Simultaneous exposure of excess fluoride and calcium deficiency alters VDR, CaR, and calbindin D 9 k mRNA levels in rat duodenal mucosa.
Fluoride ingestion reduces intestinal calcium absorption; its molecular basis has not been studied. We studied the mRNA expression of calcium-sensing receptor (CaR), vitamin D receptor (VDR) and calbindin D 9 k (D 9 k) by northern blot analysis in the duodenal mucosa of rats. Weanling pups fed with chow diet containing adequate calcium (0.5% w/w) and drinking water (NaF < 1 ppm) served as controls (Group I) and were studied at 9 and 15 weeks. The pups, born to rats fed with a calcium-deficient diet (0.03%) and excess fluoride water (NaF 50 ppm), were continued on the same diet and water (Group II) until 9 weeks of age. Subsequently, Group II rats were divided into 4 subgroups; 3 subgroups with fluoride free water [II-A adequate calcium, II-B excess calcium (Ca 2%) and II-D calcium deficient], whereas II-C received fluorinated water and adequate calcium diet until 15 weeks. At 9 weeks, as compared to group-I, group-II had decreased VDR (P < 0.001) and D 9 k mRNA (P < 0.001), whereas CaR mRNA levels increased (P < 0.05). At 15 weeks, as compared to group-I, VDR mRNA further reduced in group II-D (P < 0.001) and II-C (P < 0.001), whereas it increased in group II-A. Removal of fluoride ingestion and calcium replenishment increased D 9 k mRNA expression, maximally in adequate calcium group (P < 0.001), while it was further reduced in group II-C (P < 0.001). CaR expression decreased significantly in all the groups. We conclude that excess fluoride reduces the mRNA levels of VDR and D 9 k in the duodenal mucosa of rats, thereby possibly reducing calcium absorption. Calcium supplementation with simultaneous fluoride removal improves their expression.


Dissecting cellular components of the secretory pathway in filamentous fungi: insights into their application for protein production.
Studies on protein production using filamentous fungi have mostly focused on improvement of the protein yields by genetic modifications such as overexpression. Recent genome sequencing in several filamentous fungal species now enables more systematic approaches based on reverse genetics and molecular biology of the secretion pathway. In this review, we summarize recent molecular-based advances in our understanding of vesicular trafficking in filamentous fungi, and discuss insights into their high secretion ability and application for protein production.


[Poison centres in Germany-history, function, and relevance].
In 1963 first poison control centres (PCCs) were created in the former Federal Republic of Germany (FRG) as well as in the German Democratic Republic (GDR). In the 1980s, the GDR centralized the toxicological information service in only one centre, whereas the federal structure of the FRG resulted in a foundation of 19 centres. Today only eight German PCCs are established under the responsibility of the German states. Most of them are part of or closely related to university hospitals. In this article, the history, function and relevance of German PCCs are presented.The centres advise on about 255,000 human exposures per annum in a 24/7 service. They provide a very special service in therapeutic emergency management, which is used to a large extent in childhood poisoning. The scientific contributions of German PCCs are well represented at international congresses and two German standard textbooks about the treatment of poisonings in children and adults are published. The worthiness of PCCs in appropriate healthcare and their monetary benefit are as yet unrecognized, although the profit has already been demonstrated through a first systematic assessment in 1991. From public data sources, no sufficient data can be collected for early risk detection in Germany. However, appropriate data could be generated by PCCs and the Federal Institute for Risk Assessment (BfR), but the precondition is the need for better technical equipment and manpower.The existing German political mandate to set up a national monitoring system for poisoning will be ground-breaking for nationwide scientific evaluation and the treatment of cases of human poisoning in the future.


Engineered Ureolytic Microorganisms Can Tailor the Morphology and Nanomechanical Properties of Microbial-Precipitated Calcium Carbonate.
We demonstrate for the first time that the morphology and nanomechanical properties of calcium carbonate (CaCO3) can be tailored by modulating the precipitation kinetics of ureolytic microorganisms through genetic engineering. Many engineering applications employ microorganisms to produce CaCO3. However, control over bacterial calcite morphology and material properties has not been demonstrated. We hypothesized that microorganisms genetically engineered for low urease activity would achieve larger calcite crystals with higher moduli. We compared precipitation kinetics, morphology, and nanomechanical properties for biogenic CaCO3 produced by two Escherichia coli (E. coli) strains that were engineered to display either high or low urease activity and the native producer Sporosarcina pasteurii. While all three microorganisms produced calcite, lower urease activity was associated with both slower initial calcium depletion rate and increased average calcite crystal size. Both calcite crystal size and nanoindentation moduli were also significantly higher for the low-urease activity E. coli compared with the high-urease activity E. coli. The relative resistance to inelastic deformation, measured via the ratio of nanoindentation hardness to modulus, was similar across microorganisms. These findings may enable design of novel advanced engineering materials where modulus is tailored to the application while resistance to irreversible deformation is not compromised.


Most privately insured patients do not receive federally recommended abdominal aortic aneurysm screening.
Since 2005, the United States Preventative Services Task Force has recommended abdominal aortic aneurysm (AAA) ultrasound screening for 65- to 75-year-old male ever-smokers. Integrated health systems such as Kaiser Permanente and the Veterans Affairs (VA) health care system report 74% to 79% adherence, but compliance rates in the private sector are unknown. The IBM Marketscan Commercial and Medicare Supplemental databases (2006-2017) were queried for male ever-smokers continuously enrolled from age 65 to 75 years. Exclusion criteria were previous history of AAA, connective tissue disorder, and aortic surgery. Patients with abdominal computed tomographic or magnetic resonance imaging from ages 65 to 75 years were also excluded. Screening was defined as a complete abdominal, retroperitoneal, or aortic ultrasound. A logistic mixed-effects model utilizing state as a random intercept was used to identify patient characteristics associated with screening. Of 35,154 eligible patients, 13,612 (38.7%) underwent screening. Compliance varied by state, ranging from 24.4% in Minnesota to 51.6% in Montana (P < .05). Screening activity increased yearly, with 0.7% of screening activity occurring in 2008 vs 22.2% in 2016 (P <.05). In a logistic mixed-effects model adjusting for state as a random intercept, history of hypertension (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.13), coronary artery disease (OR, 1.17; 95% CI, 1.10-1.22), congestive heart failure (OR, 1.14; 95% CI, 1.01-1.22), diabetes (OR, 1.1; 95% CI, 1.06-1.16), and chronic kidney disease (OR, 1.4; 95% CI, 1.24-1.53) were associated with screening. Living outside of a census-designated metropolitan area was negatively associated with screening (OR, 0.92; 95% CI, 0.87-0.97). In a private claims database representing 250 million claimants, 38.7% of eligible patients received United States Preventative Services Task Force-recommended AAA screening. Compliance was nearly one-half that of integrated health systems and was significantly lower for patients living outside of metropolitan areas. Efforts to improve early detection of AAA should include targeting non-metropolitan areas and modifying Medicare reimbursement and incentivization strategies to improve guideline adherence.


OMIP-080: 29-Color flow cytometry panel for comprehensive evaluation of NK and T cells reconstitution after hematopoietic stem cells transplantation.
This 29-color panel was developed and optimized for the monitoring of NK cell and T cell reconstitution in peripheral blood of patients after HSCT. We considered major post-HSCT complications during the design, such as relapses, viral infections, and GvHD and identification of lymphocyte populations relevant to their resolution. The panel includes markers for all major NK cell and T cell subsets and analysis of their development and qualitative properties. In the NK cell compartment, we focus mainly on CD57 + NKG2C+ cells and the expression of activating (NKG2D, DNAM-1) and inhibitory receptors (NKG2A, TIGIT). Another priority is the characterization of T cell reconstitution; therefore, we included detection of CD4+ RTEs based on CD45RA, CD62L, CD95, and CD31 as a marker of thymus function. Besides that, we also analyze the emergence and properties of major T cell populations with a particular interest in CD8, Th1, ThCTL, and Treg subsets. Overall, the panel allows for comprehensive analysis of the reconstituting immune system and identification of potential markers of immune cell dysfunction.


Copper pyrithione, a booster biocide, induces abnormal muscle and notochord architecture in zebrafish embryogenesis.
The metal pyrithiones, principally zinc (ZnPT) and copper (CuPT), are replacing tributyltin (TBT) as antifouling agents. Zebrafish embryos were exposed within the first hour after fertilization to 12 and 64 µg/L of CuPT for 24 h. Morphological abnormalities in notochord and muscle architecture were observed at 96 h post fertilization (hpf). TEM revealed abnormal electron dense deposits in the notochord sheath and muscle fiber degeneration in animals treated with 12 µg/L of CuPT. Embryos that were exposed to 64 µg/L of CuPT displayed severe muscle fiber degeneration including abnormal A and I band patterning and altered z disk arrangement. Abnormalities in the notochord sheath, swelling of the mitochondria and numerous lipid whorls were also noted. Total antioxidant capacity was significantly decreased in embryos exposed to 12 and 64 µg/L of CuPT. Acridine orange staining revealed an increase in apoptosis particularly in the brain, eye, heart and tail regions of both treatment groups. Apoptosis was confirmed with an increase in caspase 3/7 activity in both treatment groups. Severe alternations in primary motor neuron axon extensions, slow tonic muscle fibers and fast twitch fibers were observed in CuPT treated embryos. There was a significant upregulation in sonic hedgehog and myod1 expression at 24 hpf in the 12 µg/L treatment group. Exposed zebrafish embryos showed ultra-structural hallmarks of peroxidative injury and cell death via apoptosis. These changes question the use of copper pyrithione as an antifouling agent.


Investigation of direct waste-activated sludge dewatering benefits and costs in a water resource recovery facility.
Dewatering of anaerobic digested (AD) sludge containing waste-activated sludge (WAS) from enhanced biological phosphorus removal (EBPR) poses numerous challenges including poor dewaterability, struvite scale formation, and recycling of high N and P levels in the sludge liquor to the treatment process. A full-scale water reclamation facility was investigated to mitigate these problems by experimenting with direct dewatering of EBPR WAS, bypassing the AD step. The investigations experimented with various blends of AD primary sludge with undigested thickened WAS to achieve dewatering performance improvements and overall operational cost savings. Direct thickened WAS dewatering has had many positive impacts including enhanced sludge cake solids concentration, reduced chemical use for facility operations, reduced struvite scaling, reduced biogas conditioning media servicing, eliminated need for centrate treatment, recovered capacity of existing unit operations including anaerobic digesters, and eliminated several proposed capital improvement projects that were previously deemed necessary. Although bypassing of WAS to AD reduced total biogas production, the specific gas yield increased to meet all of the facility's biogas demands and minimized excess gas flaring. The overall biosolids production mass increased causing increased transportation costs for disposal and caused notable odors, both of which are being currently investigated. PRACTITIONER POINTS: Direct WAS dewatering bypassing anaerobic digestion yields operational and process benefits in an EBPR water resource recovery facility Dewatered cake solids were increased compared with combined primary and WAS anaerobic digestion and dewatering Nutrient loads in sludge processing returns streams and operational costs are reduced by direct WAS dewatering.


Association Between Critical Limb Ischemia, the Society for Vascular Surgery Wound, Ischemia and Foot Infection (WIfI) Classification System and Arterial Stiffness.
Arterial stiffness analysis has been done to classify cardiovascular risk. The aim of this article is to analyze whether the group of patients with chronic limb-threatening ischemia (CLTI) has higher arterial stiffness indices than controls. The secondary objectives are to assess whether patients with advanced stages of Wound, Ischemia, and foot Infection (WIfI) classification have high levels of arterial stiffness, through multiple linear regressions to analyze whether the ankle-brachial index (ABI) and other variables are predictive of arterial stiffness. We conducted a cross-sectional study with 66 patients with CLTI and 66 age- and sex-matched controls using brachial artery oscillometry. Hemodynamic and arterial stiffness measurements, clinical characteristics, laboratory data, and stages of WIfI classification were compared between the groups CLTI and controls. Through multiple linear regression, we identified predictors of pulse wave velocity (PWV) and augmentation index normalized to 75 beats/min (AIx@75). Patients with CLTI had PWV (11.8 ± 1.6 m/sec vs. 10.0 ± 1.8 m/sec, P < 0.01) and AIx@75 (29.2 ± 9.8% vs.18. ± 10.35%, P < 0.01) higher than controls. In the multiple regression model, there was influence of age (β = 0.17, P < 0.01), antiplatelet therapy (β = -0.15, P = 0.04), peripheral systolic pressure (β = 0.03, P < 0.01), and clustered WIfI stages 3 and 4 (β = 0.17, P = 0.02) of benefit of revascularization on PWV. Multiple regression analysis identified diabetes (β = 7.51, P < 0.01) and the degree of ischemia measured by ABI (β = -23.89, P < 0.01) as predictors of elevated AIx@75. WIfI stages 3 and 4 of estimate risk of amputation at 1 year predicts a high AIx@75 (β = 9.77, P < 0.001) compared with stages 1 and 2. The degree of ischemia in CLTI patients determined by the ABI is associated with elevated arterial stiffness as measured by the AIx@75. Advanced WIfI stages were predictors of elevated PWV and AIx@75.


Adsorption of benzene and toluene from aqueous solution using a composite hydrogel of alginate-grafted with mesoporous silica.
Hydrogels are often claimed as optimal adsorbents for water treatment; however, their efficiency towards the removal of hydrophobic pollutants is still limited. As an alternative, hydrogels prepared from polymers functionalized with siliceous materials can overcome this issue. Here, a composite hydrogel (denoted as GEL-SBA15) was prepared using alginate grafted with mesoporous silica (SBA15) and poly(vinyl alcohol) for benzene and toluene adsorption from aqueous solutions. Adsorption studies demonstrated that a low dosage of GEL-SBA15 (10 mg) has a high adsorption capacity for benzene (1482.8 mg/g) and toluene (596.6 mg/g) under mild experimental conditions (pH 7.0, at 25 °C). Besides, the adsorption capacities of GEL-SBA15 for both pollutants were enhanced compared to the conventional hydrogel. Kinetic analysis showed that the adsorption of benzene and toluene follows a pseudo-second order model, while the experimental adsorption data were well-fitted by the Freundlich isotherm. According to this isotherm, the adsorption occurs via a collaborative process, and weak physical forces (π-π interactions, van der Waals and hydrophobic) are involved. Hence, the post-utilized GEL-SBA15 can be recycled and reused up to 6 times without losing adsorption performance. Although hydrogels are not common adsorbents for aromatic hydrocarbons, the results reported here rank GEL-SBA15 as a promising adsorbent for the removal of these pollutants from water.


Synchrotron X-ray micro-tomography imaging and analysis of wood degraded by Physisporinus vitreus and Xylaria longipes.
Incubation of Norway spruce with Physisporinus vitreus and sycamore with Xylaria longipes results in reduction in density of these wood species that are traditionally used for the top and bottom plate of a violin, which follows by enhanced acoustic properties. We used Synchrotron X-ray micro-tomography, to study the three-dimensional structure of wood at the micro-scale level and the alterations of the density distribution after incubation with two white-rot fungi. Micro-tomography data from wood treated at different incubation periods are analyzed and compared with untreated (control) specimens to determine the wood density map and changes at the cell-wall level. Differences between the density of early- and latewood, xylem ray and around bordered pits in both Norway spruce and sycamore are studied. Three-dimensional hyphal networks of the P.vitreus and Xylaria longipes hyphae are visualized inside the cell lumina and their significance on the density of the early- and latewood cells after different incubation periods are discussed. The study illustrates the utility of X-ray micro-tomography for both qualitative and quantitative studies of a wide variety of biological systems and due to its high sensitivity, small structural changes can be quantified.


Tissue Doppler imaging evaluation of cardiac adaptation to severe pulmonary hypertension.
Tissue Doppler imaging (TDI) was used to obtain additional insight into the cardiac adaptation to severe pulmonary arterial hypertension. Pulmonary hemodynamics and right and left ventricular function were investigated in 18 untreated patients, 12 with pulmonary arterial hypertension and 6 with chronic thromboembolic pulmonary hypertension. Fourteen age-matched healthy subjects served as controls for TDI measurements. Pulsed TDI was determined using atrioventricular planes and strain and strain rate along the right ventricular free wall, ventricular septum, and left ventricular lateral wall from 4-chamber apical views. Patients had early diastolic dysfunction, with decreased E-wave peak velocity and increased isovolumic relaxation time, both more important in the right than left ventricle. Compared with controls, strain and strain rate decreased along the right ventricular free wall with a midapical predominance (midbasal strain rate 1.7 +/- 0.6 vs 2.2 +/- 0.5; p = 0.02; midapical strain rate 0.9 +/- 0.9 vs 2.3 +/- 0.7; p <0.001), but were preserved along the left ventricular lateral wall. Tricuspid E-wave and isovolumic relaxation time (R = 0.62, p = 0.006), as well as midapical (r = 0.65, p = 0.004), but not midbasal, right ventricular strain and strain rate correlated with mean pulmonary artery pressures. In conclusion, cardiac function was abnormal in patients with severe pulmonary hypertension because of a combination of alterations in both diastolic and systolic right ventricular function and left ventricular diastolic function. Only right ventricular dysfunction correlated with pulmonary artery pressures.


MSCopilot, a new multiple sclerosis self-assessment digital solution: results of a comparative study versus standard tests.
Assessing patients' disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC). This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores. In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P < 0.001). The test-retest study demonstrated the good reproducibility of MSCopilot. This study confirms the reliability of MSCopilot and its usability in clinical practice for the monitoring of MS-related disability.


Membrane binding proteins are the major determinants for the hepatocellular transmembrane flux of long-chain fatty acids bound to albumin.
The hepatic transmembrane flux of long-chain fatty acids (LCFA) occurs through passive and fatty acid transport protein facilitated processes from blood. The extent that these transport processes can be related to the unbound and protein-bound fractions of LCFA in blood is not clear. We used hepatocyte suspensions, hepatoma monolayers, and perfused rat livers to quantitate the transport of purified [(3)H]palmitate ([(3)H]PA) and 12-(N-methyl)-N-[(7-nitrobenz-2oxa-1,3-diazol-4yl-)amino]octadecanoicacid (12-NBDS) from solutions with a constant unbound LCFA concentration with varying bovine serum albumin (BSA) concentrations and in the presence and absence of antisera raised against cytosolic liver fatty acid binding protein (L-FABP). In the absence of L-FABP antisera, using an unbound ligand concentration that was adjusted to remain constant at each BSA concentration, hepatocyte [(3)H]PA and 12-NBDS uptake rates increased linearly with an increase in BSA concentration (p < 0.0001). In the presence of L-FABP antisera, [(3)H]PA uptake showed a greater reduction in the presence of 100 muM BSA than 5 muM BSA. The calculated permeability surface area product (PS) confirmed that both unbound and bound fractions of LCFA contributed to the overall flux, but only the PS for the protein-bound fraction was reduced in the presence of L-FABP antisera. In situ rat liver perfusion studies showed that the only rate process for the disposition of [(3)H]PA in the liver inhibited by L-FABP antisera was that for influx, as defined by PS, and that it reduced PS in the perfused liver by 42%. These results suggest that, at physiological albumin concentrations, most of the LCFA uptake is mediated from that bound to albumin by a hepatocyte basolateral membrane transport protein, and uptake of unbound LCFA occurring by passive diffusion contributes a minor component.


When Ethics and the Law Collide: A Multicenter Demonstration Cohort Study of Pre-Exposure Prophylaxis Provision to Adolescent Men Who Have Sex With Men and Transgender Women in Brazil.
To explore legal and ethical challenges related to adolescents' participation in human immunodeficiency virus (HIV) research that may affect their best interests. We analyzed the ethical principles and legal aspects of the participation of 15-17-year-old men who have sex with men and transgender women in the pre-exposure prophylaxis (PrEP) 1519 study, a PrEP demonstration cohort study in three Brazilian cities. The analyses of ethics review committees' (ERCs) evaluations and court decisions followed ethical and human rights principles. An HIV vulnerability score was created, and descriptive statistics and multivariate logistic regression were performed using data from 347 participants. The ERCs evaluated the benefits and risks of research participation, all finding that the benefits outweighed the risks. ERCs deferred responsibility for decisions about waiving parental consent to the judiciary. State courts reached different decisions about waiving parental consent, reflecting variation in recognition of adolescents' evolving capacities and the adolescent as a subject of sexual rights and the primary agent capable of deciding on their health and best interests. The most vulnerable adolescent participants were found in sites where the blanket waiver was in place. Judicializing the ethical review process is detrimental to fulfilling the ethical principle of justice and vulnerable adolescents' access to health research. ERCs must be sufficiently independent and autonomous and have the capacity to respect, protect, and help fulfill the rights of participants while ensuring the generation of adequate evidence to inform public health practice.


Neuroimmune crosstalk in central nervous system injury-induced infection and pharmacological intervention.
Infection (such as pneumonia and urinary tract infection) is one of the leading causes of death in patients with acute central nervous system (CNS) injury, which also greatly affects the patients' prognosis and quality of life. Antibiotics are commonly used for the treatment of various infections, however, available evidence demonstrate that prophylactic antibiotic treatments for CNS injury-induced infection have been unsuccessful. Effective approaches for prevention of CNS injury induced-infection remain scarce, therefore, better understanding the molecular and cellular mechanisms of infection post-CNS injury may aid in the development of efficacious therapeutic options. CNS injury-induced infection is confirmed affected by the sympathetic/parasympathetic nervous system, hypothalamic-pituitary-adrenal axis, and even brain-gut axis. In this review, we summarized the mechanisms of CNS injury- induced infection, crosstalk between the CNS and the immune system and current pharmacological intervention to provide ideas for the development of new anti- infective therapeutic strategies.


Tuning the regulator: Phosphorylation of KCC2 at two specific sites is critical for neurodevelopment.
The K+/Cl- cotransporter KCC2 is a molecular switch between excitatory and inhibitory effects of GABAergic inputs into neurons. In a pair of exciting studies, Watanabe et al. and Pisella et al. elucidate the role of KCC2 dephosphorylation in this process and reveal its consequences for neurodevelopment and nervous system pathology.


Surfactant tail length-dependent lipase activity profile in cationic water-in-oil microemulsions.
The catalytic activity of Chromobacterium viscosum lipase (CV-lipase) was estimated across varying surfactant tail lengths (C-10-C-18) in water-in-oil (w/o) microemulsions of cationic surfactants containing four different hydroxyethyl-substituted head groups. An attempt to find a correlation, if any, between the activity of interfacially solubilized lipase and the varying surfactant tails was made for the first time in micellar enzymology. The second-order rate constant, k2, in lipase-catalyzed hydrolysis of p-nitrophenyl-n-hexanoate at pH 6.0 and 25 degrees C shows an improvement in enzyme activity (approximately 30-140%) across different head groups of amphiphiles with increasing tail lengths in varying solution compositions. Improvement of enzyme activity is prominent in ascending from C-10 to C-14/C-16, depending on the nature of polar head group. The hydrolytic activity of lipase in different surfactant (50 mM)/water/isooctane/n-hexanol with varying z= [alcohol]/[surfactant] (6.4 or 4.8) was amplified by 25-250% with increment in surfactant tail length in comparison with widely used cationic w/o microemulsions having solution compositions (z=16). As a notable outcome of this research, we found w/o microemulsions of 25 mM tetradecyltrimethylammonium bromide/water/isooctane/n-hexanol (z=8) producing the highest ever activity of lipase in any w/o microemulsions.


Prevalence of elevated right ventricular pressure in children with obstructive sleep apnea syndrome undergoing pulmonary hypertension screening.
Our objective was to determine the prevalence of elevated right ventricular pressure (RVP) as a surrogate marker for pulmonary hypertension in children with obstructive sleep apnea syndrome (OSAS) undergoing echocardiography. This was a retrospective chart review of children ages 2-21 years diagnosed with OSAS by an overnight polysomnogram who underwent cardiac echocardiogram to screen for pulmonary hypertension within 6 months of polysomnogram in a tertiary inner-city pediatric hospital. The primary outcome was elevated RVP defined by estimated RVP ≥ 25 mm Hg above right atrial pressure or ventricular septal configuration consistent with elevated RVP. A total of 174 children were included. The median (interquartile range) age was 8.9 (5.5-13.1) years with 59.2% male, 41.4% Hispanic, and 25.9% non-Hispanic Black patients. The prevalence of obesity was 72.0% and severe or very severe OSAS was present in 93.1%. The median (interquartile range) apnea-hypopnea index was 28.3 events/h (18.8-52.7 events/h). Seven children (4.0%) had elevated RVP. There was no association between elevated RVP and age, sex, race, body mass index percentile, apnea-hypopnea index, oxygen nadir, or severe OSAS (apnea-hypopnea index ≥ 10 events/h). Elevated RVP was rare and was not associated with OSAS severity. The prevalence in this cohort is higher than the prevalence of pulmonary hypertension noted in similar studies (0%-1.8%), which may be related to differences in methodology or unassessed cohort characteristics. Further effort to determine the optimal role for pulmonary hypertension screening in pediatric OSAS is needed. Bitners AC, Arens R, Mahgerefteh J, et al. Prevalence of elevated right ventricular pressure in children with obstructive sleep apnea syndrome undergoing pulmonary hypertension screening. J Clin Sleep Med. 2021;17(11):2225-2232.


The usefulness of HbA1c in postpartum reclassification of gestational diabetes.
To investigate the role of HbA1c in postpartum reclassification of gestational diabetes (GDM) we studied 364 women with GDM attending the postpartum reclassification assessment of their glucose tolerance status. A 75-g oral glucose tolerance test (OGTT) was performed and HbA1c was determined. Diabetes was diagnosed in 12 (3.3%), 7 (1.9%) and 2 (0.6%) women according to the fasting plasma glucose (FPG) and/or the 2-hour OGTT, the FPG alone and HbA1c levels, respectively. The sensitivity and specificity for HbA1c to diagnose diabetes was 16.7% and 100%, respectively, for FPG and OGTT criteria. The combination of a cutoff value of 5.5% for HbA1c and FPG allowed us to identify 95.1% of women with any kind of glucose intolerance. We conclude that in the early postpartum period, the cutoff of 6.5% for HbA1c alone has low sensitivity for the diagnosis of diabetes compared with OGTT, but the combination of FPG and HbA1c at a lower cutoff value is very useful to identify women with any kind of glucose intolerance.


Genotoxicity of volatile and secondary reactive oxygen species generated by photosensitization.
Reactive oxygen species were generated in the gas phase by photosensitization involving illumination of Rose Bengal. Depending on whether the chromophore is dry or solubilized, this system produces either energy-transfer reactions leading to generation of singlet oxygen specifically, or a combination of energy-transfer and electron-transfer reactions, providing both singlet oxygen and reduced forms of oxygen, such as superoxide anion and hydrogen peroxide. In neither case were the reactive species mutagenic in strain TA104 of Salmonella typhimurium, which had been previously shown to be reverted by oxygen species generated by the hypoxanthine-xanthine oxidase system in aqueous medium. However, mixed oxygen species induced an increased lethality in a variety of DNA repair-deficient Escherichia coli strains. This genotoxic effect, mainly reparable by the uvrA and recA mechanisms, was efficiently prevented by the thiol N-acetyl-L-cysteine. Singlet oxygen itself failed to exert direct genotoxic effects, although secondary reactants produced by its reaction with cell components enhanced lethality in some repair-deficient bacteria. Distance-dependence analyses provided measurements of the lifetimes of the oxygen species generated in the gas phase.


Discovery of a new NADPH-dependent aldo-keto reductase from Candida orthopsilosis catalyzing the stereospecific synthesis of (R)-pantolactone by genome mining.
(R)-Pantolactone (PL) is a key chiral intermediate for the synthesis of calcium (R)-pantothenate and (R)-panthenol used as food additives. The commercial production of (R)-pantothenate is performed by the resolution of racemic pantothenate, which is synthesized through an aldol condensation and a cyanation reaction. In this study, we investigated another synthetic method of (R)-pantothenate through the stereoselective reduction of ketopantoyl lactone (KPL) by aldo-keto reductase (AKR). A series of conjugated polyketone reductases (CPRs) were discovered from GenBank database by genome mining approach. The putative CPR gene from Candida orthopsilosis Co 90-125 (CorCPR) was cloned and functionally expressed in Escherichia coli BL21 (DE3). The optimum pH and temperature of recombinant CorCPR were 6.0-7.0 and 40 ℃, respectively. The Km and vmax toward KPL were1.3 mM and 227.3 μmol/min/mg protein, respectively. The conserved sequences suggest that CorCPR belongs to AKR3C family of AKR superfamily. Furthermore, a catalytic tetrad was proposed, and the detailed mechanism was clarified by molecular docking. In a batch reaction, 50 mM KPL was reduced to (R)-PL with 99% conversion and > 99% enantiomeric excess within 5 h. The recombinant CorCPR from C. orthopsilosis shows potential application in the asymmetric synthesis of (R)-pantothenate preparation.


The effects of intracerebroventricular injection of clonidine on conditioned pressor and adrenergic responses in rats.
Studies from this laboratory have shown that the first filial offspring of female spontaneously-hypertensive rats and male Wistar-Kyoto (WKY) normotensive rats develop stress-induced hypertension. The present study sought to examine the effects of intracerebroventricular administration of clonidine (8 micrograms) on cardiovascular and sympathoadrenal responses to aversive classical conditioning in these borderline hypertensive rats (BHR) and in normotensive WKY control rats. Clonidine caused significant reductions in resting arterial pressure, vascular resistance, heart rate and concentrations of epinephrine (E) in plasma for both hypertensive and normotensive rats. Central administration of normal saline to control rats of each strain did not alter basal cardiovascular or sympathoadrenal function. The presentation of a conditioned stimulus (CS) elicited a significant increase in arterial pressure and total peripheral resistance in hypertensive rats treated with saline and clonidine and in normotensive rats treated with saline. In contrast, normotensive rats treated with clonidine showed no increases in arterial pressure or vascular resistance following the onset of the conditioned stimulus. The aversive conditioning session instigated significant increases in the concentrations of norepinephrine (NE) and E in plasma in saline-treated rats. Hypertensive and normotensive rats treated with clonidine-showed a blunted increase in plasma concentrations of NE and E during this period; however, concentrations of E in hypertensive rats increased significantly from the baseline period after injection. These data suggest that an abnormality in central alpha 2-adrenoceptor-mediated inhibition of sympathoadrenal discharge and sympathetic vasomotor tone may predispose the hypertensive rat to develop stress-induced hypertension.


First description of qnrS1-IncN plasmid in a ST11 Salmonella Enteritidis clinical isolate from Portugal.
The presence of qnr and qepA genes was investigated among 300 nontyphoidal Salmonella showing decreased susceptibility to ciprofloxacin obtained from different sources in Portugal (2002-2004). The qnrS1 gene was located within a conjugative IncN plasmid in a ST11 Salmonella Enteritidis strain from human origin, a serotype commonly implicated in human infections and frequently encountered in poultry.


Colonic obstruction by giant pseudopolyposis.
A case of obstructing giant pseudopolyposis of the descending colon is described. A review of the clinical course of this patient and a discussion of giant pseudopolyposis is presented. The pathological features of this giant pseudopolyp is described. Carcinoma of the colon has not been found to arise in inflammatory polyps and it is felt that surgery in nonobstructed patients with giant pseudopolyposis may not be necessary.


A calibrated SVM based on weighted smooth GL1/2 for Alzheimer's disease prediction.
Alzheimer's disease (AD) is currently one of the mainstream senile diseases in the world. It is a key problem predicting the early stage of AD. Low accuracy recognition of AD and high redundancy brain lesions are the main obstacles. Traditionally, Group Lasso method can achieve good sparseness. But, redundancy inside group is ignored. This paper proposes an improved smooth classification framework which combines the weighted smooth GL1/2 (wSGL1/2) as feature selection method and a calibrated support vector machine (cSVM) as the classifier. wSGL1/2 can make intra-group and inner-group features sparse, in which the group weights can further improve the efficiency of the model. cSVM can enhance the speed and stability of model by adding calibrated hinge function. Before feature selecting, an anatomical boundary-based clustering, called as ac-SLIC-AAL, is designed to make adjacent similar voxels into one group for accommodating the overall differences of all data. The cSVM model is fast convergence speed, high accuracy and good interpretability on AD classification, AD early diagnosis and MCI transition prediction. In experiments, all steps are tested respectively, including classifiers' comparison, feature selection verification, generalization verification and comparing with state-of-the-art methods. The results are supportive and satisfactory. The superior of the proposed model are verified globally. At the same time, the algorithm can point out the important brain areas in the MRI, which has important reference value for the doctor's predictive work. The source code and data is available at http://github.com/Hu-s-h/c-SVMForMRI.


Multidrug antibiotic resistance in hospital wastewater as a reflection of antibiotic prescription and infection cases.
Antimicrobial resistance (AMR) is an escalating issue that can render illnesses more difficult to treat if effective antibiotics become resistant. Many studies have explored antibiotic resistance in bacteria (ARB) in wastewater, comparing results with clinical data to ascertain the public health risk. However, few investigations have linked the prevalence of ARB in hospital wastewater (HWW) with these outcomes. This study aimed to bridge this gap by assessing the prevalence of ARB in HWW and its receiving waters. Among the 144 isolates examined, 24 were obtained from each of the six sites (untreated wastewater, aeration tank, sedimentation tank, effluent after disinfection, upstream canal, and downstream canal). A significant portion (87.5 %) belonged to the Enterobacteriaceae family, with Klebsiella pneumoniae as the predominant species (47.9 %). The antimicrobial sensitivity testing (AST) showed that 57.6 % of the isolates were resistant to amoxicillin/clavulanic acid (AMX), the most prevalent antibiotic used within the studied hospital. The total resistance rate before and after treatment was 27.7 % and 28.0 %, respectively, with an overall multi-drug resistance (MDR) rate of 33.3 %. The multiple antibiotic resistance index (MARI) range varied between 0.0 and 0.9. The outpatient ward's three-day mean bacterial infection cases showed a significant association (Spearman's rho = 0.98) with the MARI in the sedimentation tank. Moreover, a strong correlation (Spearman's rho = 0.88) was found between hospital effluent's MARI and the seven-day mean inpatient ward case. These findings indicate that applying wastewater-based epidemiology (WBE) to hospital wastewater could provide valuable insights into understanding ARB contamination across human domains and water cycles. Future studies, including more comprehensive collection data on symptomatic patients and asymptomatic carriers, will be crucial in fully unravelling the complexities between human health and environmental impacts related to AMR.


Making Targeted Therapy Compatible with Checkpoint Immunotherapy.
Immune checkpoint blockades induced by antibodies are revolutionizing cancer therapy. Combinations of checkpoint immunotherapies with kinase inhibitors (KIs) are being clinically evaluated as oncogenic mutations arise. Off-target KI cross-reactivity will often compromise synergistic efficacy, with KIs suppressing T-cell functionalities that checkpoint blockers are purportedly boosting. This incompatibility may be removed through molecular optimization.


Vertical distributions of tropospheric SO2 based on MAX-DOAS observations: Investigating the impacts of regional transport at different heights in the boundary layer.
Information on the vertical distribution of air pollutants is essential for understanding their spatiotemporal evolution underlying urban atmospheric environment. This paper presents the SO2 profiles based on ground-based Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) measurements from March 2018 to February 2019 in Hefei, East China. SO2 decrease rapidly with increasing heights in the warm season, while lifted layers were observed in the cold season, indicating accumulation or long-range transport of SO2 in different seasons might occur at different heights. The diurnal variations of SO2 were roughly consistent for all four seasons, exhibiting the minimum at noon and higher values in the morning and late afternoon. Lifted layers of SO2 were observed in the morning for fall and winter, implying the accumulation or transport of SO2 in the morning mainly occurred at the top of the boundary layer. The bivariate polar plots showed that weighted SO2 concentrations in the lower altitude were weakly dependent on wind, but in the middle and upper altitudes, higher weighted SO2 concentrations were observed under conditions of middle-high wind speed. Concentration weighted trajectory (CWT) analysis suggested that potential sources of SO2 in spring and summer were local and transported mainly occurred in the lower altitude from southern and eastern areas; while in fall and winter, SO2 concentrations were deeply affected by long-range transport from northwestern and northern polluted regions in the middle and upper altitudes. Our findings provide new insight into the impacts of regional transport at different heights in the boundary layer on SO2 pollution.


Assessment of minimally invasive surgical skills of pre-medical students: What can we learn from future learners?
Knowledge of baseline laparoscopic and robotic surgical skills of future learners is essential to develop teaching strategies that best fit them. The objectives of this study are to determine baseline laparoscopic and robotic skills of high school and college students and compare them to those of current obstetrics and gynecology residents. A cross-sectional (Class II-2) pilot study. Laparoscopic and robotic surgical skills of college and high (secondary) school students were evaluated using simulators and compared to those of obstetrics and gynecology residents. In addition, questionnaire data were collected regarding video game playing and computer use. A total of 17 students, both high school (n=9) and college (n=8), in addition to 11 residents, completed the study. Overall, students performed comparably to the residents in simple exercises (p>.05). However, students took significantly longer time to complete complex exercises (p=.001). Finally, students played video games significantly more than residents (p<.001). Future learners may have a different background skill set. This difference may be related to improved hand-eye coordination, possibly due to playing video games. The results of this pilot study should spur more research into surgical teaching strategies.


Imaging in the presence of meroanencephaly.
Meroanencephaly occurs when there is an incomplete open median calvarial defect. This condition, which is in the spectrum of anencephaly, results in ectopic brain without skin covering and a normal foramen magnum. We present a rare case of a female fetus with meroanencephaly referred to our institution at 24 weeks and imaged with both prenatal ultrasound and MRI, demonstrating an open neural tube defect in the high parietal area and lack of visualization of the supratentorial ventricular system. Postnatal the child survived and went on to require antibiotic therapy and closure of the defect without cerebral spinal fluid diversion but demonstrates severe permanent neurologic deficits.


Informative RNA base embedding for RNA structural alignment and clustering by deep representation learning.
Effective embedding is actively conducted by applying deep learning to biomolecular information. Obtaining better embeddings enhances the quality of downstream analyses, such as DNA sequence motif detection and protein function prediction. In this study, we adopt a pre-training algorithm for the effective embedding of RNA bases to acquire semantically rich representations and apply this algorithm to two fundamental RNA sequence problems: structural alignment and clustering. By using the pre-training algorithm to embed the four bases of RNA in a position-dependent manner using a large number of RNA sequences from various RNA families, a context-sensitive embedding representation is obtained. As a result, not only base information but also secondary structure and context information of RNA sequences are embedded for each base. We call this 'informative base embedding' and use it to achieve accuracies superior to those of existing state-of-the-art methods on RNA structural alignment and RNA family clustering tasks. Furthermore, upon performing RNA sequence alignment by combining this informative base embedding with a simple Needleman-Wunsch alignment algorithm, we succeed in calculating structural alignments with a time complexity of O(n 2) instead of the O(n 6) time complexity of the naive implementation of Sankoff-style algorithm for input RNA sequence of length n.


Application of contrast-enhanced CT radiomics in prediction of early recurrence of locally advanced oesophageal squamous cell carcinoma after trimodal therapy.
Early recurrence of oesophageal squamous cell carcinoma (SCC) is defined as recurrence after surgery within 1 year, and appears as local recurrence, distant recurrence, and lymph node positive and disseminated recurrence. Contrast-enhanced computed tomography (CECT) is recommended for diagnosis of primary tumor and initial staging of oesophageal SCC, but it cannot be used to predict early recurrence. It is reported that radiomics can help predict preoperative stages of oesophageal SCC, lymph node metastasis before operation, and 3-year overall survival of oesophageal SCC patients following chemoradiotherapy by extracting high-throughput quantitative features from CT images. This study aimed to develop models based on CT radiomics and clinical features of oesophageal SCC to predict early recurrence of locally advanced cancer. We collected electronic medical records and image data of 197 patients with confirmed locally advanced oesophageal SCC. These patients were randomly allocated to 137 patients in the training cohort and 60 in the test cohort. 352 radiomics features were extracted by delineating region-of-interest (ROI) around the lesion on CECT images and clinical signature was generated by medical records. The radiomics model, clinical model, the combined model of radiomics and clinical features were developed by radiomics features and/or clinical characteristics. Predicting performance of the three models was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1 score. Eleven radiomics features and/or six clinical signatures were selected to build prediction models related to recurrence of locally advanced oesophageal SCC after trimodal therapy. The AUC of integration of radiomics and clinical models was better than that of radiomics or clinical model for the training cohort (0.821 versus 0.754 or 0.679, respectively) and for the validation cohort (0.809 versus 0.646 or 0.658, respectively). Integrated model of radiomics and clinical features showed good performance in predicting early recurrence of locally advanced oesophageal SCC for both the training and validation cohorts (accuracy = 0.730 and 0.733, and F-1score = 0.730 and 0.778, respectively). The integrated model of CECT radiomics and clinical features may be a potential imaging biomarker to predict early recurrence of locally advanced oesophageal SCC after trimodal therapy.


Special Issue "Evolution and Diversity of Insect Viruses".
Insects are crucial for ecosystem functions and services and directly influence human well-being and health [...].


Arsanilic acid contributes more to total arsenic than roxarsone in chicken meat from Chinese markets.
Organoarsenicals have been used in poultry production for years, however, studies focused on roxarsone (ROX), with little attention to p-arsanilic acid (ASA). We assessed arsenic (As) concentration and speciation in chicken meat collected from 10 cities in China. The geometric mean for total As in 249 paired raw and cooked samples was 4.85 and 7.27 μg kg-1 fw, respectively. Among 81 paired raw and cooked samples, ASA and ROX were detected in >90% samples, suggesting the prevalence of organoarsenical use in China. ASA contributed the most (45% on average) to total As in cooked samples, followed by As(V), DMA, As(III), and ROX (7.2-22%). ASA was found to contribute more to total As in chicken meat compared to ROX for the first time. Arsenic in chicken meat showed considerable geographic variation, with higher inorganic arsenic (iAs) being detected from cities with higher ROX and ASA, indicating that organoarsenical use increased iAs concentration in chicken meat. When health risk was estimated, dietary exposure to iAs would result in an increase of 3.2 bladder and lung cancer cases per 100,000 adults. The result supports the removal of organoarsenicals in poultry production from Chinese market and further supports its removal from the global markets.


Acute effects of nicotine administration during prospective memory, an event related fMRI study.
We previously demonstrated that stimulating neuronal nicotinic acetylcholine receptors modulates prospective memory (PM), the ability to remember and implement a prior intention. Here we used fMRI to explore the neuronal correlates of acute nicotinic (1mg) modulation during PM, employing a double blind, valence-matched placebo-controlled design, and a solely event-related analysis. Eight healthy adults completed on two occasions (1 week washout) a simple attentional task containing infrequent PM trials. PM activated bilateral parietal, prefrontal (BA10) and anterior cingulate, and deactivated genual cingulate and medial prefrontal regions. Further, acute nicotine administration decreased activity within a largely overlapping right parietal region. This data validates a purely event-related approach to exploring PM, and suggests procholinergic modulation of PM by parietal rather than BA10/frontal regions.


Anti-liver antibody in rabbits infected with Schistosoma japonicum.
Anti-liver antibody has been demonstrated in the sera of Schistosoma japonicum-infected rabbits. By the 8th week after exposure to cercariae, perceptible levels of autoantibody were present and appeared to be direct predominantly determinants located in the cell membrane of the hepatocyte.


Determination of toxic elements in waters and sediments from River Subin in the Ashanti Region of Ghana.
Waters and sediments of Subin River, which flows through the industrial and commercial areas of Kumasi in the Ashanti region of Ghana, were geochemically investigated to ascertain heavy metal pollution levels due to anthropogenic activities. The study shows preoccupying pollution levels that constitute a threat to public and ecological systems. The waters of Subin River are neutral to slightly basic, inferred from pH values of 6.89-7.65). Electric conductivity (EC) of the waters ranges from 822 to 1,821 mus/cm and the range of total dissolved solids (TDS) is from 409 to 913 mg/l. Toxic elements contents of sediments and waters from 10 sites along the river were analysed by instrumental neutron activation analysis (INAA), and Al, As, Cd, Cr, Cu and Zn were determined. The concentrations of Al, As, Cd, Cr, Cu and Zn in the waters range between 4.02-15.18, 0.007-0.16, 0.002-0.05, 0.001-0.019, 1.32-7.04 and 4.28-10.2 mg/l, respectively. The contamination factors (CF) computed for the elements indicate that with the exception of sampling site S10, the sediments are polluted with Cd. Chromium contamination in the sediments is observed at S6 and S7, where the CF values were 1.39 and 1.52, respectively. The pollution load indices (PLI) were low (<1) and ranged from 0.14 to 0.75, suggesting that the overall sediment column of the river is not polluted.


Electricity and catholyte production from ceramic MFCs treating urine.
The use of ceramics as low cost membrane materials for Microbial Fuel Cells (MFCs) has gained increasing interest, due to improved performance levels in terms of power and catholyte production. The catholyte production in ceramic MFCs can be attributed to a combination of water or hydrogen peroxide formation from the oxygen reduction reaction in the cathode, water diffusion and electroosmotic drag through the ion exchange membrane. This study aims to evaluate, for the first time, the effect of ceramic wall/membrane thickness, in terms of power, as well as catholyte production from MFCs using urine as a feedstock. Cylindrical MFCs were assembled with fine fire clay of different thicknesses (2.5, 5 and 10 mm) as structural and membrane materials. The power generated increased when the membrane thickness decreased, reaching 2.1 ± 0.19 mW per single MFC (2.5 mm), which was 50% higher than that from the MFCs with the thickest membrane (10 mm). The amount of catholyte collected also decreased with the wall thickness, whereas the pH increased. Evidence shows that the catholyte composition varies with the wall thickness of the ceramic membrane. The possibility of producing different quality of catholyte from urine opens a new field of study in water reuse and resource recovery for practical implementation.


Augmented renal clearance in the ICU: estimation, incidence, risk factors and consequences-a retrospective observational study.
Augmented renal clearance (ARC) remains poorly evaluated in ICU. The objective of this study is to provide a full description of ARC in ICU including prevalence, evolution profile, risk factors and outcomes. This was a retrospective, single-center, observational study. All the patients older than 18 years admitted for the first time in Medical ICU, Bichat, University Hospital, APHP, France, between January 1, 2017, and November 31, 2020 and included into the Outcomerea database with an ICU length of stay longer than 72 h were included. Patients with chronic kidney disease were excluded. Glomerular filtration rate was estimated each day during ICU stay using the measured creatinine renal clearance (CrCl). Augmented renal clearance (ARC) was defined as a 24 h CrCl greater than 130 ml/min/m2. 312 patients were included, with a median age of 62.7 years [51.4; 71.8], 106(31.9%) had chronic cardiovascular disease. The main reason for admission was acute respiratory failure (184(59%)) and 196(62.8%) patients had SARS-COV2. The median value for SAPS II score was 32[24; 42.5]; 146(44%) and 154(46.4%) patients were under vasopressors and invasive mechanical ventilation, respectively. The overall prevalence of ARC was 24.6% with a peak prevalence on Day 5 of ICU stay. The risk factors for the occurrence of ARC were young age and absence of cardiovascular comorbidities. The persistence of ARC during more than 10% of the time spent in ICU was significantly associated with a lower risk of death at Day 30. ARC is a frequent phenomenon in the ICU with an increased incidence during the first week of ICU stay. Further studies are needed to assess its impact on patient prognosis.


Perceived learning needs of patients with coronary artery disease using a questionnaire assessment tool.
To determine the perceived learning needs and their level of importance in patients with angina pectoris or myocardial infarction at hospitalization and follow-up clinic visit and to assess the reliability of a self-administered questionnaire. Longitudinal, exploratory. West Coast university-affiliated medical center and clinics that serve primarily a veteran population. Twenty-eight adults who were admitted with a diagnosis of angina pectoris or myocardial infarction. Age range was 31 to 80 years (mean 61 years). Learning needs, questionnaire. Data collection was initiated at hospitalization and continued at the first clinic visit after discharge. A self-administered questionnaire and personal data sheet were completed by the patients. Matched-pair t-tests and Pearson's correlation were used for data analysis. No statistical differences were demonstrated between learning needs at hospitalization and clinic visit. Three content areas including symptom recognition, cardiac anatomy and physiology, and medications were ranked as the most important learning needs of patients at hospitalization and follow-up clinic visit. The least important learning needs at both times were content areas of smoking, work, and sex. No correlation was found between the importance of perceived learning needs and age, occupation, smoking, and marital status. The questionnaire contains 38 items and is self-administered. It was developed on the basis of a previous tool and preliminary study results. Content and validity were supported by clinical experts. The internal consistency reliability alpha coefficients of the questionnaire were 0.96 at hospitalization and 0.93 at the clinic visit. The findings of this study suggest that the most important perceived learning needs of patients at hospitalization and follow-up clinic visit are those that affect survival. A self-administered questionnaire can be used as a practical and reliable tool to determine the perceived learning needs of patients with coronary artery disease during the recovery phase of illness. Cardiac educational programs for patients with coronary artery disease can focus on the content areas that patients consider most important.


Evaluation of two collocated federal equivalent method PM2.5 instruments over a wide range of concentrations in Sarajevo, Bosnia and Herzegovina.
Two widely used PM2.5 monitors in the United States (U.S.) designated as federal equivalent methods (FEMs) by the U.S. Environmental Protection Agency were collocated for 15 months in Sarajevo, Bosnia and Herzegovina (BiH) to evaluate their comparability. With differing measurement principles, the FEMs (Met One BAM-1020 and Teledyne API T640) exhibited unique responses to the significant range in PM2.5 over the study period. During the winter months when concentrations greatly increased (e.g., daily PM2.5 > 100 μg m-3), the BAM-1020 had intermittent malfunctioning nozzle contact to the collection tape, resulting in periods of data invalidation. Increased operator observation and doubling the cleaning frequency were required to maintain proper operation. The hourly data from the BAM-1020, which detects PM2.5 via beta-attenuation of particles loaded to the collection tape, indicated higher noise at concentrations below 40 μg m-3 relative to the T640, which detects PM2.5 via an optical method. Above this concentration threshold, the two instruments appear to have comparable hourly fluctuations in the data. Relative to the BAM-1020, the T640 reported higher concentrations when PM2.5 is above 80 μg m-3. A linear regression equation was developed and applied to adjust T640 PM2.5 high concentration values, resulting in 24-hr average T640adj PM2.5 values closely matching that from the BAM-1020 for the full concentration range. Based on the T640adj values, the annual average for Sarajevo was calculated at the site to be 42 μg m-3, with significant seasonality resulting in over 7-fold higher concentrations in the months of December-January compared to June-July.


The meaning of mammalian adult neurogenesis and the function of newly added neurons: the "small-world" network.
Adult neurogenesis has been observed in mammalian brain including human but a question remains: how do new neurons become functional in the adult brain? We propose that the random addition of only a few new neurons functions as a maintenance system for the brain's "small-world" networks. In popular parlance, the small-world network phenomenon is described by the concept of "six degrees of separation", which postulates that everyone in the world is connected to everyone else through a chain of at most six mutual acquaintances. Randomly added to an orderly network, new links enhance signal propagation speed and synchronizability. Newly generated neurons are ideally suited to become such links: they are immature, form more new connections compared to mature ones, and their number but not their precise location may be maintained by continuous proliferation and dying off. Similarly, we envisage that the treatment of brain pathologies by cell transplantation would also create new random links in small-world networks and that even a small number of successfully incorporated new neurons may be functionally important.


Effects of zinc and Bacillus subtilis on the reproductive performance, egg quality, nutrient digestion, intestinal morphology, and serum antioxidant capacity of geese breeders.
The effects of zinc (Zn) and Bacillus subtilis (B. subtilis) on reproductive performance, egg quality, nutrient digestion, intestine morphology, and antioxidant capacity were explored in geese breeders. Geese breeders (n = 120, 46-wk of age) were randomly assigned into 6 groups with 4 replicates of 5 birds each (1 male and 4 female). Breeders were fed diets with 2 levels of B. subtilis (2.5 × 109 and 5 × 109 CFU/kg) crossed with three levels of Zn (25, 45, and 65 mg/kg) for duration of 10-wk. The results showed that the egg laying rate (P < 0.05), fertility rate (P < 0.01), hatchability rate (P < 0.05), yolk color (P < 0.05), and the retentions of crude protein (P < 0.05), ether extract (P < 0.05) and phosphorus of geese breeders were improved by dietary supplementation of 5 × 109 CFU/kg B. subtilis and 25 mg or 45 mg/kg Zn. The serum T-SOD (P < 0.05) was increased by 45 mg/kg Zn supplementation. The serum T-AOC (P < 0.05) and retention of Zn (P < 0.05) were increased by 5 × 109 CFU/kg B. subtilis supplementation. The birds fed with 5 × 109 CFU/kg B. subtilis and 25 mg or 45 mg/kg Zn showed improved villus length (P < 0.01) and villus length/ crypt depth (P < 0.01) in both the jejunum and ileum. In conclusion, the combination of B. subtilis and Zn may have synergistic effects on these parameters, and dietary inclusion of 5 × 109 CFU/kg B. subtilis and 45 mg/kg Zn is recommended for improving the reproductive performance of geese breeders.


Ginsenoside Rk3 alleviates gut microbiota dysbiosis and colonic inflammation in antibiotic-treated mice.
Ginsenoside Rk3 is a natural prebiotic found in ginseng, has excellent pharmacological efficacy, especially antitumor effects, and can greatly benefit human health. Here, we investigated the impact of Rk3 intake on modulation of the gut microbiota and their metabolites as well as its effect on low-grade inflammation in mice. C57BL/6JFandd mice were administered different doses of Rk3 for two weeks after establishment of an antibiotic-mediated gut microbiota disturbance model. Interestingly, Rk3 intake induced substantial changes in the gut microbiota composition, enriched the Bacteroides, Alloprevotella and Blautia genera, and effectively ameliorated gut microbiota dysbiosis, with significantly decreased Firmicutes/Bacteroidetes ratios. These changes were accompanied by beneficial alterations in gut microbiota diversity and improved short-chain fatty acid levels. In addition, we found that Rk3 intervention repaired intestinal barrier dysfunction by increasing the expression of tight junction proteins (ZO-1, Occludin and Claudin-1), reducing colonic inflammatory cytokine levels, and suppressing TNF-α, IL-1β, and IL-6 overproduction. In conclusion, Rk3 improves intestinal inflammation and induces potentially beneficial changes in the gut microbiota, and these findings help elucidate host-microbe interactions.


Pathological characterisation of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.
Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC. Central pathology review was performed for 1483 male BCs collected through part 1 of the European Organisation for Research and Treatment of Cancer (EORTC) International Male BC Program. Pathology review included histological subtype, grade, mitotic activity index (MAI), presence of a fibrotic focus and density of tumour-infiltrating lymphocytes (TILs). These features were correlated with clinical outcome. The relationship between these features and surrogate molecular subtypes using immunohistochemistry was also assessed. Median follow-up for overall survival (OS) was 7.1 years. Overall histological grade was not significantly associated with OS (p = 0.129). MAI, the presence of a fibrotic focus and a low TIL density however were correlated with unfavourable OS (p = 0.023, p = 0.004 and p = 0.011, respectively). BC subtype correlated with TIL density (p = 0.015), as we observed a higher density for human epidermal growth factor receptor type 2 (HER2) positive BC compared to luminal HER2-negative subtype. No association was observed between subtype and fibrotic focus. Histologic grade was not significantly correlated with clinical outcome in this series, unlike what is seen in female patients. These results contribute to our understanding of male BC and indicate the importance of further research on the optimisation of risk stratification and treatment decisions for male BC patients.


STAT1 regulates interferon-γ-induced angiotensinogen and MCP-1 expression in a bidirectional manner in primary cultured mesangial cells.
Intrarenal interferon-γ significantly contributes to the development of glomerular injury in which angiotensinogen and monocyte chemoattractant protein 1 levels are elevated. However, the exact nature of the role that interferon-γ plays in regulating angiotensinogen and monocyte chemoattractant protein 1 expression has not been fully delineated. Therefore, the aim of this study was to investigate the role that interferon-γ plays in angiotensinogen and monocyte chemoattractant protein 1 expression. Primary cultured rat mesangial cells were treated with 0-20 ng/mL interferon-γ for 2, 8 or 24 hours. Expression levels of angiotensinogen, monocyte chemoattractant protein 1, suppressors of cytokine signaling 1, an intracellular suppressor of Janus kinase-signal transducers and activators of transcription signaling and activity of the Janus kinase-signal transducers and activators of transcription pathway were evaluated by reverse transcriptase polymerase chain reaction and western blot analysis. Interferon-γ increased angiotensinogen expression in mesangial cells with maximal augmentation observed following 5 ng/mL interferon-γ at 8 hours of treatment (1.87 ± 0.05, mRNA, relative ratio). Further increases were reduced or absent using higher concentrations of interferon-γ. Following treatments, monocyte chemoattractant protein 1 expression was induced in a linear dose-dependent manner (6.85 ± 0.62-fold by 20 ng/mL interferon-γ at 24 hours). In addition, interferon-γ induced STAT1 phosphorylation and suppressors of cytokine signaling 1 expression in a linear dose-dependent manner. The suppression of STAT1 and suppressors of cytokine signaling 1 expression by small interference RNAs facilitated an increase in interferon-γ-induced angiotensinogen expression, indicating that these two factors negatively regulate angiotensinogen expression. In contrast, the increase in interferon-γ-induced monocyte chemoattractant protein 1 expression was attenuated in STAT1-deficient mesangial cells, suggesting that STAT1 positively regulates monocyte chemoattractant protein 1 expression in mesangial cells. These results demonstrate that while interferon-γ increases both angiotensinogen and monocyte chemoattractant protein 1 expression, STAT1 plays an opposing role in the regulation of each factor in mesangial cells.


Short-period temporal repolarization dispersion in subjects with atrial fibrillation and decompensated heart failure.
The association between chronic heart failure (CHF) and permanent atrial fibrillation is very frequent. The repolarization duration was already found predictive for atrial fibrillation. Aim of this study was to evaluate the influence of atrial fibrillation on short period repolarization variables in decompensated CHF patients. We used 5 min ECG recordings to assess the mean, standard deviation (SD), and normalized variance (NV) of the following variables: QT end (QTe), QT peak (QTp), and T peak to T end (Te) in 121 decompensated CHF, of whom 40 had permanent atrial fibrillation, too. We reported also the 30-day mortality. QTpSD (p < .01), TeSD (p < .01), QTpVN (p < .01), and TeVN (p < .01) were higher in the atrial fibrillation than among sinus rhythm CHF subjects. Multivariable logistic analysis selected only TeSD (odd ratio, o.r.: 1.32, 95% confidence interval, c.i.: 1.06-1.65, p: .015) associated with atrial fibrillation. A total of 27 patients died during the 30-days follow-up (overall mortality rate 22%), 7 (18%), and 20 (25%) respectively in the atrial fibrillation and sinus rhythm patients. Furthermore, the following variables were associated to the morality risk: NT-pro Brain Natriuretic Peptide (o.r.: 1.00, 95% c.i.: 1.00-1.00, p: .041), left ventricular end diastolic diameter (o.r.: 0.81, 95% c.i.: 0.67-0.96, p: .010), and Te mean (o.r.: 1.04, 95% c.i.: 1.02-1.09, p: .012). In decompensated CHF subjects, Te mean seems be associated to mortality and TeSD to the permanent atrial fibrillation. We could hypothesize that, during severe CHF, the multi-level ionic CHF channel derangement could be critical in influencing these non-invasive markers. (ClinicalTrials.gov number, NCT04127162).


Prestin is expressed on the whole outer hair cell basolateral surface.
Prestin has been identified as a motor protein responsible for outer hair cell (OHC) electromotility. Previous experiments revealed that OHC electromotility and its associated nonlinear capacitance resided in the OHC lateral wall and was not detected at the apical cuticular plate and basal region. In this experiment, the distribution of prestin in adult mouse, rat, and guinea pig OHCs was re-examined by use of immunofluorescent staining and confocal microscopy. We found that prestin labeling was located at the whole OHC basolateral wall, including the basal plasma membrane. However, staining at the basal membrane was weak. As compared with the intensity at the lateral wall, the intensities of prestin labeling at the membrane at the nuclear level and basal pole were 80.5% and 61.1%, respectively. Prestin labeling was not found at the cuticular plate and stereocilia. The prestin labeling was also absent in the cytoplasm and nuclei. The OHC lateral wall above the nuclear level is composed of the plasma membrane, cortical lattice, and subsurface cisternae. By co-staining with di-8-ANEPPS, prestin labeling was found at the outer layer of the OHC lateral wall, which was further evidenced by use of a hypotonic challenge to separate the plasma membrane from the underlying subsurface cisternae. The data revealed that prestin is expressed at the whole OHC basolateral membrane. Prestin in the basal plasma membrane may provide a reservoir on the OHC surface for prestin-recycling and may also facilitate performing its hypothesized transporter function.


Genetic manipulation of butyrate formation pathways in Clostridium butyricum.
Clostridium butyricum is one of the commonly used species for fermentative hydrogen production. While producing H₂, it can produce acids (lactic, acetic and butyric acids) and CO₂, as well as a small amount of ethanol. It has been proposed that elimination of competing pathways, such as the butyrate formation pathway, should increase H₂ yields in Clostridium species. However, the application of this strategy has been hindered by the unavailability of genetic tools for these organisms. In this study, we successfully transferred a plasmid (pMTL007) to C. butyricum by inter-specific conjugation with Escherichia coli and disrupted hbd, the gene encoding β-hydroxybutyryl-CoA dehydrogenase in C. butyricum. Fermentation data showed that inactivation of hbd in C. butyricum eliminated the butyrate formation pathway, resulting in a significant increase in ethanol production and an obvious decrease in H₂ yield compared with the wild type strain. However, under low partial pressure of H₂, the hbd-deficient strain showed increased H₂ production with the simultaneous decrease of ethanol production, indicating that H₂ production by C. butyricum may compete for NADH with the ethanol formation pathway. Together with the discovery of a potential bifurcating hydrogenase, this study extends our understanding of the mechanism of H₂ production by C. butyricum.


Estimating pediatric surgical need in developing countries: a household survey in Rwanda.
Surgical services for children are often absent in resource-limited settings. Identifying the prevalence of surgical disease at the community level is important for developing evidence-based pediatric surgical services and training. We hypothesize that the untreated surgical conditions in the pediatric population are largely uncharacterized and that such burden is significant and poorly understood. Furthermore, no such data exist at the population level to describe this population. We conducted a nationwide cross-sectional cluster-based population survey to estimate the magnitude of surgical disease in Rwanda. Conducted as a verbal questionnaire, questions included representative congenital, acquired, malignant and injury-related conditions. Pediatric responses were analyzed using descriptive statistics and univariate analysis. A total of 1626 households (3175 individuals) were sampled with a 99% response rate; 51.1% of all individuals surveyed were younger than age 18. An estimated 50.5% of the total current surgical need occurs in children. Of all Rwandan children, 6.3% (95% CI 5.4%-7.4%), an estimated 341,164 individuals, were identified to have a potentially treatable surgical condition at the time of the interview. The geographic distribution of surgical conditions significantly differed between adults and children (p<0.001). The results emphasize the magnitude of the pediatric surgery need as well as the need for improved education and resources. This may be useful in developing a collaborative local training program.


Long-term results of ankle arthrodesis in children and adolescents with haemophilia.
Ankle arthrodesis in patients with haemophilia is a joint-non-preserving treatment option often resulting in substantial pain relief and termination of haemarthrosis by osseous consolidating of the joint. However, limited data are available regarding ankle arthrodesis in young patients. The aim of this study was to evaluate the long-term clinical and radiographic results with a minimum follow-up of ten years in children with haemophilia who underwent ankle arthrodesis. We retrospectively reviewed the results of ankle fusions performed in young haemophiliacs in our department between 1980 and 2006. The Méary procedure was used for arthrodesis, performed on patients with closed growth plates. Only one patient had no fixation, due to being only six years old. The modified American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score was calculated at last follow-up, and standard radiographic evaluations were performed. A total of 22 ankles were analysed from 17 patients. The mean follow-up was 19.7 ± 8 years. The mean age of the patients was 15.5 (6-23) years at the time of index surgery. There were no intra-operative or peri-operative complications related to ankle arthrodesis. The mean modified AOFAS score at last follow-up was 83 ± 10.5. Radiographic assessment demonstrated solid osseous fusion at the arthrodesis site, with no axis deformities. Two patients developed secondary subtalar arthrosis, treated by subtalar arthrodesis six years after initial ankle arthrodesis in one case. In our study, tibiotalar arthrodesis in young patients with haemophilia resulted in good long-term functional outcome with a low surgery-related complication rate.


[Patellar dislocation as a cause of osteochondral fracture of the femoro-patellar joint].
Acute traumatic dislocation of the patella may be associated with osteochondral fractures. Clinical examination invariably shows a tense effusion. A detailed radiographic examination including antero-posterior, lateral and skyline views of the patella is usually necessary to establish an exact diagnosis. Once diagnosis is made open reduction and fixation of the osteochondral fracture should be carried out if it is possible. Out of 78 patients of our own with patella dislocation 24 cases suffered an osteochondral fracture. In ten cases refixation of the osteochondral fragment was achieved. Intraoperatively the alignment of the patella was controlled in any case. In cases of lateral subluxation lateral release and medial reconstruction was performed. In two cases medial transfer of the tibial tuberosity was carried out. Osteochondral fractures of the femoro-patellar groove represent an important injury in the course of acute patellar dislocation. With exact diagnosis and correct treatment congruity of the femoro-patellar joint can be restored in many cases.


Interaction of inflammatorily activated retinal pigment epithelium with retinal microglia and neuronal cells.
In age-related macular degeneration, inflammatory events are presumed to contribute to disease development. A primary suspect of this contribution is the microglia, the innate immune cell of the retina. In addition, retinal pigment epithelium (RPE) cells can be inflammatorily activated. In this study, we investigate the effect of activated RPE cells on retinal microglia and on neuronal cells. RPE cells and microglia were harvested from porcine eyes. In addition, a neuronal cell line (SHSY-5Y) of human origin was used. For inflammatory activation, agonists of toll-like receptors in different concentrations were used: Pam2CSK4 (Pam; TLR-2), Polyinosinic:polycytidylic acid (Poly I:C; TLR-3) and lipopolysaccharid (LPS; TLR-4). Cell viability was investigated with an MTT assay. The secretion of cytokines was assessed in an ELISA and their expression in real-time PCR. There was no effect of the agonists on cell viability in RPE cells. All agonists induced the secretion of IL-6 and IL-8 in RPE cells with the strongest effect induced by LPS. In microglia, pro-inflammatory stimulation increased the metabolic activity. All agonists induced the secretion of IL-1ß, IL-8, and TNFα in microglia cells while in real-time PCR, LPS and Pam induced the expression of IL-6, IL-1ß and iNOS. Direct stimulation of SHSY-5Y with the agonists induced only minor alterations of viability. Stimulated RPE cell supernatant reduced the secretion of TNFα and IL-8 irrespective of the inducing agent in microglia cells. Additionally a slight induction of IL-1ß was found in microglia treated with supernatant of RPE cells treated with Pam. In real time PCR, the supernatant of RPE cells stimulated with LPS significantly reduced the expression of iNOS and IL-6, but not of IL-1ß. Of note, the expression of iNOS was also reduced by naive RPE cells. The treatment of the SHSY-5Y with supernatant of microglia previously treated with RPE conditioned medium significantly decreased SHSY-5Y viability with and without pro-inflammatory treatment. In conclusion, inflammatory activated RPE cells have a regulatory effect on the pro-inflammatory activation of microglia, stressing the importance of the interaction between these two retinal cell types. Microglia treated with RPE supernatant reduced viability of a neuronal cell line, indicating a neurotoxic effect.


The impact of parenteral narcotic choice in the development of acute chest syndrome in sickle cell disease.
Acute chest syndrome (ACS) represents a serious morbidity and often fatal complication in patients with sickle cell disease. Painful episodes which require hospitalization are most often treated with opioids, which may then influence the development of ACS. Nalbuphine is a parenteral opioid which effectively treats pain and may cause less ACS. This retrospective chart review documented 988 admissions for painful episodes at 2 institutions and recorded the incidence of ACS and opioid used. At the Children's Hospital in St Louis, Missouri, the incidence of ACS in patients treated with morphine alone was 10.8% versus at the Children's Mercy Hospital in Kansas City, Missouri, the incidence was 2.1% for patients treated solely with nalbuphine. When nalbuphine is used alone as the single parenteral opioid agent to treat painful episodes in patients with sickle cell disease, the incidence of ACS is less than when compared with other opioids used to treat pain.


Understanding advanced hemodynamic concepts.
This article reviews the determinants of myocardial oxygen supply (MVO2) and consumption and revisits the effects of IABC on each. Measurements of MVO2, including diastolic pressure-time index (DPTI), tension-time index (TTI), and endocardial viability ratios (EVR), demonstrate the dramatic effects of balloon deflation and the resulting afterload reduction on MVO2. IABC enhances ventricular outflow, thus decreasing preload; reduces systolic and end-diastolic aortic pressures, causing a decrease in ventricular afterload; magnifies the intrinsic Windkessel effect in the aorta, leading to an increased stroke volume; decreases static work and accordingly, MVO2; and stimulates the baroreceptors, causing a reduction in peripheral vascular resistance. IABC also increase in heart rate. Bedside computers enable the clinician to take a closer look at balloon efficacy via DPTI, TTI, and EVR. New sources of information and understanding may provide opportunities for nurses to ensure optimum patient outcomes.


Acetylcholine-induced change in intracellular Cl- activity of the mouse lacrimal acinar cells.
Using double-barreled Cl- -sensitive microelectrodes, intracellular Cl- activity (AiCl) in the mouse lacrimal acinar cells in vitro was determined in both resting and secretory phases. In the resting state AiCl was 31 mmol/l which was 1.4 times higher than that predicted for the passive distribution according to the membrane potential (Vm) of -41 mV. Addition of acetylcholine (ACh, 1 microM) hyperpolarized Vm to -63 mV and decreased AiCl to 20 mmol/l which was still twice the equilibrium activity. A-23178 produced similar changes in Vm and AiCl to those induced by ACh. It was concluded that Cl- was actively accumulated in the acinar cells and, in the secretory phase, Cl- efflux was enhanced by the increased driving force and Ca2+-mediated increase in the Cl- permeability across the cell membrane.


Safety and Efficacy of Apixaban versus warfarin in patients with atrial fibrillation or Venous Thromboembolism and End-Stage renal disease on hemodialysis: A systematic review and meta-analysis.
Warfarin is traditionally the drug of choice for stroke prophylaxis or treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) on hemodialysis as data on apixaban use is scarce. We aimed to assess the safety and efficacy of Apixaban in patients with ESRD on hemodialysis when compared with warfarin. A comprehensive literature search in PubMed, Google Scholar, and Cochrane databases from inception until Nov 25, 2019, was performed. Studies reporting clinical outcomes comparing Apixaban (2.5 mg BID or 5 mg BID) versus Warfarin in ESRD patients on hemodialysis were included. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data. Four studies (three retrospective and one randomized) with a total of 9862 patients (apixaban = 2,547, warfarin = 7315) met inclusion criteria. The overall mean age was 66.6 ± 3.9 years and mean CHA2DS2-VASc score 4.56 ± 0.58. Apixaban was associated with lower rates of major bleeding (RR 0.53, 95% CI 0.45-0.64, p < 0.0001], gastrointestinal (GI) bleed (RR 0.65, 95% CI 0.55-0.76, p < 0.0001), intracranial bleed (RR 0.56, 95% CI 0.36-0.89, p = 0.01), and stroke/systemic embolism [RR 0.65, 95% CI 0.52-0.83, p = 0.0004] compared with warfarin in patients with ESRD on hemodialysis. There was no significant increased risk of all-cause mortality with the apixaban vs. warfarin (RR 0.90, 95% CI 0.41-1.96, p = 0.78). Apixaban had an overall favorable risk-benefit profile, with significant reductions in ischemic stroke, major bleeding, and intracranial bleeding compared to Warfarin in ESRD patients on hemodialysis with non-valvular AF and/or venous thromboembolism.


Behavior modification in a residence and school for adolescent boys: a team approach.
A behavior modification program emphasizing close communication and cooperation between educators and child care workers has proved effective in a school for adolescent boys with learning and behavior problems.


CovMnet-Deep Learning Model for classifying Coronavirus (COVID-19).
Diagnosing COVID-19, current pandemic disease using Chest X-ray images is widely used to evaluate the lung disorders. As the spread of the disease is enormous many medical camps are being conducted to screen the patients and Chest X-ray is a simple imaging modality to detect presence of lung disorders. Manual lung disorder detection using Chest X-ray by radiologist is a tedious process and may lead to inter and intra-rate errors. Various deep convolution neural network techniques were tested for detecting COVID-19 abnormalities in lungs using Chest X-ray images. This paper proposes deep learning model to classify COVID-19 and normal chest X-ray images. Experiments are carried out for deep feature extraction, fine-tuning of convolutional neural networks (CNN) hyper parameters, and end-to-end training of four variants of the CNN model. The proposed CovMnet provide better classification accuracy of 97.4% for COVID-19 /normal than those reported in the previous studies. The proposed CovMnet model has potential to aid radiologist to monitor COVID-19 disease and proves to be an efficient non-invasive COVID-19 diagnostic tool for lung disorders.


Changes in psychosocial distress in outpatients with heart failure with implantable cardioverter defibrillators.
Patients given implantable cardioverter defibrillators (ICDs) after arrhythmic events or sudden cardiac arrest (SCA) experience psychosocial distress. ICDs now are inserted for the primary prevention of SCA in patients with heart failure; the psychosocial impact of ICDs on patients with heart failure is unknown. Changes in psychosocial status in these ICD recipients were examined. ICD recipients (n = 57) completed depression, anxiety, and social support inventories every 6 months for up to 2 years. Initially, 35% of recipients were depressed and 45% of recipients were anxious. In linear mixed models, depression decreased over time overall but increased in those who experienced ICD shocks. Anxiety decreased in New York Heart Association class III ICD recipients but not in class II ICD recipients. Decreases in social support were related to age: the younger the patient the greater the decrease. A significant proportion of ICD recipients were depressed or anxious, or had diminished social support even after 2 years. Investigation of strategies to improve ICD recipients' psychosocial status is warranted.


Emerging role of precision medicine in biliary tract cancers.
Biliary tracts cancers (BTCs) are a diverse group of aggressive malignancies with an overall poor prognosis. Genomic characterization has uncovered many putative clinically actionable aberrations that can also facilitate the prognostication of patients. As such, comprehensive genomic profiling is playing a growing role in the clinical management of BTCs. Currently however, there is only one precision medicine approved by the US Food and Drug Administration (FDA) for the treatment of BTCs. Herein, we highlight the prevalence and prognostic, diagnostic, and predictive significance of recurrent mutations and other genomic aberrations with current clinical implications or emerging relevance to clinical practice. Some ongoing clinical trials, as well as future areas of exploration for precision oncology in BTCs are highlighted.


Influenza virus assays based on virus-inducible reporter cell lines.
Virus-inducible reporter genes have been used as the basis of virus detection and quantitation assays for a number of viruses. A strategy for influenza A virus-induction of a reporter gene was recently described. In this report, we describe the extension of this strategy to influenza B virus, the generation of stable cell lines with influenza A and B virus-inducible reporter genes, and the use of these cells in various clinically relevant viral assays. Each of the cell lines described herein constitutively express an RNA transcript that contains a reporter gene coding region flanked by viral 5¢- and 3¢-untranslated regions (UTR) and therefore mimics an influenza virus genomic segment. Upon infection of the cells with influenza virus the virus-inducible reporter gene segment (VIRGS) is replicated and transcribed by the viral polymerase complex resulting in reporter gene expression. Reporter gene induction occurs after infection with a number of laboratory strains and clinical isolates of influenza virus including several H5N1 strains. The induction is dose-dependent and highly specific for influenza A or influenza B viruses. These cell lines provide the basis of simple, rapid, and objective assays that involve virus quantitation such as determination of viral titer, assessment of antiviral susceptibility, and determination of antibody neutralization titer. These cell lines could be very useful for influenza virus researchers and vaccine manufacturers.


Enhancing positive parent-child interactions and family functioning in a poverty sample: a randomized control trial.
This study tested the attachment-based intervention program Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) in a randomized controlled trial with poor families of toddlers screened for professional's concerns about the child's caregiving environment. The VIPP-SD is an evidence-based intervention, but has not yet been tested in the context of poverty. The sample included 43 families with 1- to 4-year-old children: mean age at the pretest was 29 months and 51% were boys. At the pretest and posttest, mother-child interactions were observed at home, and mothers reported on family functioning. The VIPP-SD proved to be effective in enhancing positive parent-child interactions and positive family relations in a severely deprived context. Results are discussed in terms of implications for support services provided to such poor families in order to reduce intergenerational risk transmission.


Inducible boron resistance via active efflux in Lysinibacillus and Enterococcus isolates from boron-contaminated agricultural soil.
Phylogenetically diverse bacteria tolerate high boron concentrations while others require it for metabolic purposes despite the metalloid being toxic beyond a threshold. Boron resistance and plant growth promoting attributes of two bacterial strains, Lysinibacillus sp. OL1 and a novel Enterococcus sp. OL5, isolated from boron-fertilizer-amended cauliflower fields were investigated in this study. OL1 and OL5 grew efficiently in the presence of 210-230 mM boron, and resistance was found to be inducible by small amounts of the element: 5 to 50 mM boron pre-exposure progressively shortened the lag phase of growth in the presence of 200 mM boron. Intracellular boron accumulation was also found to be regulated by the level of pre-exposure: no induction or induction by small amounts led to higher levels of intracellular accumulation, whereas induction by high concentrations led to lower accumulation. These data, in the context of the strains' overall resistance towards 200 mM boron, indicated that induction by higher boron concentrations turned potential efflux mechanisms on, while resistance was eventually achieved by continuous cellular entry and exit of the ions. Involvement of solute efflux in boron resistance was corroborated by the genome content of the isolates (genes encoding proteins of the ATP-binding cassette, major facilitator, small multidrug resistance, multi antimicrobial extrusion, and resistance-nodulation-cell division, family/superfamily). Bacteria such as OL1 and OL5, which resist boron via influx-efflux, potentially lower boron bioavailability, and therefore toxicity, for the soil microbiota at large. These bacteria, by virtue of their plant-growth-promoting attributes, can also be used as biofertilizers.


Cardiovascular risk factors in the Maghreb. A systematic review.
To assess the distribution of cardiovascular risk factors in Maghreb's countries. It is a systematic review including articles and reports that applied the WHO "STEPwise" approach, or a similar approach, studying cardiovascular risk factors in the Maghreb countries: Tunisia, Morocco, Algeria, Libya and Mauritania between 2004 and 2018. We selected five articles, a report for each country. The prevalence of smoking was between 13.4% (12.2-14.6) in Morocco and 29.4% (28.3-30.4%) in Tunisia. 50.6% of the population of Mauritania had insufficient physical activity. The prevalence of high blood pressure was highest in Libya (40.6%) The prevalence of obesity was up to 41.1% (37-43.3) for women and 21.4% (19-23.8) in men in Libya. The prevalence of diabetes mellitus was between 10.6% (9.7-11.6) in Morocco and 16.4% (14.7-19.1) in Libya. The distribution of cardiovascular risk factors in the Maghreb countries shows that the level of cardiovascular risk is high, particularly in the central Maghreb. This attests to the fairly advanced epidemiological transition related to the rapid modernization of the Arab countries, hence the importance of launching an integrated project for the fight against cardiovascular diseases based on the global experience.


Bloom forming and toxic phytoplankton in transitional and coastal waters of Cantabria region coast (Southeastern Bay of Biscay, Spain).
Phytoplankton monitoring has extended to practically all the regions of the European coast due to the implementation of the European Water Framework Directive. In this way, the study of phytoplankton taxonomic composition and dynamic is being performed in many areas poorly studied or not studied before. During the last years, a monitoring programme has been carried out at the coast of Cantabria region (SE Bay of Biscay); the presence of some potentially toxic and bloom forming species (>7.5 × 10⁵ cells per litre) has been observed. Diatoms and cryptophytes are the main blooming taxa in this region in the majority of the estuaries and in some of the coastal sites. All estuaries and coastal stations showed at least one potentially toxic species, being the dinoflagellates the group with the highest number of taxa observed. The potentially toxic species found in highest concentrations were the genera Pseudo-nitzschia and Chrysochromulina.


Angiotensin Blockade Modulates the Activity of PD1/L1 Inhibitors in Metastatic Urothelial Carcinoma.
The renin-angiotensin system is involved in the regulation of angiogenesis and cell proliferation. Angiotensin inhibition may improve drug delivery by enhancing tumor perfusion partly by downregulating transforming growth factor (TGF)-β. Because TGF-β is associated with resistance in patients with metastatic urothelial carcinoma (mUC) receiving programmed cell death protein 1/programmed cell death ligand 1 (PD1/L1) inhibitors, we hypothesized that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may enhance the outcomes of patients with mUC who receive PD1/L1 inhibitors. Data from patients with mUC who received PD1/L1 inhibitors as monotherapy were obtained; patients from the Dana-Farber Cancer Institute constituted the discovery dataset, and data from Moffitt Cancer Center served as the validation dataset. A logistic regression investigated the impact of concurrent ACEI/ARB primarily on any regression of tumor (ART) after controlling for prognostic factors. Data were available for 178 patients from the discovery dataset, of whom 153 (86%) had received prior platinum and 33 (18.5%) concurrent ACEIs/ARBs. Multivariable logistic regression analysis revealed that ACEIs/ARBs were associated with greater probability of ART (odds ratio [OR] = 2.69; 95% confidence interval [CI], 1.15-6.30; P = .022). In the validation dataset, 101 patients were available, of whom 59 (58.4%) had received prior platinum and 22 (21.8%) concurrent ACEIs/ARBs. ACEI/ARB demonstrated a trend for association with ART (OR = 3.28; 95% CI, 0.98-10.99; P = .054) on multivariable analysis of the validation dataset. Concurrent angiotensin blockade was associated with a higher rate of tumor regression in patients with mUC receiving PD1/L1 inhibitors. Validation is warranted in a prospective trial, especially given the cost efficacy of ACEIs/ARBs.