of a mix of didactic materials for serious general neonatal and pediatric surgery modified PALS/ATLS, in-person multidisciplinary team-based skill stations, interactive clinical scenarios and simulated trauma cases. The course was subsequently revised and delivered to 92 learners in four classes of 2.5-days sessions at two CHs between 2017 and 2019. Learners' demographics, written exams, team-based case performance, and post-course survey data were prospectively collected and retrospectively analyzed. Physician (60%) and nurse learners (40%) from pediatric critical care (36%), surgery (23%), emergency medicine (20%) and anesthesiology (9%) had 3.6 +/- 3.6 years of clinical practice; pre- and post-course written exam score of 55.4+/-15.5% vs 71.6+/-12.8%, team-based trauma scenario management 22.6 ± 7.8% vs 54.7 ± 16.6% and team-based dynamic scores 17+/- 10% vs 53.3+/- 15.5%, respectively (p<0.0001). Self-reported satisfaction scores were ≥ 95% for course method, level of difficulty, clinical applicability, and quality of instructors. PASS is well-received by LMIC learners, with short-term improvement in knowledge-, team-based management of acute pediatric surgery emergencies; and has the potential to be a model of horizontal capacity building for pediatric surgery in LMIC. II.


Mixed species flocking of tits (Parus spp.): a field experiment.
We tested two general models of flocking behaviour, namely the antipredation model and foraging efficiency model on mixed-species tit flocks (Parus spp.). After food addition the size of mixed-species flocks was significantly less than in the control samples. In the presence of extra food significantly more birds were observed either in monospecific flocks or solitary, than during the control observations. In the presence of a living predator the birds foraged in larger mixed-specifies flocks than during the control observations. In addition, the social behaviour of Great Spotted Woodpecker, Middle Spotted Woodpecker and Nuthatch shifted to mixed-specific flocking. The size of monospecific flocks was independent of both treatments. The density of birds increased significantly after food addition, while in the predator presence the birds tended to leave the forest. These results support the view that both the antipredation model and foraging efficiency model seem to be valid for mixed-species flocking. However, in the case of monospecific flocks, the territory maintenance could be the most important factor.


Solid-phase extraction clean-up of soil and sediment extracts for the determination of various types of pollutants in a single run.
A new sample clean-up procedure based on solid-phase extraction (SPE) sorbents was proposed for the determination of pesticides, polycyclic aromatic hydrocarbons and polychlorinated biphenyls in soils and sediments. The main purpose of the research was to find a combination of sorbents for the SPE method that would permit the determination of many types of analytes (polycyclic aromatic hydrocarbons, polychlorinated biphenyls, N-, P- and Cl-containing pesticides) in a single run. Elution profiles for both the analytes and the interfering components were determined for several types of SPE sorbents (alumina, silica and surface-modified silica) and combinations of them. The efficiency of the clean-up method developed was evaluated using real soil samples.


Recovery from disuse osteopenia coincident to restoration of muscle strength in mdx mice.
The objective of this study was to compare the tibial structure and the strength of the tibia during muscle weakness and after recovery in mdx mice (which demonstrate X-linked muscular dystrophy and subsequent muscle regeneration) and age-matched control mice. The extent of disuse atrophy produced by muscle weakness and recovery following restoration of normal muscle strength could then be determined. The tibiae adjacent to weakened tibialis anterior muscles of 4-week-old mdx mice had significantly reduced radiographic density (p < 0.05) and cortical thickness (p < 0.001), and increased porosity (p < 0.001) compared to age-matched controls, suggesting development of disuse osteopenia. Significantly less force was required to break mdx tibiae than age-matched control tibiae (p < 0.05). In addition, Sharpey's fiber density was reduced (p < 0.001), suggesting a weakened attachment of the tibialis anterior muscle to bone. At 12 weeks, during the period of muscle regeneration, mdx tibial cortical thickness (p < 0.001) and porosity (p < 0.01) remained significantly lower, but percent calcium and Sharpey's fiber and radiographic densities were significantly greater (p < 0.001) than in age-matched controls, suggesting that bone mineralization and muscle attachment strength had increased to above normal levels in parallel with recovery of strength by the attached muscle. By 18 weeks, mdx tibial cross-sectional area, cortical thickness, and porosity remained significantly less (p < 0.001) than normal. Although Sharpey's fiber density was greater than in age-matched controls (p < 0.001) by 18 weeks, mdx tibial percent calcium (p < 0.005) and Sharpey's fiber density (p < 0.001) were significantly reduced from levels in 12-week-old mdx animals. There was significantly less deformation of the tibia prior to fracture in mdx than control tibiae at 18 weeks of age, suggesting tibial brittleness. Thus, at the site of attachment of mdx muscle to osteopenic bone, the remodelling which accompanies recovery of muscle strength is atypical, and produces an attachment of greater strength than function appears to require. These observations suggest that data are needed regarding bone mass and muscle-bone attachments in humans with disuse osteopenia, DMD, and other neuromuscular diseases.


The spectrum of organ and systems pathology in human Lyme disease.
Lymphocytes, plasma cells, and mononuclear phagocytes are frequently found in human tissues infected by the Lyme disease spirochete, Borrelia burgdorferi. Experience has shown that these cells comprise the tissue bed inflammatory infiltrate in Lyme disease affecting the joint synovia, myocardium, and skin. While many differences otherwise exist, Lyme synovitis has lymphoplasmacellular similarities with rheumatoid synovitis, lymphoplasmacellular epimyocarditis similarities with syphilitic myocarditis, and occasionally synovial endarteritis obliterans. Silver staining can demonstrate the spirochete if a careful search is done.


Role of pregnancy hormones and hormonal interaction on the maternal cardiovascular system: a literature review.
Hormones have a vital duty in the conservation of physiological cardiovascular function during pregnancy. Alterations in oestrogen, progesterone and prolactin levels are associated with changes in the cardiovascular system to support the growing foetus and counteract pregnancy stresses. Pregnancy hormones are, however, also linked to numerous pathophysiological outcomes on the cardiovascular system. The expression and effects of the three main pregnancy hormones (oestrogen, prolactin and progesterone) vary depending on the gestation period. However, the reaction of a target cell also depends on the abundance of hormone receptors and impacts put forth by other hormones. Hormonal interaction may be synergistic, antagonistic or permissive. It is crucial to explore the cross talk of pregnancy hormones during gestation, as this may have a greater impact on the overall changes to the cardiovascular system.


Salivary Gland Diseases.
A variety of diseases ranging from obstructions, infections, to benign and malignant tumors occur in salivary glands. The most common problem is painful blockage of ducts by stones that prevents drainage of saliva. Sialadenitis can be due to either infectious or noninfectious factors. Bacterial or viral infections are the most common causes of acute sialadenitis. Staphylococcus is the usual bacterial cause, whereas paramyxovirus (mumps) is the common viral cause. Eighty percent of salivary tumors are benign, whereas about 20% are malignant. Most tumors occur in the parotid gland and on the hard palate. Classifications, imaging, and suggested treatment are described.


Comparative study of a solid-phase extraction system coupled to capillary electrophoresis in the determination of haloacetic compounds in tap water.
This study compares four different commercial sorbents, LC-SAX (a quaternary ammonium anion exchanger), LiChrolut EN (a highly crosslinked styrene-divinylbenzene), Envi-Carb (a graphitized carbon black) and Oasis HLB [a macroporous poly(divinylbenzene-co-N-vinylpyrrolidone) copolymer], for the solid-phase extraction (SPE) of various haloacetic compounds from aqueous samples. The recoveries with the different sorbents were studied by coupling an off-line SPE system to capillary electrophoresis with indirect photometric detection. The recoveries were highest when LiChrolut EN was used. The limits of detection for the compounds are in the low microgram per litre range and the recovery values are over 80% for dichloroacetic acid and trichloroacetic acid, two of the most habitual haloacetic acids in chlorinated water, when 500 ml of standard solution was preconcentrated using this sorbent. Finally, the performance of the method with different water samples, the effect of chlorination in a treatment plant and the evolution of the haloacetic acids in the water distribution system were tested and the results were compared with those obtained using liquid-liquid extraction and gas chromatography-mass spectrometry.


Industry payments to female pelvic medicine and reconstructive surgeons: an analysis of Sunshine Act open payments from 2014-2017.
We aim to examine the financial relationship between industry and female pelvic medicine and reconstructive surgeons (FPMRS) during the first four full calendar years since the implementation of the Sunshine Act. All board-certified FPMRS specialists were identified using the American Board of Medical Specialties directory. Program directors (PDs) were identified using an Accreditation Council for Graduate Medical Education (ACGME) database. All identified physicians were categorized by gender, specialty, and American Urological Association (AUA) region. Payment data for each individual from 2014 to 2017 were accessed using the Centers for Medicare and Medicaid Services (CMS) Open Payments website. Statistical analyses were performed to elucidate payment trends. Of the 1,307 FPMRS physicians identified, 25.1% (n = 328) are urology-trained and 74.9% (n = 979) are obstetrics/gynecology (OB/GYN)-trained. Of all physicians analyzed, 6.8% had no reported payments over the 4-year period. 90.1%, 86.5%, 85.3%, and 84.4% received some sort of payment in 2014 to 2017 respectively. Median total payments for all physicians decreased yearly, whereas mean payments decreased from 2014 to 2015 before increasing in all subsequent years. Median general payments were higher for men versus women, urology-trained versus OB/GYN-trained, and PDs versus non-PDs in all years analyzed. The largest contributor to overall payments was the "others" compensation category, which includes gifts, royalties, honoraria, and non-continuing medical education speaking engagements. Since institution of the Sunshine Act, the percentage of physicians receiving payments has decreased each year. Additionally, there has been a decrease in median total payments and an increase in yearly research payments in all years analyzed.


Phylogeny of the Asian Hedyotis-Oldenlandia complex (Spermacoceae, Rubiaceae): evidence for high levels of polyphyly and the parallel evolution of diplophragmous capsules.
Generic delimitation in the Hedyotis-Oldenlandia complex has a long taxonomically confused history because of the controversy of lumping or splitting these two taxa. Previous morphological and phylogenetic studies with a paucity of Asian taxa suggested that Hedyotis should include only Asian species characterized by diplophragmous capsules. In order to test the reliability of this conclusion, assess the phylogenetic value of capsular characters, and evaluate generic circumscriptions in this complex, a phylogenetic study based on expanded inclusion of 63 Asian species was performed using two nuclear regions and eight plastid regions with parsimony and likelihood analyses. The results show that the Hedyotis-Oldenlandia complex is a highly polyphyletic group. Hedyotis should only include most Asian species with erect, robust herbs or shrubs and diplophragmous capsules. Oldenlandia s. str. consists primarily of African species, including the type O. corymbosa, that are characterized by small herbs, paniculate or corymbose inflorescences, inserted styles and stamens, and loculicidally dehiscent capsules. Dimetia, Scleromitrion and Thecagonum are proposed to be resurrected to accommodate three newly resolved clades. Morphological character optimizations indicate that the diplophragmous capsule evolved independently twice within this complex. Plant habit, stipule shape, and capsular dehiscent pattern are of great value in generic circumscriptions.


Biological denitrification potential as an indicator for measuring digestate stability.
Biological stability is an essential parameter for assessing the environmental impact from the land application of digestate as organic amendment. In this paper, a new indicator, biological denitrification potential (BDP), was developed for evaluating the biological stability of digestate. Digestate samples collected along the digestion process from a mesophilic anaerobic batch digester fed with food waste were investigated under different solid retention time. The value of BDP based on nitrate removal ranged from 176.3 to 48.3 mg-N/g-VSdigestate, corresponding well to the digestion time, and strongly correlated with total organic carbon content. Evolution trends similar to respiration index (RI) and biochemical methane potential (BMP) can be also observed for BDP, indicating that values presented of these stability indices decreased with the degree of digestate stabilization. The mass balance of the BDP process indicated that nitrate was mainly converted into N2 gas with mineralizing organic carbon from digestate, implying that biostability evaluated by BDP depends on carbon source and denitrification activity in digestate. The denitrifying bacteria Thiopseudomonas and Pseudomonas accounted for the majority of microorganisms. These findings of this study concluded that BDP can be an efficient indicator to assess the bio-stability of digestate planned for agricultural or land use. Compared with the existing biostability index, BDP has the additional advantage of no exogenous inoculum addition, homogenous test condition and possibility of shortening incubation time.


Dual Interfacial Engineering Enables Efficient and Reproducible CsPbI2Br All-Inorganic Perovskite Solar Cells.
CsPbI2Br all-inorganic perovskite has shown superior photovoltaic properties particularly excellent phase and thermal stability, while the complicated film growth process requires additional research. Herein, the nucleation and crystallization process of the CsPbI2Br perovskite film is assisted by methyl acetate anti-solvent treatment. Additionally, a tailored SnO2 nanoparticle/TiO2 nanocrystal structured double electron transport layers (ETLs) is designed to remove the interfacial energy barrier, thus enhancing charge transfer and decrease charge recombination at the CsPbI2Br/ETL interfaces. Through synergistically dual interfacial engineering, we have demonstrated the preparation of a compact CsPbI2Br polycrystalline film with ordered and homogeneous grain size as well as ideal interfacial energy level alignment. In consequence, stable CsPbI2Br all-inorganic perovskite solar cells with the best power conversion efficiency of 15.86% has been successfully achieved together with a high open-circuit voltage of 1.23 V and a fill factor of 82.29%. We believe that the results here demonstrate efficient approaches to achieve high-quality inorganic perovskites for promoting their optoelectronic applications.


Sub-Tenon's anesthetic administration for cataract surgery: how much stays in?
We performed a prospective, randomized trial assessing the "remaining" volume of anesthetic solution that stays within the sub-Tenon's space after administration of 2 different volumes: 3 mL and 5 mL. The remaining volume correlated with motor block (r = 0.72; P < 0.001). The volume lost through the incision as a percentage of total volume injected was similar in both groups, suggesting sub-Tenon's space is not limited to a finite injected volume less than 5 mL and may be capable of receiving larger volumes of anesthetic to improve motor block. The volume of anesthetic solution remaining within sub-Tenon's space correlates with motor block. The amount of volume lost as a percentage of total administered is independent of the volume injected, suggesting sub-Tenon's space is not limited to a finite injected volume less than 5 mL and may be capable of receiving larger volumes of anesthetic to improve motor block.


Air pollutant emissions from vehicles in China under various energy scenarios.
Estimations of air pollutant emissions from vehicles in China under different energy and emission abatement policy scenarios are presented in this paper. Three scenarios are designed: (i) "business as usual" (BAU); (ii) "advanced fuel economy" (AFE); and (iii) "alternative energy replacement" (AER). The CO, VOCs, NOx, PM10, and CO2 emissions are predicted to reach 105.8, 5.9, 7.5, 1.1, and 3522.6 million tons, respectively, in the BAU scenario by 2030. In the AFE scenario, the CO, VOCs, NOx, PM10, and CO2 emissions in 2030 will be abated by 23.8%, 18.6%, 25.3%, 18.2%, and 24.5% respectively compared with the BAU scenario. In the AER scenario, the CO and VOCs in 2030 will be further reduced by 15.9% and 6.1% respectively, while NOx, PM10, and CO2 will be increased by 10.7%, 33.3%, and 2.0% compared with AFE. In conclusion, our models indicate that the emission abatement policies introduced by governmental institutions are potentially viable, as long as they are effectively implemented.


Insights into graphene oxide/ferrihydrite adsorption as pretreatment during ultrafiltration: Membrane fouling mitigation and disinfection by-product control.
In this study, a novel adsorbent of graphene oxide (GO) incorporated ferrihydrite (FH) was fabricated and integrated with ultrafiltration (UF) to remove natural organic matter (NOM), the crucial cause of membrane fouling and major precursor of disinfection by-products (DBPs). Compared with FH and powdered activated carbon (PAC), GO/FH exhibited superior removal for high molecular weight (HMW) humic- and fulvic-like substances and low molecular weight (LMW) protein. The cake layer formed by GO/FH alleviated the deposition of NOM on membrane surface or inside membrane pores. Therefore, GO/FH reduced 89% and 95% total fouling resistance and irreversible membrane resistance, respectively, together with the lowest increment of transmembrane pressure. Pearson correlation analysis indicated that DOC, rather than specific ultraviolet absorbance (SUVA) and UV254, was significantly correlated to the formation of trihalomethanes (THMs) and haloacetic acids (HAAs) when SUVA was below 4 L/mg-C.m. Whilst the HMW NOM (1-20 kDa) was highly related to dibromochloromethane (DBCM) (r = 0.98-1), the LMW fraction (< 1 kDa) was correlated with dibromochloromethane (TCAA) and dichloroacetic acid (DCAA) (r = 0.88-0.98). Inspiringly, GO/FH-UF reduced 90% of carbonaceous DBPs, the concentrations of which well met the WHO Guidelines. In summary, GO/FH-UF substantially alleviated membrane fouling and dramatically reduced DBP formation potential.


Transvaginal laparoscopic surgery for ovarian cysts.
To evaluate the effectiveness and feasibility of transvaginal laparoscopic surgery (TLS) using endoscopic instruments for management of ovarian cysts. In a retrospective study, data from 140 patients with benign ovarian cysts who underwent TLS at Konkuk University Hospital between June 2007 and December 2008 were evaluated. The preoperative characteristics of patients, operative time, blood loss, complications, and postoperative outcomes were evaluated. The mean age of patients was 38 years (range, 16-82 years). TLS was accomplished in 136 women (97.1%). The more common pathology findings included 35 dermoid cysts, 28 endometriotic cysts, 23 mucinous cysts, 21 serous cysts, and 13 functional ovarian cysts. The median operative time was 35 minutes (range 15-110 minutes). The maximum diameter of the ovarian cysts ranged from 3 to 20 cm (mean 6 cm). The median estimated blood loss was 38 mL (range 10-80 mL). No patients received a blood transfusion. All of the patients were discharged within 24 hours of surgery. No major complications occurred. Transvaginal laparoscopic surgery was found to be a feasible and cosmetically beneficial surgical technique for managing selected patients with benign ovarian cysts.


Interaction of calcium with negative lipids in planar bilayer membranes. Influence of the solvent.
The interaction of Ca++ with acidic phospholipids in black lipid films and lipid bilayers formed from two monolayers was studied by measuring their physical stability and conductance. It was found that the addition of CaCl2 to only one side of lipid bilayers formed from phosphatidylserine or cardiolipin does not appreciably change these parameters. In contrast, black films are unstable to the asymmetric addition of CaCl2. Therefore, the destabilizing effect of Ca++ cannot be attributed to a surface charge difference. The only variation in composition between both bilayer membranes, namely the solvent content of the bilayer, seems to be responsible for the distinctive effect of Ca++. A tentative explanation is presented.


Evaluation of available risk scores to predict multiple cardiovascular complications for patients with type 2 diabetes mellitus using electronic health records.
Various cardiovascular risk prediction models have been developed for patients with type 2 diabetes mellitus. Yet few models have been validated externally. We perform a comprehensive validation of existing risk models on a heterogeneous population of patients with type 2 diabetes using secondary analysis of electronic health record data. Electronic health records of 47,988 patients with type 2 diabetes between 2013 and 2017 were used to validate 16 cardiovascular risk models, including 5 that had not been compared previously, to estimate the 1-year risk of various cardiovascular outcomes. Discrimination and calibration were assessed by the c-statistic and the Hosmer-Lemeshow goodness-of-fit statistic, respectively. Each model was also evaluated based on the missing measurement rate. Sub-analysis was performed to determine the impact of race on discrimination performance. There was limited discrimination (c-statistics ranged from 0.51 to 0.67) across the cardiovascular risk models. Discrimination generally improved when the model was tailored towards the individual outcome. After recalibration of the models, the Hosmer-Lemeshow statistic yielded p-values above 0.05. However, several of the models with the best discrimination relied on measurements that were often imputed (up to 39% missing). No single prediction model achieved the best performance on a full range of cardiovascular endpoints. Moreover, several of the highest-scoring models relied on variables with high missingness frequencies such as HbA1c and cholesterol that necessitated data imputation and may not be as useful in practice. An open-source version of our developed Python package, cvdm, is available for comparisons using other data sources.


Puerarin promotes osteogenesis and inhibits adipogenesis in vitro.
Puerarin (daidzein 8-C-glucoside) has potential on preventing osteoporosis. This study aims to investigate the effects of puerarin on osteogenesis and adipogenesis in vitro. CCK-8 assay, alkaline phosphatase (ALP) activity and Alizarin Red S were used to measure the effects of puerarin on proliferation, osteoblastic differentiation, and mineralization in osteoblast-like MC3T3-E1 cells. The effects of puerarin on adipogenesis were measured by Oil Red O staining and intracellular triglyceride level in preadipocyte 3T3-L1 cells. The mRNA and protein levels of osteogenesis- and adiopogenesis-related factors were detected by qRT-PCR and western blot, respectively. Further, the secreted osteocalcin levels and nuclear translocation of β-catenin were detected by ELISA and immunofluorescence assay, respectively. As to osteogenesis, puerarin could stimulate proliferation (1 μM, P = 0.012; 10 μM, P = 0.015; 20 μM, P = 0.050), ALP activity (20 μM, P = 0.008) and calcium nodule formation (20 μM, P = 0.011) in a dose-dependent manner. Puerarin (20 μM) promoted osteocalcin secretion (P = 0.004) and the protein expression of both osteopontin (P = 0.001) and osteoprotegerin (P = 0.003). As to adipogenesis, puerarin suppressed adipocytes formation and intracellular triglyceride level (P = 0.001). In addition, puerarin (20 μM) decreased the mRNA and protein levels of CCAAT/enhancer binding protein α (P = 0.001, P = 0.002), proliferator-activated receptor γ (P = 0.005, P = 0.003), and adipocyte lipid-binding protein 4 (P = 0.001, P = 0.001). Moreover, phosphorylation of AKT1-Ser437 (10 μM, P = 0.003; 20 μM, P = 0.007) and GSK-Ser9 (10 μM, P = 0.005; 20 μM, P = 0.003), and the nuclear translocation of β-catenin (10 μM, P = 0.006; 10 μM, P = 0.002) were increased in 3T3-L1 cells treated by puerarin. Puerarin promoted osteogenesis and inhibited adipogenesis in vivo, and Akt/GSK-3β/β-catenin signaling pathway was involved in the suppression of adipogenesis.


Mammalian 26S proteasomes remain intact during protein degradation.
It has been suggested that degradation of polyubiquitylated proteins is coupled to dissociation of 26S proteasomes. In contrast, using several independent types of experiments, we find that mammalian proteasomes can degrade polyubiquitylated proteins without disassembling. Thus, immobilized, (35)S-labeled 26S proteasomes degraded polyubiquitylated Sic1 and c-IAP1 without releasing any subunits. In addition, it is predicted that if 26S proteasomes dissociate into 20S proteasomes and regulatory complexes during a degradation cycle, the reassembly rate would be limiting at low proteasome concentrations. However, the rate with which each proteasome degraded polyubiquitylated Sic1 was independent of the proteasome concentration. Likewise, substrate-dependent dissociation of 26S proteasomes could not be detected by nondenaturing electrophoresis. Lastly, epoxomicin-inhibited 20S proteasomes can trap released regulatory complexes, forming inactive 26S proteasomes, but addition of epoxomicin-inhibited 20S proteasomes had no effect on the degradation of either polyubiquitylated Sic1 or UbcH10 by 26S proteasomes or of endogenous substrates in cell extracts.


Synthesis and secretion of triacylglycerol lipase by cultured rat hepatocytes.
Rat hepatocytes isolated by collagenase perfusion were cultured for 48-72 h and examined for synthesis and secretion of hepatic triacylglycerol lipase activity. Low levels of enzyme activity found in the culture medium increased with time of incubation, and a 3-10-fold rise was encountered in the presence of optimal concentrations of heparin (5 U/ml). After interruption of enzyme synthesis by cycloheximide, plateauing of enzyme activity in the medium occurred, indicating that addition of heparin may not only stabilize but also enhance hepatic triacylglycerol lipase secretion. Synthesis and secretion of hepatic triacylglycerol lipase was not related to cell density, and enzyme secretion was encountered in subconfluent cultures. Release of enzyme activity into the medium was not sensitive to chlorpromazine, a lysosomal enzyme inhibitor, but was completely inhibited by treatment with tunicamycin, an inhibitor of glycosylation. As release of enzyme activity could be maintained for 12 h in the absence of serum, possible hormonal regulation was sought. Under the present experimental conditions, no modulation of hepatic triacylglycerol lipase was encountered by either gonadal or thyroid hormones. Addition of cyclic AMP to the culture medium resulted in a 30% decrease in enzyme activity. The dependence of hepatic triacylglycerol lipase secretion on the intactness of the Golgi apparatus and on vesicular transport was demonstrated by the treatment with monensin. The present results show that cultured rat hepatocytes provide a good model system by which the regulation of synthesis and secretion of hepatic triacylglycerol lipase can be studied.