Lipid Order Degradation in Autoimmune Demyelination Probed by Polarized Coherent Raman Microscopy.
Myelin around axons is currently widely studied by structural analyses and large-scale imaging techniques, with the goal to decipher its critical role in neuronal protection. Although there is strong evidence that in myelin, lipid composition, and lipid membrane morphology are affected during the progression of neurodegenerative diseases, there is no quantitative method yet to report its ultrastructure in tissues at both molecular and macroscopic levels, in conditions potentially compatible with in vivo observations. In this work, we study and quantify the molecular order of lipids in myelin at subdiffraction scales, using label-free polarization-resolved coherent anti-Stokes Raman, which exploits coherent anti-Stokes Raman sensitivity to coupling between light polarization and oriented molecular vibrational bonds. Importantly, the method does not use any a priori parameters in the sample such as lipid type, orientational organization, and composition. We show that lipid molecular order of myelin in the mouse spinal cord is significantly reduced throughout the progression of experimental autoimmune encephalomyelitis, a model for multiple sclerosis, even in myelin regions that appear morphologically unaffected. This technique permits us to unravel molecular-scale perturbations of lipid layers at an early stage of the demyelination progression, whereas the membrane architecture at the mesoscopic scale (here ∼100 nm) seems much less affected. Such information cannot be brought by pure morphological observation and, to our knowledge, brings a new perspective to molecular-scale understanding of neurodegenerative diseases.


Large-scale tethered function assays identify factors that regulate mRNA stability and translation.
The molecular functions of the majority of RNA-binding proteins (RBPs) remain unclear, highlighting a major bottleneck to a full understanding of gene expression regulation. Here, we develop a plasmid resource of 690 human RBPs that we subject to luciferase-based 3'-untranslated-region tethered function assays to pinpoint RBPs that regulate RNA stability or translation. Enhanced UV-cross-linking and immunoprecipitation of these RBPs identifies thousands of endogenous mRNA targets that respond to changes in RBP level, recapitulating effects observed in tethered function assays. Among these RBPs, the ubiquitin-associated protein 2-like (UBAP2L) protein interacts with RNA via its RGG domain and cross-links to mRNA and rRNA. Fusion of UBAP2L to RNA-targeting CRISPR-Cas9 demonstrates programmable translational enhancement. Polysome profiling indicates that UBAP2L promotes translation of target mRNAs, particularly global regulators of translation. Our tethering survey allows rapid assignment of the molecular activity of proteins, such as UBAP2L, to specific steps of mRNA metabolism.


Enhanced water permeance and EDCs rejection using a UiO-66-NH2-predeposited polyamide membrane.
Endocrine disrupting compounds (EDCs) have been increasingly detected in drinking water sources, and pose severe threat to human health. Polyamide (PA) based nanofiltration (NF) membrane has great potential for EDCs removal from water, but the removal of hydrophobic EDCs is not satisfying due to strong hydrophobic affinity. In this study, UiO-66-NH2/PA membranes were prepared by predepositing hydrophilic UiO-66-NH2 onto the substrate prior to interfacial polymerization. The UiO-66-NH2 aggregates increased the permeable area and strengthened the "gutter effect". Therefore, the pure water flux of UiO-66-NH2/PA increased by 115% compared with that of the thin-film composite (TFC) membrane, and its rejection of Na2SO4 was 96%. The hydrophilicity-enhanced PA film reduced its adsorption of EDCs and decreased the driving force for EDCs diffusion. Moreover, the UiO-66-NH2-induced hydrophilic nanochannels, including the interfacial gaps between PA film and UiO-66-NH2 aggregates, the gaps in UiO-66-NH2 aggregates, and the inherent pores in UiO-66-NH2 crystals, alleviated the hydrophobic affinity and effectively restricted EDCs diffusion. The rejection rates of methylparaben, propylparaben, bisphenol A, and benzylparaben by the optimal UiO-66-NH2/PA were 50%, 67%, 75%, and 85%, respectively, and the water/benzylparaben selectivity was 4.4 times as high as that of TFC. The results demonstrate that incorporating hydrophilic metal-organic frameworks (MOFs) can improve the membrane hydrophilicity and create hydrophilic nanochannels, and is an effective strategy to enhance EDCs removal by nanofiltration.


Spontaneous subperiosteal hematoma of the orbit.
Spontaneous subperiosteal hematoma of the orbit is extremely rare. This is a case of an 81-year-old woman. The presenting symptom was protrusion of the right eye with severe intraorbital pain. Computed tomography scanning showed a high-density area in the upper part of the right orbit, which, at operation, was found to be a subperiosteal hematoma of the orbit.


Cryo-EM structure shows how two IGF1 hormones bind to the human IGF1R receptor.
IGF1R plays an important role in regulating cellular metabolism and cell growth, and has been identified as an anti-cancer and diabetes drug target. Although research have been reported many crystal and cryo-EM structures of IGF1R, the mechanism of ligand binding remains controversial, mainly because the structure differences among its cryo-EM, crystal and homologous protein insulin receptor structures. Here, we further determined one new high-resolution symmetric cryo-EM structure of ligand-bound IGF1R and be the first to prove that the receptor could bind to two IGFI molecules by single particle cryo-electron microscopy. And the structure is very different from its homologous protein insulin receptor: the two ligands just exist at the binding site 2 with saturating ligand conditions. Then, our findings resolved the major dispute about the comformational changes of IGF1R, and proposed a new theory how IGF1R binds to its ligands. Meanwhile, these findings imply more attention may be needed to study the relationship between the special conformation and their corresponding physiological functions in future.


A Novel Surgical Technique for Repair of Congenitally Corrected Transposition of the Great Arteries With Atrioventricular Septal Defect: Avoiding Damage to the Conduction System.
We present a description of the surgical repair of the unusual anatomy of congenitally corrected transposition of the great arteries (S, L, L) and balanced atrioventricular septal defect. This anatomy not only presents a dilemma regarding palliation versus anatomic correction, but also regarding the approach to the conduction tissue during surgical repair.


Nicotinic acetylcholine currents of cultured Kkenyon cells from the mushroom bodies of the honey bee Aapis mellifera.
1. Acetylcholine-induced currents of mushroom body Kenyon cells from the honey bee Apis mellifera were studied using the whole-cell configuration of the patch clamp technique. Pressure application of 1 mM acetylcholine (ACh) induced inward currents with amplitudes between -5 and -500 pA. 2. The cholinergic agonists ACh and carbamylcholine had almost equal potencies of current activation at concentrations between 0.01 and 1 mM; nicotine was less potent. The muscarinic agonist oxotremorine did not elicit any currents. 3. Approximately 80 % of the ACh-induced current was irreversibly blocked by 1 microM alpha-bungarotoxin. Atropine (1 mM) did not block the ACh-induced current. 4. Upon prolonged ACh application the current desensitized with a time course that could be approximated by the sum of two exponentials (tau1 = 276 +/- 45 ms (mean +/- s.e.m. ) for the fast component and tau2 = 2.4 +/- 0.7 s for the slow component). 5. Noise analyses of whole-cell currents yielded elementary conductances of 19.5 +/- 2.4 pS for ACh and 23.7 +/- 5.0 pS for nicotine. The channel lifetimes, calculated from the frequency spectra, were tauo = 1.8 ms for ACh and tauo = 2.5 ms for nicotine. 6. Raising the external calcium concentration from 5 to 50 mM shifted the reversal potential of the ACh-induced current from +4. 6 +/- 0.9 to +37.3 +/- 1.3 mV. The calcium-to-sodium permeability ratio (PCa : PNa) was 6.4. 7. In high external calcium solution (50 mM) the ACh-induced current rectified in an outward direction at positive membrane potentials. 8. We conclude that Kenyon cells express nicotinic ACh receptors with functional profiles reminiscent of the vertebrate neuronal nicotinic ACh receptor subtype.


The relationship between kidney function and body mass index before and after bariatric surgery in patients with chronic kidney disease.
Improvements in kidney function post-bariatric surgery may be related to weight loss-independent effects. To characterize the dynamic relationship between body mass index (BMI) and estimated glomerular filtration rate (eGFR) before and after bariatric surgery in patients with chronic kidney disease (CKD). Kaiser Permanente Southern California (KPSC) health system. We conducted an observational, retrospective cohort study of patients with CKD stage 3 or higher who received bariatric surgery at the KPSC health system between 2007-2015. Bariatric surgery procedures included primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) procedures. Outcomes consisted of mean trajectory estimates and correlations of BMI and eGFR taken between 2 years before and 3 years after surgery. Multivariate functional mixed models were used to estimate how BMI and eGFR trajectories evolved jointly. A total of 619 RYGB and 474 SG patients were included in the final analytic sample. The measurements were available before surgery for a median time of 1.9 years for SG and 1.8 years for RYGB patients. Median follow-up times after surgery were 2.8 years for both SG and RYGB patients. The mean age at the time of surgery was 58 years; 77% of patients were women; 56% of patients were non-Hispanic White; the mean BMI was 44 kg/m2; 60% of patients had diabetes mellitus; and 84% of patients had hypertension. Compared to the presurgery eGFR declines, the postsurgery declines in eGFR were 57% slower (95% credible interval [CrI], 33%-81%) for RYGB patients and 55% slower (95% CrI, 25%-75%) for SG patients. The mean correlation between BMI and eGFR was negligible at all time points. Though bariatric surgery slowed declines in eGFR up to 3 years after surgery, changes in eGFR tracked poorly with changes in BMI. This study provides evidence that the kidney-related benefits of bariatric surgery may be at least partly independent of weight loss. Confirming this hypothesis could lead to mechanistic insights and new treatment options for CKD.


Treatment of extensive scalp lesions with segmental intensity-modulated photon therapy.
To compare static electron therapy, electron arc therapy, and photon intensity-modulated radiation therapy (IMRT) for treatment of extensive scalp lesions and to examine the dosimetric accuracy of the techniques. A retrospective treatment-planning study was performed to evaluate the relative merits of static electron fields, arcing electron fields, and five-field photon IMRT. Thermoluminescent dosimeters (TLD) were used to verify the accuracy of the techniques. The required thickness of bolus was investigated, and an anthropomorphic phantom was also used to examine the effects of air gaps between the wax bolus used for the IMRT technique and the patient's scalp. Neither static nor arcing electron techniques were able to provide a reliable coverage of the planning target volume (PTV), owing to obliquity of the fields in relation to the scalp. The IMRT technique considerably improved PTV dose uniformity, though it irradiated a larger volume of brain. Either 0.5 cm or 1.0 cm of wax bolus was found to be suitable. Air gaps of up to 1 cm between the bolus and the patient's scalp were correctly handled by the treatment-planning system and had negligible influence on the dose to the scalp. Photon IMRT provides a feasible alternative to electron techniques for treatment of large scalp lesions, resulting in improved homogeneity of dose to the PTV but with a moderate increase in dose to the brain.


Hyperthyroidism influences ultrasound bone measurement on the Os calcis.
The objective of our study was to compare bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) parameters in women with hyperthyroidism and controls. In this cross-sectional study, QUS parameters and BMD values observed in untreated hyperthyroid patients were compared with data obtained from age-matched controls. Twenty-four women with Graves' disease were studied. Eight patients were postmenopausal. All patients had evidence of thyrotoxicosis as indicated by a raised total serum thyroxine and a suppressed serum thyroid stimulating hormone. BMD of the hip, lumbar spine and whole body, and body composition, were measured by DXA. Ultrasound evaluation on the os calcis was performed with an Achilles device. All measurements were performed before antithyroid therapy. The QUS parameters of BUA, SOS and Stiffness were significantly lower in hyperthyroid patients than in controls. Similar results were observed for the BMD of lumbar spine, femoral neck and total skeleton. Lean tissue and fat mass were also significantly decreased in hyperthyroid patients. In conclusion, these findings suggest that hyperthyroidism affects cortical and trabecular bone equally, as well as bone quality. QUS measurements may be helpful for assessing, using a simple and non-irradiating method, the bone effects of thyrotoxicosis.


Tracing of afferent pathways from the femoral-saphenous vein to the dorsal root ganglia using transport of horseradish peroxidase.
The retrograde transport of horseradish peroxidase (HRP) was used to trace afferents from the femoral-saphenous vein to the dorsal root ganglia in the cat. Afferents arising along the entire length of the vein projected to very localized spinal levels; 63% of the labeled cells counted were located in the L6 dorsal root ganglion, 37% were located in the L5 ganglion and less than 1% were located at other levels. Most of the cell bodies labeled by the application of HRP to the femoral-saphenous vein were small in size (diameter less than 35 microns). However, some large cell bodies (diameter greater than 50 microns) were also noted. It was estimated that over two-thirds of the femoral-saphenous venous afferents were C fibers; at least 15% were estimated to be A fibers. The largest venous afferents were predicted to conduct action potentials at approximately 60 m/s.


Structure of a ternary Naa50p (NAT5/SAN) N-terminal acetyltransferase complex reveals the molecular basis for substrate-specific acetylation.
The co-translational modification of N-terminal acetylation is ubiquitous among eukaryotes and has been reported to have a wide range of biological effects. The human N-terminal acetyltransferase (NAT) Naa50p (NAT5/SAN) acetylates the α-amino group of proteins containing an N-terminal methionine residue and is essential for proper sister chromatid cohesion and chromosome condensation. The elevated activity of NATs has also been correlated with cancer, making these enzymes attractive therapeutic targets. We report the x-ray crystal structure of Naa50p bound to a native substrate peptide fragment and CoA. We found that the peptide backbone of the substrate is anchored to the protein through a series of backbone hydrogen bonds with the first methionine residue specified through multiple van der Waals contacts, together creating an α-amino methionine-specific pocket. We also employed structure-based mutagenesis; the results support the importance of the α-amino methionine-specific pocket of Naa50p and are consistent with the proposal that conserved histidine and tyrosine residues play important catalytic roles. Superposition of the ternary Naa50p complex with the peptide-bound Gcn5 histone acetyltransferase revealed that the two enzymes share a Gcn5-related N-acetyltransferase fold but differ in their respective substrate-binding grooves such that Naa50p can accommodate only an α-amino substrate and not a side chain lysine substrate that is acetylated by lysine acetyltransferase enzymes such as Gcn5. The structure of the ternary Naa50p complex also provides the first molecular scaffold for the design of NAT-specific small molecule inhibitors with possible therapeutic applications.


Corrigendum: Video playback speed influence on learning effect from the perspective of personalized adaptive learning: A study based on cognitive load theory.
[This corrects the article DOI: 10.3389/fpsyg.2022.839982.].


A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells.
Reactive oxygen species (ROS) and cellular oxidant stress are regulators of cancer cells. The alteration of redox status, which is induced by increased generation of ROS, results in increased vulnerability to oxidative stress. The aim of this study is to investigate the influence of O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, C13H16N6O8) on proliferation and apoptosis in bladder cancer cells and explored possible ROS-related mechanisms. Our results indicated that JS-K could suppress bladder cancer cell proliferation in a concentration- and time-dependent manner and induce apoptosis and ROS accumulation in a concentration-dependent manner. With increasing concentrations of JS-K, expression of proteins that are involved in cell apoptosis increased in a concentration-dependent manner. Additionally, the antioxidant N-acetylcysteine (NAC) reversed JS-K-induced cell apoptosis; conversely, the prooxidant oxidized glutathione (GSSG) exacerbated JS-K-induced cell apoptosis. Furthermore, we found that nitrites, which were generated from the oxidation of JS-K-released NO, induced apoptosis in bladder cancer cells to a lower extent through the ROS-related pathway. In addition, JS-K was shown to enhance the chemo-sensitivity of doxorubicin in bladder cancer cells. Taken together, the data suggest that JS-K-released NO induces bladder cancer cell apoptosis by increasing ROS levels, and nitrites resulting from oxidation of NO have a continuous apoptosis-inducing effect.


Mind the gap: analysis of two pilot projects of a home telehealth service for persons with complex conditions in a Swedish hospital.
Developing and implementing home telehealth (HTH) services for patients with chronic conditions is a challenge. HTH services provide continuous and integrated care to patients, but very often pilot projects face non-adoption and abandonment issues. Change processes in healthcare are often complex and require learning to adapt to non-linear and unpredictable events. Complexity science can thus provide a complementary view to the predominant Quality Improvement (QI) approach in healthcare. In this study of two pilot projects in a Swedish hospital, we explore how a theory-driven approach can be used (a) to support the development of a self-monitoring HTH service in hospital care and (b) to evaluate staff and patients' experiences from early adoption. To plan and evaluate the service for the recipients (i.e., patients and healthcare providers), we used the Plan-Do-Study-Act (PDSA) tool in combination with two complexity-informed frameworks: the Non-adoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework, and the joint Complexity Assessment Tool (CAT). The theory-informed development process led to two pilot projects of an HTH service for patients with heart failure and COVID-19. We collected data from multiple sources (project documents, a survey on readiness for change among staff, and semi-structured interviews with patients and staff) and analyzed the data using descriptive statistics and qualitative content analysis with a deductive approach. Patients and staff perceived the services as valuable as they enabled rapid feedback, and improved communication and collaboration between patients and healthcare providers. Yet, despite the extensive development efforts, there was a perceived gap between how individuals valued the service and the capacity of adopters, the organization, and the wider system to effectively integrate these services into routine care. The combined use of PDSA, NASSS, and CAT can support the development and evaluation of HTH services that are perceived as valuable by individual patients and staff. For successful adoption, the value for individuals must be supported by organizational efforts to learn how to integrate new routines and tasks into clinical practice and daily life, and how to coordinate multiple providers within and outside the hospital walls.


Long-term exposure to polystyrene microplastics triggers premature testicular aging.
Plastic pollution is greatly serious in the ocean and soil. Microplastics (MPs) degraded from plastic has threatened animals and humans health. The accumulation of MPs in the tissues and blood in animals and humans has been found. There is therefore a need to assess the toxicological effects of MPs on the reproductive system. In this study, we explored the effect of polystyrene microplastics (PS-MPs) on premature testicular aging in vitro and in vivo. In vitro, we found that testicular sertoli cells (TM4 cells) was prematurely senescent following PS-MPs treatment by the evaluation of a range of aging marker molecules (such as Sa-β-gal, p16 and 21). TM4 cells were then employed for in vitro model to study the potential molecular mechanism by which PS-MPs induce the premature senescence of TM4 cells. NF-κB is identified as a key molecule for PS-MPs-induced TM4 cellular senescence. Furthermore, through eliminating reactive oxygen species (ROS), the activation of nuclear factor kappa B (NF-κB) was blocked in PS-MPs-induced senescent TM4 cells, indicating that ROS triggers NF-κB activation. Next, we analyzed the causes of mitochondrial ROS (mtROS) accumulation induced by PS-MPs, and results showed that Ca2+ overload induced the accumulation of mtROS. Further, PS-MPs exposure inhibits mitophagy, leading to the continuous accumulation of senescent cells. In vivo, 8-week-old C57 mice were used as models to assess the effect of PS-MPs on premature testicular aging. The results illustrated that PS-MPs exposure causes premature aging of testicular tissue by testing aging markers. Additionally, PS-MPs led to oxidative stress and inflammatory response in the testicular tissue. In short, our experimental results revealed that PS-MPs-caused testicular premature aging is dependent on Ca2+/ROS/NF-κB signaling axis. The current study lays the foundation for further exploration of the effects of microplastics on testicular toxicology.


Gut bacteria and necrotizing enterocolitis: cause or effect?
Development of necrotising enterocolitis (NEC) is considered to be dependent on the bacterial colonisation of the gut. With little concordance between published data and a recent study failing to detect a common strain in infants with NEC, more questions than answers are arising about our understanding of this complex disease.


Real-world effect of ribavirin on quality of life in HCV-infected patients receiving interferon-free treatment.
Ribavirin (RBV) is commonly used for the treatment of hepatitis C virus (HCV) infection. However, RBV is associated with a reduced quality of life (QOL). We aim to assess the impact of RBV on QOL in a real-world setting. In a prospective study, QOL was measured by a SF-36 questionnaire in 174 patients. In all, 85 patients were treated with RBV and 89 patients without RBV. QOL was assessed at baseline, week 12 of treatment and 24 weeks after treatment. Patients treated with RBV were more likely to have HCV genotype 2 and 3 infection and cirrhosis (all P < .05). RBV-treated patients reported lower scores for several domains of QOL already at baseline. During HCV treatment, RBV-free treatment led to an increase in all measured dimensions of quality of life, whereas RBV treatment led to a decrease in the emotional and physical functioning. After treatment, all dimensions for QOL showed improvement across the study cohort, regardless whether RBV was part of the treatment regimen. However, 28.8%-45.2% of treated patients perceive a sustained reduction in their physical or mental capacity after treatment, not related to RBV usage or SVR, but related to older age (P = .03) and cirrhosis (P = .02). During treatment, RBV leads to a reduced QOL, whereas RBV-free treatment leads to an increased QOL. After treatment, QOL strongly increases in both, RBV and RBV-free treated patients. Some patients perceive a sustained reduction in QOL, which seems unrelated to treatment.


A Regenerable Hydrogel Electrolyte for Flexible Supercapacitors.
Easy regenerability of core components such as electrode and electrolyte is highly required in advanced electrochemical devices. This work reports a reliable, regenerable, and stretchable hydrogel electrolyte based on ionic bonds between polyacrylic acid (PAA) and polyallylamine (PAH). PAA-PAH electrolyte (1M LiCl addition) exhibits high ionic conductivity (0.050 S·cm-1) and excellent mechanical property (fracture strain of 1,688%). Notably, the electrolyte can be regenerated to any desired shape under mild conditions and remains 96% and 90% of the initial ionic conductivity after the first and second regeneration, respectively. PAA-PAH/LiCl-based supercapacitor exhibits nearly 100% capacitance retention upon rolling, stretching, and 5,000 charge-discharge cycles, whereas the regenerated device holds 97.6% capacitance of the initial device and 90.9% after 5,000 cycles. This low-cost, high-efficiency, and regenerable hydrogel electrolyte reveals very promising use in solid-state/flexible supercapacitors and possibly becomes a standard commercial hydrogel electrolyte for sustainable electrochemical energy devices.


Structure of oligosaccharide side chains of an intestinal immune system modulating arabinogalactan isolated from rhizomes of Atractylodes lancea DC.
An intestinal immune system modulating arabino-3,6-galactan (ALR-5IIa-1-1) has been found in rhizomes of Atractylodes lancea DC. [Planta Medica 1998, 64, 714-719; Carbohydr. Polyms. 2001, 46, 147-156], however other arabino-3,6-galactans from Larix and Acacia failed to express the modulating activity. Degradation of the galactosyl side chains in Araf-side chain-trimmed ALR-5IIa-1-1 (AF-ALR-5IIa-1-1) with an endo-beta-D-(1-->6)-galactanase remarkably decreased the activity of AF-ALR-5IIa-1-1. Structural analysis indicated that the major endo-beta-D-(1-->6)-galactanase-digestable side chains in ALR-5IIa-1-1 are composed of beta-D-(1-->6)-galactopyranosyl oligosaccharides having d.p. 1-8. Because degradation of the beta-D-(1-->3)-galactan backbone in AF-ALR-5IIa-1-1 also significantly reduced its activity, some of these galactosyl side chains attached to beta-D-(1-->3)-galactan backbone are suggested to be responsible for expression of the activity of ALR-5IIa-1-1.


Lysozyme interaction with poly(HEMA)-based hydrogel.
Lysozyme interaction with an acrylic-based hydrogel, poly(2-hydroxyethyl methacrylate) co-methacrylic acid (P(HEMA-MAA)), was investigated using a combination of quartz crystal microbalance with dissipation (QCM-D), surface plasmon resonance (SPR) and dual polarisation interferometry (DPI). This combination of techniques demonstrated that lysozyme initially absorbed into the hydrogel matrix and displaced water from the hydrogel while subsequent lysozyme additions were adsorbed onto the surface of the hydrogel material. QCM-D, being sensitive to bound water, showed an overall decrease in mass and stiffening of the layer after lysozyme addition. SPR, a water insensitive technique, showed a net mass increase after addition of lysozyme and buffer rinses. DPI showed that the first exposure of lysozyme to P(HEMA-MAA) was consistent with lysozyme absorption while subsequent lysozyme exposures were consistent with lysozyme adsorption.


Higher environmental temperatures promote acceleration of spermatogenesis in vivo in mice (Mus musculus).
Temperature is considered a crucial modulator of reproductive activity and testis homeostasis. It is well known that elevated temperatures cause several effects on testicular components, particularly on germ cells, which might lead to the impairment of spermatogenesis and loss of male fertility. The present study aimed to evaluate the effects of different environmental temperatures on several morphofunctional testis parameters, with emphasis on duration of spermatogenesis and spermatogenic efficiency. Thirty sexually mature Swiss mice (Mus musculus) were allocated in three different experimental groups, being kept in vivarium for three weeks at 16 °C, 23 °C (control group) and 32 °C. In order to estimate the duration of spermatogenesis, three animals per each group received intraperitoneal injections of tritiated thymidine and the testes were perfused-fixed and routinely processed for histological, morphometrical and immunoperoxidase analyses. Although the lower temperature (16 °C) did not change most of the evaluated testicular parameters, our findings showed that higher environmental temperature (32 °C) is able to alter important testis parameters, resulting for instance in acceleration of spermatogenesis, alterations in the stages frequencies, increased number of germ and Leydig cells apoptosis and reduced Sertoli cell and spermatogenic efficiencies. As in many conditions infertile men exhibit higher mean scrotal temperature, we believe that experimental studies with mice involving temperature might represent an interesting approach to better understand the mechanisms related to human testis function and sperm production.


Proposal of a Nomogram for Predicting Survival in Patients with Siewert Type II Adenocarcinoma of the Esophagogastric Junction After Preoperative Radiation.
Preoperative radiotherapy tends to be more frequently used for patients with adenocarcinoma of the esophagogastric junction (AEG); however, the prognostic values of postoperative pathologic characteristics in these patients remain unclear. This study aimed to examine the outcomes in Siewert type II AEG patients receiving preoperative radiotherapy to identify the predictive factors for overall survival (OS). A total of 1818 AEG patients undergoing preoperative radiotherapy were reviewed. Univariate analyses showed that age, sex, histology, tumor grade, positive lymph node (PLN), lymph node ratio, and log odds of positive lymph nodes (LODDS) were significantly correlated with OS; however, only age, grade, PLN, and LODDS were identified as independent risk factors in a multivariate regression model. Subsequently, patients were randomly grouped into training and validation cohorts (1:1 ratio), and the beta coefficients of these variables in the training set were used to generate the nomogram. The composite nomogram showed improved prognostic accuracy in the training, validation, and entire cohorts compared with that of TNM stage alone. In conclusion, our proposed nomogram represents a promising tool for estimating OS in Siewert type II AEG patients after preoperative radiotherapy.


The resin-supported iron-copper bimetallic composite as highly active heterogeneous Fenton-like catalysts for degradation of gaseous toluene.
In this study, a resin-supported iron-copper bimetallic heterogeneous Fenton catalyst with excellent removal performance, superior economy and outstanding recoverability was synthesized by an impregnation method and used to remove gaseous toluene. Experiments disclosed that 3-FeCu@LXQ-10 possessed extremely high catalytic capacity. At a temperature of 30 °C, an initial toluene concentration of 200 mg/m3 and H2O2 atomization amount of 3 mmol/h, the toluene removal efficiency of 3-FeCu@LXQ-10 was 97.50%. Experimental tests had revealed that the bimetallic supported catalysts exhibited higher catalytic activity than single metal-supported catalysts, owing to an interaction effect between iron and copper metal ions. Furthermore, electron paramagnetic resonance (EPR) and radical quenching tests were carried out, and the results indicated •OH radicals performed a key role in the Fenton-like process. In addition, the iron-copper bimetallic catalysts exhibited good reusability and stability characteristics during six degradation cycles. This study shows promising potential in using FeCu@LXQ-10 as a heterogeneous catalyst for removing toluene.


Amygdala functional connectivity in female patients with major depressive disorder with and without suicidal ideation.
Major depressive disorder (MDD) is a known major risk factor for suicide and is one of the most common mental disorders. Meanwhile, gender differences in suicidal behavior have long been recognized including the finding that women have higher rates of suicidal ideation and/or suicidal behavior than men. The mechanism underlying suicide ideation in female patients with MDD remains poorly understood. The aim of the present study was to examine possible suicidal behavior-related neural circuitry in female MDD. In this study, 15 female participants with the first-episode MDD with suicidal ideation and 24 participants with the first-episode MDD without suicidal ideation as well as 39 female participants in a healthy control (HC) group, ranging in age from 18 to 50 years, underwent resting-state functional magnetic resonance imaging. The whole-brain amygdala resting-state functional connectivity (rsFC) was compared among these three groups. Compared with female participants with the first-episode MDD without suicidal ideation and those in the HC group, female participants with the first-episode MDD with suicidal ideation showed a significant difference in rsFC between the amygdala and precuneus/cuneus (p < 0.05, corrected). No significant difference in amygdala-precuneus/cuneus rsFC was observed between female patients with the first-episode MDD without suicidal ideation and the HC group (p < 0.05, corrected). Our findings suggest that suicidal ideation in female patients with the first-episode MDD may be related to an abnormality in amygdala neural circuitry. The abnormality in amygdala-precuneus/cuneus functional connectivity might present the trait feature for suicide in women with the first-episode MDD. The precuneus/cuneus may be an important region related to suicide and require future study.


Early and late postoperative changes in the quality of life after pancreatic surgery.
To compare health-related quality of life (QoL) before and after surgery for pancreatic disease. A retrospective analysis of prospectively gathered data is presented. A total of 174 patients of 230 planned for pancreatic surgery between March and December 2009 at a German high-volume center completed the Short Form-36 (SF-36) Health Survey preoperatively, 133 of them at 3 months and 83 at 24 months after surgery. Data was analysed according to diagnosis and procedure, and compared to German population norms. QoL in the study group was worse than that of age-matched healthy population at all time points. It decreased continuously in the cancer group, decreased early and showed a trend toward recovery late in patients with benign tumors and chronic pancreatitis. Distal pancreatectomy was the best tolerated and total pancreatectomy the worst tolerated procedure. Older age and development of pancreatic insufficiency affected negatively QoL. In patients with pancreatic disease, diagnosis determined QoL preoperatively and late after surgery, while in the early postoperative period, type and extent of surgery was the leading factor. Total pancreatectomy had a profound negative effect on QoL and should be reserved for carefully selected patients only.


Dofetilide: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias.
Dofetilide is a class III antiarrhythmic agent with a selective blockade of rapid component of delayed rectifier potassium current (IKr). Dofetilide was found to be safe in patients after myocardial infarction and those with congestive heart failure and left ventricular systolic dysfunction (ejection fraction of less than 35%). An important adverse effect of dofetilide is its potential proarrhythmic risk of ventricular tachyarrhythmias, mostly torsades de pointes. Because dofetilide has about an 80% renal excretion, dose adjustment is required in patients with impaired renal function. Dofetilide should not be given or discontinued if the QTc is greater than 500 ms.


Primary biliary cirrhosis and ulcerative colitis.
Four patients with ulcerative colitis also had primary biliary cirrhosis, as judged by compatible liver histology, positive serum mitochondrial antibody tests, and normal cholangiography (in the 3 patients in whom it was performed). Primary biliary cirrhosis may be another hepatobiliary association of ulcerative colitis, and although less common than primary sclerosing cholangitis should be considered as a cause of cholestasis in these patients.


Lyotropic and interfacial behaviour of an anionic gemini surfactant.
The sodium salt of N,N'-hexane-bis (1-dodecen-1-ylsuccinamic acid) is an anionic dimeric (gemini) surfactant. A flooding penetration scan of this surfactant in water demonstrates a sequence of lyotropic phases at room temperature (20 degrees C). Preparation of surfactant-water mixtures has resulted in a phase diagram which shows that the same sequence of phases exists up to 100 degrees C. These phases are tentatively assigned to the sequence: micellar to normal hexagonal (H1) to cubic (V1) to lamellar (Lalpha). The interfacial tension at the n-heptane/water interface has been determined in the presence of this surfactant. The surfactant head group area at the interface is large (2.8+/-0.3 nm2 at 298 K) and the interfacial tension above the critical micelle concentration is low (7 mN m(-1)), but considerably higher than the ultra-low values that have been reported for cationic dimeric surfactants at various hydrocarbon-water interfaces.


Handheld miniature probe integrating diffuse optical tomography with photoacoustic imaging through a MEMS scanning mirror.
We describe a novel dual-modality imaging approach that integrates diffuse optical tomography (DOT) and photoacoustic imaging (PAI) through a miniaturized handheld probe based on microelectromechanical systems (MEMS) scanning mirror. We validate this dual-modal DOT/PAI approach using extensive phantom experiments, and demonstrate its application for tumor imaging using tumor-bearing mice systematically injected with targeted contrast agents.


Retinopathy of Prematurity: The Role of Nutrition.
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. ROP occurs in infants who are born very preterm. In ROP, retinal blood vessel development, which is prematurely arrested in preterm infants, is altered by perinatal exposures like oxygen and inflammation. Optimizing nutritional practices for preterm infants may mitigate the risk of ROP. In this article, we review the evidence that postnatal growth, hyperglycemia, polyunsaturated fatty acids, and breast milk provision may affect ROP risk. We also outline the current management strategies for ROP and describe the vision outcomes of children affected by ROP. [Pediatr Ann. 2023;52(8):e303-e308.].


Early discontinuation of intravenous prostaglandin E1 after balloon atrial septostomy is associated with an increased risk of rebound hypoxemia.
A comparison of the effects of early (<2 h) and late (>or=2 h) discontinuation of prostaglandin E1 (PGE1), on systemic oxygenation following a successful balloon atrial septostomy (BAS), in neonates with confirmed diagnosis of d-transposition of the great arteries (d-TGA). Neonates with a postnatal diagnosis of d-TGA who were admitted to a quaternary neonatal intensive care unit between January 1999 and December 2004 were identified from the local database. The effects of time of discontinuation of PGE1 on oxygen saturations, oxygen requirement, need for reinstitution of prostaglandin infusion and postoperative stability were analyzed. Sixty neonates with a diagnosis of d-TGA were identified, 45 of whom had a BAS performed. Of these, 25 cases had early (<2 h) discontinuation of PGE1 whereas in the remaining 20 discontinuation was late (>or=2 h). PGE1 infusion was recommenced in 20 neonates (20/45 (44%)) after a successful BAS due to rebound hypoxemia. Of these, there was a threefold increase in the need for reinstitution of prostaglandin in the early compared to late discontinuation group (16/25 (64%) vs 4/20 (20%), P<0.006). There was no difference in postoperative cardiorespiratory stability. Early discontinuation of intravenous PGE1 following BAS was associated with an increased risk of rebound hypoxemia, necessitating the recommencement of PGE1. We speculate the rapid improvement in oxygenation on reinstitution of PGE1 is secondary to pulmonary vasodilation and improved pulmonary blood flow. We propose a more cautious and graded approach to discontinuation of PGE1 based on illness severity and the magnitude and duration of hypoxemia at presentation.


PM2.5 exposure stimulates COX-2-mediated excitatory synaptic transmission via ROS-NF-κB pathway.
Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the neuroinflammation and synaptic dysfunction, but the mechanisms underlying the process remain unclear. Cyclooxygenase-2 (COX-2) is a key player in neuroinflammation, and has been also implicated in the glutamatergic excitotoxicity and synaptic plasticity. Thus, we hypothesized that COX-2 was involved in PM2.5-promoted neuroinflammation and synaptic dysfunction. Our results revealed that PM2.5 elevated COX-2 expression in primary cultured hippocampal neurons and increased the amplitude of field excitatory postsynaptic potentials (fEPSPs) in hippocampal brain slices. And the administration of NS398 (a COX-2 inhibitor) prevented the increased fEPSPs. PM2.5 also induced intracellular reactive oxygen species (ROS) generation accompanied with glutathione (GSH) depletion and the loss of mitochondrial membrane potential (MMP), and the ROS inhibitor, N-acetyl-L-cystein (NAC) suppressed the COX-2 overexpression and the increased fEPSPs. Furthermore, the nuclear factor kappa B (NF-κB) was involved in ROS-induced COX-2 and fEPSP in response to PM2.5 exposure. These findings indicated that PM2.5 activated COX-2 expression and enhanced the synaptic transmission through ROS-NF-κB pathway, and provided possible biomarkers and specific interventions for PM2.5-induced neurological damage.


A modeling study of solute reabsorption along rat proximal tubule.
We present a model of steady state solute and water reabsorption along the rat proximal tubule. Major co- and counter-transport systems in the apical and basolateral cell membranes are described using kinetic descriptions based on data from the flows and solute concentrations along the length of the proximal tubule as a function of filtration rate and peritubular solute concentrations. We show that for many aspects of proximal tubule transport physiology this kinetics-based model is an adequate representation of the mammalian proximal tubule.


Cyclosporine combined with nonlytic interleukin 2/Fc fusion protein improves immune response to hepatitis B vaccination in a mouse skin transplantation model.
Improving immune responses to vaccination in immunosuppressed patients is extremely important. Previously, we observed that cyclosporine (CsA) combined with a nonlytic interleukin (IL)-2/fragment crystallizable (Fc) fusion protein induces immune tolerance to mouse skin transplantations. In the present study, we asked whether this combination improved hepatitis B (HBV) vaccine efficacy in immunosuppressed mice while also prolonging skin graft survival. After C57BL/6 mice received DBA/2 skin grafts, they were administered a 14-day course of CsA (30 mg/kg intraperitoneal) combined with IL-2/Fc (1 μg, intraperitoneal). HBV vaccine (2 μg) was injected intramuscularly on the day of skin transplantation. On day 14, the serum levels of hepatitis B surface antibody (HBsAb), IL-4, IL-10, interferon (IFN-γ), and IL-2 were measured by enzyme-linked immunosorbent assay. We assessed the percentages of CD4(+)CXCR5(+) follicular T helper cells, CD4(+)FoxP3(+) regulatory T cells (Treg) and expressions of IL-17, IL-21, FoxP3, Bcl-6 in the spleen. Animals were divided into four groups: control, vaccine-treated, CsA + vaccine-treated, CsA + IL-2/Fc + vaccine-treated hosts. Combination therapy significantly increased HBsAb levels and also prolonged skin graft survival. Serum levels of Th1 cytokines IL-2 and IFN-γ were significantly higher in the combination group, while Th2 cytokines, IL-4 and IL-10 were lower. Combined treatment increased the percentage of Treg and the expression of Foxp3 and IL-21, meanwhile inhibiting the expression of Bcl-6. But the percentage of Tfh did not significantly change among the groups. These observations suggested that a combination of CsA and IL-2/Fc fusion protein enhanced immune responses after HBV vaccination and prolonged skin graft survival.


Activation of the renin-angiotensin-aldosterone system is associated with Acute Kidney Injury in COVID-19.
The pathophysiology of acute kidney injury (AKI) in COVID-19 patients is still poorly understood. SARS-CoV-2 has been suggested to modulate the renin-angiotensin-aldosterone system (RAAS). In this series of COVID-19 critically ill patients, we report evidence of activation of the RAAS in COVID-19 patients with AKI.


Beneficial effects of silibinin against the progression of metabolic syndrome, increased oxidative stress, and liver steatosis in Psammomys obesus, a relevant animal model of human obesity and diabetes.
Insulin resistance and oxidative stress are major pathogenic mechanisms leading to chronic liver diseases in diabetic subjects. The gerbil Psammomys obesus is a unique model of nutritional diabetes resembling the disease in humans. This study investigated whether the natural ingredient silibinin, known as hepatoprotective, could decrease oxidative stress and reduce liver damage in obese gerbils. Control animals were fed their vegetable-based low caloric diet while two other rat groups ingested a high calorie diet for 14 weeks. Silibinin, or its vehicle, was administrated by gastric intubation (100 mg/kg per day) from the 7th week of treatment, which corresponds to an established insulin resistance state. At the end of the experiments, the hepatic biochemical profile, markers of oxidative stress in either plasma or liver tissue, and histological alterations were examined. Diabetic P. obesus displayed many metabolic disturbances (hyperinsulinemia, hyperglycemia, dyslipidemia), which were aggravated for the last 8 weeks. These events were coupled with greater oxidative stress (decline in glutathione, rise in lipoperoxidation). In addition, glutathione peroxidase activity was reduced while the level of superoxide dismutase was elevated. Interestingly, treatment with silibinin alleviated most of the metabolic defects, especially high triglyceride levels, reduced insulin resistance and largely restored antioxidant status. Also, Masson's trichrome staining revealed distinct steatosis, yet silibinin partially reversed this manifestation. Silibinin affords substantial protection against the progression of insulin resistance in Type 2 diabetes mellitus for P. obesus by hampering the oxidative process and improving hepatic metabolism.


Management of viral hepatitis in hematologic malignancies.
Viral hepatitis is the third major cause of liver dysfunction in allogeneic transplant recipients and has become a significant concern in patients with hematological malignancies receiving chemotherapy. Thus, identification of patients at risk for viral hepatitis is very important when evaluating and treating hematological malignancies. Serologic screening for all patients should include anti-HCV, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) testing. Current therapies for hepatitis B (HBV) virus infection are aimed at viral suppression, while treatment for hepatitis C (HCV) virus can eradicate infection in many treated patients. To prevent HBV viral reactivation, prophylaxis with nucleoside analogues should be initiated for all HBsAg-positive patients. HCV infection appears to have little impact on short-term survival after bone marrow transplantation (BMT), but eventually can impact long-term survival due to progression of liver disease. In this review we will highlight the mechanisms of virus reactivation, clinical manifestations, and management strategies to minimize acute and chronic morbidity in this population.


Different influence of incongruent follicular development on in vitro fertilization-embryo transfer and gamete intrafallopian transfer pregnancy rates.
To compare the influence of incongruent (asymmetric) follicular development on treatment outcome in IVF-ET and GIFT cycles. A retrospective comparative study. Tertiary referral center for infertility. Five hundred forty-three consecutive assisted reproduction cycles (428 IVF-ET and 115 GIFT) in 422 infertile patients. Controlled ovarian hyperstimulation (COH) and IVF-ET or GIFT. The incongruity ratio as a parameter of the asymmetry in follicular development and pregnancy rate (PR). For GIFT cycles, the PRs were 37.8% and 15.7% in cycles with congruent and incongruent follicular development, respectively. However, for IVF-ET cycles, the PR was not affected by incongruent follicular development: 28.2% and 29.0%, respectively. An inverse relationship was observed between the degree of incongruity and the estimated probability of pregnancy in GIFT cycles but not in IVF-ET cycles. Neither the side of the dominant ovary nor the degree of incongruity were consistent in consecutive cycles. Incongruent follicular development during COH has a significantly negative influence on the outcome of GIFT cycles but not on the outcome of IVF-ET cycles. The reason for this difference is not clear. We recommend considering IVF-ET instead of GIFT if incongruent follicular development occurs.


GlassesValidator: A data quality tool for eye tracking glasses.
According to the proposal for a minimum reporting guideline for an eye tracking study by Holmqvist et al. (2022), the accuracy (in degrees) of eye tracking data should be reported. Currently, there is no easy way to determine accuracy for wearable eye tracking recordings. To enable determining the accuracy quickly and easily, we have produced a simple validation procedure using a printable poster and accompanying Python software. We tested the poster and procedure with 61 participants using one wearable eye tracker. In addition, the software was tested with six different wearable eye trackers. We found that the validation procedure can be administered within a minute per participant and provides measures of accuracy and precision. Calculating the eye-tracking data quality measures can be done offline on a simple computer and requires no advanced computer skills.


Computational insight towards the binding affinity and participation of aliphatic unsaturated sidearms of aza-18-crown-6 extractants for Sr2+ encapsulation in different solvent medium.
Macrocyclic extractants capture cations in solution phase; therefore, their structures and energetics in different solvents are worth investigating. In this computational research work, the optimized geometry of three aza-18-crown-6 extractants (1-3) has been obtained in suitable solvent mediums to work out the influence of the solvation on their binding affinity with Sr2+. The designed macrocyclic extractants are remarkable as the N-substituted side chain bears the rarely examined simple aliphatic unsaturated double and triple bond. All significant structural perturbations of the macro ring wherein Sr2+ binds are examined. Prediction of the auxiliary effect of the simple aliphatic unsaturated side arm on the binding of Sr2+ through solvent competition or cation-pi interaction is undertaken. The binding affinity of the complex formed in the solvent and gas phases is calculated. Results obtained in this study favor the utilization of solvents of low dielectric constant (CHCl3 and DCM) for effective binding of Sr2+ ions by the extractants. All DFT calculations were performed using the Gaussian 09 program. The optimized geometries and their structural features were visualized by GaussView. Density functional calculation involving B3LYP functional and LANL2DZ basis set was employed to obtain optimized geometry and energy of the extractants and their Sr2+ complex. The solvation effects were considered by employing the calculations with the polarized continuum model (PCM). The computational method's reliability was assured by comparing the optimized structure with that of X-ray reported structure of a similar type of complex.


Tibial Tubercle Osteotomy With Distalization for the Treatment of Patella Alta.
One of the most common osseous abnormalities associated with patellar instability and patellofemoral osteochondral disease is patella alta, characterized by an Insall-Salvati ratio ≥1.2 or a Caton-Deschamps Index ≥1.2. Despite being the most common surgical treatment option for patella alta, tibial tubercle osteotomy with distalization raises concerns due to the complete detachment of the tubercle, which may lead to damage of local vascularity from periosteal detachment and increased mechanical stress at the attachment site. These factors are related to greater risk of complications, such as fractures, loss of fixation, delayed union, or nonunion of the tuberosity. We describe a technique for tibial tubercle osteotomy with distalization that aims to minimize these complications through care with the osteotomy, stabilization, bone cut thickness, and local periosteum.


Attentional modulation by reward and punishment cues in relation to depressive symptoms.
Research indicates that individuals at-risk for depression are characterized by high sensitivity to loss and reduced sensitivity to reward. Moreover, it has been shown that attentional bias plays an important role in depression vulnerability. The current study aimed to examine the interplay between these risk factors for depression by examining the development of attentional bias toward reward and loss signals in dysphoric participants (individuals with elevated levels of depressive symptoms). Shapes were conditioned to reward and loss and subsequently presented in a dot probe task in a sample of dysphoric and nondysphoric participants. Nondysphoric individuals oriented towards reward-related signals whereas dysphoric individuals failed to develop a reward-related attentional bias. This attentional effect was observed in the absence of group differences in motivational factors. No group differences were found for attentional bias for loss-related signals, despite the fact that dysphoric individuals performed worse in response to losing. The current sample is not clinical thus generalization to clinical depression is not warranted. We argue that impaired early attentional processing of rewards are an important cognitive risk factor for anhedonic symptoms in persons with dysphoria.


Status of Emergency Signal Functions in Myanmar Hospitals: A Cross-Sectional Survey.
Low- and middle-income countries (LMICs) have a large percentage of global mortality and morbidity rates from non-communicable diseases, including trauma. The establishment and development of emergency care systems is crucial for addressing this problem. Defining gaps in the resources and capacity to provide emergency healthcare in LMICs is essential for proper design and operation of ECS (emergency care services) reinforcement programs. Myanmar has particular challenges with road access for providing timely emergency medical care, and a shortage of trained health workers. To examine the ECS capacity in Myanmar, we used the Emergency Care Assessment Tool (ECAT), which features newly developed tools for assessing sentinel conditions and signal functions (key interventions to address morbidity and mortality) in emergency care facilities. ECAT is composed of six emergent sentinel conditions and corresponding signal functions. We surveyed a total of nine hospitals in five states in Myanmar. A constructed survey sheet was delivered by e-mail, and follow-up interviews were conducted via messenger to clarify ambiguous answers. We categorized the nine participating institutions according to predefined criteria: four basic-level hospitals; four intermediate-level; and one advanced-level hospital. All basic hospitals were weak in trauma care, and two of 12 signal functions were unavailable. Half of the intermediate hospitals showed weakness in trauma care, as well as critical care such as shock management. Only half had a separate triage area for patients. In contrast, all signal functions and resources listed in ECAT were available in the advanced-level hospital. Basic-level facilities in Myanmar were shown to be suboptimal in trauma management, with critical care also inadequate in intermediate facilities. To reinforce signal functions in Myanmar health facilities, stakeholders should consider expanding critical functions in selected lower-level health facilities. A larger scale survey would provide more comprehensive data to improve emergency care in Myanmar.


Profile of ambulatory blood pressure in resistant hypertension.
Resistant hypertension (HT) is a condition that confers a high cardiovascular risk to the patient due to both persistent blood pressure elevation and the high prevalence of comorbidities and organ damage. Ambulatory blood pressure monitoring (ABPM) has become an important tool in the diagnosis and follow-up of the hypertensive patient, and it is even more important in the evaluation of those with resistant HT. Data from the Spanish ABPM Registry have allowed the comparison between large groups of resistant hypertensive patients seen in daily life and those controlled on antihypertensive treatment, as well as in resistant hypertensive patients who are classified based on ambulatory blood pressure values. In comparison with controlled patients, the cohort of resistant hypertensives has a worse circadian profile with a high proportion of nondipping, but also stark differences between office and ambulatory blood pressures. This enhanced white-coat effect was responsible for more than one-third of resistant hypertensive patients having normal 24-h blood pressures. Clinical data, including comorbidities, organ damage and circadian patterns, suggest a lower cardiovascular risk among white-coat resistant hypertensives. This finding was in agreement with longitudinal studies in smaller cohorts, suggesting fewer cardiovascular events and less mortality. In summary, it seems reasonable to routinely use ABPM in the initial evaluation of all resistant hypertensive patients. In a significant number of these patients, ABPM will also be an essential tool in follow-up, especially regarding the possible effects of all therapeutic maneuvers that are devoted to bringing blood pressure into target ranges.


Purification and properties of tRNA nucleotidyl transferase from Musca domestica.
The enzyme tRNA nucleotidyl transferase (EC 188.8.131.52) has been highly purified from whole adult houseflies. A molecular weight of 30 000 has been determined. The enzyme requires Mg2+ and tRNA deprived of the 3' terminal sequence CCA for activity in the incorporation of AMP and CMP onto the tRNA. UMP can be incorporated instead of CMP but the latter has a higher affinity than UMP as shown by competition experiments. A complex between the enzyme and tRNA has been shown by sucrose gradient centrifugation, nitrocellulose binding and protection by tRNA against enzyme denaturation at 50 degrees C. Comparative studies with tRNA nucleotidyl transferase purified from larvae, pupae and adult insects indicate that tRNA nucleotidyl transferase from these three developmental stages have the same molecular weight, sedimentation coefficient and optimum pH while the larval enzyme differs from the pupae and adult enzymes in the elution behaviour from a DEAE-cellulose column.


Tridemethylisovelleral, a potent cytotoxic agent.
The synthesis and in vitro cytotoxicity toward various tumor cell lines of (+/-)-tridemethylisovelleral, an analogue of the bioactive fungal sesquiterpene (+)-isovelleral retaining the bicyclo[4,1,0]hept-2-en-1,2-dicarbaldehyde system but lacking the three methyl groups, is reported. The cytotoxicity of tridemethylisovelleral toward several tumor cell lines was found to be comparable with those of established antitumor drugs, and significantly higher than that of isovelleral.


Opportunistic intruders: how viruses orchestrate ER functions to infect cells.
Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co-opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus-ER interactions has become available, these insights may lead to the development of crucial therapeutic agents.


When less is more: like humans, chimpanzees (Pan troglodytes) misperceive food amounts based on plate size.
We investigated whether chimpanzees (Pan troglodytes) misperceived food portion sizes depending upon the context in which they were presented, something that often affects how much humans serve themselves and subsequently consume. Chimpanzees judged same-sized and smaller food portions to be larger in amount when presented on a small plate compared to an equal or larger food portion presented on a large plate and did so despite clearly being able to tell the difference in portions when plate size was identical. These results are consistent with data from the human literature in which people misperceive food portion sizes as a function of plate size. This misperception is attributed to the Delboeuf illusion which occurs when the size of a central item is misperceived on the basis of its surrounding context. These results demonstrate a cross-species shared visual misperception of portion size that affects choice behavior, here in a nonhuman species for which there is little experience with tests that involve choosing between food amounts on dinnerware. The biases resulting in this form of misperception of food portions appear to have a deep-rooted evolutionary history which we share with, at minimum, our closest living nonhuman relative, the chimpanzee.


A-Lister: a tool for analysis of differentially expressed omics entities across multiple pairwise comparisons.
Researchers commonly analyze lists of differentially expressed entities (DEEs), such as differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and differentially methylated positions/regions (DMPs/DMRs), across multiple pairwise comparisons. Large biological studies can involve multiple conditions, tissues, and timepoints that result in dozens of pairwise comparisons. Manually filtering and comparing lists of DEEs across multiple pairwise comparisons, typically done by writing custom code, is a cumbersome task that can be streamlined and standardized. A-Lister is a lightweight command line and graphical user interface tool written in Python. It can be executed in a differential expression mode or generic name list mode. In differential expression mode, A-Lister accepts as input delimited text files that are output by differential expression tools such as DESeq2, edgeR, Cuffdiff, and limma. To allow for the most flexibility in input ID types, to avoid database installation requirements, and to allow for secure offline use, A-Lister does not validate or impose restrictions on entity ID names. Users can specify thresholds to filter the input file(s) by column(s) such as p-value, q-value, and fold change. Additionally, users can filter the pairwise comparisons within the input files by fold change direction (sign). Queries composed of intersection, fuzzy intersection, difference, and union set operations can also be performed on any number of pairwise comparisons. Thus, the user can filter and compare any number of pairwise comparisons within a single A-Lister differential expression command. In generic name list mode, A-Lister accepts delimited text files containing lists of names as input. Queries composed of intersection, fuzzy intersection, difference, and union set operations can then be performed across these lists of names. A-Lister is a flexible tool that enables the user to rapidly narrow down large lists of DEEs to a small number of most significant entities. These entities can then be further analyzed using visualization, pathway analysis, and other bioinformatics tools.


Adsorptive removal of trivalent and pentavalent arsenic from aqueous solutions using iron and copper impregnated melanin extracted from the marine bacterium Pseudomonas stutzeri.
The metalloid arsenic is one of the most conspicuous groundwater contaminants in the Indian subcontinent and its removal from aqueous medium is the main focus of this study. The study aims at functionalising melanin using iron and copper for the efficient removal of arsenic and rendering water fit for consumption. Melanin obtained from the marine bacteria Pseudomonas stutzeri was functionalised by iron impregnation (Fe-melanin) and copper impregnation (Cu-melanin). Morphological studies using FESEM portrayed the impregnated iron and copper granules on the surface of melanin, while XRD analysis confirmed the presence of Fe2O3 and CuO on melanin. Adsorption studies on As (V) and As (III) were conducted using Fe-melanin and Cu-melanin for different operating variables like pH, temperature and contact time. More than 99% per cent of As (III) and As (V) from water was removed at a pH range between 4 and 6 within 50 min in the case of Fe-melanin and 80 min for Cu-melanin. Adsorption equilibrium studies showed better fit with Langmuir adsorption isotherm and had good agreement with Redlich-Peterson's three-parameter model. The maximum adsorption capacities of Fe-melanin and Cu-melanin obtained from Langmuir adsorption model are 50.12 and 20.39 mg/g, respectively, for As (V) and similarly 39.98 and 19.52 mg/g, respectively, for As (III). Arsenic-binding to the functionalised melanin was confirmed using FT-IR and the XPS analysis. Reuse of the adsorbent was effectively done by desorbing the iron and copper together with the bound As (III) and As (V) and further re-impregnation of iron and copper in melanin. Re-functionalised melanin showed 99% adsorption efficiency up to four cycles of adsorption/desorption.


Management of Periprosthetic Bone Cysts After Total Ankle Arthroplasty.
Modern improvements in total ankle arthroplasty (TAA) have increased the performance of this procedure for treatment of end-stage ankle arthritis. A common finding after TAA is the formation of periprosthetic bone cysts, which can be clinically silent or result in TAA failure. The exact cause of periprosthetic bones cysts has not been established, but major theories are related to osteolysis secondary to implant wear, micromotion, and stress shielding. Treatment can be nonoperative with clinical observation for small, asymptomatic cysts. Large, progressive, and symptomatic cysts often merit surgical treatment with debridement and grafting, revision TAA, or salvage arthrodesis.


Dark repair of sunlight-inactivated tetracycline-resistant bacteria: Mechanisms and important role of bacteria in viable but non-culturable state.
The spread of antibiotic resistant bacteria (ARB) in the environment poses a potential threat to human health, and the reactivation of inactivated ARB accelerated the spread of ARB. However, little is known about the reactivation of sunlight-inactivated ARB in natural waters. In this study, the reactivation of sunlight-inactivated ARB in dark conditions was investigated with tetracycline-resistant E. coli (Tc-AR E. coli) as a representative. Results showed that sunlight-inactivated Tc-AR E. coli underwent dark repair to regain tetracycline resistance with dark repair ratios increasing from (0.124 ± 0.012)‱ within 24 h dark treatment to (0.891 ± 0.033)‱ within 48 h. The presence of Suwannee River fulvic acid (SRFA) promoted the reactivation of sunlight-inactivated Tc-AR E. coli and tetracycline inhibited their reactivation. The reactivation of sunlight-inactivated Tc-AR E. coli is mainly attributed to the repair of the tetracycline-specific efflux pump in the cell membrane. Tc-AR E. coli in a viable but non-culturable (VBNC) state was observed and dominated the reactivation as the inactivated ARB remain present in the dark for more than 20 h. These results explained the reason for distribution difference of Tc-ARB at different depths in natural waters, which are of great significance for understanding the environmental behavior of ARB.


Probing the mechanism of Prins cyclisations and application to the synthesis of 4-hydroxytetrahydropyrans.
Trapping intermediates on the Prins cyclisation pathway with carbon-based nucleophiles has given further insight into factors affecting the acid-mediated reactions of homoallylic alcohols with aldehydes, enabling the design of efficient syntheses of 4-hydroxy-2,6-disubstituted tetrahydropyrans.


Advances in nano/microscale electrochemical sensors and biosensors for analysis of single vesicles, a key nanoscale organelle in cellular communication.
The study of subcellular targets and biochemical processes within a living cell is valuable for biological and medical research. Secretory vesicles, one such important intracellular target, are nanoscale lipid structures that are capable of storage, transport, and secretion of, for example, neurotransmitters, hormones, proteins or waste products. Vesicles play an essential role in intercellular communication systems, as they facilitate the release of chemical messaging agents. If deregulated, these communication processes can be a central part in the pathogenesis of some neurodegenerative diseases or diabetes. Generally, due to their nanometer size and intracellular location, the analysis of single vesicles and their content is a great challenge. It requires sensitive techniques, micro/nanoscale tools and sensitive instruments with extreme spatio-temporal resolution. This review focuses on electrochemical sensors to study the biochemistry and quantification of messenger molecules and other species (e.g., reactive oxygen and nitrogen species) stored in organelles, providing new trends and developments in this field. Furthermore, we review the effect of the chemical environment of single cells (e.g., treatment with chemicals, drugs, lipids, and ions) on regulation of the physical and chemical properties of vesicles. Finally, unsolved challenges of and perspectives on vesicle electroanalysis are discussed.


Aesthetic surgery for benign disorders of the breast.
Those benign breast disorders that are amenable to improvement by aesthetic surgery are discussed from the points of view of indications, techniques, and results.


Protease inhibitors from Theobroma cacao impair SARS-CoV-2 replication in vitro.
SARS-CoV-2 is a newly emerging virus from the Coronaviridae family that has already infected over 700 million people worldwide and killed over 6 million. This virus uses protease molecules to replicate and infect the host, which makes these molecules targets for therapeutic substances to eliminate the virus and treat infected people. Through the protein-protein molecular docking approach, we detected two cystatins from Theobroma cacao, TcCYS3 and TcCYS4, described as papain-like protease inhibitors. These inhibitors decreased SARS-CoV-2 genomic copies without toxicity to Vero cells. There is a need to perform comprehensive studies in relevant animal models and to investigate the action mechanisms of protease inhibitors from Theobroma cacao that control the replication of SARS-CoV-2 in human cells.


The measurement of foot preference.
Foot preference has been given only superficial attention in studies of hemispheric lateralization, although it has potential utility for predicting hemispheric dominance. This paper reports the development of a reliable (alpha = 0.89) 11-item behavioral inventory of foot preference. Since footedness and handedness are only partially related, both must be measured reliably to identify individuals who have a consistent right or left side preference. It has yet to be determined whether footedness or handedness has the stronger relationship to other aspects of cerebral lateralization and whether both measures together predict lateralization better than one of them alone.


1-Indanone and 1,3-indandione Derivatives as Ligands for Misfolded α-Synuclein Aggregates.
The development of imaging agents for in vivo detection of alpha-synuclein (α-syn) pathologies faces several challenges. A major gap in the field is the lack of diverse molecular scaffolds with high affinity and selectivity to α-syn fibrils for in vitro screening assays. Better in vitro scaffolds can instruct the discovery of better in vivo agents. We report the rational design, synthesis, and in vitro evaluation of a series of novel 1-indanone and 1,3-indandione derivatives from a Structure-Activity Relationship (SAR) study centered on some existing α-syn fibril binding ligands. Our results from fibril saturation binding experiments show that two of the lead candidates compounds 8 and 32 bind α-syn fibrils with binding constants (Kd ) of 9.0 and 18.8 nM, respectively, and selectivity of greater than 10× for α-syn fibrils compared with amyloid-β (Aβ) and tau fibrils. Our results demonstrate that the lead ligands avidly label all forms of α-syn on PD brain tissue sections, but only the dense core of senile plaques in AD brain tissue, respectively. These results are corroborated by ligand-antibody colocalization data from Syn211, which shows immunoreactivity toward all forms of α-syn aggregates, and Syn303, which displays preferential reactivity toward mature Lewy pathology. Our results reveal that 1-indanone derivatives have desirable properties for the biological evaluation of α-synucleinopathies.


Generation of Fibrodysplasia ossificans progressiva and control integration free iPSC lines from periodontal ligament fibroblasts.
Fibrodysplasia ossificans progressiva (FOP) is a very rare devastating heterotopic ossification disorder, classically caused by a heterozygous single point mutation (c.617G>A) in the ACVR1gene, encoding the Bone morphogenetic protein (BMP) type I receptor, also termed activin receptor-like kinase (ALK)2. FOP patients develop heterotopic ossification episodically in response to inflammatory insults, thereby compromising tissue sampling and the development of in vitro surrogate models for FOP. Here we describe the generation and characterization of a control and a classical FOP induced pluripotent stem cell (iPSC) line derived from periodontal ligament fibroblast cells using Sendai virus vectors.


Study: temporary nurses not a threat to quality.
Work environment is much more likely to be a cause of poor hospital quality. Poor deployment of supplemental nurses, inadequate orientation can also threaten quality. Get staff on your side by using supplemental nurses to reach a goal all staff value.


Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys.
Preclinical assessment of monoclonal antibody (mAb) disposition during drug development often includes investigations in non-human primate models. In many cases, mAb exhibit non-linear disposition that relates to mAb-target binding [i.e., target-mediated disposition (TMD)]. The goal of this work was to develop a physiologically-based pharmacokinetic (PBPK) model to predict non-linear mAb disposition in plasma and in tissues in monkeys. Physiological parameters for monkeys were collected from several sources, and plasma data for several mAbs associated with linear pharmacokinetics were digitized from prior literature reports. The digitized data displayed great variability; therefore, parameters describing inter-antibody variability in the rates of pinocytosis and convection were estimated. For prediction of the disposition of individual antibodies, we incorporated tissue concentrations of target proteins, where concentrations were estimated based on categorical immunohistochemistry scores, and with assumed localization of target within the interstitial space of each organ. Kinetics of target-mAb binding and target turnover, in the presence or absence of mAb, were implemented. The model was then employed to predict concentration versus time data, via Monte Carlo simulation, for two mAb that have been shown to exhibit TMD (2F8 and tocilizumab). Model predictions, performed a priori with no parameter fitting, were found to provide good prediction of dose-dependencies in plasma clearance, the areas under plasma concentration versu time curves, and the time-course of plasma concentration data. This PBPK model may find utility in predicting plasma and tissue concentration versus time data and, potentially, the time-course of receptor occupancy (i.e., mAb-target binding) to support the design and interpretation of preclinical pharmacokinetic-pharmacodynamic investigations in non-human primates.


Association Between Long-Term Aspirin Use and Frailty in Men: The Physicians' Health Study.
Chronic inflammation may lead to frailty, however the potential for anti-inflammatory medications such as aspirin to prevent frailty is unknown. We sought to examine the association between long-term aspirin use and prevalent frailty. We included 12 101 men ≥60 years who participated in the Physicians' Health Study I, a completed aspirin randomized controlled trial (1982-1989). Annual questionnaires collected self-reported data on daily aspirin use, lifestyle, and clinical variables. Average aspirin use was summed into 2 categories: ≤60 days/year and >60 days/year. Frailty was assessed using a 33-item index 11 years after trial completion. A score of ≥0.21 was considered frail. Propensity score inverse probability of treatment weighting was used for statistical control of confounding. Logistic regression models estimated odds of frailty as a function of categories of average aspirin use. Mean age was 70.5 years (range 60-101). Following an average of 11 ± 0.6 years of follow-up, aspirin use was reported as ≤60 days/year for 15%; 2413 participants (20%) were frail. Frequency of aspirin use was associated with smoking, alcohol consumption, hypertension, and cardiovascular disease, but negatively associated with bleeding and Coumadin use. The odds ratio (95% confidence intervals) for frailty was 0.85 (0.76-0.96) for average aspirin use >60 days/year versus aspirin use ≤60 days/year. Results were similar using an alternate definition of frailty. Long-term regular aspirin use is inversely associated with frailty among older men, even after consideration of multimorbidity and health behaviors. Work is needed to understand the role of medications with anti-inflammatory properties on aging.


Brexpiprazole suppresses cell proliferation and de novo lipogenesis through AMPK/SREBP1 pathway in colorectal cancer.
In the present study, we investigated the role of brexpiprazole on cell proliferation and lipogenesis in colorectal cancer (CRC) and its molecular mechanism. The effect of brexpiprazole on CRC cell proliferation was determined by CCK-8, EdU assay, cell clone formation. The flow cytometry was evaluated cell cycle. Differential expression genes (DEGs) were identified by RNA-seq assay after treating HCT116 cells with or without 20 μM brexpiprazole for 24 h. Then, the top 120 DEGs were analyzed by GO and KEGG enrichment analysis. After that, Oil red O staining and the levels of total cholestenone and triglyceride were measured to assess lipogenesis capacity in CRC cells. The related molecules of cell proliferation, lipogenic and AMPK/SREBP1 signal pathways were measured by q-PCR, western blot and immunohistochemical staining. Brexpiprazole remarkably suppressed cell proliferation, lipogenesis, and induced cell cycle arrest in CRC. The underlying mechanisms probably involved the suppression of SREBP1 and the stimulation of AMPK. Brexpiprazole inhibited cell proliferation and de novo lipogenesis through AMPK/SREBP1 pathway in CRC.


Hiccups: a new explanation for the mysterious reflex.
The hiccup may have evolved to remove swallowed air from the stomach, which may help suckling mammals to consume more milk.


Surfactant-enhanced in-situ oxidation of DNAPL source zone: Experiments and numerical modeling.
In this study we investigate the synergetic effects of combining surfactant-enhanced dissolution with in-situ oxidation of a pool-dominated PCE DNAPL source zone entrapped in porous media. Flow cell flushing experiments packed with silica sand and natural calcareous soil were conducted with a surfactant (Tween 80) and permanganate (MnO4-) used as dissolution and oxidation agents, respectively. The resultant breakthrough curves exhibited a multiple step behavior with mass removal controlled in the latter stages by the less-accessible DNAPL mass. DNAPL spatial architecture, flow-field heterogeneity, and flushing solution all influenced the remediation effort. When taking into account both the surfactant-enhanced dissolution and permanganate oxidation processes, mass-flux reduction/mass-removal behavior relationships indicated that the inclusion of oxidation in the remediation scheme delayed the drop in mass flux from the source zone, leading to improved DNAPL removal efficiency. Numerical modeling was also performed to further evaluate the efficacy of the surfactant-enhanced chemical oxidation of DNAPL PCE with permanganate. The system of reaction equations available in the multiphase flow simulator UTCHEM were adapted to simulate the chemical oxidation process in the presence of a surfactant. The model results yield lower oxidation reaction rate constants in the presence of Tween 80, indicating that Tween 80 can interfere with the reaction rate. However, the increase in the solubility of PCE in the presence of Tween 80 more than compensates for the decrease in reaction rate constant. Overall, for Tween 80/MnO4- applied at sufficient dosages, more efficient DNAPL zone remediation was achieved compared to surfactant flushing or permanganate oxidation alone.


General versus spinal anaesthesia and postoperative delirium in an orthogeriatric population.
Postoperative delirium is common among elderly hip surgery patients. We aimed to pragmatically evaluate whether type of anaesthesia influenced postoperative delirium in an orthogeriatric population following hip fracture. This observational study comprises prospectively collected data on hip fracture patients admitted between October 2010 and November 2011. Delirium was diagnosed clinically by geriatricians. Of the 344 patients admitted, seven managed conservatively and 19 with incomplete data were excluded; 318 patients were analysed. Average age was 81.6 (SD 9.8) years; 28% were men and 167 (53%) were administered general anaesthesia. Mean length of stay was 18 (SD 9.4) days. Overall, 172 patients (54%) experienced delirium. There was no apparent difference in postoperative delirium by anaesthetic type (88 vs 84, P = 0.15). Delirium was common in both general and spinal anaesthetic patients. Further randomised controlled trials would be required to determine whether anaesthesia type influenced delirium rates.


Effects of high pressure in liquid chromatography.
All the experimental parameters that the chromatographers are used to consider as constant (the column length and its diameter, the particle size, the column porosities, the phase ratio, the column hold-up volume, the pressure gradient along the column, the mobile phase density and its viscosity, the diffusion coefficients, the equilibrium constants, the retention factors, the efficiency parameters) depend on pressure to some extent. While this dependence is negligible as long as experiments, measurements, and separations are carried out under conventional pressures not exceeding a few tens of megapascal, it is no longer so when the inlet pressure becomes much larger and exceeds 100 MPa. Equations are developed to determine the extent of the influence of pressure on all these parameters and to account for it. The results obtained are illustrated with graphics. The essential results are that (1) many parameters depend on the inlet pressure, hence on the flow rate; (2) the apparent reproducibility of parameters as simple as the retention factor will be poor if measurements are carried out at different flow rates, unless due corrections are applied to the results; (3) the influence of the temperature on the equilibrium constants should be studied under constant inlet pressure rather than at a constant flow rate, to minimize the coupling effect of pressure and temperature through the temperature dependence of the viscosity; and (4) while reproducibility of results obtained at constant pressure and flow rate will not be affected, method development becomes far more complex because of the pressure dependence of everything.


Successful implantation of in vitro cultured rabbit embryos after uterine transfer: a role for mucin.
The functional role of the mucin layer for development of rabbit embryos was examined by uterine transfer of embryos with different thicknesses of mucin. Embryos collected at various intervals after human chorionic gonadotropin (hCG) injection were cultured until 90 hr post-coitum (p.c.) and transferred to the uterus of synchronized recipients. When embryos collected at 20 or 25 hr p.c. were used for transfer, no implantation occurred. By contrast, embryos collected at 35 or 40 hr p.c. developed to term at high rates (53 and 80%, respectively). The thickness of the mucin layer on the embryos was different between these two groups. Embryos collected before 25 hr p.c. have less than 11.2 +/- 0.2 microns of thickness of mucin and embryos collected after 35 hr p.c. have more than 34.3 +/- 5.5 microns. To examine whether mucin deposition is required for in vitro cultured rabbit blastocysts to continue development after uterine transfer, embryos were collected at 20 hr p.c., cultured for 60 or 70 hr in vitro, and then temporarily transferred to the oviducts of recipient does to add mucin. These embryos were recovered from the oviducts at 24 hr after transfer, classified according to the thickness of mucin deposition, and transferred again to the uterus of synchronized recipients. Twenty live young were obtained from 67 embryos with a 20-40 microns thick mucin layer. No live young were obtained from 57 embryos with less than a 20 microns thick mucin. The thickness of the mucin layer appears to be an important factor for successful implantation of rabbit embryos.


A new virtual environment for testing and hardware implementation of closed-loop control algorithms in the artificial pancreas.
This article presents a new simulation tool for designing and testing blood glucose control algorithms in patients with type 1 diabetes. The control algorithms can be designed and implemented either with textual or graphical programming languages or by importing them from several frameworks. Realistic scenarios and protocols can be customized and built through graphical user interfaces, where several outcomes are available to evaluate control performance. Sophisticated models of the glucose-insulin system, as well as representative models of the instrumentation, have been included. Unlike existing systems, this simulation tool allows integrating the control algorithms into an electronic control unit, thus reusing the entire code in a straightforward way.


Identification of caregiver's knowledge and perceptions of pediatric asthma management: A quality improvement initiative.
Asthma is the most prevalent chronic disease of childhood. Caregiver knowledge is essential to optimize patient quality and safety. Asthma education is an opportunity that can lead to decreased morbidity and mortality, reduced admission rates, lower cost, and improved outcomes for a child with chronic asthma. The purpose of this quality improvement study was to obtain information from caregivers of children with asthma to gain insight into their knowledge gaps and needs as a critical first step towards the provision of patient centered effective and efficient care. This was a descriptive educational knowledge assessment conducted using questionnaires via a hand-held electronic device (iPad). All caregivers in this study reported that they desired more education. Specific knowledge deficits were identified and included: understanding the pathophysiology of asthma, mechanism of action of use of medications including both rescue and maintenance agents, and initial actions to implement during an acute asthma exacerbation. Caregivers in this sample population had a suboptimal understanding of the asthma disease process and home management strategies. To maximize education strategies and achieve symptom control and risk reduction in the care of children with asthma, it is imperative that caregivers clearly understand asthma home management and actively participate in all aspects of their child's care. The identification of specific gaps and needs in caregiver's knowledge base is a critical first step towards the provision of patient-centered effective and efficient pediatric asthma care.


Titanium Nitride Coated Implant Abutments: From Technical Aspects And Soft tissue Biocompatibility to Clinical Applications. A Literature Review.
To review the most up to date scientific evidence concerning the technical implications, soft tissue biocompatibility, and clinical applications derived from the use of titanium nitride hard thin film coatings on titanium alloy implant abutments. A review was performed to answer the following focused question: "What is the clinical reliability of nitride coated titanium alloy abutments?". A MEDLINE search between 1980 and 2021 was performed for investigations pertaining to the clinical use of nitride coated titanium alloy implant abutments (TiN) in case reports, case series, and short- and long-term non/randomized controlled clinical trials. Literature analysis led to addition evaluation of research related to the technical and biological aspects, as well as the physicochemical characteristics of TiN hard thin film coatings and their impact on titanium abutment biocompatibility, mechanical properties, macroscopic surface topography, and optical properties. Therefore, preclinical data from biomechanical and in vitro investigations were also considered as inclusion criteria. The limited number of clinical investigations published made a systematic review and meta-analysis not possible, therefore a narrative review was conducted. TiN coatings have been applied to dental materials and instruments to improve their clinical longevity. Implant abutments are coated with titanium nitride to mask the titanium oxide surface and enhance its surface characteristics providing the TiN abutment surface with a low friction coefficient and a very high chemical inertness. TiN coating is suggested to reduce early bacterial colonization and biofilm formation and enhance fibroblast cell proliferation, attachment and adhesion when compared to Ti controls. Additionally, studies indicate that hard thin film coatings enhance the mechanical properties (hardness and wear resistance) of titanium alloy and appears as a yellow color when deposited on the titanium alloy substrate. To date, clinical investigations show that nitride coated titanium abutments provide promising short-term clinical outcomes. Published research on nitride-coated abutments is still limited, however, the available biomedical research, mechanical engineering tests, in vitro investigations, and short-term clinical trials have, to date, reported promising mechanical, biological, and esthetic outcomes.


Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease. The vasopressin V2 receptor (VPV2R) antagonist OPC31260 has been effective in two animal models of PKD with pathologies that are probably related. Here we show, in a mouse model of ADPKD (Pkd2(-/tm1Som)), a similar cellular phenotype and response to OPC31260 treatment, with reduction of renal cyclic AMP (cAMP) levels, prevention of renal enlargement, marked inhibition of cystogenesis and protection of renal function.


Adjunct fixation in upper extremity long bone fracture plating.
A variety of adjunct fixation methods to supplement primary plate and screw constructs are available. There are no large clinical series of these techniques in the upper extremity. The purpose of this study was to review patients with upper extremity fractures that underwent primary plating with adjunct fixation. This study was a retrospective review of plate fixation of humeral, radial and ulnar fractures over a 12-year period. Measurable outcomes for this study included rates of non-union, complications, and implant removal. Thirty-nine humeral shaft fractures had supplemental fixation 97% of the time, with a 100% union rate. Supplemental fixation was used in 79% of forearm cases. There was a 98% initial union rate in 48 acutely plated forearm fractures. Although a variety of techniques were employed, the mini-fragment (2.7 mm or smaller) was the most common strategy for adjunctive fixation of long bone fractures in the upper extremity.


Repeatability of the Pentacam HR in Various Grades of Keratoconus.
To evaluate the repeatability of an extensive number of relevant indices with the Pentacam HR in keratoconus of varying severity and normal eyes. Reliability analysis. This study was performed at Antwerp University Hospital, Belgium, and enrolled 20 healthy volunteers (20 eyes) and 69 patients (69 eyes) with keratoconus. Three consecutive measurements were performed by the same operator with Pentacam HR in keratoconus and normal eyes. Exclusion criteria included past ocular surgery, recent rigid contact lens wear, and corneal scarring. The keratoconus group was subdivided according to the Belin/Ambrosio total deviation value: subclinical, mild, and moderate. The within-subject standard deviation and repeatability limit were computed for repeatability assessment. The tolerance index (TI) was calculated to compare across parameters with different measurement scales. For the sample size included, TI > 0.36 signified statistical significance at the 0.05 level. Repeatability in subclinical keratoconus did not differ significantly from controls (P > .05), except for wavefront aberrations. In mild keratoconus, 11 of 18 (61.1%) anterior corneal, 7 of 14 (50%) posterior corneal, 2 of 5 (40%) pachymetry, 7 of 11 (63.6%) combined, and 1 of 6 (16.7%) densitometry parameters showed significantly worse repeatability compared to controls (TI > 0.36). Repeatability of most parameters worsened in moderate disease. In particular, maximal keratometry and anterior astigmatism showed significantly worse repeatability in moderate keratoconus. Measurement variability of Pentacam HR is of clinical relevance when assessing for progression of keratoconus. We provide reference repeatability values and scale independent analysis of relevant corneal parameters in keratoconus of varying degrees.


A novel scavenger receptor 5-based antibiotic-independent selection method for generation of stable recombinant protein-producing mammalian cell lines especially suitable for proteins affecting cell adhesion.
The establishment of stable recombinant protein-producing mammalian cell lines is an expensive, time-consuming, tedious procedure. In some cases, expressed recombinant proteins have adverse effects on host cell function, including cell adhesion. Based on the adhesive properties of SCARA5, a scavenger receptor (SR) of the class A SR family, we developed a method for selection of stable recombinant protein-producing cell clones that relies on an internal ribosome entry site (IRES) vector where the protein of interest is expressed in the same messenger RNA as SCARA5, resulting in improved adhesion and increased cell viability of recombinant protein-producing cells in serum-free media. This method does not depend on antibiotics, complicated selective cell culture media or equipment, and thus offers the advantages of being inexpensive, environmentally friendly, and simple.