Genetic risk prediction in a small cohort of healthy adults in Atlanta.
Compared with single markers, polygenic scores that evaluate the joint effects of multiple trait-associated variants are more effective in explaining the variance of traits and risk of diseases. In total, 182 CHDWB (Emory-Georgia Tech Center for Health Discovery and Well Being study) adults were genotyped to investigate the common variant contributions to three traits (height, BMI, serum triglycerides) and three diseases (coronary artery disease (CAD), type 2 diabetes (T2D) and asthma). Association was contrasted between weighted and simple allelic sum polygenic scores with quantitative traits, and with the Framingham risk scores for CAD and T2D. Although the cohort size is two or three orders of magnitude smaller than typical discovery cohorts, we were able to detect significant associations and to explain up to 5% of the traits by the genetic risk scores, despite a strong influence of outliers. An unexpected finding was that CAD-associated single nucleotide polymorphisms (SNPs) explain a significant amount of the variation for total serum cholesterol. Forward step-wise sequential addition of SNPs into the regression model showed that the top-ranked SNPs explain a large proportion of variance, whereas inclusion of gender and ethnicity also affect the performance of polygenic scores.


Effectiveness of narrow-band imaging magnification for invasion depth in early colorectal cancer.
To evaluate the surface microvascular patterns of early colorectal cancer (ECC) using narrow-band imaging (NBI) with magnification and its effectiveness for invasion depth diagnosis. We studied 112 ECC lesions [mucosal/submucosal superficial (m/sm-s), 69; sm-deep (sm-d), 43] > or = 10 mm that subsequently underwent endoscopic or surgical treatment at our hospital. We compared microvascular architecture revealed by NBI with magnification to histological findings and then to magnification colonoscopy pit pattern diagnosis. Univariate analysis indicated vessel density: non-dense (P < 0.0001); vessel regularity: negative (P < 0.0001); caliber regularity: negative (P < 0.0001); vessel length: short (P < 0.0001); and vessel meandering: positive (P = 0.002) occurred significantly more often with sm-d invasion than m/sm-s invasion. Multivariate analysis showed sm-d invasion was independently associated with vessel density: non-dense [odds ratio (OR) = 402.5, 95% confidence interval (CI): 12.4-13 133.1] and vessel regularity: negative (OR = 15.9, 95% CI: 1.2-219.1). Both of these findings when combined were an indicator of sm-d invasion with sensitivity, specificity and accuracy of 81.4%, 100% and 92.9%, respectively. Pit pattern diagnosis sensitivity, specificity and accuracy, meanwhile, were 86.0%, 98.6% and 93.8%, respectively, thus, the NBI with magnification findings of non-dense vessel density and negative vessel regularity when combined together were comparable to pit pattern diagnosis. Non-dense vessel density and/or negative vessel regularity observed by NBI with magnification could be indicators of ECC sm-d invasion.


Horizontal changes in the condylar head after sagittal split ramus osteotomy with bent plate fixation.
The purpose of this study was to evaluate the horizontal changes in the condylar head with bent plate fixation after sagittal split ramus osteotomy (SSRO) with and without a Le Fort I osteotomy. Of 47 Japanese patients with mandibular prognathism, 24 underwent SSRO and 23 underwent SSRO in combination with a Le Fort I osteotomy. A 3-5-mm gap was made between the proximal and distal segments, and a bent plate was fixed with 4 screws in each side of the mandible. The angle of the condylar long axis, as well as the anteroposterior and mediolateral displacement of the condylar head were assessed preoperatively and postoperatively by computerized tomography (CT). There was no significant difference in reduction in mandibular length between SSRO alone and SSRO with Le Fort I on the axial view of a 3-dimensional CT. There were no significant differences between pre- and postoperative horizontal changes in the condylar long axis or in the anteroposterior and mediolateral displacement of the condylar head, although the length of the proximal segment in SSRO with Le Fort I osteotomy was significantly shorter than in SSRO alone (P < .05). These results suggest that the use of a bent plate for SSRO does not change preoperative angle or position significantly in setback surgery, regardless of the addition of Le Fort I osteotomy.


[Unrecognized causes of chronic cough].
Chronic cough is defined as persistence of the symptom for longer than one month. It is a common reason for consultation. A systematic diagnostic approach based on the history, clinical examination and a number of investigations (chest x-ray, lung function tests, oesophageal pH monitoring and sinus x-rays) reveals the cause in most cases. The main aetiologies are post-nasal drip, gastro-oesophageal reflex, asthma, chronic bronchitis, and the use of angiotensin converting enzyme inhibitors. Nevertheless, in some cases, the cause is not found. In this situation it is necessary to search for less common pathologies where cough is just a symptom of systemic disease, such as connective tissue disorder (Sjogren's syndrome, atrophic polychondritis), vasculitis (Wegener's granulomatosis), Horton's syndrome (cluster headaches), amyloidosis and inflammatory bowel disease. It may also be a matter of local pathology of the tracheo-bronchial tree, such as tracheo-bronchomegaly, tracheopathia osteoplastica, rare or unrecognized infections (whooping cough, post-viral cough, bronchial tuberculosis), reactive bronchial dysfunction, eosinophilic bronchitis or radiologically occult bronchial carcinoma. Il is also necessary to consider vocal cord dysfunction and cough due to medication before accepting a diagnosis of psychogenic cough.


Preliminary information on prevention of infections caused by SARS-COV-2 virus in endoscopic laboratories.
On 11 March 2020, the Director-General of the World Health Organization (WHO) announced COVID-19 (Coronavirus Disease 2019) as a global pandemic Currently, no vaccines are available and there is little evidence of the efficacy of potential therapeutic agents. Furthermore, there is presumably no pre-existing immunity in the population to the new coronavirus, and it is as-sumed that everyone in the population is susceptible. The aim of the procedures described in the article is to minimize the risk of human-to-human transmission of the SARS-CoV-2 (Severe acute respiratory syndrome - coronavirus 2) virus during procedures carried out in endoscopic laboratories. SARS-CoV-2 infection can be asymptomatic, cause severe pneumonia, or lead to death. Symptoms of COVID-19 range from none (asymptomatic) to severe pneumonia and it can be fatal. Case studies to-date indicate that this infection causes a mild illness (i.e. pneumonia or mild pneumonia) in approximately 80% of cases, and most cases recove; 14% have a more severe illness, 6% experience a critical illness. The vast majority of the most serious illnesses and deaths have occurred among the elderly and people with other chronic underlying diseases. Average progression times include: • in mild cases: from the onset of symptoms to recovery in almost 2 weeks; • in severe cases: from the onset of symptoms to recovery in 3-6 weeks, and from symptoms to death in 2-8 weeks. Special precautions should be taken and procedures followed when performing invasive medical procedures in endoscopic laboratories in patients with specific or clinically probable SARS-CoV-2 infection. This article contains up-to-date information as at 04/04/2020.


Predictors of autopsy following stillbirth in Queensland, Australia: A population-based study.
Accurate determination of causes of stillbirth is critical to effective prevention. Autopsy remains the gold standard investigation for stillbirth; however, with low autopsy rates many stillbirths are likely to be 'unexplored' rather than 'unexplained'. To determine factors associated with autopsy following stillbirth. Routinely collected population-based data on all singleton stillbirths of at least 400 g birthweight or 20 weeks gestation in Queensland between July 2000 and December 2011 were examined. Adjusted odds ratios (aOR, 99% CI) were calculated accounting for sociodemographic, pregnancy and medical factors. Of interest was initially unexplained stillbirth on the death certificate; analysis was stratified by gestational age group (<24, 24-27, 28-36 and ≥37 weeks). Of 3842 singleton stillbirths included in these analyses, 1356 (35.3%) had an autopsy performed. Initially unexplained stillbirth was associated with decreased odds of autopsy at late gestation (28-36 weeks, aOR 0.63 (99% CI 0.42-0.93); ≥37 weeks, aOR 0.53 (99% CI 0.35-0.81)) as was intrapartum stillbirth (<24 weeks, aOR 0.63 (99% CI 0.43-0.94); 28-36 weeks, aOR 0.37 (99% CI 0.14-0.98)). Congenital abnormality (<24 weeks, ≥37 weeks), small-for-gestational age (<24 weeks), and primigravidity (≥37 weeks) were associated with increased odds of autopsy following stillbirth. Pregnancy factors are associated with stillbirth autopsy. These findings have implications for development of appropriate information for parents and education of clinical staff. Further research is needed into factors influencing autopsy following stillbirth.


Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study.
As a possible treatment for common colds, we tested zinc gluconate lozenges in a double-blind, placebo-controlled, clinical trial. One 23-mg zinc lozenge or matched placebo was dissolved in the mouth every 2 wakeful h after an initial double dose. After 7 days, 86% of 37 zinc-treated subjects were asymptomatic, compared with only 46% of 28 placebo-treated subjects (P = 0.0005). Side effects or complaints were usually minor and consisted mainly of objectionable taste and mouth irritation. Zinc lozenges shortened the average duration of common colds by about 7 days.


Choice of loco-regional anesthetic technique affects operating room efficiency for carpal tunnel release.
Intravenous regional anesthesia (Bier block) is indicated for minor procedures such as carpal tunnel release but must be performed in the operating room. We hypothesize that preoperative peripheral nerve blocks decrease anesthesia-controlled time compared to Bier block for carpal tunnel release. With IRB approval, we reviewed surgical case data from a tertiary care university hospital outpatient surgery center for 1 year. Unilateral carpal tunnel release cases were grouped by anesthetic technique: (1) preoperative nerve blocks, or (2) Bier block. The primary outcome was anesthesia-controlled time (minutes). Secondary outcomes included surgical time and time for nerve block performance in minutes, when applicable. Eighty-nine cases met criteria for analysis (40 nerve block and 49 Bier block). Anesthesia-controlled time [median (10th-90th percentiles)] was shorter for the nerve block group compared to Bier block [11 (6-18) vs. 13 (9-20) min, respectively; p = 0.02). Surgical time was also shorter for the nerve block group vs. the Bier block group [13 (8-21) and 17 (10-29) min, respectively; p < 0.01), but nerve blocks took 10 (5-28) min to perform. Ultrasound-guided nerve blocks performed preoperatively reduce anesthesia-controlled time compared to Bier block and may be a useful anesthetic modality in some practice environments.


Type I interferon response against viral and non-viral gene transfer in human tumor and primary cell lines.
Type I interferon (IFN-alpha/beta) response is one of the major host defence mechanisms against viruses. Some recent reports suggest that IFNs may interfere with the efficacy of both non-viral and virus-vector-mediated therapeutic gene transfer. The type I IFN response upon different gene transfer methods in human tumor and primary cell lines was studied by analysing IFN-beta mRNA expression, secretion of type I IFNs and accumulation of IFN-alpha/beta-induced MxA protein (myxovirus resistance protein A). Infection with avirulent Semliki Forest virus A7[74] induced MxA protein accumulation and increased the IFN-beta mRNA level, whereas none of the studied virus vectors (adenovirus, CRAd, lentivirus or AAV) induced IFN response. However, plasmid DNA induced the accumulation of MxA protein when transfected with several commercial transfection reagents. RNA transfection appeared to be an efficient inducer of type I IFN response: replicating alphaviral RNA, eukaryotic total RNA, or mRNA all induced both MxA protein accumulation and IFN-beta expression. siRNA transfection failed to induce MxA response. The non-viral gene transfer methods have gained more interest in recent years due to their better safety profiles when compared to their viral counterparts. However, the efficiency of non-viral gene transfer is well below those reached by viral vector systems. The type I interferon response induced by non-viral methods may in part contribute to this inefficiency, while most currently used viral gene transfer vectors fail to induce or are able to suppress type I IFN response.


Metal-filled resin composites. II.
Various particulate materials were combined with a BIS-GMA resin, and the resulting composites were evaluated. The fillers prevented, altered, had no apparent effect, or accelerated polymerization. Coupling agents also influenced polymerization. Physical properties varied widely with different fillers.


Metabolic and molecular effects of dietary extra virgin olive oil in blood and placenta of women with GDM.
Gestational diabetes mellitus (GDM) increases the risks of maternal, placental, and neonatal complications. Previously, we found that a diet enriched in extra virgin olive oil (EVOO) prevents increased maternal triglyceridemia and placental proinflammatory markers in a cohort of GDM patients. The aim of this work was to evaluate maternal circulating markers of insulin resistance, placental collagen, glycogen and lipid levels, and placental levels of proteins, mRNAs, and a microRNA involved in the endocytic pathway in the same cohort of control women and women with GDM who received or did not receive a diet enriched in EVOO (36 g/day) from weeks 24 to 28 of pregnancy until term. At term, the TG/HDL cholesterol ratio, fatty acid binding protein 4 circulating levels, and maternal BMI were increased in the GDM patients, alterations prevented by the maternal diet enriched in EVOO. Although there were no changes in placental lipid levels and lipid profile, GDM placentas were thicker than controls and showed increased glycogen and collagen content, alterations prevented by the EVOO enriched diet. GDM placentas showed increases in megalin levels, in the expression of several genes involved in the endocytic pathway, and in miR-199, which targets these genes, alterations prevented by the maternal diet enriched in EVOO. We identified novel beneficial effects of an EVOO-enriched diet in GDM women, a diet capable of regulating maternal insulin resistance, the structure and metabolism of the placenta, and the placental endocytic pathway, suggesting effects that may be beneficial for fetal development.


Aberrant expression of adaptation to phenobarbital may cause selective growth of foci of altered cells in rat liver.
According to the multistage concept of carcinogenesis, promoters induce selective or preferential multiplication of initiated cells, thereby accelerating one of the rate-limiting steps in cancer formation. The driving force for this selective growth of initiated cells is not known. In normal liver, various liver tumour promoters induce expression of adaptive programmes. One such programme, induced by phenobarbital, consists of organ growth and an increase in the activity of various enzymes involved in the metabolism of lipophilic substrates. In foci of altered rat liver cells (the putative progeny of initiated cells), expression of the programme is still possible and is coupled to certain regulatory defects (excessive, unbalanced proliferation; independence from position-specific restrictions within the hepatic acinus; autonomous expression of some adaptive changes). Promoters seem to switch on this aberrant expression of the programme of adaptation, thereby leading to preferential growth of foci.


The Tegula tango: a coevolutionary dance of interacting, positively selected sperm and egg proteins.
Reproductive proteins commonly show signs of rapid divergence driven by positive selection. The mechanisms driving these changes have remained ambiguous in part because interacting male and female proteins have rarely been examined. We isolate an egg protein the vitelline envelope receptor for lysin (VERL) from Tegula, a genus of free-spawning marine snails. Like VERL from abalone, Tegula VERL is a major component of the VE surrounding the egg, includes a conserved zona pellucida (ZP) domain at its C-terminus, and possesses a unique, negatively charged domain of about 150 amino acids implicated in interactions with the positively charged lysin. Unlike for abalone VERL, where this unique VERL domain occurs in a tandem array of 22 repeats, Tegula VERL has just one such domain. Interspecific comparisons show that both lysin and the VERL domain diverge via positive selection, whereas the ZP domain evolves neutrally. Rates of nonsynonymous substitution are correlated between lysin and the VERL domain, consistent with sexual antagonism, although lineage-specific effects, perhaps owing to different ecologies, may alter the relative evolutionary rates of sperm- and egg-borne proteins.


Energy-Efficient Neural Network for Epileptic Seizure Prediction.
Seizure prediction for drug-refractory epilepsy patients can improve their quality of life, reduce their anxiety, and help them take the necessary precautions. Nowadays, numerous deep learning algorithms have been proposed to predict seizure onset and obtain better performance than traditional machine learning methods. However, these methods require a large set of parameters and large hardware resources; they also have high energy consumption. Therefore, these methods cannot be implemented on compact, low-power wearable, or implantable medical devices. The devices should operate on a real-time basis to continually inform the epileptic patients. In this paper, we describe energy-efficient and hardware-friendly methods to predict the epileptic seizures. A model of only 45 kB was obtained by the neural architecture search and was evaluated across three datasets. The overall sensitivity, false prediction rate, and area under receiver operating characteristic curve were 99.81%, 0.005/h, 1 and 93.48%, 0.063/h, 0.977 and 85.19%, 0.116/h, 0.933, respectively, for three public datasets. This model was further reduced with several methods for model compression. The performances for the model sizes less than 50 kB for scalp EEG data and less than 10 kB for intracranial EEG data outperformed all the other models of similar model sizes. In particular, the energy consumption estimation was less than 10 mJ per inference for scalp EEG signal and less than 0.5 mJ per inference for intracranial EEG signal, which meet the requirements for low-power wearable and implantable devices, respectively.


Light-induced oxidation of unsaturated lipids as sensitized by flavins.
Triplet-excited riboflavin ((3)RF*) was found by laser flash photolysis to be quenched by polyunsaturated fatty acid methyl esters in tert-butanol/water (7:3, v/v) in a second-order reaction with k approximately 3.0 x 10(5) L mol(-1) s(-1) at 25 degrees C for methyl linoleate and 3.1 x 10(6) L mol(-1) s(-1), with DeltaH(double dagger) = 22.6 kJ mol(-1) and DeltaS(double dagger) = -62.3 J K(-1) mol(-1), for methyl linolenate in acetonitrile/water (8:2, v/v). For methyl oleate, k was <10(4) L mol(-1) s(-1). For comparison, beta-casein was found to have a rate constant k approximately 4.9 x 10(8) L mol(-1) s(-1). Singlet-excited flavin was not quenched by the esters as evidenced by insensitivity of steady-state fluorescence to their presence. Density functional theory (DFT) calculations showed that electron transfer from unsaturated fatty acid esters to triplet-excited flavins is endergonic, while a formal hydrogen atom transfer is exergonic (DeltaG(o)(HAT) = -114.3, -151.2, and -151.2 kJ mol(-1) for oleate, linoleate, and linolenate, respectively, in acetonitrile). The reaction is driven by acidity of the lipid cation radical for which a pK(a) approximately -0.12 was estimated by DFT calculations. Absence of electrochemical activity in acetonitrile during cyclic voltammetry up to 2.0 V versus NHE confirmed that DeltaG(o)(ET) > 0 for electron transfer. Interaction of methyl esters with (3)RF* is considered as initiation of the radical chain, which is subsequently propagated by combination reactions with residual oxygen. In this respect, carbon-centered and alkoxyl radicals were detected using the spin trapping technique in combination with electron paramagnetic resonance spectroscopy. Moreover, quenching of (3)RF* yields, directly or indirectly, radical species which are capable of initiating oxidation in unsaturated fatty acid methyl esters. Still, deactivation of triplet-excited flavins by lipid derivatives was slower than by proteins (factor up to 10(4)), which react preferentially by electron transfer. Depending on the reaction environment in biological systems (including food), protein radicals are expected to interfere in the mechanism of light-induced lipid oxidation.


Generation of activin receptor type IIB isoform-specific hypomorphic alleles.
Activin receptor type IIB (Acvr2b) mediates multiple signals for transforming growth factor-beta (TGF-beta) family members, including Activin, Nodal, Bmp7, Gdf1, Gdf3, Myostatin (Gdf8), and Gdf11. Mouse Acvr2b gene generates four transcriptional isoforms (Acvr2b(1-4)) via alternative splicing of two sequence domains located at the juxtaposition of the transmembrane domain. To investigate whether these splicing domains are essential for signal transduction of the Acvr2b receptor in vivo, we have generated a strain of mutant mice (Acvr2b(4/4)) which produce only the Acvr2b(4) isoform, which lacks both splicing domains. Most homozygous Acvr2b(4(neo)/4(neo)) mice, in which a neomycin-resistant cassette was inserted in Intron 4 displayed a mild form of anterior vertebral transformations. However, the penetrance of the vertebral defect was dramatically decreased when the neomycin-resistant cassette was deleted. These results suggest that the Acvr2b(4) isoform is capable of compensating for the deficiency of the other three isoforms. In the absence of its subfamily receptor Acvr2a, however, the development of Acvr2b(4/4) mice was arrested at the gastrulation stage, recapitulating the Acvr2a(-/-); Acvr2b(+/-) mutant phenotype. In this study, we demonstrate that this phenomenon is most likely due to the reduction in the expressed Acvr2b(4) levels rather than to the functional deficiency of the Acvr2b(4) isoform itself.


A composite of hydroxyapatite with electrospun biodegradable nanofibers as a tissue engineering material.
Biodegradable and biocompatible poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a copolymer of microbial polyester, was fabricated as a nanofibrous film by electrospinning and composited with hydroxyapatite (HAp) by soaking in simulated body fluid. Compared with a PHBV cast (flat) film, the electrospun PHBV nanofibrous film was hydrophobic. However, after HAp deposition, both of the surfaces were extremely hydrophilic. The degradation rate of HAp/PHBV nanofibrous films in the presence of polyhydroxybutyrate depolymerase was very fast. Nanofiber formation increased the specific surface area and HAp enhanced the invasion of enzyme into the film by increasing surface hydrophilicity. The surface of the nanofibrous film showed enhanced cell adhesion over that of the flat film, although cell adhesion was not significantly affected by the combination with HAp.


Education and training for acute care delivery: a needs analysis.
Technological and clinical advances have led to increased levels of patient dependency and shorter hospital stay, such that they are now often managed on general wards. Have staff been trained or educated for this change in focus? This project was designed to identify the education and training needs of health care professionals in assessing and managing acutely physically ill hospital patients, within the boundaries of one Strategic Health Authority (SHA) in the UK. Participants identified the knowledge, skills and resources required to assess and manage acutely ill patients. These issues may be addressed through the provision of an appropriate range of structured educational programmes and experiences with the ultimate aim of improving standards of patient care.


Solvent-dependent mixed complex formation-NMR studies and asymmetric addition reactions of lithioacetonitrile to benzaldehyde mediated by chiral lithium amides.
Lithioacetonitrile and a chiral lithium amide with an internally coordinating methoxy group form mixed dimers in diethyl ether (DEE) and in tetrahydrofuran (THF) according to NMR studies. Based on the observed (6)Li,(1)H heteronuclear Overhauser effects, in THF lithioacetonitrile is present in a mixed complex with the chiral lithium amide, and this complex has a central N-Li-N-Li core. In DEE, on the other hand, the acetonitrile anion bridges two lithiums of the dimer to form a central six-membered Li-N-C-C-Li-N ring. Gauge individual atomic orbital DFT calculations of the (13)C NMR chemical shifts of the DEE- and THF-solvated mixed dimers show good agreement with those obtained experimentally. Lithioacetonitrile complexed to the chiral lithium amide has been employed in asymmetric addition to benzaldehyde in both DEE and THF. In THF the product, (S)-3-phenyl-3-hydroxy propionitrile, is formed in 55 % ee and in DEE the R enantiomer is formed in 45 % ee. This change in stereoselectivity between solutions in DEE and THF was found to be general among a number of different chiral lithium amides, all with an internal chelating methoxy group.


Co(OH)2 @PANI Hybrid Nanosheets with 3D Networks as High-Performance Electrocatalysts for Hydrogen Evolution Reaction.
Hybrid electrocatalysts with excellent electrocatalytic activity for hydrogen reduction are fabricated using an efficient and facile electrochemical route. The electronic and synergistic effects between Co(OH)2 and polyaniline (PANI) in the composite structure are the key factors that generate the high electrocatalytic activity and excellent stability. A highly efficient, non-precious metal-based flexible electrocatalyst for high-performance electrocatalysts is shown, which reveals a novel route for the design and synthesis of electrocatalysts.


Pivotal Role of Quantum Dots in the Advancement of Healthcare Research.
The quantum dot is a kind of nanoparticle whose dimension is smaller than the size of a typical nanoparticle ranging from tens of nanometers to a few hundredths of nanometers. The quantum mechanical behavior associated with the quantum dot displays different optical and electronic properties, enabling the quantum dot to find potential applications in a multitude of areas such as solar cells, light-emitting diodes, lasers, and biomedical applications. The objective of this investigation is to explore its fundamentals, synthesis, and applications, especially in the healthcare domain. We have discussed the quantum dot synthesis techniques using chemical methods, namely, wet-chemical methods and vapor-phase methods and plasma processing methods, namely, an ion sputtering method and plasma-enhanced chemical vapor deposition method. We have thoroughly investigated the application of quantum dots in imaging, diagnostics, and gene therapy areas. A significant outcome of this review is to propose quantum dots as a new modality in the treatment of cancer and gene therapeutics in the healthcare domain and the potentials of artificial intelligence to improve their performance via the applications of neural networks.


Coupled straintronic-optoelectronic effect in Mott oxide films.
Controlling the electronic properties of complex oxides by an external stimulus is of significant importance for exploring exotic quantum states and developing modern electronic devices with low-level energy consumption. Here, we demonstrate the electro-photo double control of electronic transport for Mott insulating LaVO3 thin films deposited onto ferroelectric 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 substrates. An electrically driven linear electroresistance effect is acquired at room temperature through the converse piezoelectric response, which can be optically regulated by 79%. Furthermore, the visible light-activated photoresistance response can be efficiently tuned by piezo strain. These results demonstrate that the strain-excited effect and photo-generated effect strongly correlated with each other, mediated by lattice-charge-orbital coupling. Our work points to an effective strategy for realizing the coupled straintronic-optoelectronic effect in hybrid correlated oxide/ferroelectric systems and delivering multi-field tunable low-dissipation versatile electronic and photonic devices.


Biotechnology in India: An Analysis of 'Biotechnology Industry Research Assistance Council' (BIRAC)-Supported Projects.
A comprehensive analysis of 2165 projects funded by India's Department of Biotechnology since 2005 through private-public partnerships, and as of 2012 through the 'Biotechnology Industry Research Assistance Council (BIRAC)' until BIRAC's tenth anniversary at the end of March 2022 reveals details of the science and technology underpinning past and current biotechnology research and development projects in the country. They are led by human healthcare projects (74.9 % overall), of which medical technology (58.7 %) and therapeutics (24.5 %) are the main drivers, ahead of vaccines (4.3 %), regenerative medicine (3.9 %), public health (3.5 %) and others (5.1 %). Agricultural projects (15.2 % overall) have mainly been driven by plant breeding and cloning (24.6 %), animal biotechnology (20.4 %), agri-informatics (13.4 %), aquaculture (6.1 %), and (bio)fertilizers (4.3 %). The key components of industrial biotechnology (9.9 % overall) have been fine chemicals (44.7 %), environmental projects (23.3 %), clean energy (18.1 %) and industrial enzymes (12.1 %). Analysis of the projects funded pre- versus post-2017, compared to the distribution of equity funding as of early 2022 identifies trends in terms of growth areas and locations of industrial biotechnology projects and activities in India.


Transdermal fentanyl for chronic low back pain.
Chronic low back pain is a common clinical problem. As medication, non-steroidal anti-inflammatory drugs are generally used; however, they are sometimes non-effective. Recently, opioids have been used for the treatment of chronic low back pain, and since 2010, transdermal fentanyl has been used to treat chronic non-cancer pain in Japan. The purpose of the current study was to examine the efficacy of transdermal fentanyl in the treatment of chronic low back pain. This study included patients (n=62) that suffered from chronic low back pain and were non-responsive to non-steroidal anti-inflammatory drugs. Their conditions consisted of non-specific low back pain, multiple back operations, and specific low back pain awaiting surgery. Patients were given transdermal fentanyl for chronic low back pain. Scores of the visual analogue scale and the Oswestry Disability Index, as well as adverse events were evaluated before and after therapy. Overall, visual analogue scale scores and Oswestry Disability Index scores improved significantly after treatment. Transdermal fentanyl (12.5 to 50 μg/h) was effective in reducing low back pain in 45 of 62 patients; however, it was not effective in 17 patients. Patients who experienced the most improvement were those with specific low back pain awaiting surgery. Adverse events were seen in 40% of patients (constipation, 29%; nausea, 24%; itching, 24%). Transdermal fentanyl significantly improved visual analog scale scores and Oswestry Disability Index scores in 73% of patients, especially those with specific low back pain awaiting surgery; however, it did not decrease pain in 27% of patients, including patients with non-specific low back pain or multiple back operations.


Effect of tumor type on response to adjuvant platinum-based chemotherapy and prognosis in patients with stage II-IV epithelial ovarian carcinoma.
To evaluate the effect of histological subtype on oncological outcome and adjuvant platinum-based chemotherapy response in patients with epithelial ovarian cancer (EOC). The study group was created with stage II-IV EOC patients. Progression-free survival (PFS) and disease-specific survival (DSS) estimates were determined by using the Kaplan-Meier method. The log-rank test and cox proportional hazards model were performed. A total 396 patients were included the study. Tumor type was serous in 332 (83.8%). Two hundred and thirty-one patients (58.3%) had maximal cytoreduction. Three hundred and twenty-seven (82.6%) patients received complete clinical response. Refractory disease was present in 69 (17.4%) patients. In patients with complete clinical response, 183 (56%) patients recurred. Five-year PFS was 32% in serous group and 31% in non-serous group (p = 0.755). Five-year DSS was 78% in serous group and 87% in non-serous group (p = 0.084). On multivariate analysis, recurrence rates 1.959 times (95% CI: 1.224-3.085; p = 0.004), death rates 2.624 times (95% CI: 1.328-5.185; p = 0.005) higher in patients with optimal cytoreduction than patients with maximal cytoreduction, respectively. Although the rate of maximal cytoreduction was higher in patients with non-serous tumor type, the rate of refractory disease was higher after adjuvant chemotherapy. However, the recurrence rate was higher in serous tumor type. Survival rates were similar in serous and non-serous tumor types. Maximal cytoreduction was an independent predictor factor for survival. Maximal cytoreduction should be the main target in EOC.


A method for confirming a third-party assay of I-125 seeds used for prostate implants.
The purpose of this work is to describe a method and apparatus that can be used to confirm the source strength of a large number of I-125 seeds while maintaining sterility, accuracy, reproducibility, and time efficiency. Source strengths ranging from 0.395 to 0.504 U/seed were available for this study. Three different seed configurations were measured: loose, linked, and loaded needles. A third-party 10% assay (NIST traceable) was provided. A custom stand was built out of aluminum to hold an exposure meter [Inovision (Fluke) 451P pressurized ion chamber] at 25 cm above the I-125 sources to measure the exposure rate. The measurements were made in an operating room, and a sterile sheet was placed under the nonsterile aluminum stand on a sterile loading table. Seeds and needles were placed in a sterile tray for these measurements. Two hundred and six loose seeds in six batches (0.395, 0.395, 0.409, 0.444, 0.444, and 0.444 U/seed) and 1434 seeds in 10 batches containing various strands (0.444, 0.444, 0.444, 0.444, .0444, 0.466, 0.466, 0.504, and 0.504 U/seed) were measured. For the loose and stranded seeds, the average exposure rate per unit activity was measured to be 0.589 mR/h·U with a standard deviation of 0.017. Loaded needles were measured with an average exposure rate per unit activity to be 0.269 mR/h·U with a standard deviation of 0.014. We conclude that the method described here is capable of confirming a third-party assay when performed on a large number of loose or stranded seeds in bulk. It is less reliable for preloaded needles.


Anti-Obesity Effects of a Mixture of Fermented Ginseng, Bifidobacterium longum BORI, and Lactobacillus paracasei CH88 in High-Fat Diet-Fed Mice.
Ginseng and probiotics have anti-obesity effects in mice fed a high-fat diet (HFD). Absorption of ginsenoside and colonization of probiotics occur in the intestine. In this study, a mixture of fermented ginseng and two probiotics, Bifidobacterium longum BORI and Lactobacillus paracasei CH88, was administered to HFD-fed mice for 9 weeks. The mixture significantly suppressed weight gain (p < 0.05, n = 8) and lipid deposition in the liver and adipose tissues as well as increased the mice's food intake. The adipocyte size of the adipose tissue was significantly decreased in the mixture-fed group, especially when 0.5% fermented ginseng and 5 × 10⁸/ml of the two probiotics were used (p < 0.05, n = 10). The expression of TNF-α in adipose tissue was efficiently downregulated in the mixture-fed group (p < 0.05, n = 4). The supplement also improved the mice's fasting blood glucose levels (p < 0.05, n = 8) and total cholesterol feces excretion (p < 0.05, n = 8). The mixture of fermented ginseng and B. longum BORI and L. paracasei CH88 could have an anti-obesity effect and suppress lipid deposit in the liver and adipose tissues.


Recommended revisions to American Dental Association guidelines for acceptance of chemotherapeutic products for gingivitis control. Report of the Task Force on Design and Analysis in Dental and Oral Research to the Council on Therapeutics of the American Dental Association.
This paper presents suggested revisions to the American Dental Association's 1985 guidelines for acceptance of anti-gingivitis chemotherapeutic agents. The areas of study design, choice and quality control of clinical gingivitis measurements, statistical analysis, and minimum strength of effect, are addressed. The revisions articulate certain aspects of study design which were implicit in the 1985 guidelines, clarify language on cross-over designs and independence of studies, and recommend use of a United States population in at least one trial supporting a product. Separate recording and analysis of a product's effect on gingival bleeding is proposed, and quality control of clinical measurements receives enhanced emphasis. Modestly elaborated statistical reporting guidelines and strengthened approval criteria, based on size of estimated effect as well as statistical significance, are advocated.


Effect of demographic features on morphometric variables of the knee joint: Sample of a 20 to 40-year-old Turkish population.
This study aimed to investigate the relationship between body mass index (BMI), age, and sex and morphological risk factors that may cause internal knee injuries. The magnetic resonance images of 728 participants who met the inclusion criteria and had a mean age of 34.4 ± 6.8 years were analyzed retrospectively. Demographic differences were analyzed by measuring 17 morphological parameters known to be associated with internal knee injuries. Men had a higher anterior cruciate ligament length (ACLL), anterior cruciate ligament width, (ACLW) lateral femoral condylar width (LFCW), medial femoral condylar width (MFCW), lateral femoral condylar depth (LFCD), distal femoral width (DFW), and intercondylar femoral width (IFW) than women (P < .05). By contrast, the medial meniscus bone angle (MMBA) was lower in men than in women (P < .05). Women aged 31 to 40 years had a lower Insall-Salvati index (ISI) and lateral tibial posterior slope (LTPS) than those aged 21 to 30 years (P < .05), whereas men aged 31 to 40 years had a lower ISI than those aged 21 to 30 years (P < .05). Women with BMI ≥ 30 had a higher LFCW and MFCW but a lower ISI than those with BMI < 30 (P < .05). Men with BMI ≥ 30 had a higher LFCW, MFCW, DFW, and MMBA than those with BMI < 30 (P < .05). The use of value ranges structured according to demographic characteristics, rather than a single value range for all patient groups, may contribute to the evaluation and treatment of the morphological features that are thought to be effective in the development of internal knee injuries. These values may also shed light on future radiological risk scoring systems and artificial intelligence applications in medicine.


The impact of single-cell RNA sequencing on understanding the functional organization of the immune system.
Application of single-cell genomics technologies has revolutionized our approach to study the immune system. Unravelling the functional diversity of immune cells and their coordinated response is key to understanding immunity. Single-cell transcriptomics technologies provide high-dimensional assessment of the transcriptional states of immune cells and have been successfully applied to discover new immune cell types, reveal haematopoietic lineages, identify gene modules dictating immune responses and investigate lymphocyte antigen receptor diversity. In this review, we discuss the impact and applications of single-cell RNA sequencing technologies in immunology.


Comparative Evaluation of Chemotactic Factor Effect on Migration and Differentiation of Stem Cells of the Apical Papilla.
Cell homing strategies could potentially be used in regenerative endodontic procedures (REPs) to promote the progressive coronal migration of stem cells, including stem cells of the apical papilla (SCAPs), along with formation of a new vascular network without the need for intentional apical trauma and intracanal bleeding. Although many chemotactic factors have been investigated for different mesenchymal stem cells, their effect on SCAP migration and differentiation is not fully understood. This study aimed to comparatively evaluate the effect of stromal cell-derived factor 1 (SDF-1), transforming growth factor beta 1 (TGF-β1), platelet-derived growth factor, granulocyte colony-stimulating factor (G-CSF), or fibroblast growth factor 2 (FGF-2) on the migration and differentiation of SCAPs. A characterized SCAP cell line was fluorescently labeled with Vybrant DiO dye (Life Technologies, Grand Island, NY) and used in transwell migration assays. Cells were subjected to 1, 10, or 100 ng/mL of each factor or a combination of factors followed by detection in a fluorescent plate reader. Lastly, SCAP differentiation into a mineralizing phenotype was evaluated in the presence or absence of the tested factors by quantitative alizarin red staining and alkaline phosphatase activity. Data were analyzed with 1-way analysis of variance with the Tukey post hoc test. Maximum migration was observed with G-CSF or FGF-2, which was significantly greater than the effects observed by the other tested factors. A combination of G-CSF with TGF-β1 significantly augmented both migration and differentiation into a mineralizing phenotype. G-CSF appears to be well suited to be further investigated as a key chemotactic factor in cell homing-based regenerative endodontic procedures.


Altered Concentrations in Dyslipidemia Evidence a Role for ANGPTL8/Betatrophin in Lipid Metabolism in Humans.
Angiopoietin-like protein 8 (ANGPTL8)/betatrophin is a secreted protein initially involved in β-cell replication. Recent data in humans and mice models suggest that ANGPTL8/betatrophin is more related to lipid metabolism. The aim of the present study was to compare the circulating concentrations of ANGPTL8/betatrophin in individuals with dyslipidemia defined as having high or low levels of high-density lipoprotein (HDL)-cholesterol or triglycerides, respectively. Serum concentrations of ANGPTL8/betatrophin were measured by an ELISA in 177 subjects. We studied two different selected case-control dyslipidemic cohorts including individuals with high (n = 43) or low (n = 46) circulating concentrations of HDL-cholesterol or with low (n = 48) or high (n = 40) levels of triglycerides. Circulating concentrations of ANGPTL8/betatrophin were significantly lower in individuals with dyslipidemia (P < .001) in both males (controls 27.8 ± 15.2 vs dyslipidemic 17.0 ± 11.2 ng/mL) and females (controls 50.0 ± 22.2 vs dyslipidemic 27.0 ± 16.5 ng/mL). The magnitude of the differences was higher in dyslipidemic patients with low HDL-cholesterol than in those with high triglyceride concentrations. ANGPTL8/betatrophin levels were lower in subjects with type 2 diabetes (P < .001), but the impact of type 2 diabetes vanished (P = .257) when the effect of dyslipidemia was included in the analysis. We conclude that serum ANGPTL8/betatrophin concentrations are altered in human dyslipidemia. ANGPTL8/betatrophin emerges as a potential player in dyslipidemia with a strong association with HDL-cholesterol and a potential therapeutic tool for the treatment of dyslipidemia.


Nucleotide sequence of the chicken proto-oncogene c-erbA corresponding to domain 1 of v-erbA.
The nucleotide sequence of the chicken proto-oncogene c-erbA, the cellular counterpart of the viral oncogene v-erbA domain 1, has been determined. The c-erbA gene has an exon-intron structure characteristic of the eukaryotic split genes. The c-erbA domain 1 is composed of at least eight exons and seven introns. Analysis of the sequence data reveals a long open reading frame of 239 amino acid residues that share highly significant homology with the viral protein. Our results show that the viral erbA oncogene is a truncated form of its cellular homologue. In fact the cellular gene is 42 nucleotides longer at its 5' coding extremity. The presence of a gag-specific (17/20) nucleotide stretch in this region favours the hypothesis of a homologous recombination event between the cellular erbA and the gag gene of a parental retrovirus. We have also sequenced 1400 bp of DNA lying 5' to the long open reading frame in search of the transcription initiation sites for the c-erbA messenger RNAs. Our findings and interpretations are presented here.


[Temporal arteritis with necrotizing angiitis of the muscles].
A 71 year old woman with typical giant-cell arteritis experienced myalgia of the legs immediately at the end of steroid therapy, 3 months after the onset of her illness. Muscle biopsy showed a focal necrotising panarteritis whereas the muscular fibres remained unchanged. The patient is now asymptomatic after 3 years' follow-up on prednisolone therapy (10 mg per day). This case demonstrates that giant cell arteritis can also involve the muscular arteries.


[Ewing sarcoma--analysis of epidemiological parameters and their relation to clinical characteristics].
The purpose of this investigation was to evaluate epidemiologic features of Ewing sarcoma in children treated in the Institute for Orthopedic Surgery "Banjica: as well as to establish relation of these features to clinical findings. Study involved 78 patients treated over 20-year period (1980-2000). Analysis included standard epidemiologic data (age, sex, tumor localization) and diagnostic clinical features on presentation (major symptoms, time elapsed between presentation and diagnosis, presence of metastases). Most of the patients were in the age group of 15-18 years (50.0%), predominantly males. In general, the results of our study were consistent with data reported in literature. Nevertheless, this investigation revealed slightly higher incidence in patients younger than four years of age (5.1%); localization on the upper extremity was found to be more frequent (upper to lower extremity ratio was nearly 3:1 in our study), and the time lost between presentation and diagnosis was markedly reduced (average time elapsed between presentation and diagnosis was 2.5 months). The results of our study may improve efficiency and success of treatment, thus providing the basis of better prognosis in management of such a serious illness.


Does pregnancy affect otosclerosis?
To evaluate the effect of pregnancy on the hearing of women with otosclerosis. A retrospective study of women who had undergone stapedectomy. The women were equally divided into two groups: one group with children and a control group without children. Air and bone conduction, as well as discrimination, were measured before and after stapedectomy in both groups. Ninety-four women (47 with children and 47 without) were evaluated. Because many of the women had bilateral otosclerosis, the total number of ears studied was 128. Mean pure tone air and bone conduction thresholds were not worse in women with children versus those women without children. In fact, mean pre- and postoperative pure tone air and bone conduction thresholds from 500 Hz through 4,000 Hz in women with children were slightly but significantly better than women without children. There was no difference in discrimination scores between groups. Within the group with children, no significant correlation was found between number of children and hearing loss. Also, no correlation was found between breastfeeding and the amount of hearing loss. We found no adverse effect on hearing in otosclerotic women who had children compared with women without children. Even with increasing numbers of pregnancies, no deleterious impact was noted. Air conduction, bone conduction, and discrimination were not worse in women with children versus childless women. No significant correlation was found between the number of children and hearing loss, and neither did breastfeeding affect the amount of hearing loss.


Success in Adopting Technique of Alpine Skiing with Respect to Motor Abilities of the Children Aged 7-8 Years.
The aim of this research was to determine relations between estimated motor abilities and efficiency of alpine ski learning in children ski beginners. It included 54 children between 7 and 8 years of age (average 7.44 ± 0.52 years). Children were tested for balance, agility, strength, coordination and frequency of movement on ten motor ability tests. After motor abilities were assessed, participants learned alpine skiing during six-day alpine ski school and upon completion of ski school program, were tested on three elements of alpine ski technique (stopping in a snow-plough, uphill turn and turns around the posted marks) by three independent judges. According to achieved level of ski knowledge, they were allocated to three groups differing by the level of success; less successful (N = 18; 26-44 points), moderately successful (N = 11; 45-48 points) and successful (N = 25; 49-55 points). Significant differences in success of adopting basic ski technique were noticed with respect to the results achieved in the task polygon backwards (F = 6.162, p = 0.004), foot tapping (F = 6.337, p = 0.003) and crossed arm sit-ups (F = 3.099, p = 0.053). The participants who successfully adopted the basic ski technique also achieved good results in tests: polygon backwards, foot tapping, crossed arm sit-ups, side steps, balancing on left leg perpendicular on balance board, vertical jump and medium results in tests 20m dash and balancing on right leg perpendicular on balance board. Our results suggest that successful participants have better developed coordination, frequency of movement, strength and agility.


Cancerization of eccrine sweat ducts in Bowen's disease as studied by light microscopy, DNA spectrophotometry and immunohistochemistry.
This study assesses the incidence, histogenesis, and significance of eccrine sweat duct involvement in Bowen's disease (BD). In a review of 96 cases of BD, four showed eccrine duct involvement on hematoxylin and eosin-stained histologic sections. One case was analyzed for deoxyribonucleic acid (DNA) ploidy by using computerized image analysis on Feulgen-stained slides. Sections were also stained immunohistochemically, using antibodies to carcinoembryonic antigen (CEA), gross cystic disease fluid protein (GCDFP), and S-100 protein, and for cytokeratins (CAM 5.2, AE 1/3). Our results showed that, in BD, (a) the eccrine sweat ducts can be extensively involved by atypical cells, (b) the atypical eccrine duct cells had an aneuploid DNA pattern, and (c) the atypical eccrine duct cells were negative for CEA, GCDFP, and S-100 protein but were positive for cytokeratins. We conclude that (a) the frequency of eccrine duct involvement in BD is relatively low (approximately 4 to 9%), (b) the aneuploid DNA pattern makes a benign squamous metaplasia unlikely, (c) the immunohistochemical results exclude coincidental Paget's disease or carcinoma of eccrine sweat glands, (d) the involvement of eccrine sweat ducts may represent a direct extension of the neoplastic epidermal keratinocytes, and (e) this process may have practical implications in the recurrence of superficially treated cases of BD.


Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1.
Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by the development of multiple neurofibromas, cafe-au-lait spots, and Lisch nodules. Individuals with NF1 are at increased risk of developing various tumors, such as malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, leukemia, glioma, rhabdomyosarcoma, and breast cancer. Here, we describe the exome sequencing of breast cancer, MPNST, and neurofibroma from a patient with NF1. We identified a germline mutation in the NF1 gene which resulted in conversion of leucine to proline at amino acid position 847. In addition, we showed independent somatic NF1 mutations in all the three tumors (frameshift insertion in breast cancer (p.A985fs), missense mutation in MPNST (p.G23R), and inframe deletion in dermal neurofibroma (p.L1876del-Inf)), indicating that a second hit in NF1 resulting in the loss of function could be important for tumor formation. Each tumor had a distinct genomic profile with mutually exclusive mutations in different genes. Copy number analysis revealed multiple copy number alterations in the breast cancer and the MPNST, but not the benign neurofibroma. Germline loss of chromosome 6q22.33, which harbors two potential tumor suppressor genes, PTPRK and LAMA2, was also identified; this may increase tumor predisposition further. In the background of NF1 syndrome, although second-hit NF1 mutation is critical in tumorigenesis, different additional mutations are required to drive the formation of different tumors.


Molecular Detection of Severe Combined Immunodeficiency Disorder in Arabian Horses in Egypt.
Severe combined immunodeficiency (SCID) is a fatal genetic disorder and one of the common genetic diseases of the Arabian horse. The genetic mutation responsible for this disease is a five base pair deletion (TCTCA) in the DNA-protein kinase catalytic subunit gene. Severe combined immunodeficiency is a recessive autosomal genetic disorder with 25% chance inheritance of the disease among the progeny of carrier parents. It causes complete absence of certain immune cells, like B and T lymphocytes, leaving foals with immunodeficiency and exposing them to early death within 4 to 6 months. This study aimed to establish a reliable DNA test for detection of asymptomatic SCID carriers in the Egyptian Arabian horse population and to re-examine cases of unexplained foal death to exclude presence of SCID disease. Samples collected from live horses were chosen at random from the registered population, as well as postmortem samples from reported cases died at different ages in Arabian farms. Among these samples, we did not identify SCID carriers. Improved SCID diagnostic assays will help in selection within breeding programs to avoid carrier-to-carrier mating and the birth of clinically affected foals. This will have a positive effect on the financial value of Arabian horse production by decreasing economic losses due to affected foal deaths, extended veterinary care, and intensive but futile treatments. Application of the DNA test overall Egyptian population is recommended.


EPS-LASSO: test for high-dimensional regression under extreme phenotype sampling of continuous traits.
Extreme phenotype sampling (EPS) is a broadly-used design to identify candidate genetic factors contributing to the variation of quantitative traits. By enriching the signals in extreme phenotypic samples, EPS can boost the association power compared to random sampling. Most existing statistical methods for EPS examine the genetic factors individually, despite many quantitative traits have multiple genetic factors underlying their variation. It is desirable to model the joint effects of genetic factors, which may increase the power and identify novel quantitative trait loci under EPS. The joint analysis of genetic data in high-dimensional situations requires specialized techniques, e.g. the least absolute shrinkage and selection operator (LASSO). Although there are extensive research and application related to LASSO, the statistical inference and testing for the sparse model under EPS remain unknown. We propose a novel sparse model (EPS-LASSO) with hypothesis test for high-dimensional regression under EPS based on a decorrelated score function. The comprehensive simulation shows EPS-LASSO outperforms existing methods with stable type I error and FDR control. EPS-LASSO can provide a consistent power for both low- and high-dimensional situations compared with the other methods dealing with high-dimensional situations. The power of EPS-LASSO is close to other low-dimensional methods when the causal effect sizes are small and is superior when the effects are large. Applying EPS-LASSO to a transcriptome-wide gene expression study for obesity reveals 10 significant body mass index associated genes. Our results indicate that EPS-LASSO is an effective method for EPS data analysis, which can account for correlated predictors. The source code is available at https://github.com/xu1912/EPSLASSO. Supplementary data are available at Bioinformatics online.


Integration of freshwater environmental policies and wastewater treatment plant management.
In the last decade the political awareness of river water quality issues has grown substantially over the world and legislation is accordingly adapting. In the European Union (EU), two different directives regulate separately the characteristics of the discharged water and the chemical status of the receiving freshwater ecosystem. On the one hand, the characteristics of the urban effluents are regulated by the EU Directive 91/271/EEC, which defines limits on different elements set in the form of both static emission limits and minimum percentage load reductions. On the other hand, the characteristics of the receiving freshwater ecosystems are described in the EU Water Framework Directive (2000/60/EEC), which sets minimum 'good' chemical and ecological status in water bodies that should be achieved by 2015, and aims for an ecosystem-based management. With the support of an example, we show that there is a gap in these EU environmental policies leading to non-integrated management, which may result on adverse environmental and economical consequences. We believe that these policies should be updated and tuned to account for an integrated perspective, allowing a more efficient and sustainable management of wastewater treatment plants, maximizing the ecological, economical and social benefits of the system as a whole.


An interrelationship between autophagy and filamentous growth in budding yeast.
Over the last 15 years, yeast pseudohyphal growth (PHG) has been the focus of intense research interest as a model of fungal pathogenicity. Specifically, PHG is a stress response wherein yeast cells deprived of nitrogen form filaments of elongated cells. Nitrogen limitation also induces autophagy, a ubiquitous eukaryotic stress response in which proteins are trafficked to the vacuole/lysosome for degradation and recycling. Although autophagy and filamentous growth are both responsive to nitrogen stress, a link between these processes has not been investigated to date. Here, we present several studies describing an interrelationship between autophagy and filamentous growth. By microarray-based expression profiling, we detect extensive upregulation of the pathway governing autophagy during early PHG and find both processes active under conditions of nitrogen stress in a filamentous strain of budding yeast. Inhibition of autophagy results in increased PHG, and autophagy-deficient yeast induce PHG at higher concentrations of available nitrogen. Our results suggest a model in which autophagy mitigates nutrient stress, delaying the onset of PHG; conversely, inhibition of autophagy exacerbates nitrogen stress, resulting in precocious and overactive PHG. This physiological connection highlights the central role of autophagy in regulating the cell's nutritional state and the responsiveness of PHG to that state.


Impact of paroxetine on proximal β-adrenergic receptor signaling.
β-adrenergic receptors (βAR) regulate numerous functions throughout the body, however G protein-coupled receptor kinase (GRK)-dependent desensitization of βAR has long been recognized as a maladaptive process in the progression of various disease states. Thus, the development of small molecule inhibitors of GRKs for the study of these processes and as potential therapeutics has been at the forefront of recent research efforts. Via structural and biochemical analyses, the selective serotonin reuptake inhibitor (SSRI) paroxetine was identified as a GRK2 inhibitor that enhances βAR-dependent cardiomyocyte and cardiac contractility and reverses cardiac dysfunction and myocardial βAR expression in mouse models of heart failure. Despite these functional outcomes, consistent with diminished βAR desensitization, the proximal βAR signaling mechanisms sensitive to paroxetine have not been reported. In this study, we aimed to determine whether paroxetine prevents classic βAR desensitization-related signaling mechanisms at a molecular level. Therefore, via immunoblotting, radioligand binding, fluorescence resonance energy transfer (FRET) and microscopy assays, we have performed an assessment of the effect of paroxetine on proximal βAR signaling responses. Indeed, paroxetine treatment inhibited ligand-induced β2AR phosphorylation in a concentration-dependent manner. Additionally, for both β1AR and β2AR, paroxetine decreased ligand-induced βarrestin2 recruitment and subsequent receptor internalization. Thus, paroxetine inhibits βAR desensitization mechanisms consistent with GRK2 inhibition and provides a useful pharmacological tool for studying these proximal GPCR signaling responses.


Learning about and from others' prudence, impatience or laziness: The computational bases of attitude alignment.
Peoples' subjective attitude towards costs such as, e.g., risk, delay or effort are key determinants of inter-individual differences in goal-directed behaviour. Thus, the ability to learn about others' prudent, impatient or lazy attitudes is likely to be critical for social interactions. Conversely, how adaptive such attitudes are in a given environment is highly uncertain. Thus, the brain may be tuned to garner information about how such costs ought to be arbitrated. In particular, observing others' attitude may change one's uncertain belief about how to best behave in related difficult decision contexts. In turn, learning from others' attitudes is determined by one's ability to learn about others' attitudes. We first derive, from basic optimality principles, the computational properties of such a learning mechanism. In particular, we predict two apparent cognitive biases that would arise when individuals are learning about others' attitudes: (i) people should overestimate the degree to which they resemble others (false-consensus bias), and (ii) they should align their own attitudes with others' (social influence bias). We show how these two biases non-trivially interact with each other. We then validate these predictions experimentally by profiling people's attitudes both before and after guessing a series of cost-benefit arbitrages performed by calibrated artificial agents (which are impersonating human individuals).


Dedifferentiated liposarcoma of the retroperitoneum.
A dedifferentiated liposarcoma of the retroperitoneum is an extremely rare tumor. A 51-year old man was admitted to our department because a retroperitoneal mass was seen on abdominal computed tomography at another hospital. Computed tomography of the abdomen and magnetic resonance imaging showed a large pelvic mass located in the right hemipelvis, and it was pushing the right ureter and invading the right kidney, duodenum, colon and inferior vena cava. The patient underwent right radical nephrectomy, pylorus preserving pancreatoduodenectomy, right hemicolectomy and artificial blood vessel replacement for the inferior vena cava. The histopathological diagnosis was dedifferentiated liposarcoma and the patient was free from recurrence on the computed tomography that was done 6 months after the operation.


Cardiac findings in children admitted to a hospital general ward in South Africa: a comparison of HIV-infected and uninfected children.
The aim of this prospective observational study was to determine the presence of cardiac abnormalities in HIV infected versus uninfected children who were admitted to a general paediatric ward during a two-month period. HIV status was determined by antibody and p24 antigen testing. Clinical information, echocardiography and electrocardiography (ECG) were performed for all children. There were 90 HIV-infected and 118 uninfected children. The median age was 9.6 and 11.8 months for infected and uninfected children, respectively. Baseline left ventricular dysfunction, defined as a shortening fraction < or = 25%, was found in 13 (17%) of the HIV-infected children compared to 5 (8%) uninfected children (p < 0.05). Left ventricular end-diastolic enlargement above the 98th percentile for age was found in 24% of the infected and 20% of uninfected children. Pericardial effusions, although common, were sub-clinical and not different in the groups. ECG findings and resting heart rates were also similar. Left ventricular dysfunction was the most significant cardiac abnormality present in hospitalised HIV-infected children. Other abnormalities, although common, were mostly asymptomatic and found with the same frequency in uninfected children. Further studies are indicated.


Sensitivity of EIA in the diagnosis of tuberculosis using 38-kDa antigen.
Patients, who reported to Government Medical College Hospital, Chandigarh with suspected signs and symptoms of pulmonary tuberculosis, were examined. Their sputum was investigated for the presence of acid-fast bacilli, using the routine Ziehl-Neelsen staining, for 3 consecutive days. The positive cases were referred for treatment and the rest were referred for supplementary tests like x-ray, Mantoux test, FNAC and the presence of IgG antibodies in their serum against recombinant 38-kDa antigen derived from Mycobacterium tuberculosis, using micro-ELISA plates. It was found that 37.8% of the cases who were negative for acid-fast bacilli found to be positive for the presence of antimycobacterial IgG antibodies with an antibody titre greater than the cut off value in addition to one of the above mentioned positive supplementary finding. Hence, EIA for tuberculosis is more sensitive as compared to the routine acid-fast bacilli staining.


Impact of Crude Oil Quality on the Refining Conditions and Composition of Nutraceuticals in Refined Palm Oil.
Palm oil is the major vegetable oil used worldwide due to its unique properties. The effect of crude palm oil acidity on the final free fatty acids (FFA) content, neutral oil loss (NOL), and nutraceutical compounds, such as carotenes, total tocols (tocopherols and tocotrienols), squalene, and phytosterols was investigated. A central composite design was employed to study the influence of the refining conditions: temperature (200 to 260 °C), steam percentage (0.5% to 3.5%), and initial FFA content (2.2% to 6.0%) on the quality of the refined product. The results revealed that initial palm oil acidity is a statistically important parameter to obtain commercially acceptable values for final FFA content. The increase of temperature presented the most important effect on the reduction of all nutraceutical compounds. The highest tocopherols (88%), phytosterols (98%), and squalene retention (84%) was obtained when applying the mildest temperature (200 °C). From the experimental results, 3 equations were generated enabling the prediction of the free fatty acids content, the tocols content, and the losses of neutral oil. Therefore, this work contributes to the understanding and optimization of the process for the production of palm oil with high nutraceutical quality and low free fatty acid contents.


Predominance of HIV-1 among patients with AIDS and AIDS-related complex in Ghana.
We determined the prevalence of HIV among AIDS and AIDS-Related Complex (ARC) patients seen within one year in two hospitals in southern Ghana. Subjects were screened by an ELISA procedure for anti-HIV antibodies. Specific identification of the HIV type was done with a particle agglutination (PA) kit. All PA-determined dual specimens were then confirmed by Western blotting and Pepti-Lav 1/2 monoepitope kit. Virus isolation was attempted from symptomatic patients by co-culturing patient peripheral blood monocyte cells (PBMCs) and CD4+ cell lines. PBMCs and HIV isolates were characterised by PCR. By ELISA, 43.5% of the subjects (253) had anti-HIV antibodies. Of these, 61 (24%) were HIV-1 positive and 42 (18.6%) were dually reactive by PA. However, only 19% were confirmed as true dually-infected cases by western blotting and Pepti-Lav through all 42 samples were HIV-1 positive on the two tests. No subject was infected with HIV-2 alone. Three viruses were isolated. By PCR two of them had both HIV-1 and HIV-2 proviral sequences while the third virus was HIV-1 only. HIV-1 prevalence now predominates over HIV-2 implying a switch in the HIV infection pattern in Ghana. Furthermore mixed infections exist. The predominance of HIV-1 infection in Ghana may indicate a similar trend in other parts of West Africa.


Sagittal tibiotalar translation and clinical outcomes in mobile and fixed-bearing total ankle replacement.
Sagittal implant malalignment after total ankle replacement (TAR) has been considered to be a possible cause for premature implant failure. In a prior study, the change over time of the tibiotalar ratio (T-T ratio), which is the ratio between the posterior longitudinal talar length and the full longitudinal talar length, was assessed in 66 TARs where an unconstrained, mobile-bearing implant was implanted. The analysis documented an increase in the T-T ratio between 2 and 6 months post-surgery (on average from 34.6% to 37.2%). We hypothesized that this change might have been related to the presence of a mobile-bearing insert. In order to test our hypothesis, we designed a study to compare the translation of the talus in TARs performed with an unconstrained, mobile-bearing implant (designated the "Mobile ankle") and those performed with a semi-constrained, fixed-bearing implant (designated the "Fixed ankle"). The study included 71 consecutive patients (71 ankles) who underwent TAR with the Mobile ankle and 24 consecutive patients (24 ankles) who received the Fixed ankle from May 2011 to December 2014. Patients were assessed clinically and radiologically preoperatively (T0), at 6 months (T2) and 12 months (T3) post-surgery. There was also a radiological assessment at 2 months post-surgery (T1). The comparison of the T-T ratio between the two implant groups and over time indicated an interaction between time and group, therefore the changes of the T-T ratio over time were affected by the implant type factor (P<0.001). The changes of the postoperative T-T ratio over time were not significant in the Fixed ankle group (35.7±6.7% at T1, T2, and T3; P=1.0 for each pairwise comparison). In the Mobile ankle group, the T-T ratio at 2 months (34.4±5.5%) was significantly different to the T-T ratio at 6 months (37.0±5.8%; P<0.001; i.e. there was a significant posterior translation of the talus). The AOFAS score increased from preop to 12 months post-surgery in both the Mobile ankle (72.7±12.8 at 12 months; P<0.001) and the Fixed ankle (85.0±9.7 at 12 months; P<0.001). The significant posterior translation of the talus from 2 to 6 months documented only in the Mobile ankle group may have been associated with the presence of the mobile bearing interface.


Adrenoceptor-mediated regulation of the contractility in horse penile resistance arteries.
The receptors mediating the contractions to both exogenously applied noradrenaline and electrical field stimulation (EFS) were characterized in horse isolated penile resistance arteries. The alpha 1-adrenoceptor-selective antagonist, prazosin, caused competitive rightward shifts of the contractile concentration-response curves (CRC) to phenylephrine. The alpha 2-antagonist, rauwolscine, also displaced to the right the CRC to the alpha 2-adrenoceptor-selective agonist, BHT 920. EFS (0.3 ms, 20-second trains) caused tetrodotoxin-sensitive frequency-dependent contractions which were enhanced in the presence of NG-nitro-L-arginine (L-NOARG, 3 x 10(-5) M), but not affected by mechanical endothelial cell removal. In experiments performed in the presence of L-NOARG, prazosin inhibited contractions to EFS, while rauwolscine inconsistently enhanced the contractile responses. Exogenously added noradrenaline induced contractions which were not changed in endothelium-denuded arteries, but significantly increased in the presence of L-NOARG. Prazosin inhibited the noradrenaline-induced contractions, while rauwolscine did not change the response to noradrenaline either alone or in the presence of prazosin. In the presence of phentolamine (10(-5) M), isoprenaline, adrenaline and the beta 2-adrenoceptor agonist, salbutamol, concentration-dependently relaxed penile resistance arteries, while the relaxations to noradrenaline and dobutamine, which activate beta 1-adrenoceptors, were negligible. Isoprenaline-induced relaxations were not changed in the presence of the beta 1-antagonist, atenolol (10(-7)-10(-6) M), but competitively inhibited by the beta 2-adrenoceptor antagonist, butoxamine (10(-6)-10(-5) M). The present results indicate that stimulation of adrenergic nerves in horse penile resistance arteries releases noradrenaline, which induces vasoconstriction through a predominant activation of alpha 1-adrenoceptors, while postjunctional alpha 2-adrenoceptors apparently play a minor role. Functional beta 2-adrenoceptors are also present in these arteries.


Effects of sinusoidal electromagnetic field on structure and function of different kinds of cell lines.
This study investigated that whether a 2 mT, 60 Hz, sinusoidal electromagnetic field (EMF) alters the structure and function of cells. This research compared the effects of EMF on four kinds of cell lines: hFOB 1.19 (fetal osteoblast), T/G HA-VSMC (aortic vascular smooth muscle cell), RPMI 7666 (B lymphoblast), and HCN-2 (cortical neuronal cell). Over 14 days, cells were exposed to EMF for 1, 3, or 6 hours per day (hrs/d). The results pointed to a cell type-specific reaction to EMF exposure. In addition, the cellular responses were dependent on duration of EMF exposure. In the present study, cell proliferation was the trait most sensitive to EMF. EMF treatment promoted growth of hFOB 1.19 and HCN-2 compared with control cells at 7 and 14 days of incubation. When the exposure time was 3 hrs/d, EMF enhanced the proliferation of RPMI 7666 but inhibited that of T/G HA- VSMC. On the other hand, the effects of EMF on cell cycle distribution, cell differentiation, and actin distribution were unclear. Furthermore, we hardly found any correlation between EMF exposure and gap junctional intercellular communication in hFOB 1.19. This study revealed that EMF might serve as a potential tool for manipulating cell proliferation.


Survival behavior in the cyclic Lotka-Volterra model with a randomly switching reaction rate.
We study the influence of a randomly switching reproduction-predation rate on the survival behavior of the nonspatial cyclic Lotka-Volterra model, also known as the zero-sum rock-paper-scissors game, used to metaphorically describe the cyclic competition between three species. In large and finite populations, demographic fluctuations (internal noise) drive two species to extinction in a finite time, while the species with the smallest reproduction-predation rate is the most likely to be the surviving one (law of the weakest). Here we model environmental (external) noise by assuming that the reproduction-predation rate of the strongest species (the fastest to reproduce and predate) in a given static environment randomly switches between two values corresponding to more and less favorable external conditions. We study the joint effect of environmental and demographic noise on the species survival probabilities and on the mean extinction time. In particular, we investigate whether the survival probabilities follow the law of the weakest and analyze their dependence on the external noise intensity and switching rate. Remarkably, when, on average, there is a finite number of switches prior to extinction, the survival probability of the predator of the species whose reaction rate switches typically varies nonmonotonically with the external noise intensity (with optimal survival about a critical noise strength). We also outline the relationship with the case where all reaction rates switch on markedly different time scales.


Botulinum toxin injection into rabbit vitreous.
Botulinum A toxin in a dose of 5.0 X 10(-4) micrograms was injected into the vitreous of eight rabbit eyes. An equal volume of normal saline was injected into the fellow eye as a control. External examination, intraocular pressure, ophthalmoscopy, electroretinography, and light microscopy showed no significant difference between toxin injected and control eyes over a two-month period.


Atomistic simulation of the growth of defect-free carbon nanotubes.
Atomistic simulation of defect-free single-walled carbon nanotube (SWCNT) growth is essential for the insightful understanding of the SWCNT's growth mechanism. Despite the extensive effort paid in the past two decades, the goal has not been completely achieved, due to the huge timescale discrepancy between atomistic simulation and the experimental synthesis of SWCNTs, as well as the lack of an accurate classical potential energy surface for large scale simulation. Here, we report atomistic simulations of defect-free SWCNT growth by using a new generation of carbon-metal potential and a hybrid method, in which a basin-hopping strategy is applied to facilitate the defect healing during the simulation. The simulations reveal a narrow diameter distribution and an even chiral angle distribution of the growth of SWCNTs from liquid catalyst, which is in agreement with most known experimental observations.


Increased salinization of fresh water in the northeastern United States.
Chloride concentrations are increasing at a rate that threatens the availability of fresh water in the northeastern United States. Increases in roadways and deicer use are now salinizing fresh waters, degrading habitat for aquatic organisms, and impacting large supplies of drinking water for humans throughout the region. We observed chloride concentrations of up to 25% of the concentration of seawater in streams of Maryland, New York, and New Hampshire during winters, and chloride concentrations remaining up to 100 times greater than unimpacted forest streams during summers. Mean annual chloride concentration increased as a function of impervious surface and exceeded tolerance for freshwater life in suburban and urban watersheds. Our analysis shows that if salinity were to continue to increase at its present rate due to changes in impervious surface coverage and current management practices, many surface waters in the northeastern United States would not be potable for human consumption and would become toxic to freshwater life within the next century.


Right frontal brain activity at rest in the early 20s predicts threat-related bias ten years later among extremely low birth weight survivors.
Exposure to early adversity is known to shape brain-behavior relations, which in turn can lead to hypersensitivity to threat and an increased risk of developing a range of psychopathologies. To date, much of the work in this area has considered exposure to negative post-natal events (e.g., maltreatment) in shaping these relations in humans. Here we examined the influence of prenatal adversity in the form of a suboptimal intra-uterine environment (i.e., being born at extremely low birth weight; [ELBW i.e., < 1000 g]). ELBW babies are the tiniest and most at-risk infants and are known to be at risk for internalizing problems (e.g., depression and anxiety) from childhood through early adulthood. However, we know relatively little about the mechanism(s) underlying this risk. Using the oldest known prospectively followed cohort of ELBW survivors, we examined associations among birth weight status, individual differences in frontal brain electrical activity (EEG) at rest (a marker of affective style) at age 22-26 years, and threat-related biases to angry faces (using the dot probe task) at 30-35 years of age. We found that among ELBW adults, those displaying greater relative right frontal EEG activity at rest exhibited greater vigilance to angry faces than those exhibiting greater relative left frontal EEG activity (n = 34, r = -0.40, p = .02). This pattern was not observed among normal birth weight (NBW) control participants (n = 47, r = .08, p > .05). As well, the relation between frontal EEG asymmetry and vigilance to angry faces was stronger for the ELBW group versus the NBW group (z = -2.21, p = .03). These findings suggest that exposure to significant prenatal adversity may have long-term programming effects on biological and cognitive systems associated with emotion regulatory processes in the fourth decade of life. We speculate that these vulnerabilities may contribute to making some ELBW survivors susceptible to psychopathology.


External Validation and Recalibration of the CURB-65 and PSI for Predicting 30-Day Mortality and Critical Care Intervention in Multiethnic Patients with COVID-19.
To validate and recalibrate the CURB-65 and pneumonia severity index (PSI) in predicting 30-day mortality and critical care intervention (CCI) in a multiethnic population with COVID-19, along with evaluating both models in predicting CCI. Retrospective data was collected for 1181 patients admitted to the largest hospital in Qatar with COVID-19 pneumonia. The area under the curve (AUC), calibration curves, and other metrics were bootstrapped to examine the performance of the models. Variables constituting the CURB-65 and PSI scores underwent further analysis using the Least Absolute Shrinkage and Selection Operator (LASSO) along with logistic regression to develop a model predicting CCI. Complex machine learning models were built for comparative analysis. The PSI performed better than CURB-65 in predicting 30-day mortality (AUC 0.83, 0.78 respectively), while CURB-65 outperformed PSI in predicting CCI (AUC 0.78, 0.70 respectively). The modified PSI/CURB-65 model (respiratory rate, oxygen saturation, hematocrit, age, sodium, and glucose) predicting CCI had excellent accuracy (AUC 0.823) and good calibration. Our study recalibrated, externally validated the PSI and CURB-65 for predicting 30-day mortality and CCI, and developed a model for predicting CCI. Our tool can potentially guide clinicians in Qatar to stratify patients with COVID-19 pneumonia.


Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage.
Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05) between the F3 and reference drug in terms of MDT and T50% with p-values of 1.00 and 0.995 respectively.


Use of vacuum-assisted closure negative pressure wound therapy in combat-related injuries--literature review.
Despite surgical and technological advances, managing combat-related injuries remains challenging both within and outside of the war theater. Unique characteristics of a war theater such as environmental contamination, varying evacuation procedures, and differing levels of medical care, add to the complexity. The advent of body armor has increased blast survival rates and soldiers are surviving with increasingly mangled limbs that require lengthy, multifaceted care. An inherent high risk of infection contraindicates immediate closure for these wounds. There is growing reported use of negative pressure wound therapy with reticulated open-cell foam (NPWT/ROCF) as delivered by vacuum-assisted closure (VAC) therapy (KCI Licensing Inc., San Antonio, TX) as an adjunctive therapy in these open soft-tissue combat wounds. This review evaluates the efficacy of NPWT/ROCF for adjunctive treatment of wartime wounds. Following a literature review, data are summarized and presented.


Cardiovascular and mood responses to an acute bout of cold water immersion.
Cold water immersion (CWI) may provide benefits for physical and mental health. Our purpose was to investigate the effects of an acute bout of CWI on vascular shear stress and affect (positive and negative). Sixteen healthy adults (age: 23 ± 4 y; (9 self-reported men and 7 self-reported women) completed one 15-min bout of CWI (10 °C). Self-reported affect (positive and negative) was assessed at pre-CWI (Pre), 30-min post-immersion, and 180-min post-immersion in all participants. Brachial artery diameter and blood velocity were measured (Doppler ultrasound) at Pre, after 1-min and 15-min of CWI, and 30-min post-immersion (n = 8). Total, antegrade, and retrograde shear stress, oscillatory shear index (OSI), and forearm vascular conductance (FVC) were calculated. Venous blood samples were collected at Pre, after 1-min and 15-min of CWI, 30-min post-immersion, and 180-min post-immersion (n = 8) to quantify serum β-endorphins and cortisol. Data were analyzed using a one-way ANOVA with Fisher's least significance difference and compared to Pre. Positive affect did not change (ANOVA p = 0.450) but negative affect was lower at 180-min post-immersion (p < 0.001). FVC was reduced at 15-min of CWI and 30-min post-immersion (p < 0.020). Total and antegrade shear and OSI were reduced at 30-min post-immersion (p < 0.040) but there were no differences in retrograde shear (ANOVA p = 0.134). β-endorphins did not change throughout the trial (ANOVA p = 0.321). Cortisol was lower at 180-min post-immersion (p = 0.014). An acute bout of CWI minimally affects shear stress patterns but may benefit mental health by reducing negative feelings and cortisol levels.


[Identification of Amur like virus in Apodemus peninsulae and its molecular characteristics in China].
To confirm the existence of Amur-like viruses in Apodemus peninsulae in China, and to understand the molecular characteristics of these viruses. Total RNA was extracted from lungs of A. peninsulae captured in Jilin of Northeast China with Trizol reagent. Complete S and partial M segments of Amur virus were amplified and sequenced. Phylogenetic analyses on multiple nucleotide sequences were performed with the Clustal method and DNASTAR software. 383 bp cDNA of M segment and 1696 bp of S segment of Amur like virus were recovered from lung tissue of A. peninsulae, named JilinAP06. The full-length of its S gene comprised of 1696 nucleotides with ORF including 1287 nucleotides and encoding a protein which comprised 429 amino acids. The phylogenetic analysis of this sample with other hantaviruses revealed that the complete S and partial M segment sequence of JilinAP06 both were closely related to those Amur viruses such as AP63, AP61, AP1371 and AP1168 found in A. peninsulae from Far East region of Russia and B78 strain, Liu strain and H5 strain, which were all from Chinese patients. The complete S and partial M segment sequence of JilinAP06 had only 81.0% identities with the nucleotide sequences of HV prototype 76-118 strain. Amur-like viruses did exist in A. peninsulae from Northeasern China while A. peninsulae might be the natural reservoir of Amur-like viruses in China and was the important infectious source to HFRS patients which were caused by Amur-like viruses.


A Comparative Evaluation of Revascularization Done in Traumatized Immature, Necrotic Anterior Teeth with and without Platelet-rich Fibrin: A Case Report.
The aim of this paper is to present two methods of revascularization done in traumatized immature, nonvital anterior teeth using platelet-rich fibrin (PRF) and natural blood clot as a scaffold material. This was performed after disinfection of the root canal space using tri-antibacterial paste. In one tooth, PRF prepared from autologous blood was placed in the canal and in the other tooth, natural bleeding was induced to obtain a fresh blood clot. The patient was recalled regularly at 1, 3, 6, 9, and 12 months' interval for evaluation. After 12 months, on clinical examination, both teeth showed negative response to percussion and palpation tests but positive response to cold and electric pulp tests. On radiographic examination, the tooth treated with PRF exhibited comparatively faster root lengthening, complete closure of the root apex, more thickening of the root dentinal walls, and narrowing of root canal space compared to conventionally revascularized tooth. How to cite this article: Nagaveni NB, Poornima P, Mathew MG, et al. A Comparative Evaluation of Revascularization Done in Traumatized Immature, Necrotic Anterior Teeth with and without Platelet-rich Fibrin: A Case Report. Int J Clin Pediatr Dent 2020;13(1):98-102.


Activating STAT6 mutations in follicular lymphoma.
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the Western world. FL cell-intrinsic and cell-extrinsic factors influence FL biology and clinical outcome. To further our understanding of the genetic basis of FL, we performed whole-exome sequencing of 23 highly purified FL cases and 1 transformed FL case and expanded findings to a combined total of 114 FLs. We report recurrent mutations in the transcription factor STAT6 in 11% of FLs and identified the STAT6 amino acid residue 419 as a novel STAT6 mutation hotspot (p.419D/G, p.419D/A, and p.419D/H). FL-associated STAT6 mutations were activating, as evidenced by increased transactivation in HEK293T cell-based transfection/luciferase reporter assays, heightened interleukin-4 (IL-4) -induced activation of target genes in stable STAT6 transfected lymphoma cell lines, and elevated baseline expression levels of STAT6 target genes in primary FL B cells harboring mutant STAT6. Mechanistically, FL-associated STAT6 mutations facilitated nuclear residency of STAT6, independent of IL-4-induced STAT6-Y641 phosphorylation. Structural modeling of STAT6 based on the structure of the STAT1-DNA complex revealed that most FL-associated STAT6 mutants locate to the STAT6-DNA interface, potentially facilitating heightened interactions. The genetic and functional data combined strengthen the recognition of the IL-4/JAK/STAT6 axis as a driver of FL pathogenesis.


[Corrigendum] MicroRNA‑92a contributes to tumor growth of human hepatocellular carcinoma by targeting FBXW7.
Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that certain of the control western blotting data featured in Fig. 5 on p. 2581 had also appeared in a couple of other articles featuring several of the same authors [Tu K, Dou C, Zheng X, Li C, Yang W, Yao Y and Liu Q: Fibulin‑5 inhibits hepatocellular carcinoma cell migration and invasion by down‑regulating matrix metalloproteinase‑7 expression. BMC Cancer 14: 938, 2014; and Gai X, Tu K, Li C, Roberts LR and Zheng X: Histone acetyltransferase PCAF accelerates apoptosis by repressing a GLI1/BCL2/BAX axis in hepatocellular carcinoma. Cell Death Dis 6: e1712, 2015]. In addition, the authors drew to the attention of the Editorial Office that a couple of mistakes were made during the assembly of Fig. 2D on p. 2579. The authors were able to re-examine their original data files, and realized that these figures had been inadvertently assembled incorrectly (they were also able to present the raw data from which these figures had been assembled to the Editorial Office). The revised versions of Figs. 2 and 5, containing the intended flow cytometric and western blotting data for these figures respectively, is shown on the next page. The authors wish to emphasize that the corrections made to these figures do not affect the overall conclusions reported in the paper, and they are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this corrigendum. All the authors agree to the publication of this corrigendum, and also apologize to the readership for any inconvenience caused. [Oncology Reports 34: 2576‑2584, 2015; DOI: 10.3892/or.2015.4210].


Deep learning for the dynamic prediction of multivariate longitudinal and survival data.
The joint model for longitudinal and survival data improves time-to-event predictions by including longitudinal outcome variables in addition to baseline covariates. However, in practice, joint models may be limited by parametric assumptions in both the longitudinal and survival submodels. In addition, computational difficulties arise when considering multiple longitudinal outcomes due to the large number of random effects to be integrated out in the full likelihood. In this article, we discuss several recent machine learning methods for incorporating multivariate longitudinal data for time-to-event prediction. The presented methods use functional data analysis or convolutional neural networks to model the longitudinal data, both of which scale well to multiple longitudinal outcomes. In addition, we propose a novel architecture based on the transformer neural network, named TransformerJM, which jointly models longitudinal and time-to-event data. The prognostic abilities of each model are assessed and compared through both simulation and real data analysis on Alzheimer's disease datasets. Specifically, the models were evaluated based on their ability to dynamically update predictions as new longitudinal data becomes available. We showed that TransformerJM improves upon the predictive performance of existing methods across different scenarios.


Apoptosis induced by lipid-associated membrane proteins from Mycoplasma hyopneumoniae in a porcine lung epithelial cell line with the involvement of caspase 3 and the MAPK pathway.
Lipid-associated membrane proteins (LAMPs) are important in the pathogenicity of the Mycoplasma genus of bacteria. We investigated whether Mycoplasma hyopneumoniae LAMPs have pathogenic potential by inducing apoptosis in a St. Jude porcine lung epithelial cell line (SJPL). LAMPs from a pathogenic strain of M. hyopneumoniae (strain 232) were used in the research. Our investigation made use of diamidino-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB) staining, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) analysis, and Annexin-V-propidium iodide staining. After LAMP treatment for 24 h, typical changes were induced, chromosomes were concentrated, apoptotic bodies were observed, the 3'-OH groups of cleaved genomes were exposed, and the percentage of apoptotic cells reached 36.5 ± 11.66%. Caspase 3 and caspase 8 were activated and cytochrome c (cyt c) was released from the mitochondria into the cytoplasm; poly ADP ribose polymerase (PARP) was digested into two fragments; p38 mitogen-activated protein kinase (MAPK) was phosphorylated; and the expression of pro-apoptosis protein Bax increased while the anti-apoptosis protein Bcl-2 decreased. LAMPs also stimulated SJPL cells to produce nitric oxide (NO) and superoxide. This study demonstrated that LAMPs from M. hyopneumoniae can induce apoptosis in SJPL cells through the activation of caspase 3, caspase 8, cyt c, Bax, and p38 MAPK, thereby contributing to our understanding of the pathogenesis of M. hyopneumoniae, which should improve the treatment of M. hyopneumoniae infections.


Trends in access surgery for hemodialysis.
Vascular access for chronic hemodialysis is for both doctors and nurses on one side and patients on the other a permanent, challenging problem. In respect to patency and complication rate, the direct AV fistula represents the most satisfactory solution and therefore should be achieved whenever feasible. In addition to the classic Brescia-Cimino and the brachiocephalic fistula, the most distal location in the snuff-box on one end and a transposed basilic vein at the upper arm on the other offer most satisfactory angioaccess alternatives that must be used stepwise from the periphery to more proximal sites. Graft fistulas should clearly be reserved for the patient for whom all autologous possibilities (with the exclusion of the autologous saphenous vein graft) have been used. Only ePTFE grafts have a patency rate comparable with direct autologous fistulas at a much higher cost.