Construction and analysis of competing endogenous RNA network and patterns of immune infiltration in abdominal aortic aneurysm.
Various studies have highlighted the role of circular RNAs (circRNAs) as critical molecular regulators in cardiovascular diseases, but its role in abdominal aortic aneurysm (AAA) is unclear. This study explores the potential molecular mechanisms of AAA based on the circRNA-microRNA (miRNA)-mRNA competing endogenous RNA (ceRNA) network and immune cell infiltration patterns. The expression profiles of circRNAs (GSE144431) and mRNAs (GSE57691 and GSE47472) were obtained from the Gene Expression Omnibus (GEO). Then, the differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) between AAA patients and healthy control samples, and the target miRNAs of these DEmRNAs and DEcircRNAs were identified. Based on the miRNA-DEmRNAs and miRNA-DEcircRNAs pairs, the ceRNA network was constructed. Furthermore, the proportion of the 22 immune cell types in AAA patients was assessed using cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. The expressions of key genes and immune cell infiltration were validated using clinical specimens. A total of 214 DEmRNAs were identified in the GSE57691 and GSE47472 datasets, and 517 DEcircRNAs were identified in the GSE144431 dataset. The ceRNA network included 19 circRNAs, 36 mRNAs, and 68 miRNAs. Two key genes, PPARG and FOXO1, were identified among the hub genes of the established protein-protein interaction between mRNAs in the ceRNA network. Moreover, seven types of immune cells were differentially expressed between AAA patients and healthy control samples. Hub genes in ceRNA, such as FOXO1, HSPA8, and RAB5C, positively correlated with resting CD4 memory T cells or M1 macrophages, or both. In conclusion, a ceRNA interaction axis was constructed. The composition of infiltrating immune cells was analyzed in the abdominal aorta of AAA patients and healthy control samples. This may help identify potential therapeutic targets for AAA.


The density and distribution of six GABAA receptor subunits in primary cultures of rat cerebellar granule cells.
In cultured cerebellar granule neurons (seven days in vitro) the expression of GABAA receptor subunits was quantified by using freeze-fracture immunocytochemical techniques with antibodies that specifically recognize the alpha 1, alpha 6, beta 2-3, gamma 2 and delta subunits of the GABAA receptor. In some experiments we have also used a less specific antibody that recognizes several alpha receptor subunits (alpha-total). The specificity of these antibodies was verified in human embryonic kidney cell line no. 293 cells transfected with complementary DNAs codifying for various GABAA receptor subunits. The most abundant labeling in granule cells was generated by the antibody against the beta 2-3 subunits (approximately 44 colloidal gold particles/microns2), while the specific antibodies against alpha 1 and alpha 6 subunits show a labeling of about 16 colloidal gold particles/microns2. The alpha-total antibody shows a labeling of approximately 37 gold particles/microns2. Both the gamma 2 and delta antibodies show a labeling of about 10 gold particles/microns2. In granule cells, the relative proportion of the label density revealed with antibodies against alpha-total, beta 2-3, gamma 2 and delta subunits is approximately 4:4:1:1. Assuming that one molecular form of the alpha subunit is assembled in a GABAA receptor, it can be estimated that in granule cells about 50% of receptors include the alpha 1 subunit. A similar relative abundance can be estimated for the alpha 6 subunit. The proportion of GABAA receptors containing the gamma 2 or delta subunits can be estimated to be about 50% in each case. Cerebellar granule cells express various abundances of GABAA receptor subunits which can be estimated by freeze-fracture immunocytochemistry. Fifty to sixty percent of these subunits form small receptor clusters, which appear to be associated with neuronal cytoskeleton proteins.


Renal sympathetic denervation for treatment of electrical storm: first-in-man experience.
Sympathetic activity plays an important role in the pathogenesis of ventricular tachyarrhythmia. Catheter-based renal sympathetic denervation (RDN) is a novel treatment option for patients with resistant hypertension, proved to reduce local and whole-body sympathetic activity. Two patients with chronic heart failure (CHF) (non-obstructive hypertrophic and dilated cardiomyopathy, NYHA III) suffering from therapy resistant electrical storm underwent therapeutic renal denervation. In both patients, RDN was conducted with agreement of the local ethics committee and after obtaining informed consent. The patient with hypertrophic cardiomyopathy had recurrent monomorphic ventricular tachycardia despite extensive antiarrhythmic therapy, following repeated endocardial and epicardial electrophysiological ablation attempts to destroy an arrhythmogenic intramural focus in the left ventricle. The second patient, with dilated nonischemic cardiomyopathy, suffered from recurrent episodes of polymorphic ventricular tachycardia and ventricular fibrillation. The patient declined catheter ablation of these tachycardias. In both patients, RDN was performed without procedure-related complications. Following RDN, ventricular tachyarrhythmias were significantly reduced in both patients. Blood pressure and clinical status remained stable during the procedure and follow-up in these patients with CHF. Our findings suggest that RDN is feasible even in cardiac unstable patients. Randomized controlled trials are urgently needed to study the effects of RD in patients with electrical storm and CHF.


Surgical management of critical congenital malformations in the delivery room.
Newborn emergencies that occur in the delivery room are frequently the result of life-threatening congenital anomalies that can result in death or severe disability if not treated in the immediate postnatal period. Prompt recognition and treatment of such disorders are paramount to ensuring the wellbeing of the infant. As congenital anomalies are frequently being diagnosed earlier due to improved prenatal detection, the coordination of planned interventions for life-threatening malformations is also becoming more common. This article serves as a guide for the presentation and initial management of the most common non-cardiac, newborn surgical emergencies.


CircRNAs in diagnosis, prognosis, and clinicopathological features of multiple myeloma; a systematic review and meta-analysis.
Unlike improved treatment response in multiple myeloma (MM), the mortality rate in MM is still high. The study's aim is to investigate the potential role of circRNAs as a new biomarker for diagnosis, prognosis, and clinicopathological features of MM. We identified studies through Web of Science, Scopus, PubMed and ProQuest databases, and Google Scholar to August 2022. The SEN, SPE, PLR, NLR, DOR, and AUC were combined to investigate the diagnostic performance of circRNAs in MM. Also, HR and RR were used for prognostic and clinicopathological indicators, respectively. 12 studies for prognosis, 9 studies about diagnosis, and 13 studies regarding clinicopathological features. The pooled SEN, SPE, DOR, and AUC were 0.82, 0.76, 14.70, and 0.86, respectively for the diagnostic performance of circRNAs. For the prognostic performance, oncogene circRNAs showed a poor prognosis for the patients (HR = 3.71) and tumor suppressor circRNAs indicated a good prognosis (HR = 0.31). Finally, we discovered that dysregulation of circRNAs is associated with poor clinical outcomes in beta-2-microglobulin (RR = 1.56), Durie-Salmon stage (RR = 1.36), and ISS stage (RR = 1.79). Furthermore, the presence of del(17p) and t(4;14) is associated with circRNA dysregulation (RR = 1.44 and 1.44, respectively). Our meta-analysis demonstrates that the expression analysis of circRNAs is valuable for MM's diagnosis and prognosis determination. Also, dysregulation of circRNAs is associated with poor clinicopathological features and can be used as the applicable biomarkers for evaluating treatment effectiveness.


Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice.
We investigated whether heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K) mediate insulin inhibition of renal Agt expression and prevention of hypertension and kidney injury in an Akita mouse model of type 1 diabetes. Adult male Akita mice (12 weeks old) were treated with insulin implants and killed at week 16. Untreated non-Akita littermates served as controls. The effects of insulin on blood glucose, systolic BP (SBP), renal proximal tubular cell (RPTC) gene expression and interstitial fibrosis were studied. We also examined immortalised rat RPTCs stably transfected with control plasmid or with plasmid containing rat Agt promoter in vitro. Insulin treatment normalised blood glucose levels and SBP, inhibited renal AGT expression but enhanced hnRNP F, hnRNP K and angiotensin-converting enzyme-2 expression, attenuated renal hypertrophy and glomerular hyperfiltration and decreased urinary albumin/creatinine ratio, as well as AGT and angiotensin II levels, in Akita mice. In vitro, insulin inhibited Agt but stimulated Hnrnpf and Hnrnpk expression in high-glucose media via p44/42 mitogen-activated protein kinase signalling in RPTCs. Transfection with Hnrnpf or Hnrnpk small interfering RNAs prevented insulin inhibition of Agt expression in RPTCs. These data indicate that insulin prevents hypertension and attenuates kidney injury, at least in part, through suppressing renal Agt transcription via upregulation of hnRNP F and hnRNP K expression in diabetic Akita mice. HnRNP F and hnRNP K may be potential targets in the treatment of hypertension and kidney injury in diabetes.


Evaluation of Risk Factors for Antipsychotic Polypharmacy in Inpatient Psychiatry Units of a Community Hospital: A Retrospective Analysis.
Antipsychotic polypharmacy (APP) is a common practice while treating severe mental illness but the benefits of APP over antipsychotic monotherapy is controversial. This is a retrospective analysis comparing risk factors for people on APP and those on non-APP in inpatient psychiatry units. Two years data with 72 people in non-APP group and 82 people in APP group were analyzed quantitatively. The diagnoses of schizoaffective disorder (OR 11.5), schizophrenia (OR 4.65) and depression (OR 0.31), and history of > 2 psychiatric admissions (OR 3.2) and > 2 psychiatric emergency visits (OR 2.87) in 2 years were studied as potential risk factors for APP. Similarly, history of violence (OR 1.7) and history of substance abuse (OR 0.51) were also studied. Schizophrenia spectrum disorder, higher number of psychiatric hospitalizations, and psychiatric emergency visits were positively associated while depression and substance abuse were negatively associated with APP in our study.


Cocaine adversely affects development of cortical embryonic neurons in vitro: immunocytochemical study of calcium-binding proteins.
Neurons of cerebral cortex from 15-16 day old embryos of white rats (Sprague-Dawley) were cultured in MEM enriched with 5% horse serum. On the 7th day after plating the cultures were divided into three experimental and one control groups (6-8 Petri dishes in each group). In group 1, cultures were grown without additives. In group 2, cocaine chloride was added at concentrations 0.3, 0.6 and 1 mg/ml of culture. In group 3, a monoclonal antibody against calcium-binding proteins, parvalbumin (APV) or calbindin (ACB) was added at a concentration 25 microl/ml. In group 4, a combination of cocaine +APV was added at a concentration 1 mg+25 microl/ml of culture media. On the 10th day cultures were immunostained using APV and ACB antibodies. In developing GABAergic neurons of group 2 cocaine produced cytotoxic effects that were expressed in drastic decrease in number of neurons and in degeneration of their processes. The lower concentrations of cocaine caused milder cytotoxity and their effects were reversible. The highest concentration of cocaine caused irreversible degeneration of neurons. Similar cytotoxity was caused by APV or ACB in group 3. The most severe cytotoxic effects were seen in group 4, where a mixture of cocaine and APV was used. Overall, it can be concluded that cocaine in higher concentrations directly affects development of GABAergic neurons in vitro.


Taking your own path: Individual differences in executive function and language processing skills in child learners.
Children as old as 5 or 6 years display selective difficulties in revising initial interpretive commitments, as indicated by both online and offline measures of sentence comprehension. It is likely, however, that individual children differ in how well they can recover from misinterpretations and in the age at which they become adult-like in these abilities. To better understand the cognitive functions that support sentence processing and revision, the current work investigated how individual differences in children's ability to interpret temporarily ambiguous sentences relate to individual differences in other linguistic and domain-general cognitive abilities. Children were tested over 2 days on a battery of executive function, working memory, and language comprehension tasks. Performance on these tasks was then used to predict online and offline measures of children's ability to revise initial misinterpretations of temporarily ambiguous sentences. We found two measures of children's cognitive flexibility to be related to their ambiguity resolution abilities. These results provide converging evidence for the hypothesis that the ability to revise initial interpretive commitments is supported by domain-general executive function abilities, which are highly variable and not fully developed in children.


Motexafin gadolinium induces mitochondrially-mediated caspase-dependent apoptosis.
Motexafin gadolinium (MGd, Xcytrin) is a tumor-localizing redox mediator that catalyzes the oxidation of intracellular reducing molecules including NADPH, ascorbate, protein and non-protein thiols, generating reactive oxygen species (ROS). MGd localizes to tumors and cooperates with radiation and chemotherapy to kill tumor cells in tissue culture and animal models. In this report, we demonstrate that MGd triggers the mitochondrial apoptotic pathway in the HF-1 lymphoma cell line as determined by loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, activation of caspase-9 prior to caspase-8, cleavage of PARP and annexin V binding. There was minimal effect on MGd-induced apoptosis by the caspase inhibitor z-VAD-fmk, even though caspase-3 activity (as measured by DEVD-cleavage) was completely inhibited. However, MGd-induced apoptosis was reduced to baseline levels by the more potent caspase inhibitor Q-VD-OPh, demonstrating that MGd-induced apoptosis is indeed caspase-dependent. Apoptosis induced by dexamethasone, doxorubicin and etoposide (mediated through the mitochondrial pathway) was also more sensitive to inhibition by Q-VD-OPh than z-VAD-fmk. Our results demonstrating differential sensitivity of drug-induced apoptosis to caspase inhibitors suggest that the term "caspase-independent apoptosis" cannot be solely defined as apoptosis that is not inhibited by z-VAD-fmk as has been utilized in some published studies.


Bioengineering functional smooth muscle with spontaneous rhythmic contraction in vitro.
Oriented smooth muscle layers in the intestine contract rhythmically due to the action of interstitial cells of Cajal (ICC) that serve as pacemakers of the intestine. Disruption of ICC networks has been reported in various intestinal motility disorders, which limit the quality and expectancy of life. A significant challenge in intestinal smooth muscle engineering is the rapid loss of function in cultured ICC and smooth muscle cells (SMC). Here we demonstrate a novel approach to maintain the function of both ICC and SMC in vitro. Primary intestinal SMC mixtures cultured on feeder cells seeded electrospun poly(3-caprolactone) scaffolds exhibited rhythmic contractions with directionality for over 10 weeks in vitro. The simplicity of this system should allow for wide usage in research on intestinal motility disorders and tissue engineering, and may prove to be a versatile platform for generating other types of functional SMC in vitro.


Development of immune cellular biosensing system for assessing chemicals on inducible nitric oxide synthase signaling activator.
An immune cellular biosensing system has been constructed to assess immunomodulating effects of chemicals. Production of nitric oxide in the immune cellular biosensing system was used as readout of an immune cellular response for assessing the immunomodulating effects of chemicals. The macrophage-like cell line RAW264.7, which has signaling pathways of inducible nitric oxide synthase, was employed in the cellular biosensing system. The immune cellular biosensing system consisted of a Pt counter electrode, an Ag/AgCl reference electrode, and a gold electrode onto which a polyion complex layer was coated to allow adherence of the RAW264.7 cells. As the results of evaluating effects of a polyion complex layer on cell viabilities by using WST-8 assay, the polyion complex layer did not affect RAW264.7 cells. The polyion-coated gold electrode could measure NO without the drawback of electrochemical interference that occurs with differential pulse voltammetry. The detection limit of the immune cellular biosensing system was 4.2 nM released NO as measured by double potential step chronoamperometry. The potent immune activating abilities of lipopolysaccharide and interferon-gamma could be assessed by the cellular biosensing system; NO release from cells was detected within 600 ms.


[Aneurysms of the superior mesenteric artery and of its branches. Report of three cases (author's transl)].
The authors report three cases of atheromatous aneurysm revealed by a complication (e.g. rupture, thrombosis, peripheral embolisation) and propose an etiological, physio-pathological, clinical and therapeutic study of aneurysms of the superior mesenteric artery. They emphasise the advantages of early diagnosis leading to arteriography, which alone permits appropriate surgical treatment.


Identification of immunohistochemical factors that predict the synchronous or metachronous development of bladder tumors in patients with upper urinary tract tumors.
To identify markers that predict the synchronous or metachronous development of bladder cancer in patients with upper urinary tract (UUT) tumors. Between March 2001 and December 2005, we identified 38 consecutive patients who had been histologically diagnosed as having transitional cell carcinoma in the renal pelvis and ureter. These patients were divided into 2 groups (n = 19 per group): group 1 patients with metachronous or synchronous bladder cancer, and group 2 patients with UUT tumors only. We analyzed the differences between the 2 groups with respect to the expression of various biomarkers (p53, Rb, Ki-67, PTEN, and bcl-2) and in terms of clinical parameters. The 2 groups differed significantly in terms of multiplicity (p = 0.029), papillary configuration (p = 0.001), the presence of lymphovascular emboli (p = 0.019), and Ki-67 overexpression (p = 0.029) in UUT tumors. Multivariate analysis revealed that Ki-67 overexpression in UUT tumor tissues significantly predicts bladder cancer development (HR 6.440; 95% CI 1.121-37.014; log rank p = 0.037). Ki-67 overexpression in UUT tumor tissues was found to be an independent predictor of the development of bladder cancer in UUT tumor patients.


Effects of argatroban, danaparoid, and fondaparinux on trombin generation in heparin-induced thrombocytopenia.
There is no in vitro data on the comparison of the effects of danaparoid, argatroban and fondaparinux on thrombin generation in patients with heparin-induced thrombocytopenia. It was the study objective to compare the in vitro anticoagulant potential of argatroban, danaparoid and fondaparinux using a thrombin generation assay TGA on a mixture of control platelet-rich plasma (PRP) and HIT patient platelet-poor plasma (PPP). The plasma of seven patients with a clear HIT diagnosed at our institution was selected. Mixtures of donor PRP and patient PPP were incubated with unfractionated heparin 0.2 U.mL⁻¹, argatroban at 600 ng.mL⁻¹, argatroban at 400 ng.mL⁻¹, danaparoid at 0.65 IU.mL⁻¹ and fondaparinux at 1 μg.mL⁻¹. Thrombin generation was assessed by calibrated thrombinography. The percentage of inhibition of the endogenous thrombin potential observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with fondaparinux (median: 53.6% vs. 3.9%; p=0.031) but not compared with argatroban at 400 ng.mL⁻¹ and danaparoid. The percentage of inhibition of the thrombin peak observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with danaparoid (median: 71.2 vs. 56.8; p=0.031) and fondaparinux (mean: 71.2 vs. 30; p=0.031) but not with argatroban at 400 ng.mL⁻¹. In conclusion, the in vitro effect of argatroban and danaparoid on thrombin generation seems to corroborate the results of clinical studies of these drugs in the treatment of HIT in term of efficiency. Fondaparinux showed a very small effect on thrombin generation evaluated by calibrated thrombinography.


PPARα in lysosomal biogenesis: A perspective.
Lysosomes are membrane-bound vesicles containing hydrolytic enzymes, ubiquitously present in all eukaryotic cells. Classically considered to be central to the cellular waste management machinery, recent studies revealed the role of lysosomes in a wide array of cellular processes like, degradation, cellular development, programmed cell death, secretion, plasma membrane repair, nutritional responses, and lipid metabolism. We recently studied the regulation of TFEB, considered to be the master regulator of lysosomal biogenesis, by activation of peroxisomal proliferator activated receptor α (PPARα), one of the key regulators of lipid metabolism. In this article, we discuss how the recent finding could be put in to perspective with the previous findings that relate lysosomal biogenesis to lipid metabolism, and comment on the possibility of a bi-directional interplay between these two distinct cellular processes upon activation of PPARα.


[Assessment of total complement activity of blood plasma (serum) using reader for immunoenzyme analysis].
A method for instrumental assessment of the total complementary activity of human blood plasma (serum) by the classical and alternative activation is proposed. The test is carried out by the micromethod in round-bottom 96-well plates for immunological tests. The results are read by automated analyzer for enzyme immunoassay recording at 405 nm wavelength.


Dose response studies with propofol ('Diprivan') in unpremedicated patients.
In younger patients, 2.25 mg/kg is a reliable induction dose of propofol, whereas this level falls to 1.5 mg/kg in older patients. The incidence of hypotension and apnoea is dose-dependent in all patients.


[Challenges in the surgical management of hearts with a functional single ventricle].
Nowadays, the complex congenital heart diseases with a functional single ventricular haemodynamics can be treated with good results with bi-directional Glenn (BDG) and total cavopulmonary connection (TCPC) procedure. The late results are determined by the ventricular function. To assess the surgical results of "high risk" BDG and TCPC procedures, where the functional single ventricle were complicated by left sided SVS and IVC, total anomalous pulmonary venous connection (TAPVC) and severe atrioventricular valve insufficiency. These patients' were refused for surgery earlier. Between 01. 01. 1994. and 30. 06. 2004. 112 BDG and 93 TCPC (42 pts with extracardiac conduit--ECC) procedures were performed. AGE: 3 months-29 yrs mean: 4,7 yrs, weight: 4-46 kg, mean: 15,5 kg. Among the "high risk" pts.: 1. Bilateral BDG in 19, left BDG in 9, left sided TCPC with ECC in 3 pts. were performed, 2. The associated TAPVC were operated on successfully in 3 pts. (bilateral BDG in 1, left BDG in 1, left sided TCPC with ECC in 1), 3. Mitral valvuloplasty in 2, artificial (mitral) valve implantation in 1, tricuspid valve closure or valvuloplasty in 3, (tricuspid) valve replacement in 1, common AV valve replacement in 1 pts were performed, 4. In 4 infants BDG was performed after Norwood I. procedure. Five pts. were lost after BDG procedure (Damous-Kaye-Stansen operation were performed as well in 3 pts.), and another 5 patients' systemic pulmonary shunts were re-done. Four patients after TCPC were lost and reoperation to BDG (n = 1) or shunt procedure (n = 2) was performed in 3 pts. Pre-discharge echocardiography confirmed mitral valvuloplasty with good results. No intervention was necessary in the follow up (1-3 yrs period) due to AV insufficiency and ventricular functions improved. On the basis of our series the "high risk" BDG and TCPC operations can be performed with an encouraging early result. The authors previously contraindicated associated defects can be surgically managed. Our short and mid-term results are feasible in this aspect. The long-term control of the "uni-ventricular" heart's ventricular function needs further investigation.


Muscarine affects calcium-currents in rat hippocampal pyramidal cells in vitro.
Ca2+-currents were recorded from single CA3 pyramidal cells in hippocampal slice cultures, voltage-clamped through a single Cs+ - or K+-filled microelectrode and perfused with Hanks' balanced salt solution containing 1 microM tetrodotoxin and 10 mM tetraethylammonium. The Ca2+-current was reversibly reduced by bath-perfused muscarine (10-100 microM). This effect was inhibited by pirenzepine (10 microM) or atropine (1 microM). In K+-filled cells, inhibition was preceded by a phase of inward current enhancement; this was considered to be secondary to rapid outward current inhibition induced it by muscarine since it was reduced when outward currents were previously inhibited with Ba2+. In partially clamped or unclamped cells inhibition of Ca2+-current leads to a shortening of the Ca2+-spike plateau.


Fabrication of a sensitive electrochemical sensor based on electrospun magnetic nanofibers for morphine analysis in biological samples.
A sensitive electrochemical sensor for detection of morphine (MPH) at the surface of electrode modified with electrospun magnetic nanofibers (MNFs) was prepared. The features of constructed sensor were evaluated by scanning electron microscopy (SEM), X ray diffraction (XRD) and electrochemical impedance spectroscopy (EIS). The modified sensor was used for MPH analysis using of cyclic voltammetry (CV) and differential pulse voltammetry (DPV) method. The calibration curve has been composed of a linear portion in the concentration range of 0.0033-55 μM and 55-245 μM and the detection limit was 1.9 nM. The reproducibility of the peak current with a reliable relative standard deviation (RSD) value was acquired. Based on the results, the fabricated sensor has good stability and reproducibility, as well as the sensitive and selective analysis of MPH in human serum samples as real samples had effectively been feasible. The results of the actual sample were measured by HPLC procedure, and the results were compared with the results of the electrochemical method and corroborated them.


Eliminating Stubborn Insulated Deposition by Coordination Effect to Boost Zn Electrode Reversibility in Aqueous Electrolyte.
Aqueous rechargeable zinc-ion batteries (ZIBs) have recently shined in energy storage and transmission, which are due to high safety and low cost. However, the extremely stubborn by-products in the Zn anode severely inhibited the Zn2+ adsorption/desorption and exacerbated the dendrite formation. Herein, we report a facile strategy to eliminate inert Zn4(OH)6SO4·xH2O for the improvement of ZIBs according to the coordination effect by employing ethylenediaminetetraacetic acid-diamine (EDTA-2Na) as a coordination additive in traditional electrolyte. Zn2+ is coordinated with the carboxyl group of the four acetyl carboxyl groups and the N in C-N bonds, forming a new chelating structure, and thus stubborn deposition will be dissolved in the electrolyte. As a result, the discharge capacity of 102 mAh g-1 in the ZnSO4/Li2SO4 with EDTA-2Na electrolyte at a current density of 4 C and a stable cycle life with a capacity of 90.3% after 150 cycles are achieved. It has been concluded that the coordination effect strategy provides a valuable idea for solving the defects of ZIBs.


Contribution of arsenic and uranium in private wells and community water systems to urinary biomarkers in US adults: The Strong Heart Study and the Multi-Ethnic Study of Atherosclerosis.
Chronic exposure to inorganic arsenic (As) and uranium (U) in the United States (US) occurs from unregulated private wells and federally regulated community water systems (CWSs). The contribution of water to total exposure is assumed to be low when water As and U concentrations are low. We examined the contribution of water As and U to urinary biomarkers in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially/ethnically diverse urban U.S. communities. We assigned residential zip code-level estimates in CWSs (µg/L) and private wells (90th percentile probability of As >10 µg/L) to up to 1485 and 6722 participants with dietary information and urinary biomarkers in the SHFS (2001-2003) and MESA (2000-2002; 2010-2011), respectively. Urine As was estimated as the sum of inorganic and methylated species, and urine U was total uranium. We used linear mixed-effects models to account for participant clustering and removed the effect of dietary sources via regression adjustment. The median (interquartile range) urine As was 5.32 (3.29, 8.53) and 6.32 (3.34, 12.48) µg/L for SHFS and MESA, respectively, and urine U was 0.037 (0.014, 0.071) and 0.007 (0.003, 0.018) µg/L. In a meta-analysis across both studies, urine As was 11% (95% CI: 3, 20%) higher and urine U was 35% (5, 73%) higher per twofold higher CWS As and U, respectively. In the SHFS, zip-code level factors such as private well and CWS As contributed 46% of variation in urine As, while in MESA, zip-code level factors, e.g., CWS As and U, contribute 30 and 49% of variation in urine As and U, respectively. We found that water from unregulated private wells and regulated CWSs is a major contributor to urinary As and U (an estimated measure of internal dose) in both rural, American Indian populations and urban, racially/ethnically diverse populations nationwide, even at levels below the current regulatory standard. Our findings indicate that additional drinking water interventions, regulations, and policies can have a major impact on reducing total exposures to As and U, which are linked to adverse health effects even at low levels.


Physicians in police tactical teams - ethical considerations.
High-profile mass shootings, terrorist attacks, and experience acquired during recent conflicts have led to a shift in police tactics, who now follow an aggressive approach to immediately neutralize the threat in addition to providing early tactical medical care. A growing number of police tactical teams now include physicians in their ranks to increase the level of forward care. Many ethical questions arise from having physicians on police tactical teams, such as the notion of risk, the use of force, and the ultimate role the physician is expected to play. Having a physician in such a team may be an invaluable asset to increase the team's safety and allow for advanced forward care, however, this requires two important conditions. The first is that the role of the physician is clearly defined and that what is expected of him is in line with medical ethics, while the second is extensive tactical training with the team to collaborate flawlessly in this complex, high-stress environment.


CAR T Cells with a Dominant-Negative TGFβ Receptor Are Safe and Feasible.
PSMA-targeting CAR T cells with a dominant-negative TGFβR show safety and feasibility in prostate cancer.


A simple and rapid treatment (trichloroacetic acid precipitation) of serum samples to prevent non-specific reactions in the immunoassay of a proteoglycan.
In our laboratory serum components interfering in the immunoassay of the schistosome proteoglycan circulating anodic antigen (CAA) in serum necessitated us to develop a simple technique by which the non-specific reaction of negative control sera could be prevented. Trichloroacetic acid was added to serum samples to precipitate interfering (glyco-)proteins. After centrifugation, the supernatant was neutralized and used directly either in the ELISA or in the indirect haemagglutination. This method gave satisfactory results, i.e., negative control sera did no longer give false positive reactions, while the titre of the positive controls remained unaffected. This method could also be successfully applied for the pretreatment of urine samples.


Self-reported quality of life among inner-city youth with asthma: an empirical examination of the PedsQL 3.0 Asthma Module.
Asthma disproportionately affects African American youth and may significantly impair their daily functioning. Although a number of self-reported health-related quality of life (HRQoL) measures have been developed, many rely on parent proxy report rather than youth self-report. Few validity studies have been undertaken to evaluate youth self-report instruments, and studies of economically disadvantaged ethnic minority populations are particularly lacking. To examine the psychometric properties of the PedsQL 3.0 Asthma Module, a widely available self-report index of HRQoL in a sample of inner-city African American youth. Seventy African American youth with asthma (age range, 9-17 years) and their primary caregivers participated. Youth completed the PedsQL 3.0 Asthma Module (developed for youth aged 5-18 years), whereas caregivers provided reports of youth HRQoL, asthma symptoms, health care use, and school absences. Ratings of asthma severity were obtained via physician rating and spirometry. The PedsQL 3.0 Asthma Module total and subscale scores evidenced adequate internal consistency (alpha values >.70), convergent validity with parent proxy ratings of HRQoL and other indexes of functional impairment and differentiated between youth with greater and lesser disease severity. HRQoL can be reliably assessed using the self-report form of the PedsQL 3.0 Asthma Module among 9- to 17-year-old African American youth from economically disadvantaged backgrounds.


Optimization and characterization of a rat model of prostate cancer-induced bone pain using behavioral, pharmacological, radiological, histological and immunohistochemical methods.
The major limitation of currently utilized rodent models of prostate cancer (PCa)-induced bone pain (PCIBP) involving intra-osseous injection of PCa cells, is their relatively short-term applicability due to progressive deterioration of animal health necessitating euthanasia. Here, we describe establishment of an optimized rat model of PCIBP where good animal health was maintained for at least 90-days following unilateral intra-tibial injection (ITI) of PCa cells. We have characterized this model using behavioral, pharmacological, radiological, histological and immunohistochemical methods. Our findings show that following unilateral ITI of 4×10(4) AT3B PCa cells (APCCs), there was temporal development of bilateral hindpaw hypersensitivity that was fully developed between days 14 and 21 post-ITI. Although there was apparent spontaneous reversal of bilateral hindpaw sensitivity that was maintained until at least day 90 post-ITI, administration of bolus doses of the opioid receptor antagonist, naloxone, rescued the pain phenotype in these animals. Hence, upregulation of endogenous opioid signaling mechanisms appears to underpin apparent spontaneous resolution of hindpaw hypersensitivity. Importantly, the histological and radiological assessments confirmed that tumor formation and development of osteosclerotic metastases was confined to the APCC-injected tibial bones. In our rat model of PCIBP, single bolus doses of morphine, gabapentin, meloxicam and amitriptyline produced dose-dependent relief of mechanical allodynia and thermal hyperalgesia in the bilateral hindpaws. The optimized rat model of PCIBP characterized herein has potential to provide new insights into the pathophysiological mechanisms associated with long-term (mal)adaptive pain due to advanced PCa-induced bony metastases and for screening novel compounds with potential for improved alleviation of this condition.


A cross-sectional study of associations between casual partner, friend discrimination, social support and anxiety symptoms among Chinese transgender women.
Anxiety symptoms are the prevalent mental disorders for transgender women. However, only a few studies are available pertaining to this problem among Chinese Transgender women. Chinese Transgender women are a vulnerable population which is exposed to discrimination and loss of social support due to their gender identity and transition. This study was conducted to estimate the prevalence and factors associated with anxiety symptoms among Chinese transgender women. A cross-sectional study was performed by convenience sampling. This comprised of 209 Chinese transgender women in Shenyang, China. The Zung Self-Rating Anxiety Scale (SAS) was used to assess anxiety symptoms for these transgender women. Hierarchical multiple regression analysis was performed to explore the associated factors of SAS. The prevalence of anxiety symptoms in Chinese transgender women was found to be 34.5%. Regression analyses indicated that SAS was associated with casual partnership, friend discrimination and social support in the final model. Sexual partnership and discrimination contributed the most to the model, R-square, accounting for 19.2% and 15.5% of the total variance respectively. Chinese transgender women showed considerably high level of anxiety symptoms. It was also found that they were exposed to significant transition challenges, such as high risk sexual partnership, excessive discrimination and a reduction in social support. Furthermore, anxiety symptoms was best predicted by the absence or presence of a casual partner, friend discrimination and social support rather than the disclosure of their gender identity, knowledge of HIV prevention and health service. Improvement of social support, reduction of friend discrimination and determination of the characteristics of risky sexual partnerships especially for the casual partner can help to attenuate anxiety symptoms and increase mental well-being for transgender women.


Predictors of neurocognitive and psychological disorders in children after intensive care admission: A prospective cohort study.
Children admitted in the pediatric intensive care unit (PICU) often deal with long-term morbidities affecting physical, cognitive, emotional, social, and psychiatric symptoms. We aimed to identify the internal and external factors which predict the occurrence of neurocognitive and psychological disorders in survivors at 3 months after PICU discharge. We identified 53 critically ill children, ages 4-18 years old, admitted in PICU for more than 24 h, and survived. We evaluated neurocognitive disorder with Pediatric Cerebral Perfomance Category (PCPC) and psychological disorders with Strengths and Difficulties Questionnaire (SDQ) at the time of PICU discharge and repeated in 3 months afterward. We evaluated the internal and external risk factors related to neurocognitive and psychological disorders in PICU survivors. The internal risk factors were age, gender, family composition, and socioeconomic status. The external risk factors were: surgical intervention, neurological disease, predicted death rate by pediatric index mortality (PIM)-2 score, PICU length of stay (LOS), days of mechanical ventilation, and the number of therapeutic interventions. There were significant improvement in neurocognitive disorders (p < 0.001), peer problems, (p = 0.01), and prosocial behaviors (p = 0.00) in children at 3 months after the PICU discharge. Age of 4-5 years has a significant effect on neurocognitive disorders (p = 0.04), while male gender (p = 0.02), low-social economy, non-intact family composition (p = 0.01), neurological disease (p = 0.04), surgical intervention (p = 0.01), and TISS score (p = 0.00) have a significant effect on psychological disorders in children at 3 months after the PICU discharge. Neurocognitive disorders, peer problems, and prosocial behaviors improved in a few patients 3 months after PICU discharge. Age of 4-5 years was a risk factor of the persisted neurocognitive disorder, whereas male gender, low-social economy, non-intact family composition, neurological disease, surgical intervention, and TISS score were risk factors of persisted psychological disorder at 3 months after PICU.


State-level women's status and psychiatric disorders among US women.
Although greater gender equality at the state-level is associated with fewer depressive symptoms in women after controlling for individual-level confounders, the extent to which state-level women's status is related to psychiatric disorders in women and gender differences in psychopathology has never been examined. We examined these associations in the current report. We used data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=34,653), a national probability sample of US adults. Respondents completed structured diagnostic assessments of DSM-IV psychiatric disorders. We used generalized estimating equations to examine associations between four state-level indicators of women's status (political participation, employment/earnings, social/economic autonomy, and reproductive rights) and odds of 12-month mood and anxiety disorders among women. We also tested whether women's status predicted the magnitude of gender differences in psychiatric disorders. State-level political participation, employment/earnings, and social/economic autonomy were unrelated to odds of 12-month mood and anxiety disorders among women. However, the prevalence of major depression and post-traumatic stress disorder was lower in states where women have greater reproductive rights (OR 0.93-0.95), controlling for individual-level risk factors. None of the women's status indicators predicted gender differences in mood and anxiety disorder prevalence. State-level women's status was largely unrelated to mood and anxiety disorders in women or to gender differences in these disorders. Investigation of social factors that play a role in shaping the distribution of individual-level risk factors that are associated with gender disparities in psychiatric disorders represents an important avenue for future research.


Surgical Indications and Outcomes of Resection for Pancreatic Neuroendocrine Tumors with Vascular Involvement.
Complete surgical resection of pancreatic neuroendocrine tumors (pNETs) has been suggested as the only potentially curative treatment. A proportion of these tumors will present late during disease progression, and invade or encase surrounding vasculature; therefore, surgical treatment of locally advanced disease remains controversial. The role of surgery with vascular reconstruction in pNETs is not well defined, and there is considerable variability in the use of aggressive surgery for these tumors. Accurate preoperative assessment is critical to evaluate individual considerations, such as anatomical variants, areas and lengths of vessel involvement, proximal and distal targets, and collateralization secondary to the degree of occlusion. Surgical approaches to address pNETs with venous involvement may include thrombectomy, traditional vein reconstruction, a reconstruction-first approach, or mesocaval shunting. Although the amount of literature on pNETs with vascular reconstruction is limited to case reports and small institutional series, the last two decades of studies have demonstrated that aggressive resection of these tumors can be performed safely and with acceptable long-term survival.


A randomized trial of the effect of automated ventricular capture on device longevity and threshold measurement in pacemaker patients.
An automatic capture (AC) algorithm adjusts ventricular pacing output to capture the ventricle while optimizing output to 0.5 V above threshold. AC maintains this output and confirms capture on a beat-to-beat basis in bipolar and unipolar pacing and sensing. To assess the AC algorithm and its impact on device longevity. Patients implanted with a pacemaker were randomized 1:1 to have the AC feature on or off for 12 months. Two threshold tests were conducted at each visit- automatic threshold and manual threshold. Average ventricular voltage output and projected device longevity were compared between AC on and off using nonparametric tests. Nine hundred ten patients were enrolled and underwent device implantation. Average ventricular voltage output was 1.6 V for the AC on arm (n = 444) and 3.1 V for the AC off arm (n = 446) (P < 0.001). Projected device longevity was 10.3 years for AC on and 8.9 years for AC off (P < 0.0001), or a 16% increase in longevity for AC on. The proportion of patients in whom there was a difference between automatic threshold and manual threshold of <or=0.5 V through follow-up was 99.0% (95% CI: 98.6, 99.3). The average difference between automatic threshold and manual threshold was 0.07 V (P = 0.002). This study showed that automatic threshold testing at follow-up provided comparable information to manually measured threshold testing. AC provided a significant increase in projected device longevity compared to standard programing.


3D TiO2@Ni(OH)2 Core-shell Arrays with Tunable Nanostructure for Hybrid Supercapacitor Application.
Three dimensional hierarchical nanostructures have attracted great attention for electrochemical energy storage applications. In this work, self-supported TiO2@Ni(OH)2 core-shell nanowire arrays are prepared on carbon fiber paper via the combination of hydrothermal synthesis and chemical bath deposition. In this core-shell hybrid, the morphology and wall size of the interconnected nanoflake shell of Ni(OH)2 can be tuned through adjusting the concentration of ammonia solution. Heterogeneous nucleation and subsequent oriented crystal growth are identified to be the synthesis mechanism affecting the nanostructure of the shell material, which consequently determines the electrochemical performance in both energy storage and charge transfer. Superior capabilities of 264 mAh g(-1) at 1 A g(-1) and 178 mAh g(-1) at 10 A g(-1) are achieved with the core-shell hybrids of the optimized structure. The asymmetric supercapacitor prototype, comprising of TiO2@Ni(OH)2 as the anode and mesoporous carbons (MCs) as the cathode, is shown to exhibit superior electrochemical performance with high energy and power densities. The present work provides a clear illustration of the structure-property relationship in nanocrystal synthesis and offers a potential strategy to enhance the battery type Ni(OH)2 electrode in a hybrid supercapacitor device.


Cyanotoxins dissipation in soil: Evidence from microcosm assays.
Cyanobacteria proliferate in warm, nutrient-rich environments, and release cyanotoxins into natural waters. If cyanotoxin-contaminated water is used to irrigate agricultural crops, this could expose humans and other biota to cyanotoxins. However, cyanotoxins may be degraded by the diverse microbial consortia, be adsorbed or otherwise dissipate in agricultural soil. This study investigates the disappearance and transformation of 9 cyanotoxins in controlled soil microcosms after 28 d. Six soil types were exposed to factorial combinations of light, redox conditions and microbial activity that influenced the recovery of anabaenopeptin-A (AP-A), anabaenopeptin-B (AP-B), anatoxin-a (ATX-a), cylindrospermopsin (CYN), and the microcystin (MC) congeners -LR, -LA, -LY, -LW, and -LF. Cyanotoxins estimated half-lives were from hours to several months, depending on the compound and soil conditions. Cyanotoxins were eliminated via biological reactions in aerobic and anaerobic soils, although anaerobic conditions accelerated the biological dissipation of ATX-a, CYN and APs. ATX-a was sensitive to photolytic degradation, but CYN, and MCs were not reduced through photochemical transformation. MC-LR and -LA were recovered after exposure to light, redox conditions and low microbial activity, suggesting that they persisted in extractable forms, compared to other cyanotoxins in soil. Cyanotoxin degradation products were identified using high-resolution mass spectrometry, revealing their potential degradation pathways in soil.


Conversion in vitro of urinary (+)-penicillamine to its major metabolites, PSSP and PSSC.
To investigate the discrepancy between the apparent pharmacokinetic disposition of (+)-penicillamine in plasma and urine, the spontaneous degradation of (+)-penicillamine was studied in acidified and non-acidified urine. Degradation was prevented by acidification. The oxidized metabolites were converted to reduced (+)-penicillamine by electrolysis.


Genome-wide Association Studies Categorized by Class of Antihypertensive Drugs Reveal Complex Pathogenesis of Hypertension with Drug Resistance.
Resistant hypertension is defined as uncontrolled blood pressure (BP) despite the use of three or more antihypertensive drugs of different classes. Although genetic factors may greatly contribute to hypertension with resistance to multiple drug classes, more than for general hypertension, its pathogenesis remains unknown. To reveal the genetic background of resistant hypertension, we categorized 32,239 patients whose data were obtained from the BioBank Japan Project, by prescription of 7 classes of antihypertensive drugs and performed genome-wide association studies (GWAS). Our GWAS identified four loci with significant association (P < 5 × 10-8 ): rs6445583 in CACNA1D and rs12308051 in the intergenic region on chromosome 12 for angiotensin II receptor blockers, rs35497065 in FOXA3 for calcium channel blockers, and rs11066280 in HECTD4 for αβ-blockers. Because these loci are known to be susceptibility loci for hypertension and/or BP, our results indicate that resistant hypertension is caused by a combination of excessive BP and drug resistance to each antihypertensive pharmacological class. Furthermore, to investigate the genetic difference between BP traits and the treatment effectiveness of antihypertensive drugs, we performed gene-set analysis and calculated the genetic correlation continuously. Most of the genetic factors were in common between BP traits and antihypertensive effectiveness, but it seems that the genetic architecture of the drug response to antihypertensive treatment is more complicated than BP traits. This corresponds to the well-known mosaic theory of hypertension. Our findings reveal the complex pathogenesis of hypertension with resistance to multiple classes of antihypertensive drugs.


Statistical modeling of phosphorus solubilization from chemical sludge and evaluation of optimal sodium hydroxide dose.
Phosphorus (P) recovery from sludge has drawn widespread attention across the world to minimize the P load to the watershed, a concern for eutrophication, and to meet the stringent effluent discharge regulations in some countries. Waste activated sludge (WAS) and dewatered sludge (DS) were treated with a wide range of NaOH doses (0-0.75 g g-1 TS). The WAS sludge was diluted to 4.5%-2.25% of TS before the treatment to make comparable amount of TS as of DS (2.25%-1.5%). The kinetic study illustrated that P solubilization reached equilibrium within the first 20 min of treatment duration. Significant positive correlation was found between solution pH and P solubilization, whereas effect of TS was mostly insignificant. The experimental data was well fitted to the exponential models and exhibited maximum P solubilization of about 67% and 56% from the DS and WAS at NaOH doses of 0.71 and 0.27 g g-1 TS, respectively. The optimal NaOH application dose of 0.36 g g-1 TS for DS and 0.20 g g-1 TS for WAS were obtained with 64% and 48% of P solubilization, respectively. The modeling approach and the optimal dose of NaOH illustrated in this study could be utilized for other types of sludges having similar P to TS ratio and P solubilization mechanisms could be further extended to other type of P recovery techniques.


Global and local mobility as a barometer for COVID-19 dynamics.
. The spreading of infectious diseases including COVID-19 depends on human interactions. In an environment where behavioral patterns and physical contacts are constantly evolving according to new governmental regulations, measuring these interactions is a major challenge. Mobility has emerged as an indicator for human activity and, implicitly, for human interactions. Here we study the coupling between mobility and COVID-19 dynamics and show that variations in global air traffic and local driving mobility can be used to stratify different disease phases. For ten European countries, our study shows maximal correlation between driving mobility and disease dynamics with a time lag of 14.6 +/- 5.6 days. Our findings suggests that local mobility can serve as a quantitative metric to forecast future reproduction numbers and identify the stages of the pandemic when mobility and reproduction become decorrelated.


Demography of an ice-obligate mysticete in a region of rapid environmental change.
Antarctic minke whales (Balaenoptera bonaerensis, AMW) are an abundant, ice-dependent species susceptible to rapid climatic changes occurring in parts of the Antarctic. Here, we used remote biopsy samples and estimates of length derived from unoccupied aircraft system (UAS) to characterize for the first time the sex ratio, maturity, and pregnancy rates of AMWs around the Western Antarctic Peninsula (WAP). DNA profiling of 82 biopsy samples (2013-2020) identified 29 individual males and 40 individual females. Blubber progesterone levels indicated 59% of all sampled females were pregnant, irrespective of maturity. When corrected for sexual maturity, the median pregnancy rate was 92.3%, indicating that most mature females become pregnant each year. We measured 68 individuals by UAS (mean = 8.04 m) and estimated that 66.5% of females were mature. This study provides the first data on the demography of AMWs along the WAP and represents the first use of non-lethal approaches to studying this species. Furthermore, these results provide baselines against which future changes in population status can be assessed in this rapidly changing marine ecosystem.


Characteristic accumulation and soil penetration of polychlorinated biphenyls and polybrominated diphenyl ethers in wastewater irrigated farmlands.
The impact of wastewater irrigation on the distribution of two groups of persistent organic pollutants (POPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), in farm soil was investigated in this study. The concentrations of total analyzed PCBs were in the range 256-2140pgg(-1) on dry weight basis in surface soils. There was a higher accumulation of PCBs in farms irrigated by wastewater, with decachlorobiphenyl (CB-209) as the predominant congener. The spatial distributions of PBDEs were similar although not as obvious as that of PCBs, and BDE-209 was the predominant congener at 2040-496000pgg(-1)dw, accounting for >96% of the total analyzed PBDEs. However, no significant correlations could be found between PCB and PBDE concentrations in the topsoil samples, and also with soil organic content between the different sites. On the other hand, soil vertical profiles showed significant relationship with soil organic content in cores taken from farms irrigated with wastewater. The vertical distribution was quite uniform at the topsoil, corresponding to the plowed layer, and decreased thereafter exponentially. Furthermore, the soil vertical distribution was found to be congener specific for PCBs, where less chlorinated congeners were able to penetrate deeper into the soil while heavier congeners were more restricted in their movement. This fractionation process was however not found for PBDEs. Also, the prevalence and high relative concentrations of CB-11 and CB-209 suggests that these PCB congeners should more often be included in routine environmental analysis in order to identifying unusual contamination sources.


Relative body fat and anthropometric prediction of body density of male athletes.
Two hundred and seven male members of South Australian representative squads in 18 sports (mean +/- s = 24.2 +/- 4.7 years) were tested in order to provide descriptive data on relative body fat (% BF), develop a population specific equation and cross-validate existing equations. Measurements were taken of 10 circumferences, 2 diameters and 8 skinfolds; body density (BD) was measured by underwater weighing with the residual volume (RV) being determined by He dilution. The overall mean BD was 1.0761 g X cm-3 (s = 0.0085 g X cm-3; range = 1.0465-1.0968 g X cm-3) which corresponded to 10.0% BF according to Siri (s = 3.7%; range = 1.3-23.0%). The games players (n = 129) registered an overall mean of 10.3% BF (s = 3.7%; range = 2.2-23.0%). There were significant differences (p less than 0.05) for % BF between the lacrosse players (mean = 12.3%) an both the Australian Rules footballers (mean = 8.0%) and track and field athletes (mean = 8.7%). A stepwise multiple regression on 185 subjects yielded the following equation, which had an R of 0.787: BD = 1.078865-0.000419 (sigma abdominal, medial calf, front thigh and juxta-nipple skinfolds in mm) +0.000948 (neck circumference in cm) -0.000266 (age in decimal years) -0.000564 (ankle circumference in cm). Only those predictors which resulted in a significantly increased correlation (p less than or equal to 0.05) were included. The standard error of estimate of 0.00537 g X cm-3 was equivalent to 2.3% BF at the mean. This equation was satisfactorily cross-validated against the BD of a separate sample (n = 22) from the same population. However, cross-validation of 11 previously published equations indicated that they have limited applicability to State representative sportsmen.


Modified β-casein restores thermal reversibility of human carbonic anhydrase II: the salt bridge mechanism.
Modified β-casein (mβ-CN) was investigated as an efficient additive for thermal reversibility of human carbonic anhydrase II (HCA II) at pH 7.75. The mβ-CN was obtained via modification of β-casein (β-CN) acidic residues using Woodward's reagent K. The effects of mβ-CN on the reversibility and stability of HCA II were determined by differential scanning calorimetry, UV-vis, and 1-anilinonaphthalene-8-sulfonic acid fluorescence spectroscopic methods. The mβ-CN, as an additive, enhanced thermal reversibility of HCA II by 33%. Together, our results indicated that mβ-CN is very efficient in decreasing thermal aggregation and enhancing the stability of HCA II. Using theoretical studies, we propose that the mechanism for thermal reversibility is mediated through formation of a salt bridge between the Woodward part of mβ-CN and the Zn ion of HCA II.


The Adelaide preschool language unit: results of follow-up.
To determine educational, social and behavioural functioning of children who had been involved in a preschool language intervention programme between 1982 and 1990. Fifty children who attended the Unit were available for follow-up. The children were divided into three groups: (i) language disorder; (ii) speech disorder; and (iii) mixed speech and language disorder. A psychologist administered educational, cognitive and social behavioural tests. Speech, language and articulation were assessed by a speech pathologist. Cognitively, the 'mixed' speech and language group obtained lower scores than the speech and language disorder children; results on educational tests were also generally lower. All three groups were significantly underachieving in areas of language, reading, spelling and arithmetic relative to their performance IQ. No socialization problems were found. Severe speech and language disorders in young children, even after periods of intensive intervention, have a significant effect on later educational achievement even when children appear to be 'coping' in their educational settings.


Koleobacter methoxysyntrophicus gen. nov., sp. nov., a novel anaerobic bacterium isolated from deep subsurface oil field and proposal of Koleobacteraceae fam. nov. and Koleobacterales ord. nov. within the class Clostridia of the phylum Firmicutes.
An anaerobic thermophilic, rod-shaped bacterium possessing a unique non-lipid sheathed-like structure enveloping a single-membraned cell, designated strain NRmbB1T was isolated from at the deep subsurface oil field located in Yamagata Prefecture, Japan. Growth occurred with 40-60°C (optimum, 55°C), 0-2% (2%), NaCl and pH 6.0-8.5 (8.0). Fermentative growth with various sugars was observed. Glucose-grown cells generated acetate, hydrogen, pyruvate and lactate as the main end products. Syntrophic growth occurred with glucose, pyruvate and 3,4,5-trimethoxybenzoate in the presence of an H2-scavenging partner, and growth on 3,4,5-trimethoxybenzoate was only observed under syntrophic condition. The predominant cellular fatty acids were C16:0, iso-C16:0, anteiso-C15:0, and iso-C14:0. Respiratory quinone was not detected. The genomic G+C content was 40.8mol%. Based on 16S rRNA gene phylogeny, strain NRmbB1T belongs to a distinct order-level clade in the class Clostridia of the phylum Firmicutes, sharing low similarity with other isolated organisms (i.e., 87.5% for top hit Moorella thermoacetica DSM 2955T). In total, chemotaxonomic, phylogenetic and genomic characterization revealed that strain NRmbB1T (=KCTC 25035T, =JCM 39120T) represents a novel species of a new genus. In addition, we also propose the associated family and order as Koleobacteraceae fam. nov and Koleobacterales ord. nov., respectively.


The atypical β-blocker S-oxprenolol reduces cachexia and improves survival in a rat cancer cachexia model.
Beta-blockers and selected stereoisomers of beta-blockers, like bisoprolol and S-pindolol (ACM-001), have been shown to be effective in preclinical cancer cachexia models. Here, we tested the efficacy of stereoisomers of oxprenolol in two preclinical models of cancer cachexia-the Yoshida AH-130 rat model and the Lewis lung carcinoma (LLC) mouse model. In the Yoshida AH130 hepatoma rat cancer cachexia model and compared with placebo, 50 mg/kg/d S-oxprenolol (HR: 0.49, 95% CI: 0.28-0.85, P = 0.012) was superior to 50 mg/kg/d R-oxprenolol (HR: 0.83, 95% CI 0.38-1.45, P = 0.51) in reducing mortality (= reaching ethical endpoints). Combination of the three doses (12.5, 25 and 50 mg/kg/d) that had a significant effect on body weight loss in the S-oxprenolol groups vs the same combination of the R-oxprenolol groups lead to a significantly improved survival of S-oxprenolol vs R-oxprenolol (HR: 1.61, 95% CI: 1.08-2.39, P = 0.0185). Interestingly, there is a clear dose dependency in S-oxprenolol-treated (5, 12.5, 25 and 50 mg/kg/d) groups, which was not observed in groups treated with R-oxprenolol. A dose-dependent attenuation of weight and lean mass loss by S-oxprenolol was seen in the Yoshida rat model, whereas R-oxprenolol had only had a significant effect on fat mass. S-oxprenolol also non-significantly reduced weight loss in the LLC model and also improved muscle function (grip strength 428 ± 25 and 539 ± 37 g/100 g body weight for placebo and S-oxprenolol, respectively). However, there was only a minor effect on quality of life indicators food intake and spontaneous activity in the Yoshida model (25 mg/kg/S-oxprenolol: 11.9 ± 2.5 g vs placebo: 4.9 ± 0.8 g, P = 0.013 and also vs 25 mg/kg/d R-oxprenolol: 7.5 ± 2.6 g, P = 0.025). Both enantiomers had no effects on cardiac dimensions and function at the doses used in this study. Western blotting of proteins involved in the anabolic/catabolic homoeostasis suggest that anabolic signalling is persevered (IGF-1 receptor, Akt) and catabolic signalling is inhibited (FXBO-10, TRAF-6) by S-pindolol, but not he R-enantiomer. Expression of glucose transporters Glut1 and Glut 4 was similar in all groups, as was AMPK. S-oxprenolol is superior to R-oxprenolol in cancer cachexia animal models and shows promise for a human application in cancer cachexia.


Glucagon-induced small bowel air reflux: degrading effects on double-contrast colon examination.
Glucagon-induced small bowel air reflux and its effect on the diagnostic quality of the double-contrast barium enema examination was prospectively evaluated in 103 patients. These were randomly assigned to receive 0.5 mg intravenous glucagon (50 patients) or to a control group without such medication (53 patients). The group receiving glucagon demonstrated an increased amount of small bowel air and a greater magnitude of change in its volume secondary to reflux, as well as degradation in the quality of barium enema study when compared to the nonglucagon group. No significant improvement in visualization of the appendix after glucagon was observed. We conclude that routine administration of glucagon during double-contrast enema would degrade the quality of examination primarily because it promotes retrograde reflux of air into the small intestine.


Scaffolding function of PAK in the PDK1-Akt pathway.
Many extracellular signals stimulate phosphatidylinositol-3-kinase, which in turn activates the Rac1 GTPase, the protein kinase Akt and the Akt Thr 308 upstream kinase PDK1. Active Rac1 stimulates a number of events, including substrate phosphorylation by a subgroup of the PAK family of kinases. The combined effects of Rac1, PDK1 and Akt are crucial for cell migration, growth, survival, metabolism and tumorigenesis. Here we show that Rac1 stimulates a second, kinase-independent function of PAK1. The PAK1 kinase domain serves as a scaffold to facilitate Akt stimulation by PDK1 and to aid recruitment of Akt to the membrane. PAK differentially activates subpopulations of Akt. These findings reveal scaffolding functions of PAK that regulate the efficiency, localization and specificity of the PDK1-Akt pathway.


Pre-admission ambient air pollution and blood soot particles predict hospitalisation outcomes in COVID-19 patients.
Air pollution exposure is one of the major risk factors for aggravation of respiratory diseases. We investigated whether exposure to air pollution and accumulated black carbon (BC) particles in blood were associated with coronavirus disease 2019 (COVID-19) disease severity, including the risk for intensive care unit (ICU) admission and duration of hospitalisation. From May 2020 until March 2021, 328 hospitalised COVID-19 patients (29% at intensive care) were recruited from two hospitals in Belgium. Daily exposure levels (from 2016 to 2019) for particulate matter with aerodynamic diameter <2.5 µm and <10 µm (PM2.5 and PM10, respectively), nitrogen dioxide (NO2) and BC were modelled using a high-resolution spatiotemporal model. Blood BC particles (internal exposure to nano-sized particles) were quantified using pulsed laser illumination. Primary clinical parameters and outcomes included duration of hospitalisation and risk of ICU admission. Independent of potential confounders, an interquartile range (IQR) increase in exposure in the week before admission was associated with increased duration of hospitalisation (PM2.5 +4.13 (95% CI 0.74-7.53) days, PM10 +4.04 (95% CI 1.24-6.83) days and NO2 +4.54 (95% CI 1.53-7.54) days); similar effects were observed for long-term NO2 and BC exposure on hospitalisation duration. These effect sizes for an IQR increase in air pollution on hospitalisation duration were equivalent to the effect of a 10-year increase in age on hospitalisation duration. Furthermore, for an IQR higher blood BC load, the OR for ICU admission was 1.33 (95% CI 1.07-1.65). In hospitalised COVID-19 patients, higher pre-admission ambient air pollution and blood BC levels predicted adverse outcomes. Our findings imply that air pollution exposure influences COVID-19 severity and therefore the burden on medical care systems during the COVID-19 pandemic.


The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1.
Some experts maintain that (1) > 90% of patients with multiple endocrine neoplasia type 1 (MEN1) are first seen with hyperparathyroidism (HPTH) so that routine screening for other features is unnecessary and (2) MEN1 has > or = 94% penetrance by age 50 years. We constructed a regional registry of patients with or at risk for MEN1 and examined phenotypic profiles in 34 patients. MEN1 was defined as (1) endocrinopathy of 2 of the 3 principal related tissues (parathyroid, gastrointestinal endocrine, pituitary) or (2) 1 such feature plus a first-degree relative with MEN1. The initial feature of MEN1 was HPTH in 50%, pituitary tumor in 18%, and gastrointestinal endocrine tumor in 32% of patients, with overall incidences of 82%, 65%, and 74%, respectively. HPTH developed by age 50 years in 73% of patients and by age 70 years in 83%. Penetrance of MEN1 at age 50 years was 82%. Associated features included renal (1) and rectal (1) cancer, malignant thymic carcinoid (1), and malignant pheochromocytoma (1). Expression of MEN1 can vary considerably from established patterns. In our geographic region HPTH does not routinely precede other features of MEN1 and cannot be used to distinguish affected patients among those at risk. MEN1 can be inapparent until late in life and may be significantly underdiagnosed.


Identification of microRNA target genes in vivo.
MicroRNAs (miRNAs) are short non-coding RNAs transcribed from intergenic or intronic sequences as long precursors that are sequentially processed by the endonucleases Drosha and Dicer into short double-stranded sequences. It is clear that miRNAs play essential roles in gene expression, development, and cell fate specification in animals. However, one of the barriers of miRNA research is how to find the target genes. In this study, we have developed a rapid and effective method to isolate miRNA target genes in vivo. MicroRNA was synthesized in vitro and labeled by biotin. After transfected into cells, the miRNA/mRNA complexes were isolated by streptavidin-coated magnetic beads. hsa-miR155 was taken as model to validate this method, which is a very important modulator in tumor development. It is useful for validation of targets predicted in silico, and, potentially, for discovery of previously uncharacterized targets.


Efficacy of a self-management intervention for weight control in overweight and obese adults: a randomized controlled trial.
Brief self-management interventions to engender successful weight maintenance are seldom tested in obese and overweight populations without diabetes. To test the efficacy of the intervention, aimed at improving proactive coping, in obese and overweight adults at risk for diabetes. Participants (N = 255) were randomly assigned to two experimental groups (N = 185) and a control group (N = 70). Experimental groups received the same intervention in week 1-8 (initial phase) and booster sessions with different content ("standard" vs. "relapse prevention") during week 9-24 (continuance phase). Primary outcomes were proactive coping, diet and Body Mass Index (BMI) at four time points (1 year between first and last measurement). Experimental groups improved in proactive coping during the initial phase and BMI during the continuance phase, whereas the control group did not. No differences emerged in diet. Brief self-management interventions can play a preventive role in chronic illnesses associated with obesity.


Effects of estradiol on the development of sexual dimorphism in the bed nucleus of the accessory olfactory tract in the rat.
Orchidectomized males injected with a single dose of estradiol benzoate (EB) on the day of birth (D1) showed a volume and neuron number in the nucleus of the accessory olfactory tract (BAOT) similar to that of control males. However, orchidectomized males and those orchidectomized and given a single dose of DHT on D1 showed a decrease in BAOT volume and neuron number with respect to control males. These results support the notion that estradiol induces the morphological masculinization of this structure. The inability of DHT in counteracting the effect of orchidectomy is addressed taking into account the inhibitory action of androgens.


Rat brain slices produce and liberate kynurenic acid upon exposure to L-kynurenine.
The incorporation of L-kynurenine (L-KYN) into kynurenic acid (KYNA) was examined in rat brain slices. KYNA was measured in the slices and in the incubation medium after purification by ion-exchange and HPLC chromatography. In pilot experiments, the formation of KYNA was confirmed by gas chromatography. KYNA was produced stereoselectively from L-KYN, and approximately 90% of the newly synthesized KYNA was recovered from the incubation medium. Intracellular KYNA was not actively retained by the tissue and was lost from the cells upon repeated washes. Thus, regulation of the levels of extracellular KYNA appears to occur at the level of L-KYN uptake and/or kynurenine transaminase, the biosynthetic enzyme of KYNA. KYNA production from L-KYN was linear up to 4 h and reached a plateau at a L-KYN concentration of 250 microM. The process was effectively inhibited by the transaminase inhibitor aminooxyacetic acid (IC50, approximately 25 microM), and showed pronounced regional distribution (hippocampus greater than cortical areas greater than thalamus much greater than cerebellum). The conversion of L-KYN to KYNA was dependent on oxygenation and on the presence of glucose in the incubation medium. Neither deletion of Ca2+ or Mg2+ nor addition of 20 mM Mg2+ had any effect. However, KYNA production was significantly attenuated in the absence of Cl- or in the presence of 50 mM K+ in the incubation medium. In Na+-free medium, the production of KYNA from L-KYN was increased by 30%.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of methanogenic activity in a thermophilic-dry anaerobic reactor: use of fluorescent in situ hybridization.
Methanogenic activity in a thermophilic-dry anaerobic reactor was determined by comparing the amount of methane generated for each of the organic loading rates with the size of the total and specific methanogenic population, as determined by fluorescent in situ hybridization. A high correlation was evident between the total methanogenic activity and retention time [-0.6988Ln(x)+2.667] (R(2) 0.8866). The total methanogenic activity increased from 0.04x10(-8) mLCH(4) cell(-1)day(-1) to 0.38x10(-8) mLCH(4) cell(-1)day(-1) while the retention time decreased, augmenting the organic loading rates. The specific methanogenic activities of H(2)-utilizing methanogens and acetate-utilizing methanogens increased until they stabilised at 0.64x10(-8) mLCH(4) cell(-1)day(-1) and 0.33x10(-8) mLCH(4) cell(-1)day(-1), respectively. The methanogenic activity of H(2)-utilizing methanogens was higher than acetate-utilizing methanogens, indicating that maintaining a low partial pressure of hydrogen does not inhibit the acetoclastic methanogenesis or the anaerobic process.


Antagonism of behavioral effects of bromocriptine by prolactin in female cats.
The effects of the dopaminergic agonist bromocriptine (BC) and exogenously administered prolactin (PRL) on the spontaneous behavior of female cats were investigated. The objective was to test whether BC-induced behavioral effects may be antagonized by PRL. BC (6 mg/kg ip) administration induced abnormal behaviors such as limb flicks, abortive grooms, head/body shakes, and hallucinatory-like behavior/escape as well as excessive grooming. PRL (5 mg/kg ip) administration induced biphasic changes in grooming. The first change was an increase in grooming frequency averaging 256% of baseline control values and lasting for 1 h. This change was followed by reductions in grooming of 75 and 82.5% below baseline during Hours 2 and 3 postinjection, respectively. Combined BC and PRL treatment antagonized the frequency of BC-induced motor effects such as limb flicks, abortive grooms, and head/body shakes. Limb flicks occurred nine times more often 2 h after BC alone than after BC and PRL. The combined treatment also antagonized the excessive grooming observed after separate administrations of BC and PRL. The observed interactions between PRL and BC behavioral effects support the notion that PRL may be an important modulator of dopamine-dependent motor behavior in female cats.


Therapeutic plasma-exchange in hematologic disease: results from a single center in Eastern Anatolia.
Therapeutic plasma-exchange (TPE) is used as primary and adjunctive therapy in treatment of several hematologic diseases. We retrospectively evaluated the results of TPE in hematologic diseases during 2008-2012. A total of 301 TPE procedures were performed in 44 patients (19 male and 25 female, with mean age of 50.6±15years). Fifteen of 44 patients had thrombotic thrombocytopenic purpura (TTP), 14 patients had HELLP syndrome (Hemolysis Elevated Liver enzymes, Low Platelet count), 10 patients had multiple myeloma-hyperviscosity and the rest five patients had snake bite. Fresh frozen plasma (FFP) was used as replacement fluid. Complete response (CR) was achieved on 13 patients (87%) in primarily TTP. CR was achieved in all other three diseases. Total complications were detected in 8.1% of the TPE procedures. Adverse events (AEs), were seen in 5.4% of all procedures. None of the patients died from any complication. AE occurred in 4% (Grade-I), 1% (Grade-II), and 0.3% (Grade-III) of the procedures. The most common AE were nausea/vomiting, hypotension, pruritus and abdominal pain. TPE is effectively and safely carried out in our center in hematologic diseases.


Use of chlorotetracycline fluorescence to demonstrate Ca2+-induced release of Ca2+ from the sarcoplasmic reticulum of skinned cardiac cells.
It has been proposed that the trans-sarcolemmal influx of Ca2+ occurring during the plateau of the mammalian cardiac action potentials is insufficient in itself to activate the myofilaments, but can trigger a release of Ca2+ from the sarcoplasmic reticulum (SR) which is sufficient for activation. The demonstration of this Ca2+-induced release of Ca2+ relied entirely on experiments in which the tension developed by the myofilaments was used as a sensor of the changes of myoplasmic free Ca2+ concentration ([free Ca2+]) in segments of single cardiac cells from which the sarcolemma had been removed by microdissection (skinned cardiac cells). The small size of these preparations has previously prevented the use of more direct methods for the detection of myoplasmic Ca2+ movements. The present study is a direct demonstration of Ca2+-induced release of Ca2+ from the SR of skinned cardiac cells treated with chlorotetracycline (CTC), a fluorescent chelate probe which enables changes in the amount of Ca2+ bound to a variety of biological membranes or micelles to be monitored. The fluorescence increases when more Ca2+ is bound.


A Comparison Study of Esophageal Findings on (18)F-FDG PET/CT and Esophagogastroduodenoscopy.
The aim of this study was to compare the esophageal findings of 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography-computed tomography ((18)F-FDG PET/CT) and esophagogastroduodenoscopy (EGD). We retrospectively reviewed (18)F-FDG PET/CT and EGD findings of 369 subjects who underwent medical examination between January 2014 and December 2014. The range and intensity of esophageal (18)F-FDG uptake were visually analyzed. The maximum standardized uptake value (SUVmax) of the esophagus and around the esophagogastric (EG) junction was measured. EGD results were provided by the gastroenterologist. We compared the esophageal findings obtained using (18)F-FDG PET/CT and EGD. There were typical linear FDG uptakes in (18)F-FDG PET/CT patients who underwent EGD the same day. In visual analysis of the range and intensity of the (18)F-FDG uptake, the patients who underwent (18)F-FDG PET/CT and EGD on the same day showed relatively diffuse and discernible (18)F-FDG uptake in the esophagus. Reflux esophagitis was diagnosed in 59 subjects, and 27 of these were classified as higher than Los Angeles classification A. With an increasing degree of reflux esophagitis observed on EGD, the SUVmax in the esophagus and around the EG junction was also increased. Our study showed that FDG uptake at the esophagus or the EG junction might be clinically significantly related to esophagitis. However, EGD performed before (18)F-FDG PET/CT on the same day may affect the esophageal (18)F-FDG uptake.


Data mean and ratio of absorbance to concentration methods: A novel optimization strategy for near infrared spectroscopy modeling.
For the modeling of near infrared spectroscopy (NIRS), the accuracy of the basic data, the stability of the spectra and the optimality of variables selection method were the important factors. In this paper, a novel optimization strategy for NIRS modeling was proposed, which was formed by data mean and ratio of absorbance to concentration (RATC) methods. The data mean method was aim to obtain accurate basic data and stable spectra, the RATC method was aim to select the optimal variables and compared with other variables selection methods (FiPLS, BiPLS, CC, UVE). The experimental subject was raw human plasma, with this novel optimization strategy, the predictive capability of NIRS model of its total protein (TP) content had been improved. At the same time, the public NIRS testing data (water, protein, oil, starch of corn and octane of gasoline) were used to verify the proposed variables selection method, and the predictive capability of these models of different parameters were also improved. To some extent, the optimization strategy of NIRS modeling provided theoretical supports for the development of protein content analyzer of NIRS and the quick determination of parameters of biologics and other materials.


Drug-coated balloon in the treatment of coronary left main true bifurcation lesion: A patient-level propensity-matched analysis.
An increasing body of evidence suggests that drug-coated balloon (DCB) angioplasty represents a valuable option for revascularization in selected patients with coronary bifurcation disease. However, there remains a paucity of real-world observational evidence on the efficacy of DCB in left main (LM) true bifurcation lesion. We compared clinical and angiographic outcomes of hybrid [DCB + drug-eluting stent (DES)] versus DES-only strategy (provisional stenting or two-stent strategies) in de novo LM true bifurcated lesions. The primary endpoint was the 2-year composite rate of target lesion failure (TLF): cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target lesion revascularization (CD-TLR). A routine 1-year angiographic follow-up was scheduled. Propensity-score matching was utilized to assemble a cohort of patients with similar baseline characteristics. Among 1077 eligible patients, 199 who received DCB treatment and 398 who were assigned to DES therapy had similar propensity scores and were included in the analysis. TLF within 2 years occurred in 13 patients (7.56%) assigned to DCB group, and 52 patients (14.36%) assigned to DES group (odds ratio: 0.487; 95% confidence interval: 0.258-0.922; P = 0.025; Log-rank P = 0.024). Compared with the DES group, the DCB group resulted in a lower rate of CD-TLR (2.91% vs. 9.42%; P = 0.007). Cardiac death, TVMI, all-cause mortality, and stent thrombosis were comparable between both groups. Patients treated with DES-only were associated with a higher late lumen loss (0.42 ± 0.62 mm vs. 0.13 ± 0.42 mm, P < 0.001) compared with the DCB group at 1 year. In sensitivity analysis, the DCB group also presented a lower incidence of TLF, CD-TLR and stent thrombosis both compared to the two-stent strategy and compared to provisional stenting (Ps < 0.05). The 2-year results of PCI utilizing DCB for LM true bifurcation lesions are superior to employing DES alone in terms of safety and effectiveness.


Treatment of recurrent rectal cancer by electroresection/coagulation after low anterior resection.
Fifteen patients with recurrent rectal cancer after low anterior resection were treated by electroresection/coagulation in order to avoid colostomy. Nine patients were alive without colostomy eight to 16 months after the first treatment and three died without colostomy from metastatic disease 24 to 36 months after the first electroresection. Electroresection/coagulation as treatment of inoperable recurrence after low anterior resection should be considered an alternative to colostomy.


Intracellular pH regulation in isolated cochlear outer hair cells of the guinea-pig.
1. The intracellular pH (pHi) regulation mechanisms of the outer hair cell (OHC) isolated from the guinea-pig were studied using fluorescence ratio imaging microscopy. 2. The OHC pHi in the resting condition was 7.26 +/- 0.08 (mean +/- S.D., n = 49) when the standard solution buffered with HEPES-Tris was superfused. 3. Exposure to 25 mM-NH4+ in the absence of HCO3- caused biphasic changes in pHi; a transient increase (7.89 +/- 0.14, n = 22) followed by a slow decrease (7.57 +/- 0.12; mean +/- S.D.). Removal of external NH4+ by introducing the N-methyl-D-glucamine (NMDG+) solution in the absence of HCO3- markedly acidified the pHi to 6.38 +/- 0.12 with little pHi recovery. Subsequent application of the standard Na+ solution restored the pHi to the initial value. The recovery was inhibited by 0.5 mM-amiloride but not by 0.3 mM-DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid). 4. In the presence of HCO3-, removal of both external NH4+ and Na+ promptly caused an intracellular acidification followed by a pHi recovery. The pHi recovery from an acid load was inhibited by 0.3 mM-DIDS or 10 microM-NPPB (5-nitro-2-(3-phenylpropyl-amino)-benzoate). However, the pHi in the steady state in the presence or absence of HCO3- was not altered by addition of 0.5 mM-amiloride or NMDG+ solution. 5. The intracellular buffering power obtained from the NH4+ exposure and withdrawal was -15.1 +/- 8.7 mM (pH unit)-1 (n = 6) and -14.3 +/- 5.8 mM (pH unit)-1, respectively. 6. Replacement of external Cl- with gluconate in the HCO3- solution increased the pHi from 7.22 +/- 0.12 to 7.51 +/- 0.20 (n = 6), which was inhibited by 0.3 mM-DIDS. Moreover, addition of DIDS to the HCO3- solution increased the pHi by 0.13 +/- 0.08 (n = 8). 7. When the external standard solution buffered with HEPES-Tris was replaced with the HCO3- solution, the basal pHi (7.27 +/- 0.10) was promptly acidified to 6.87 +/- 0.10 then relaxed slowly to 7.00 +/- 0.15 (n = 16). 8. The pHi showed an initial alkalinization and a subsequent slow acidification after the HCO3(-)-free standard solution replaced the HCO3- solution. The slow acidification was inhibited by low external Cl- concentration or by addition of 0.3 mM-DIDS.(ABSTRACT TRUNCATED AT 400 WORDS)


Selective targeting of nuclear receptor FXR by avermectin analogues with therapeutic effects on nonalcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. Farnesoid X receptor (FXR) is an ideal target for NAFLD drug development due to its crucial roles in lipid metabolism. The aim of this work is to examine the molecular mechanisms and functional roles of FXR modulation by avermectin analogues in regulating metabolic syndromes like NAFLD. We found that among avermectin analogues studied, the analogues that can bind and activate FXR are effective in regulating metabolic parameters tested, including reducing hepatic lipid accumulation, lowering serum cholesterol and glucose levels, and improving insulin sensitivity, in a FXR dependent manner. Mechanistically, the avermectin analogues that interact with FXR exhibited features as partial agonists, with distinctive properties in modulating coregulator recruitment. Structural features critical for avermectin analogues to selectively bind to FXR were also revealed. This study indicated that in addition to antiparasitic activity, avermectin analogues are promising drug candidates to treat metabolism syndrome including NAFLD by directly targeting FXR. Additionally, the structural features that discriminate the selective binding of FXR by avermectin analogues may provide a unique safe approach to design drugs targeting FXR signaling.


Depression as a disease of modernity: explanations for increasing prevalence.
There has been much speculation about modern environments causing an epidemic of depression. This review aims to (1) determine whether depression rates have increased and (2) review evidence for possible explanations. While available data indicate rising prevalence and an increased lifetime risk for younger cohorts, strong conclusions cannot be drawn due to conflicting results and methodological flaws. There are numerous potential explanations for changing rates of depression. Cross-cultural studies can be useful for identifying likely culprits. General and specific characteristics of modernization correlate with higher risk. A positive correlation between a country's GDP per capita, as a quantitative measure of modernization, and lifetime risk of a mood disorder trended toward significance (p=0.06). Mental and physical well-being are intimately related. The growing burden of chronic diseases, which arise from an evolutionary mismatch between past human environments and modern-day living, may be central to rising rates of depression. Declining social capital and greater inequality and loneliness are candidate mediators of a depressiogenic social milieu. Modern populations are increasingly overfed, malnourished, sedentary, sunlight-deficient, sleep-deprived, and socially-isolated. These changes in lifestyle each contribute to poor physical health and affect the incidence and treatment of depression. The review ends with a call for future research and policy interventions to address this public health crisis.


Pyruvate cycling involving possible oxaloacetate decarboxylase activity.
With high concentrations of pyruvate as substrate for hepatocytes from fasted rats, high rates of cycling between pyruvate and the dicarboxylic acids occur, as shown isotopically. This rate of cycling is adequate to account for the hydrogen translocation from the mitochondria to the cytosol to furnish NADH for lactate formation. Addition of sufficiently high concentrations of mercaptopicolinate to block almost completely glucose formation from pyruvate, depresses isotopic cycling and lactate formation by only about 50-75%. Under some conditions, when the normal phosphoenolpyruvate carboxykinase activity is inhibited, cytosolic oxaloacetate may be decarboxylated directly to pyruvate, possibly via the decarboxylase activity of phosphoenolpyruvate carboxykinase.


Predictive genetic testing for hereditary breast and ovarian cancer: psychological distress and illness representations 1 year following disclosure.
This prospective study evaluates emotional functioning and illness representations in 68 unaffected women (34 carriers/34 noncarriers) 1 year after predictive testing for BRCA1/2 mutations when offered within a multidisciplinary approach. Carriers had higher subjective risk perception of breast cancer than noncarriers. Carriers who did not have prophylactic oophorectomy had the highest risk perception of ovarian cancer. No differences were found between carriers and noncarriers regarding perceived seriousness and perceived control of breast and ovarian cancer. Mean levels of distress were within normal ranges. Only few women showed an overall pattern of clinically elevated distress. Cancer-specific distress and state-anxiety significantly decreased in noncarriers from pre- to posttest while general distress remained about the same. There were no significant changes in distress in the group of carriers except for ovarian cancer distress which significantly decreased from pre- to posttest. Our study did not reveal adverse effects of predictive testing when offered in the context of a multidisciplinary approach.


The effect of phospholipid-containing surfactant from nickel exposed rabbits on pulmonary macrophages in vitro.
Alveolar macrophages from 9 normal rabbits were incubated in vitro for 3 h with and without phospholipid-containing surfactant from nickel-treated ones. The macrophages treated with surfactant showed morphological and functional criteria of increased activity. The cell surface had many protrusions and the cytoplasma contained several lamellated structures. The oxidative metabolism, measured by the nitroblue tetrazolium (NBT)-test, at rest and after E. coli stimulation was increased, as was the attachment and ingestion of yeast particles. The NBT-values were about the same as corresponding values of macrophages lavaged from the lungs of nickel-treated rabbit. Macrophages incubated with surfactant from untreated animals, had NBT values and phagocytic activity similar to cells incubated without surfactant. As this substance was administered in excess, the difference in macrophage response would probably be due to a qualitative alteration of the surfactant after nickel exposure.


Data-driven models to predict shale wettability for CO2 sequestration applications.
The significance of CO2 wetting behavior in shale formations has been emphasized in various CO2 sequestration applications. Traditional laboratory experimental techniques used to assess shale wettability are complex and time-consuming. To overcome these limitations, the study proposes the use of machine learning (ML); artificial neural networks (ANN), support vector machines (SVM), and adaptive neuro-fuzzy inference systems (ANFIS) tools to estimate the contact angle, a key indicator of shale wettability, providing a more efficient alternative to conventional laboratory methods. A dataset comprising various shale samples under different conditions was collected to predict shale-water-CO2 wettability by considering shale properties, operating pressure and temperature, and brine salinity. Pearson's correlation coefficient (R) was utilized to assess the linearity between the contact angle (CA) value and other input parameters. Initial data analysis showed that the elements affecting the shale wettability are primarily reliant on the pressure and temperature at which it operates, the total organic content (TOC), and the mineral composition of the rock. Between the different ML models, the artificial neural network (ANN) model performed the best, achieving a training R2 of 0.99, testing R2 of 0.98 and a validation R2 of 0.96, with an RMSE below 5. The adaptive neuro-fuzzy inference system (ANFIS) model also accurately predicted the contact angle, obtaining a training R2 of 0.99, testing R2 of 0.97 and a validation R2 of 0.95. Conversely, the support vector machine (SVM) model displayed signs of overfitting, as it achieved R2 values of 0.99 in the training dataset, which decreased to 0.94 in the testing dataset, and 0.88 in the validation dataset. To avoid rerunning the ML models, an empirical correlation was developed based on the optimized weights and biases obtained from the ANN model to predict contact angle values using input parameters and the validation data set revealed R2 of 0.96. The parametric study showed that, among the factors influencing shale wettability at a constant TOC, pressure had the most significant impact, and the dependency of the contact angle on pressure increased when TOC values were high.


The effect of glass ionomer and adhesive cements on substance P expression in human dental pulp.
The purpose of this study was to quantify the effect of glass ionomer and adhesive cements on SP expression in healthy human dental pulp. Forty pulp samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. In thirty of these premolars a Class V cavity preparation was performed and teeth were equally divided in three groups: Experimental Group I: Glass Ionomer cement was placed in the cavity. Experimental Group II: Adhesive Cement was placed in the cavity. Positive control group: Class V cavities only. The remaining ten healthy premolars where extracted without treatment and served as a negative control group. All pulp samples were processed and SP was measured by radioimmunoassay. Greater SP expression was found in the adhesive cement group, followed by the glass ionomer and the positive control groups. The lower SP values were for the negative control group. ANOVA showed statistically significant differences between groups (p<0.0001). Tukey HSD post hoc tests showed statistically significant differences in SP expression between negative control group and the 3 other groups (p<0.01). Differences between the cavity-only group and the two experimental groups were also statistically significant (p<0.05 and p<0.01 respectively). There is also a statistically significant difference between the two experimental groups (p<0.01). These findings suggest that adhesive cements provoke a greater SP expression when compared with glass ionomer.