Monoclonal gammopathy in rheumatic diseases.
To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P = 0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P = 0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P = 0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P = 0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015-1.251), P = 0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011-1.242), P = 0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype switch, 1 progressed to multiple myeloma (MM), and another 2 experienced renal injuries attributed by monoclonal or polyclonal plasma cell interstitial infiltration. Seven (17.1%) of the 41 MG patients presented hematological neoplasias, 4 with MM, 2 with smoldering multiple myeloma, and 1 with B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The presence of light-chain MG was associated with the development of MM [OR 17.5 (95%CI 1.551-197.435), P = 0.041], but not with an increased risk of lymphoma or SMM. MG was observed in patients with various rheumatic disorders, with SS being the most common type. The presence of MG might be associated with higher disease activity. The development of hematological neoplasias including MM and lymphoma was seen in this setting. Therefore, we recommend the screening for MG and close monitoring for potential malignant transformation in patients with rheumatic diseases as needed.


Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells.
Garlic-derived organosulfur compounds such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) provide significant protection against carcinogenesis. Dose-dependent cytotoxic effects of the garlic compounds (DAS, DADS, and DATS) were tested in human glioblastoma T98G and U87MG cells. Wright staining and ApopTag assay confirmed induction of apoptosis. Measurements showed that production of reactive oxygen species (ROS) and an increase in intracellular free [Ca(2+)] promoted apoptosis. Western blot analysis indicated that increased expression and activities of the stress kinases and cysteine proteases caused apoptosis. Use of JC-1 showed changes in mitochondrial membrane potential (Delta psi(m)) for mediation of apoptosis. Use of the specific inhibitors monitored the activation of different kinases and proteases in apoptosis. Treatment of glioblastoma cells with garlic compounds triggered production of ROS that induced apoptosis with the phosphorylation of p38 MAPK and activation of the redox-sensitive JNK1 pathway. Pretreatment of cells with ascorbic acid attenuated ROS production, p38 MAPK phosphorylation, and JNK1 activation. Pretreatment with JNK1 inhibitor I also significantly reduced cell death. Increases in intracellular free [Ca(2+)], expression of calreticulin, and activation of caspase-4 indicated involvement of endoplasmic reticulum (ER) stress in apoptosis. Other events in apoptosis included overexpression of Bax, down-regulation of Bcl-2 and some BIRC proteins, mitochondrial release of cytochrome c and Smac into the cytosol, and activation of calpain, caspase-9, and caspase-3. Garlic compounds induced apoptosis in glioblastoma cells due toproduction of ROS, increase in ER stress, decrease in Delta psi(m), and activation of stress kinases and cysteine proteases.


Innovative care models for high-cost Medicare beneficiaries: delivery system and payment reform to accelerate adoption.
About a third of Medicare beneficiaries are covered by Medicare Advantage (MA) plans or accountable care organizations (ACOs). As a result of assuming financial risk for Medicare services and/or being eligible for shared savings, these organizations have an incentive to adopt models of delivering care that contribute to better care, improved health outcomes, and lower cost. This paper identifies innovative care models across the care continuum for high-cost Medicare beneficiaries that MA plans and ACOs could adopt to improve care while potentially achieving savings. It suggests policy changes that would accelerate testing and spread of promising care delivery model innovations. Targeted review of the literature to identify care delivery models focused on high-cost or high-risk Medicare beneficiaries. This paper presents select delivery models for high-risk Medicare beneficiaries across the care continuum that show promise of yielding better care at lower cost that could be considered for adoption by MA plans and ACOs. Common to these models are elements of the Wagner Chronic Care Model, including practice redesign to incorporate a team approach to care, the inclusion of nonmedical personnel, efforts to promote patient engagement, supporting provider education on innovations,and information systems allowing feedback of information to providers. The goal of these models is to slow the progression to long-term care, reduce health risks, and minimize adverse health impacts, all while achieving savings.These models attempt to maintain the ability of high-risk individuals to live in the home or a community-based setting, thereby avoiding costly institutional care. Identifying and implementing promising care delivery models will become increasingly important in launching successful population health initiatives. MA plans and ACOs stand to benefit financially from adopting care delivery models for high-risk Medicare beneficiaries that reduce hospitalization. Spreading these models to other organizations will require provider payment policy changes. Integration of acute and long-term care would further spur adoption of effective strategies for reducing or delaying entry into long-term institutional care.


Low linolenate and commercial soybean oils diminish serum HDL cholesterol in young free-living adult females.
A mutant soybean line (A16) low in linolenic acid content (2% of oil by weight) was developed to increase oil oxidative stability. It was unknown whether serum lipid and lipoprotein concentrations in humans would be affected should A16 soybean oil (A16 oil) replace commercial soybean oil in diets. This study was conducted to examine the hypothesis that in free-living normolipidemic women, the consumption of A16 oil at approximately 10% of energy intake (en%) would not affect serum lipids and lipoproteins differently than would the consumption of the same amount of a commercial soybean oil with 7% of linolenic acid content. Fifteen free-living female college students consumed the soybean oil daily with regular meals for 9 weeks in different orders, with each test oil being eaten for 3 weeks. During the study, 13 en% was provided by each test oil and a total of 35 en% was from dietary fat. Serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), low-density lipoprotein cholesterol (LDL cholesterol) and triacylglycerides (TAG) were measured. Serum total fatty acid patterns were analyzed as well. Each of the three test oils decreased serum total cholesterol, LDL cholesterol and TAG concentrations from the baseline values. The feeding of A16 and commercial soybean oils decreased serum HDL cholesterol significantly compared with coconut oil (p < 0.05). Dietary inclusion of coconut oil increased serum myristic acid significantly more than did either soybean oil (p < 0.01). Serum arachidonic acid concentrations were significantly greater with A16 consumption than with commercial soybean oil consumption (p < 0.001). A16 and commercial soybean oils both diminished serum HDL cholesterol. Although the fatty acid composition differed between the two soybean oils, A16 oil and commercial oil had similar effects on serum concentrations of lipoproteins and lipids. With increased oxidative stability, A16 oil is a good alternative to commercial soybean oil.


Thermogymnomonas acidicola gen. nov., sp. nov., a novel thermoacidophilic, cell wall-less archaeon in the order Thermoplasmatales, isolated from a solfataric soil in Hakone, Japan.
A novel thermoacidophilic, cell wall-less archaeon, strain IC-189T, was isolated from a solfataric field in Ohwaku-dani, Hakone, Japan. The cells were irregular cocci, sometimes lobed, club-shaped or catenated, and were highly variable in size, ranging from 0.8 to 8.0 microm in diameter. The strain grew at temperatures in the range 38-68 degrees C (optimally at 60 degrees C) and at pH 1.8-4.0 (optimally at around pH 3.0). Strain IC-189T was obligately aerobic and heterotrophic, requiring yeast extract for growth. Yeast extract, glucose and mannose served as carbon and energy sources. The polar lipids consisted mainly of cyclic or acyclic glycerol-bisdiphytanyl-glycerol tetraethers, and the predominant quinone was a menaquinone with seven isoprenoid units (MK-7). The G+C content of total DNA was 56.1 mol%. 16S rRNA gene sequence analysis revealed that strain IC-189T was a member of the order Thermoplasmatales, but diverged from the hitherto known species of the genera Thermoplasma, Picrophilus and Ferroplasma (86.2-91.0% sequence similarity). These phenotypic and phylogenetic properties clearly support a separate taxonomic status for this strain. Therefore, strain IC-189T represents a novel genus (order Thermoplasmatales) and species, for which the name Thermogymnomonas acidicola gen. nov., sp. nov. is proposed, with type strain IC-189T (=JCM 13583T=DSM 18835T).


Fatigue and phosphocreatine depletion during carbon dioxide-induced acidosis in rat muscle.
Isolated extensor digitorum longus muscles from rat were exposed to atmospheres of 30% CO2 (high-CO2 muscles) or 6.5% CO2 (control muscles) in O2 for 95 min. Muscle contraction characteristics were studied before and after the incubation. Tetanic tension decreased in high-CO2 muscles to 55% of initial value but remained unchanged in control muscles. Relaxation time was prolonged in high-CO2 muscles but not in control muscles. Intracellular pH was 6.67 +/- 0.04 (SD) in high-CO2 muscles and 7.01 +/- 0.04 in control muscles. CO2-induced acidosis had a marked influence on the intermediary energy metabolism as shown by a fourfold increase of glucose 6-phosphate, a 14% increase of ADP, and a decrease of phosphocreatine to 44% of the control value. Lactate and pyruvate contents were unchanged. The observed metabolic changes can be explained by an effect of H+ on the activity of phosphofructokinase and on the creatine kinase equilibrium. It can be concluded that H+ concentration causes muscular fatigue. It is, however, uncertain whether this is an effect of increased H+ per se or by high-energy phosphate depletion induced by acidosis.


The nature of the interactions of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. II. Patch clamp studies.
Patch clamping of myoballs to record single channels was performed to examine the interaction of the anticholinesterase agent pyridostigmine (Pyr) with the acetylcholine (ACh) receptor-ion channel complex. Single ACh channel currents were recorded from tissue-cultured muscle cells of neonatal rats (myoballs). Pyr (50-100 microM) decreased the frequency of channel-opening events activated by ACh, and induced a modified form of the ACh channel currents. Channel conductance was lower in the presence of Pyr, and channel lifetime remained unaltered or only slightly prolonged. In addition, channel openings were frequently interrupted by fast flickers in the presence of Pyr. Higher concentrations (200 microM-1 mM) of the drug induced irregular waves of bursting activity during the initial phase of the application, and, subsequently, significantly reduced the frequency of channel openings. Infrequent channel openings with low conductance were observed in the patch when the micropipette was filled with Pyr alone. These results suggest that, in addition to its anticholinesterase activity, Pyr reacts with the ACh receptor, and both alone or in combination with ACh induces an altered, desensitized species of the nicotinic receptor-ion channel complex.


A first insight into genetic diversity of Mycobacterium bovis isolated from extrapulmonary tuberculosis patients in South Tunisia assessed by spoligotyping and MIRU VNTR.
In Tunisia, almost 77% of clinically and bacteriologically diagnosed cases of extrapulmonary tuberculosis (EPTB) are zoonotic TB, caused by M. bovis. Although several studies have analyzed bovine TB in cattle in Tunisia, no study has evaluated the risk of transmission to humans in such an endemic country. We aimed to study the genetic diversity of M. bovis human isolates, to ascertain the causes of human EPTB infection by M. bovis and to investigate the distribution and population structure of this species in Tunisia. A total of 110 M. bovis isolates taken from patients with confirmed EPTB were characterized by spoligotyping and MIRU-VNTR typing methods. Among the 15 spoligotypes detected in our study, 6 (SB0120, SB0121, SB2025, SB1200, SB1003 and SB0134) were the most prevalent (83.5%) of which SB0120, SB0121 and SB2025 were the most prevailing. MIRU-VNTR typing method showed a high genotypic and genetic diversity. The genetic differentiation based on MIRU-VNTR was significant between populations from South East (Tataouine, Medenine) and Central West (Gafsa, Sidi Bouzid, Kasserine) regions. Of note, 13/15 (86.7%) spoligotypes detected in our study were previously identified in cattle in Tunisia with different frequencies suggesting a peculiar ability of some genotypes to infect humans. Using combined spoligotyping and MIRU-VNTR method, a high clustering rate of 43.9% was obtained. Our results underlined that human EPTB due to M. bovis was more commonly found in female gender and in young patients. Most of our patients, 66.4% (73/110) were raw milk or derivatives consumers, whereas 30.9% (34/110) patients would have contracted EPTB through contact with livestock. The findings suggest that the transmission of Zoonotic TB caused by M. bovis to humans mainly occurred by oral route through raw milk or derivatives. Our study showed the urgent need of a better veterinary control with the implementation of effective and comprehensive strategies in order to reach a good protection of animals as well as human health.


[Combined use of metronidazole and short-term hyperglycemia during radiation therapy of tumors in rats].
A simultaneous combined treatment with metronidazole and short-term hyperglycaemia, in contrast to application of each of these agents alone, enhanced considerably the therapeutic effect of radiation (a single and fractionated exposure). This was indicated by the increased rate of tumor regression, the number of animals with transient remission, and the number of cured animals which exhibited no relapse throughout the entire 90-day period of observation.


Riboflavin as a tracer of medication compliance.
Three experiments were conducted to evaluate the accuracy of urine ultraviolet fluorescent tests for riboflavin, which has been used as a tracer for medication compliance in several clinical drug trials. Observer accuracy in discriminating riboflavin-positive or negative urine samples was found to vary with the method of observation, dose of riboflavin, observer experience, and time postingestion. The results showed that, while the 5-mg dose used in previous clinical trials was too small to permit reliable assessment of compliance, larger doses of riboflavin could produce nearly 100% accuracy for minimally trained observers who used a matching-to-sample observation procedure. The findings are discussed in terms of the potential clinical and research applications of this type of simple but reliable compliance assessment procedure.


CytoDirect: A Nucleic Acid Nanodevice for Specific and Efficient Delivery of Functional Payloads to the Cytoplasm.
Direct and efficient delivery of functional payloads such as chemotherapy drugs, siRNA, or small-molecule inhibitors into the cytoplasm, bypassing the endo/lysosomal trapping, is a challenging task for intracellular medicine. Here, we take advantage of the programmability of DNA nanotechnology to develop a DNA nanodevice called CytoDirect, which incorporates disulfide units and human epidermal growth factor receptor 2 (HER2) affibodies into a DNA origami nanostructure, enabling rapid cytosolic uptake into targeted cancer cells and deep tissue penetration. We further demonstrated that therapeutic oligonucleotides and small-molecule chemotherapy drugs can be easily delivered by CytoDirect and showed notable effects on gene knockdown and cell apoptosis, respectively. This study demonstrates the synergistic effect of disulfide and HER2 affibody modifications on the rapid cytosolic delivery of DNA origami and its payloads to targeted cells and deep tissues, thereby expanding the delivery capabilities of DNA nanostructures in a new direction for disease treatment.


[Surgical treatment of patients with advanced bilateral destructive pulmonary tuberculosis].
The paper analyzes the outcomes of surgical treatment of 135 patients operated on at the Surgery Clinic of the Institute. A set of surgical techniques, including pulmonectomy, collapsosurgical interventions, local cavernous exposures, thoroscopic surgery, thoracic caustic under artificial pneumothorax, was applied. The used system of surgical treatment was found to be beneficial for these patients, as confirmed by fewer surgical (3.0%) and postoperative (7.8%) complications, lower postoperative mortality rates (2.2%), and steady state clinical recovery in 91% and working capacity restoration in 76%.


Fragment quantum mechanical calculation of proteins and its applications.
Conspectus The desire to study molecular systems that are much larger than what the current state-of-the-art ab initio or density functional theory methods could handle has naturally led to the development of novel approximate methods, including semiempirical approaches, reduced-scaling methods, and fragmentation methods. The major computational limitation of ab initio methods is the scaling problem, because the cost of ab initio calculation scales nth power or worse with system size. In the past decade, the fragmentation approach based on chemical locality has opened a new door for developing linear-scaling quantum mechanical (QM) methods for large systems and for applications to large molecular systems such as biomolecules. The fragmentation approach is highly attractive from a computational standpoint. First, the ab initio calculation of individual fragments can be conducted almost independently, which makes it suitable for massively parallel computations. Second, the electron properties, such as density and energy, are typically combined in a linear fashion to reproduce those for the entire molecular system, which makes the overall computation scale linearly with the size of the system. In this Account, two fragmentation methods and their applications to macromolecules are described. They are the electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method and the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach. The EE-GMFCC method is developed from the MFCC approach, which was initially used to obtain accurate protein-ligand QM interaction energies. The main idea of the MFCC approach is that a pair of conjugate caps (concaps) is inserted at the location where the subsystem is divided by cutting the chemical bond. In addition, the pair of concaps is fused to form molecular species such that the overcounted effect from added concaps can be properly removed. By introducing the electrostatic embedding field in each fragment calculation and two-body interaction energy correction on top of the MFCC approach, the EE-GMFCC method is capable of accurately reproducing the QM molecular properties (such as the dipole moment, electron density, and electrostatic potential), the total energy, and the electrostatic solvation energy from full system calculations for proteins. On the other hand, the AF-QM/MM method was used for the efficient QM calculation of protein nuclear magnetic resonance (NMR) parameters, including the chemical shift, chemical shift anisotropy tensor, and spin-spin coupling constant. In the AF-QM/MM approach, each amino acid and all the residues in its vicinity are automatically assigned as the QM region through a distance cutoff for each residue-centric QM/MM calculation. Local chemical properties of the central residue can be obtained from individual QM/MM calculations. The AF-QM/MM approach precisely reproduces the NMR chemical shifts of proteins in the gas phase from full system QM calculations. Furthermore, via the incorporation of implicit and explicit solvent models, the protein NMR chemical shifts calculated by the AF-QM/MM method are in excellent agreement with experimental values. The applications of the AF-QM/MM method may also be extended to more general biological systems such as DNA/RNA and protein-ligand complexes.


Retrospective Analysis of Lipid-Lowering and Antiplatelet Therapy Regimen by Clinical Decision Support Service Based on Real-World Data from Electronic Medical Records "Intellect 3 Study".
Aim To evaluate prescription of lipid-lowering and antithrombotic therapy in clinical practice and to compare differences in recommendations using the clinical decision support service (CDSS).Material and methods Electronic medical records (EMR) of 300 patients from the Chazov National Medical Research Center of Cardiology, as well as from medical organizations controlled by the Department of Health of the Lipetsk Region and the Ministry of Health of the Voronezh Region, were analyzed for the period of August - December 2022, during the pilot implementation of CDSS. Retrospective information about the prescription of lipid-lowering and antithrombotic therapy from the EMR was compared with the CDSS guidelines under the expert supervision based on digitized clinical and laboratory profiles of patients. The study primary endpoint was a change in the initially prescribed lipid-lowering and / or antithrombotic therapy as per CDSS guidelines.Results Overall 292 patients were included in the final analysis; 46 (15.7 %) were from the primary prevention group and 246 (84.3 %) from the secondary prevention group. In group 1, the lipid-lowering therapy recommended by the CDSS differed by 50 % (p<0.001) from the baseline therapy recorded in the EMR. In the secondary prevention group, 78.9 % (p<0.001) differences were found in the lipid-lowering therapy recommended in the CDSS guidelines compared to the prescriptions in the EMR. In 76.8 % (p<0.001) of patients, antithrombotic therapy was significantly different from the baseline therapy in the EMR.Conclusion The use of CDSS may improve the practice of choosing lipid-lowering and antithrombotic therapy for prevention of cardiovascular complications.


Perspectives of Black women in the United States on salon-based intervention to promote the uptake of pre-exposure prophylaxis (PrEP) for HIV.
To understand Black women's perspectives on a pre-exposure prophylaxis (PrEP) education intervention in a salon setting. Black women have a significant lifetime risk of acquiring HIV. Pre-exposure prophylaxis (PrEP) is an effective prevention approach in reducing that risk. Despite this, Black women are least likely to use PrEP. This was a qualitative study to identify Black women's perspectives on acceptability of a PrEP education intervention in a salon setting using hair stylists. The paper adhered to the COREQ checklist in reporting. Seven focus groups among Black women (n = 44) living in north-central North Carolina were conducted. Ethical approval was obtained. The interview guide included questions on knowledge of PrEP and barriers and facilitators to a PrEP promotion programme in a salon setting. Conventional content analysis considered content in relation to themes of facilitators, barriers and women's preferences for intervention delivery. Facilitators included the salon characteristics, social culture and relationship with the stylist. Women noted concerns of accuracy of content from stylists and privacy as barriers. Participants' trust with their stylists make a PrEP education salon-based intervention feasible. Salon-based interventions are not one-size-fits-all and researchers interested in this setting should tailor interventions to the individual salon. Interventions for PrEP in a salon setting should be culturally appropriate, confidential and consider the potential reach to the social networks of Black women in the salon. The insights shared by Black women can contribute to developing a PrEP uptake intervention as a way of reducing new cases of HIV.


C1q/TNF-related protein 5 contributes to diabetic vascular endothelium dysfunction through promoting Nox-1 signaling.
Dysregulated adipokine profiles contribute to the pathogenesis of diabetic cardiovascular complications. Endothelial cell (EC) dysfunction, a common pathological alteration in cardiovascular disorders, is exaggerated in diabetes. However, it is unclear whether and how dysregulated adipokines may contribute to diabetic EC dysfunction. Serum C1q/TNF-Related Protein 5 (CTRP5) were determined in control/diabetes patients, and control/diabetic mice (high-fat diet, HFD). We observed for the first time that serum total CTRP5 was increased, high molecular weight (HMW) form was decreased, but the globular form (gCTRP5) was significantly increased in diabetic patients. These pathological alterations were reproduced in diabetic mice. To determine the pathological significance of increased gCTRP5 in diabetes, in vivo, ex vivo and in vitro experiments were performed. Diabetic atherosclerosis and EC dysfunction were significantly attenuated by the in vivo administration of CTRP5 neutralization antibody (CTRP5Ab). EC apoptosis was significantly increased in diabetic EC (isolated from HFD animal aorta) or high glucose high lipid (HGHL) cultured HUVECs. These pathological alterations were further potentiated by gCTRP5 and attenuated by CTRP5Ab. Pathway specific discovery-driven approach revealed that Nox1 expression was one of the signaling molecules commonly activated by HFD, HGHL, and gCTRP5. Treatment with CTRP5Ab reversed HFD-induced Nox1 upregulation. Finally, Nox1siRNA was used to determine the causative role of Nox1 in gCTRP5 induced EC apoptosis in diabetes. Results showed that gCTRP5 activated the mitochondrial apoptotic signal of EC in diabetes, which was blocked by the silencing Nox1 gene. We demonstrated for the first time that gCTRP5 is a novel molecule contributing to diabetic vascular EC dysfunction through Nox1-mediated mitochondrial apoptosis, suggesting that interventions blocking gCTRP5 may protect diabetic EC function, ultimately attenuate diabetic cardiovascular complications.


Anterior quadratus lumborum block does not reduce postoperative opioid consumption following laparoscopic hemicolectomy: a randomized, double-blind, controlled trial in an ERAS setting.
An opioid-sparing postoperative analgesic regimen following laparoscopic hemicolectomy is optimal to promote minimal postoperative pain, early mobilization, and improved quality of recovery. Various regional anesthesia techniques have been tested to improve postoperative pain management after laparoscopic hemicolectomy. In this study, we aimed to assess the effect of administering a preoperative bilateral ultrasound-guided anterior quadratus lumborum nerve block on postoperative opioid consumption after laparoscopic colon cancer surgery. In this randomized, controlled, double-blinded trial, 69 patients undergoing laparoscopic hemicolectomy due to colon cancer were randomized to receive an anterior quadratus lumborum block with ropivacaine 0.375% 30 mL on each side or isotonic saline (placebo). The primary outcome measure was total opioid consumption during the first 24 hours postsurgery. The secondary outcome measures were pain scores, accumulated opioid consumption in 6-hour intervals, nausea and vomiting, ability of postoperative ambulation, time to first opioid, orthostatic hypotension or intolerance, postoperative Quality of Recovery-15 scores, surgical complications, length of hospital stay, and adverse events. The total opioid consumption in the first 24 hours postsurgery was not significantly reduced in the ropivacaine group compared with the saline group (mean 129 mg (SD 88.4) vs mean 127.2 mg (SD 89.9), p=0.93). In addition, no secondary outcome measures showed any statistically significant intergroup differences. The administration of a preoperative bilateral anterior quadratus lumborum nerve block as part of a multimodal analgesic regimen for laparoscopic hemicolectomy did not significantly reduce opioid consumption 24 hours postsurgery. Trial registration number NCT03570541.


Timing of precipitation in an arid environment: Effects on population performance of a large herbivore.
Climate models predict that shifts in temperature and precipitation patterns are likely to occur across the globe. Changing climate will likely have strong effects on arid environments as a result of increased temperatures, increasing frequency and intensity of droughts, and less consistent pulses of rainfall. Therefore, understanding the link between patterns of precipitation, temperature, and population performance of species occupying these environments will continue to increase in importance as climatic shifts occur within these natural ecosystems. We sought to evaluate how individual, maternal, population, and environmental, particularly temperature and precipitation, level factors influence population performance of a large herbivore in an arid environment. We used mule deer (Odocoileus hemionus) as a representative species and quantified juvenile survival to test hypotheses about effects of environmental factors on population performance. Precipitation events occurring in mid- to late-pregnancy (January-April) leading to spring green-up, as indexed by normalized difference in vegetation index, had the strongest positive effect on juvenile survival and recruitment. In addition, larger neonates had an increased probability of survival. Our findings indicate that timing and amount of precipitation prior to parturition have strong influences on maternal nutritional condition, which was passed on to young. These results have important implications for understanding how animal populations may benefit from timing of precipitation during spring and prior to parturition, especially in arid environments.


Effects of supermagnetic iron oxide labeling on the major functional properties of human mesenchymal stem cells from multiple sclerosis patients.
In the last few years, treatment protocols using mesenchymal stem cells (MSC) in various experimental models and human diseases have been investigated. MSCs are on the focus of stem cell research, since they are considered as a type of adult stem cells with low toxicity and acceptable side effects profile and they can be administered autologously. In addition several studies have revealed significant immunomodulatory properties of MSCs and a potential for transdifferentiation, including neural differentiation, both in vivo and in vitro. Magnetic resonance imaging (MRI) is a non-invasive technique that can be used to track labeled cells and evaluate their migration ability in various clinical settings. In this study we investigated whether such labeling of MSCs with the commercially used para-magnetic material, Feridex, has any negative effect on the above mentioned functional properties of MSCs. We labeled human mesenchymal stem cells (hMSC) with poly-L-lysine coated Feridex(®) and evaluated their cellular differentiation and immunomodulatory properties, in vitro. In comparison with unlabeled cells, labeled hMSC exhibited normal adipogenic and osteogenic differentiation, but decreased chondrogenic differentiation. Regarding neural differentiation, labeled and unlabeled cells were similar in their ability to express neural-like and glial like surface proteins. Finally, both labeled and unlabeled MSCs exhibited a dose-dependent, significant blocking effect on the proliferation of healthy donors lymphocytes following mitogen stimulation. These findings indicate that labeling with Feridex does not affect the immunomodulatory, nor the neural transdifferentiation potential of MScs and therefore, Feridex may be used for the tracking of this type of stem cells in clinical applications, without compromising their major functional properties.


Description of Auriculotrema lechneri n. gen., n. sp. (Digenea: Choanocotylidae), a parasite of freshwater turtles (Testudines: Pleurodira: Chelidae) from Queensland, Australia.
Auriculotrema lechneri n. gen., n. sp. is described from the small intestine of Emydura krefftii and Elseya latisternum from northern Queensland, Australia. The new species strongly resembles species of Choanocotyle in body shape, ventral incision of the oral sucker, structure of the cirrus sac, and location of the genital pore. The distinctive taxonomic feature is the presence of 2 winglike projections extending beyond the lateral margins of the oral sucker, in contrast to the extremely large, expanded oral sucker diagnostic of Choanocotyle spp. Auriculotrema n. gen. is the second genus included in the formerly monotypic Choanocotylidae Jue Sue and Platt, 1998.


Recurrent psychogenic coma following tracheal stenosis repair.
Medication, intracranial hemorrhage, infarction, infection, hypoxia, organ failure, and nutritional deficiency may cause unconsciousness following successful emergence from anesthesia. A 39-year-old woman with a history of tracheal stenosis, depression, and anxiety had complete unconsciousness on 3 separate occasions following surgical repair of her tracheal stenosis. In each case, the patient's endotracheal tube had been removed; she was alert and oriented to person, time, and place; and she was admitted to the hospital for observation. Within a few hours after the tube was removed, the patient became abruptly unconscious for periods of 36, 18, and 30 hours. Each time, the results of cardiac, pulmonary, metabolic, and neurologic examinations and radiological studies were normal. We hypothesize that the patient's apparent comas were the result of an underlying conversion disorder precipitated by unresolved psychological conflict surrounding a long history of abuse in which she was repeatedly smothered by a pillow.


Effects of type 2 diabetes on insulin secretion, insulin action, glucose effectiveness, and postprandial glucose metabolism.
In this study, we sought to determine whether postprandial insulin secretion, insulin action, glucose effectiveness, and glucose turnover were abnormal in type 2 diabetes. Fourteen subjects with type 2 diabetes and 11 nondiabetic subjects matched for age, weight, and BMI underwent a mixed-meal test using the triple-tracer technique. Indexes of insulin secretion, insulin action, and glucose effectiveness were assessed using the oral "minimal" and C-peptide models. Fasting and postprandial glucose concentrations were higher in the diabetic than nondiabetic subjects. Although peak insulin secretion was delayed (P < 0.001) and lower (P < 0.05) in type 2 diabetes, the integrated total postprandial insulin response did not differ between groups. Insulin action, insulin secretion, disposition indexes, and glucose effectiveness all were lower (P < 0.05) in diabetic than in nondiabetic subjects. Whereas the rate of meal glucose appearance did not differ between groups, the percent suppression of endogenous glucose production (EGP) was slightly delayed and the increment in glucose disappearance was substantially lower (P < 0.01) in diabetic subjects during the first 3 h after meal ingestion. Together, these defects resulted in an excessive rise in postprandial glucose concentrations in the diabetic subjects. When measured using methods that avoid non-steady-state error, the rate of appearance of ingested glucose was normal and suppression of EGP was only minimally impaired. However, when considered in light of the prevailing glucose concentration, both were abnormal. In contrast, rates of postprandial glucose disappearance were substantially decreased due to defects in insulin secretion, insulin action, and glucose effectiveness.


A comparison of X-ray fluorescence and wet chemical analysis of air filter samples from a scrap lead smelting operation.
Personal and area air samples were taken at a scrap lead smelter operation in a bullet manufacturing facility. Samples were taken using the 37-mm styrene-acrylonitrile closed-face filter cassette (CFC, the current US standard device for lead sampling), the 37-mm GSP or "cone" sampler, the 25-mm Institute of Occupational Medicine (IOM) inhalable sampler, and the 25-mm Button sampler (developed at the University of Cincinnati). Polyvinylchloride filters were used for sampling. The filters were pre- and post-weighed, and analyzed for lead content using a field-portable X-ray fluorescence (XRF) analyzer. The filters were then extracted with dilute nitric acid in an ultrasonic extraction bath and the solutions were analyzed by inductively coupled plasma optical emission spectroscopy. The 25-mm filters were analyzed using a single XRF reading, while three readings on different parts of the filter were taken from the 37-mm filters. The single reading from the 25-mm filters was adjusted for the nominal area of the filter to obtain the mass loading, while the three readings from the 37-mm filters were inserted into two different algorithms for calculating the mass loadings, and the algorithms were compared. The IOM sampler was designed for material collected in the body of the sampler to be part of the collected sample as well as that on the filter. Therefore, the IOM sampler cassettes were rinsed separately to determine if wall-loss corrections were necessary. All four samplers gave very good correlations between the two analytical methods above the limit of detection of the XRF procedure. The limit of detection for the 25-mm filters (5 microg) was lower than for the 37-mm filters (10 microg). The percentage of XRF results that were within 25% of the corresponding ICP results was evaluated. In addition, the bias from linear regression was estimated. Linear regression for the Button sampler and the IOM sampler using single readings and the GSP using all tested techniques for total filter loading gave acceptable XRF readings at loadings equivalent to sampling at the OSHA 8-hour Action Level and Permissible Exposure Limit. However, the CFC only had acceptable results when the center reading corrected for filter area was used, which was surprising, and may be a result of a limited data set. In addition to linear regression, simple estimation of bias indicated reasonable agreements between XRF and ICP results for single XRF readings on the Button sampler filters, (82% of the individual results within criterion), and on the IOM sampler filters (77% or 61%--see text), and on the GSP sampler filters using the OSHA algorithm (78%). As a result of this pilot project, all three samplers were considered suitable for inclusion in further field research studies.


The Unplugged program in Chile ("Yo Sé Lo Que Quiero") for substance use prevention among early adolescents: study protocol for a randomized controlled trial.
Substance use is among the main contributors to disease among children and adolescents in the Americas region. The call for effective prevention of substance use among adolescents has resulted in numerous school-based programs, and particularly the Unplugged program has been proved to be successful in reducing the prevalence of different substances in seven European countries. The purpose of this study is to test the effectiveness of the Unplugged program in Chile ("Yo Sé Lo Que Quiero"). This is a cluster randomized controlled trial, parallel-group type, where "Yo Sé Lo Que Quiero" is compared to standard school preventive curricula in control schools. A total of 70 schools and 8400 adolescents are expected to be randomized with 1:1 allocation. During formative work, the Unplugged program was culturally adapted to Chile, and the instrument to assess the primary and secondary outcomes was validated. The effectiveness of this program will be assessed using the European Drug Addiction Prevention Trial Questionnaire (EU-Dap), measuring substance use prevalence and risk and protective factors in baseline, post-intervention, and four months after the end of the intervention. The proposed study will be the first to test the effectiveness of a school-based substance use prevention program in Chile in a cluster randomized control trial and the first study evaluating the Unplugged program in Spanish-speaking Latin America. A model for disseminating the Unplugged program inside Europe already exists and has been implemented successfully in several countries. Thus, if the effects of the program are positive, wide implementation in Chile and Latin American countries is possible soon. ClinicalTrials.gov NCT04236999 . Registered on January 17, 2020.


Genetic evidence for a western Chinese origin of broomcorn millet (Panicum miliaceum).
Broomcorn millet (Panicum miliaceum) is a key domesticated cereal that has been associated with the north China centre of agricultural origins. Early archaeobotanical evidence for this crop has generated two major debates. First, its contested presence in pre-7000 cal. BP sites in eastern Europe has admitted the possibility of a western origin. Second, its occurrence in the 7th and 8th millennia cal. BP in diverse regions of northern China is consistent with several possible origin foci, associated with different Neolithic cultures. We used microsatellite and granule-bound starch synthase I (GBSSI) genotype data from 341 landrace samples across Eurasia, including 195 newly genotyped samples from China, to address these questions. A spatially explicit discriminative modelling approach favours an eastern Eurasian origin for the expansion of broomcorn millet. This is consistent with recent archaeobotanical and chronological re-evaluations, and stable isotopic data. The same approach, together with the distribution of GBSSI alleles, is also suggestive that the origin of broomcorn millet expansion was in western China. This second unexpected finding stimulates new questions regarding the ecology of wild millet and vegetation dynamics in China prior to the mid-Holocene domestication of millet. The chronological relationship between population expansion and domestication is unclear, but our analyses are consistent with the western Loess Plateau being at least one region of primary domestication of broomcorn millet. Patterns of genetic variation indicate that this region was the source of populations to the west in Eurasia, which broomcorn probably reached via the Inner Asia Mountain Corridor from the 3rd millennium BC. A secondary westward expansion along the steppe may have taken place from the 2nd millennium BC.


Protein requirements for endurance athletes.
Acute endurance exercise results in the oxidation of several amino acids. The total amount of amino acid oxidation during endurance exercise amounts to only 1-6% of the total energy cost of exercise. The branched chain amino acid, leucine, has been most often studied in relation to endurance exercise. Leucine is oxidized by the enzyme, branched-chain oxo-acid dehydrogenase (BCOAD). BCOAD is relatively inactive at rest ( approximately 4-7%) and is activated at the onset of exercise by dephosphorylation (to about 25%). After a period of endurance exercise training, the activation of BCOAD and amino acid oxidation are attenuated, however the total amount of BCOAD enzyme is up-regulated. A low energy and/or carbohydrate intake will increase amino acid oxidation and total protein requirements. With adequate energy and carbohydrate intake, low to moderate intensity endurance activity has little impact on dietary protein requirements and 1.0 gPRO/kg/d is sufficient. The only situation where dietary protein requirements exceed those for relatively sedentary individuals is in top sport athletes where the maximal requirement is approximately 1.6 gPRO/kg/d. Although most endurance athletes get enough protein to support any increased requirements, those with low energy or carbohydrate intakes may require nutritional advice to optimize dietary protein intake.


Decentralized wastewater treatment in an urban setting: a pilot study of the circulating fluidized bed bioreactor treating septic tank effluent.
To meet the increasing wastewater treatment demand while minimizing the land footprint of the treatment systems and plants, more efficient and compact processes are needed. The circulating fluidized bed bioreactor (CFBBR) has been proven to achieve high levels of biological nutrient removal. Past studies at the lab and pilot scale achieved 94% COD removal and 80% nitrogen removal at HRT's of 2-4 h. A collaborative project between Western University and the Guangzhou Institute of Energy Conversion (GIEC), in Guangzhou, China, further explored the treatment of municipal wastewater with the CFBBR. A pilot CFBBR, with aerobic and anoxic columns for nitrification and denitrification, was constructed at the GIEC for in-situ treatment of septic tank effluent from a residential building. Due to high concentrations of ammonia (NH4-N), the wastewater had a COD/N ratio of 2-3. Thus, operating at a longer HRT and supplementing COD, in the form of glucose, was necessary to achieve a high nitrogen removal efficiency. The system was run both with and without supplemental COD at HRT's between 16 and 21 h, treating approximately 1000-1270 L/d. Overall, a COD removal efficiency of at least 92%, ammonia removal of 97%, and nitrogen removal of 82% was achieved. The CFBBR system achieved an effluent with BOD and NH4-N concentrations both below 5 mg/L, a NO3-N concentration below 15 mg/L, and a total nitrogen concentration below 25 mg/L. The compact design of this pilot-CFBBR, coupled with its high BNR performance make it an excellent option for decentralized treatment of urban wastewaters.


[Transfer of species of the genus Actinomadura Lechevalier et Lechevalier 1970 to the genus Nocardiopsis Meyer 1976].
The type cultures of four Actinomadura species (A. africana, A. coeruleofusca, A. flava, A. longispora) were studied and compared with the type culture belonging to the genus Nocardiopsis. In their morphological properties and in the composition of the cell wall, these cultures were shown to be closer to the genus Nocardiopsis Meyer 1976 rather than to the genus Actinomadura Lechevalier et Lechevalier 1970. Basing on these data, the species have been transferred to the genus Nocardiopsis.


Impact of fluorescent protein fusions on the bacterial flagellar motor.
Fluorescent fusion proteins open a direct and unique window onto protein function. However, they also introduce the risk of perturbation of the function of the native protein. Successful applications of fluorescent fusions therefore rely on a careful assessment and minimization of the side effects, but such insight is still lacking for many applications. This is particularly relevant in the study of the internal dynamics of motor proteins, where both the chemical and mechanical reaction coordinates can be affected. Fluorescent proteins fused to the stator of the Bacterial Flagellar Motor (BFM) have previously been used to unveil the motor subunit dynamics. Here we report the effects on single motors of three fluorescent proteins fused to the stators, all of which altered BFM behavior. The torque generated by individual stators was reduced while their stoichiometry remained unaffected. MotB fusions decreased the switching frequency and induced a novel bias-dependent asymmetry in the speed in the two directions. These effects could be mitigated by inserting a linker at the fusion point. These findings provide a quantitative account of the effects of fluorescent fusions to the stator on BFM dynamics and their alleviation- new insights that advance the use of fluorescent fusions to probe the dynamics of protein complexes.


Some observatoons on the carotid bodies of the New Zealand strain of genetically hypertensive rats.
We report preliminary studies of the carotid bodies in the New Zealand strain of hypertensive rats. Female animals have a higher blood pressure than males of the same colony, but in both sexes mean arterial pressure is elevated significantly when compared to normal animals. The carotid bodies are enlarged in both the hypertensive and normotensive animals and there is no correlation between carotid body size and arterial pressure. The only structural abnormality detected in the hypertensive carotid bodies was a gross thickening of the intimal layer of the arterioles. The content of dopamine in the organs was similar in normotensives and hypertensives but the noradrenaline levels were some 50% lower in the hypotensives. These results are discussed and compared with data available for SHR animals.


Volatile anaesthetic effects on Na+-Ca2+ exchange in rat cardiac myocytes.
We examined the influence of two clinically relevant concentrations (1 and 2 MAC (minimum alveolar concentration)) of halothane and sevoflurane on both efflux and reverse modes of Na+-Ca2+ exchange (NCX) in enzymatically dissociated adult rat cardiac myocytes. We hypothesised that a volatile anaesthetic-induced decrease in myocardial contractility is mediated by a reduction in intracellular calcium concentration ([Ca2+]i) via inhibition of NCX. Cells were exposed to cyclopiazonic acid and zero extracellular Na+ and Ca2+ to block sacroplasmic reticulum (SR) re-uptake and NCX efflux, respectively. As [Ca2+]i increased under these conditions, extracellular Na+ was rapidly (< 300 ms) reintroduced in the presence or absence of a volatile anaesthetic to selectively promote Ca2+ efflux via NCX. Other cells exposed to cyclopiazonic acid and ryanodine to inhibit SR Ca2+ re-uptake and release were Na+ loaded in zero extracellular Ca2+. The reintroduction of extracellular Ca2+ was used to selectively activate Ca2+ influx via NCX. Compared to controls, both 1 and 2 MAC halothane as well as sevoflurane reduced NCX-mediated efflux. The reduction in NCX-mediated influx was concentration dependent, but comparable between the two anaesthetics. Both anaesthetics at each concentration also shifted the relationship between extracellular Na+ (or extent of Na+ loading) and NCX-mediated efflux (or influx) to the right. These data indicate that despite inhibition of NCX-mediated Ca2+ efflux, volatile anaesthetics produce myocardial depression. However, the inhibition of NCX-mediated Ca2+ influx may contribute to decreased cardiac contractility. The overall effect of volatile anaesthetics on the [Ca2+]i profile is likely to be determined by the relative contributions of influx vs. efflux via NCX during each cardiac cycle.


Morphology controlled bulk synthesis of disc-shaped WO3 powder and evaluation of its photocatalytic activity for the degradation of phenols.
The surfactant assisted synthesis of disc-shaped WO3 powder and its photocatalytic performance in sunlight exposure is reported. UV-vis DRS, XRD and FESEM characterized the synthesized WO3. The synthesized powder exhibited a bandgap of ∼2.55eV with cubic lattice and high crystallinity. The photocatalytic activity of the synthesized WO3 was examined for the degradation of phenol, resorcinol, 2-chlorophenol and 2-nitrophenol in complete spectrum and visible segment of sunlight. The highly efficient degradation/mineralization of 2-chloro and 2-nitrophenol compared to that of phenol and resorcinol, under identical experimental conditions, suggested the regulatory role of substituents attached to the aromatic ring in degradation/mineralization process. The time-scale HPLC degradation profiles, identification of intermediates by GC-MS and removal of organic carbon during the course of reaction were utilized to approximate the possible route of degradation/mineralization of phenolic substrates. The measurement of the anions released during the photocatalytic process was used to identify the nature of the major oxidants (O2(•-), OH(•)) and the possible interaction sites. A significant decrease in the photocatalytic activity of synthesized WO3, ∼50%, was observed in visible portion of sunlight however, a sustained activity was observed in the repeated exposures.


Photodynamic therapy for cancer of the upper aerodigestive tract using tetra(m-hydroxyphenyl)chlorin.
A major step in the development of photodynamic therapy (PDT) is the clinical optimization and evaluation of new photosensitizers (PS). Ideally, new compounds should be more effective and/or induce fewer side effects than the first generation PS such as hematoporphyrin derivative and Photofrin. We report the results of our study of PDT applied in the human upper aerodigestive tract, using tetra(m-hydroxyphenyl)chlorin (mTHPC) as the photosensitizing drug. Twenty-seven patients with early (i.e., in situ or microinvasive) squamous cell carcinomas and 4 patients with T1 or T2 cancers were studied. In most cases, illumination of the tumor was performed 4 days after i.v. injection of 0.15 mg/kg of mTHPC using 652 or 514 nm laser light. Of the 36 early tumors evaluated 30 (83%) showed no recurrence after a mean disease-free follow-up of 15.3 months (3-35 months). Of the T1 and T2 cancers, only one achieved a complete response. Major complications, all following red light illuminations, included 1 bronchial stenosis, 1 esophagotracheal fistula, and 2 probable occult perforations of the esophagus. PDT in the esophagus with green light renders such perforations essentially impossible, without, however, reducing the efficacy of the treatment. Skin photosensitization, never observed later than the first week after injection, was seen in 12 patients. In conclusion, photodynamic therapy with mTHPC is a safe and effective technique for the treatment of early carcinomas of the upper aerodigestive tract. Its efficacy is much lower for more advanced cancers.


Home range plus: a space-time characterization of movement over real landscapes.
Advances in GPS technology have created both opportunities in ecology as well as a need for analytical tools that can deal with the growing volume of data and ancillary variables associated with each location. We present T-LoCoH, a home range construction algorithm that incorporates time into the construction and aggregation of local kernels. Time is integrated with Euclidean space using an adaptive scaling of the individual's characteristic velocity, enabling the construction of utilization distributions that capture temporal partitions of space as well as contours that differentiate internal space based on movement phase and time-use metrics. We test T-LoCoH against a simulated dataset and provide illustrative examples from a GPS dataset from springbok in Namibia. The incorporation of time into home range construction expands the concept of utilization distributions beyond the traditional density gradient to spatial models of movement and time, opening the door to new applications in movement ecology.


Phenyl-pyta-tricarbonylrhenium(I) complexes: combining a simplified structure and steric hindrance to modulate the photoluminescence properties.
Strongly luminescent tricarbonylrhenium(I) complexes are promising candidates in the field of optical materials. In this study, three new complexes bearing a 3-(2-pyridyl)-1,2,4-triazole (pyta) bidentate ligand with an appended phenyl group were obtained in very good yields owing to an optimized synthetic procedure. The first member of this series, i.e. complex 1, was compared with the previously studied complex RePBO to understand the influence of the fluorescent benzoxazole unit grafted on the phenyl ring. Then, to gauge the effect of steric hindrance on the luminescence properties, the phenyl group of complex 1 was substituted in the para position by a bulky tert-butyl group or an adamantyl moiety, affording complexes 2 and 3, respectively. The results of theoretical calculations indicated that these complexes were quite similar from an electronic point of view, as evidenced by the electrochemical study. In dichloromethane solution, under excitation in the UV range, all the complexes emitted weak phosphorescence in the red region. In the solid state, they could be excited in the blue region of the visible spectrum and they emitted strong yellow light. The photoluminescence quantum yield was markedly increased with raising the size of the substituent, passing from 0.42 for 1 to 0.59 for 3. The latter complex also exhibited clear waveguiding properties, unprecedented for rhenium complexes. From this point of view, these easy-synthesized and spectroscopically attractive complexes constitute a new generation of emitters for use in imaging applications and functional materials. However, the comparison with RePBO showed that the presence of the benzoxazole group leads to unsurpassed mechanoresponsive luminescence (MRL) properties, due to the involvement of a unique photophysical mechanism that takes place only in this type of complex.


Death from methamphetamine intoxication in a body stuffer.
A 28-year-old man was admitted dead to the emergency department of the regional hospital. All resuscitation attempts were unsuccessful in this case. Attending officers stated that he was suspected of possessing drugs at the time of arrest and had taken them quickly to cover up. Upon arrival at the hospital, signs of violence were noted all over his body. During the autopsy, two large blue plastic packages were found in the antrum of the stomach. The first was 6.3 × 2.2 cm and had two tight knots, while the second was 7.6 x 1.7 cm and had a single knot. Both packages were irregularly shaped and contained tablet debris that was clearly leaking, as a large amount of gastric juice was present in both packages. A confirmatory forensic toxicology analysis revealed toxic concentrations of methamphetamine in the blood of the dissected case. The patient died of acute methamphetamine intoxication associated with a severe stress condition resulting from violent resistance during arrest.


In situ spectroscopic analysis of Lactobacillus rhamnosus GG flow on an abiotic surface reveals a role for nutrients in biofilm development.
In this work, infrared spectroscopy was used to monitor the changes in the biochemical composition of biofilms of the probiotic bacterium Lactobacillus rhamnosus GG (LGG) in three nutritive media (10-fold diluted MRS, AOAC, and mTSB), in situ and under flow conditions. Epifluorescence microscopy was used to observe the shape of LGG cells and their distribution on the surface. Spectroscopic fingerprints recorded as a function of time revealed a medium-dependent content of nucleic acids, phospholipids and polysaccharides in the biofilms. In addition, time-dependent synthesis of lactic acid was observed in MRS/10 and AOAC/10. Polysaccharides were produced to the highest extent in mTSB/10, and the biofilms obtained were the densest in this medium. The rod shape of the cells was preserved in MRS/10, whereas acidic stress induced in AOAC/10 and the nutritional quality of mTSB/10 led to strong morphological changes. These alterations due to the nutritive environment are important to consider in research and use of LGG biofilms.


Stakeholders' Consensus on Strategies for Self- and Other-Regulation of Video Game Play: A Mixed Methods Study.
Background: Little is known about strategies or mechanics to improve self-regulation of video game play that could be developed into novel interventions. This study used a participatory approach with the gaming community to uncover insider knowledge about techniques to promote healthy play and prevent gaming disorder. Methods: We used a pragmatic approach to conduct a convergent-design mixed-methods study with participants attending a science fiction and education convention. Six participants answered questions about gaming engagement and self- or game-based regulation of gaming which were then categorized into pre-determined (a priori) themes by the presenters during the presentation. The categorized themes and examples from participant responses were presented back to participants for review and discussion. Seven participants ranked their top choices of themes for each question. The rankings were analyzed using a nonparametric approach to show consensus around specific themes. Results: Participants suggested several novel potential targets for preventive interventions including specific types of social (e.g., play with others in a group) or self-regulation processes (e.g., set timers or alarms). Suggestions for game mechanics that could help included clear break points and short missions, but loot boxes were not mentioned. Conclusions: Our consensus development approach produced many specific suggestions that could be implemented by game developers or tested as public health interventions, such as encouraging breaks through game mechanics, alarms or other limit setting; encouraging group gaming; and discussing and supporting setting appropriate time or activity goals around gaming (e.g., three quests, one hour). As some suggestions here have not been addressed previously as potential interventions, this suggests the importance of including gamers as stakeholders in research on the prevention of gaming disorder and the promotion of healthy gaming. A large-scale, online approach using these methods with multiple stakeholder groups could make effective use of players' in-depth knowledge and help speed discovery and translation of possible preventive interventions into practice and policy.


Effects of captopril (SQ 14, 225) on the renin-angiotensin-aldosterone system in normal rats.
High doses of captopril (SQ 14, 225) (120-160 mg/kg/day) were administered orally to normal rats, and the effects on the renin-angiotensin-aldosterone system were observed. Plasma angiotensin converting enzyme (ACE) activity was elevated significantly on the 3rd, 7th and 30th days of captopril administration. ACE activity in the lung and the kidney was significantly decreased on the 1st day then gradually increased, becoming significantly higher than that of controls by the 30th day. Plasma renin activity (PRA) was significantly elevated on the 1st day and remained at a high level until the 30th day. Renal renin content was found to be significantly lower on the 1st and 3rd days. Plasma aldosterone concentration was not affected by captopril treatment, whereas serum potassium concentration was found to be significantly lower on the 1st, 3rd and 30th days. It is suggested that besides its inhibitory action on ACE, captopril has a direct or indirect stimulating action on ACE production as well as on renin release.


Muscimol suppression of the dorsal cochlear nucleus impairs frequency discrimination in rats.
The cochlear nucleus is composed of three sub-nuclei: the dorsal (DCN), anteroventral (AVCN) and posteroventral cochlear nucleus (PVCN). In addition to connections between these sub-nuclei, each nucleus receives frequency specific tonotopically organised input from the cochlea. Evidence suggests that connections from the DCN to the AVCN are inhibitory and organised tonotopically but the functional significance of this pathway has yet to be elucidated. The possible role of this pathway in frequency discrimination using a T-maze behavioural paradigm and DCN suppression was examined. Five rats were trained on a two choice frequency discrimination task. Once frequency difference limens for 10-30% performance above chance were determined, rats had cannulae implanted bilaterally over the DCN. After recovery rats were tested on the behavioural task with nothing, saline and the GABA agonist muscimol injected into the DCN via the cannulae. Muscimol alone significantly reduced the rats ability to perform the task. This performance decrease was attributed to an inability to discriminate high frequency and not low frequency tones suggesting that place and not temporal coding of sound was compromised by DCN suppression. These results are consistent with the hypothesis that inhibitory drive from the DCN to AVCN may be crucial for the fine tuning of frequency information.


Alleviation of brain hypoperfusion after preventative treatment with lomerizine in an elderly migraineur with aura.
Previous studies of brain single-photon emission tomography (SPECT) showed changes of regional cerebral blood flow (rCBF) in migraineurs during prodromes or headache attacks. Little is known about how successful medication of migraine prevention can reflect rCBF in migraineurs. We highlighted alternation of brain SPECT findings in a migraineur with aura before and after prophylactic treatment with lomerizine, a calcium channel blocker. A 70-year-old man with migraine developed visual disturbance frequently at walking exercise for the recent 3 months. After this visual attack, a mild-degree of throbbing headache occured occasionally. Brain SPECT using (99m)Tc-ethyl cysteinate dimer was performed at interictal time of migraine. Brain SPECT before lomerizine treatment revealed hypoperfusion in the frontal, parietal, and occipital regions. He was diagnosed with recurrence of migraine with aura (MA). Lomerizine (10 mg/day, po) was administered for 3 months. MA and visual aura without headache were dramatically improved. Migraine attacks and visual disturbance were not induced at exercise. At 3 months after lomerizine medication, brain SPECT showed remarkable increase of rCBF. These SPECT changes of our patient indicated that antimigraine mechanism of lomerizine could contribute to restoration of cerebral hypoperfusion.


Improved Survival of Children, Adolescents, and Young Adults With Head and Neck Soft Tissue Sarcomas in Denmark.
The aim of this study was to estimate nationally the survival of children, adolescents, and young adults with head and neck soft tissue sarcomas. The authors included patients 0 to 21 years of age and diagnosed with rhabdomyosarcoma (RMS) or nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) located in the head and neck between 1980 and 2014. Survival probabilities were estimated using the Kaplan-Meier method. The authors estimated the effect of covariates with univariate and multivariate Cox regression analyses. The cumulative recurrence in RMS was estimated when considering death as a competing risk. We identified 72 patients (50% male individuals, whereas 72% had RMS). Elder patients (older than 15 y) did worse compared with younger patients (log-rank test P=0.001). Patients diagnosed from 1980 to 1999 did worse than patients diagnosed from 2000 to 2014 (log-rank test P=0.02). Similarly, younger (younger than 15 y) patients did significantly better when diagnosed from 2000 to 2014 with reference to those diagnosed from 1980 to 1999 (log-rank test P=0.026). The multivariate hazard ratio was 0.46 (95% confidence interval, 0.23-0.92) for patients diagnosed from 2000 to 2014 with reference to patients diagnosed from 1980 to 1999. The 1-year cumulative recurrence for RMS was 21.2% (95% confidence interval, 12.3%-35.0%). Overall survival has improved throughout the study period, which is attributable to advancement in diagnostics, treatment, and the application of standardized guidelines from international protocols.


Role of alphabeta and gammadelta T cells in the host response to Salmonella infection as demonstrated in T-cell-receptor-deficient mice of defined Ity genotypes.
Salmonella spp. are facultative intracellular bacteria which enter the body through the intestinal tract. We studied the roles of T cells expressing either the alpha and beta chains or the gamma and delta chains of the T-cell receptor (alphabeta T cells or gammadelta T cells, respectively) in the host defense against Salmonella using mice genetically deficient in either alphabeta T cells, gammadelta T cells, or both T-cell subsets. These mutant strains of mice were infected orally or intraperitoneally with Salmonella dublin, and the progression of the disease was monitored by determining bacterial numbers in the feces, gut wall, Peyer's patches, mesenteric lymph nodes, spleen, and liver. Since susceptibility to Salmonella infection in mice is strongly affected by the alleles at the Ity locus, T-cell-mutant mice with either the Ity-sensitive or Ity-resistant phenotype were tested for resistance to S. dublin infection. We found that even though large numbers of intraepithelial and mucosal alphabeta and gammadelta T cells populate the normal intestine, they have no role in controlling the invasion of S. dublin into the intestine or the subsequent bacterial replication in the Peyer's patches or gut wall. Furthermore, systemic infections were equally severe for the first 6 days in normal, alphabeta T-cell-deficient, and gammadelta T-cell-deficient mice, and alphabeta but not gammadelta T cells were required for clearance of S. dublin, regardless of the Ity phenotype. However, mice that lacked both T-cell subsets had higher bacterial counts in their livers 15 to 18 days after infection than did alphabeta T-cell-deficient mice, suggesting that gammadelta T cells can contribute to acquired immunity to S. dublin.


Neuropsychological correlates of subjective fatigue in non-demented older adults and the moderating effect of physical activity.
This study examined the association between self-reported fatigue and neuropsychological performance in 167 middle-aged and older (age range: 50-91 years) adults without dementia. Participants completed the Fatigue Symptom Inventory, a comprehensive neuropsychological evaluation, and frailty assessment. Higher levels of fatigue were significantly associated with poorer attention/information processing, executive functioning, and psychomotor speed, even after controlling for depression, sleep quality, physical weakness, and other covariates. Participants endorsing moderate-severe fatigue faced higher odds (OR = 6.6, 95% CI = 1.1, 39.1) of exhibiting clinical attention/information processing impairments than those without. Moderation analyses showed that fatigue was related to select cognitive deficits among those reporting mean or lower levels of activity, but not high levels. These findings highlight fatigue as an important clinical marker of select cognitive deficits in non-demented older adults that is distinct from the common confounding conditions examined in this study. High levels of physical activity may buffer this relationship.


VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis.
Vascular endothelial growth factor receptor-2 (VEGFR-2) activation by VEGF-A is essential in vasculogenesis and angiogenesis. We have generated a pan-phosphorylation site map of VEGFR-2 and identified one major tyrosine phosphorylation site in the kinase insert (Y951), in addition to two major sites in the C-terminal tail (Y1175 and Y1214). In developing vessels, phosphorylation of Y1175 and Y1214 was detected in all VEGFR-2-expressing endothelial cells, whereas phosphorylation of Y951 was identified in a subset of vessels. Phosphorylated Y951 bound the T-cell-specific adapter (TSAd), which was expressed in tumor vessels. Mutation of Y951 to F and introduction of phosphorylated Y951 peptide or TSAd siRNA into endothelial cells blocked VEGF-A-induced actin stress fibers and migration, but not mitogenesis. Tumor vascularization and growth was reduced in TSAd-deficient mice, indicating a critical role of Y951-TSAd signaling in pathological angiogenesis.


How to use telesimulation to reduce COVID-19 training challenges: A recipe with free online tools and a bit of imagination.
This article was migrated. The article was marked as recommended. In response to COVID-19 outbreak, alternatives to face-to-face classes/seminars rapidly emerged and telecommunication platforms become the new classrooms. Although with additional challenges, telesimulation based classes can benefit from online platforms and innovative strategies, to promote a meaningful and interactive distance-learning experience. A combination of several free online resources is used to recreate (at distance) emergency simulation scenarios. Practicalities involving this strategy are described in the form of a recipe, including supplemental guides and an illustrative video, allowing its rapid implementation. Feedback from students on the educational gains was surveyed, as a preliminary evaluation of this methodology. The use of free online tools makes it accessible off-site and worldwide, including in low-resources locations. This strategy has high potential to be used in the transitional post-confinement period or as a future complement to physical settings.


Deciphering structural elements of mucin glycoprotein recognition.
Mucin glycoproteins present a complex structural landscape arising from the multiplicity of glycosylation patterns afforded by their numerous serine and threonine glycosylation sites, often in clusters, and with variations in respective glycans. To explore the structural complexities in such glycoconjugates, we used NMR to systematically analyze the conformational effects of glycosylation density within a cluster of sites. This allows correlation with molecular recognition through analysis of interactions between these and other glycopeptides, with antibodies, lectins, and sera, using a glycopeptide microarray. Selective antibody interactions with discrete conformational elements, reflecting aspects of the peptide and disposition of GalNAc residues, are observed. Our results help bridge the gap between conformational properties and molecular recognition of these molecules, with implications for their physiological roles. Features of the native mucin motifs impact their relative immunogenicity and are accurately encoded in the antibody binding site, with the conformational integrity being preserved in isolated glycopeptides, as reflected in the antibody binding profile to array components.


Obesity in Adolescence Predicts Lower Educational Attainment and Income in Adulthood: The Project EAT Longitudinal Study.
Prospective associations between obesity in adolescence and adult socioeconomic outcomes, and potential mediators, were examined in a contemporary cohort. Longitudinal data collected in 1998 to 1999 (Project EAT-I) and 2015 to 2016 (EAT-IV) were analyzed for 1,796 participants who provided data at both time points. Adolescents (mean age = 14.8 years) self-reported demographic and psychosocial variables (EAT-I) and follow-up outcomes (EAT-IV). Body weight and height were directly measured. Bachelor's degree or more education, income ≥ US $50,000, and partnered status at follow-up were examined by baseline obesity (>95th BMI percentile) using logistic regression. Self-esteem, depression, and weight-related teasing were examined as mediators using multivariate probit regressions. All analyses were adjusted for race, baseline age, and parent socioeconomic status. Girls with obesity were significantly less likely to have achieved a bachelor's degree (OR 0.32, 95% CI [0.18, 0.58]; P < 0.001), earn ≥ $50,000 annually (OR 0.57, 95% CI [0.33, 0.99]; P < 0.04), or be partnered (OR 0.45, 95% CI [0.27, 0.75]; P < 0.002) in adulthood. No associations were observed among boys. Among girls, depression mediated 8.5% and 23.6% of the association between adolescent obesity and adult education and income, respectively. Adolescent girls with obesity have lower educational attainment and income and are less likely to be partnered in later adulthood. Depression may partly mediate the associations.


Surface modification of interconnected porous scaffolds.
Surface properties of scaffolds play an important role in cell adhesion and growth. Biodegradable poly(alpha-hydroxy acids) have been widely used as scaffolding materials for tissue engineering; however, the lack of functional groups is a limitation. In this work, gelatin was successfully immobilized onto the surface of poly(alpha-hydroxy acids) films and porous scaffolds by a new entrapment process. The surface composition and properties were examined using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectra (XPS), and contact angle measurements. Control over the amount of entrapped gelatin was achieved by varying the solvent composition, the duration of soaking, the concentration of gelatin in solution, and chemical crosslinking. The amount of entrapped gelatin increased with the ratio of dioxane/water in the solvent mixture used. Chemical crosslinking after physical entrapment considerably increased the amount of retained gelatin on the surface of poly(alpha-hydroxy acids). Osteoblasts were cultured on these films and scaffolds. The surface modification significantly improved cell attachment and proliferation. Cell numbers on the surface-modified films and scaffolds were significantly higher than those on controls 4 h and 1 day after cell seeding. The osteoblasts showed higher proliferation on surface-modified scaffolds than on the control during 4 weeks of in vitro cultivation. More collagen fibers and other cell secretions were deposited on the surface-modified scaffolds than on the control scaffolds. This novel surface treatment strategy provides a convenient and universal way to modify the surface properties of three-dimensional scaffolds and thus promote cell adhesion and proliferation for tissue engineering.


Diagnosis of systemic inflammatory diseases among patients admitted for acute pericarditis with pericardial effusion.
Acute pericarditis may be the heralding manifestation of various systemic inflammatory diseases (SIDs). The aim of this study was to identify clinical indicators for SIDs in patients admitted for acute pericarditis with pericardial effusion. All consecutive adult patients hospitalized in a Department of Internal Medicine over a 10-year period for acute pericarditis with pericardial effusion were retrospectively reviewed. Patients with cancer and tuberculosis were excluded. A structured clinical panel for extra-cardiac symptoms of SIDs was applied. SIDs were classified using current international criteria. Ninety-nine patients were admitted for acute pericarditis with pericardial effusion. After exclusion, 74 (49.7 ± 19.7 years, 56.7% women) patients were analyzed. Among them, 23 (23.2%) patients had a SID that was revealed by pericarditis in 12 cases. Systemic lupus erythematosus, undifferentiated connective-tissue disease, and Sjogren's syndrome accounted for 75% of the SID. Patients with SIDs were younger (P < 0.001), more frequently of female sex (P = 0.025), and had a higher frequency of extra-cardiac symptoms (P < 0.001) including arthralgia, myalgia, Raynaud phenomenon, and skin rash, as compared with patients with idiopathic pericarditis (n = 51). Overall, after exclusion of neoplasm and tuberculosis, the probability of SIDs in patients admitted with an acute pericarditis with pericardial effusion was 89.7% in patients younger than 50 who had extra-cardiac symptoms. Conversely, the probability fell to 8.4% in patients older than 50 with no extra-cardiac symptoms. Both age and extra-cardiac symptoms suggest an underlying SID as a possible cause of acute pericarditis.


Designing and Validation of Health-Related Quality of Life Inventory for Family Caregivers of Hemodialysis Patients.
Family caregivers are important sources of care for hemodialysis patients. Although caring for a family member is a pleasant feeling, experiencing lots of physical and psychological caregiving burden influences the quality of life among family caregivers of hemodialysis patients. This study aimed to design and validate the quality of life inventory for family caregivers of patients on hemodialysis. A sequential-exploratory mixed method was conducted in Tehran, Iran, in 2017-2018. In the qualitative phase, the researcher conducted in-depth semi-structured interviews with 19 participants. Finally, a pool of 93 items was extracted from this phase. Then, psychometric properties such as face validity (Impact Score>1.5), content validity ratio (CVR>0.63), content validity index (Item Content Validity Index: ICVI>0.78 , Scale Content Validity Index/Average: SCVI/Ave>0.8) and Kappa value (Kappa>0.7, internal consistency (Cronbach's alpha>0.7), relative reliability (ICC: interclass correlation coefficient), absolute reliability (Standard Error of Measurement: SEM and Minimal Detectable Changes: MDC), convergent validity (Correlation Coefficient between 0.4-0.7), interpretability, responsiveness, feasibility, and ceiling and floor effects were assesse. The quality of life inventory for family caregivers of hemodialysis patients was developed with 34 items and five factors (namely patient care burden, conflict, positive perception of situations, self-actualization, fear, and concern). The findings confirm that the scale is acceptable regarding validity, reliability and other measurement features. This inventory is consistent with the health care status in Iran. Therefore, it can be used to measure the quality of life among family caregivers of hemodialysis patients.


The European Union One Health 2022 Zoonoses Report.
This report by the European Food Safety Authority and the European Centre for Disease Prevention and Control presents the results of the zoonoses monitoring and surveillance activities carried out in 2022 in 27 Member States (MSs), the United Kingdom (Northern Ireland) and 11 non-MSs. Key statistics on zoonoses and zoonotic agents in humans, food, animals and feed are provided and interpreted historically. In 2022, the first and second most reported zoonoses in humans were campylobacteriosis and salmonellosis, respectively. The number of cases of campylobacteriosis and salmonellosis remained stable in comparison with 2021. Nineteen MSs and the United Kingdom (Northern Ireland) achieved all the established targets in poultry populations for the reduction of Salmonella prevalence for the relevant serovars. Salmonella samples from carcases of various animal species, and samples for Campylobacter quantification from broiler carcases, were more frequently positive when performed by the competent authorities than when own checks were conducted. Yersiniosis was the third most reported zoonosis in humans, followed by Shiga toxin-producing Escherichia coli (STEC) and Listeria monocytogenes infections. L. monocytogenes and West Nile virus infections were the most severe zoonotic diseases, with the most hospitalisations and highest case fatality rates. In 2022, reporting showed an increase of more than 600% compared with 2021 in locally acquired cases of human West Nile virus infection, which is a mosquito-borne disease. In the EU, the number of reported foodborne outbreaks and cases, hospitalisations and deaths was higher in 2022 than in 2021. The number of deaths from outbreaks was the highest ever reported in the EU in the last 10 years, mainly caused by L. monocytogenes and to a lesser degree by Salmonella. Salmonella and in particular S. Enteritidis remained the most frequently reported causative agent for foodborne outbreaks. Norovirus (and other calicivirus) was the agent associated with the highest number of outbreak human cases. This report also provides updates on brucellosis, Coxiella burnetii (Q fever), echinococcosis, rabies, toxoplasmosis, trichinellosis, infection with Mycobacterium tuberculosis complex (focusing on Mycobacterium bovis and Mycobacterium caprae) and tularaemia.


Segond Fractures Are Not a Risk Factor for Anterior Cruciate Ligament Reconstruction Failure.
Segond fractures may be identified when an anterior cruciate ligament (ACL) tear is diagnosed and likely represent an avulsion of the anterolateral ligament. It is currently unclear whether these fractures can be ignored at the time of ACL reconstruction or if they should be addressed surgically. To compare the incidence of Segond fractures in patients undergoing primary ACL reconstruction compared with those undergoing revision ACL reconstruction in an attempt to determine if the presence of a Segond fracture predisposes to ACL reconstruction failure. Cross-sectional study; Level of evidence, 3. A retrospective review of all patients undergoing primary or revision ACL reconstruction between 2007 and 2014 was performed. Demographic data (age, sex, body mass index), injury variables (acuity, mechanism of injury), and radiographic features (concomitant ligamentous injuries, growth plate status) were documented. Each Segond fracture was analyzed for its specific location, size, displacement, and healing using both radiographs and magnetic resonance imaging. Statistical analysis was performed using a P value of <.05. A total of 552 patients underwent primary ACL reconstruction, and 47 patients underwent revision ACL reconstruction who met inclusion criteria. The incidence of Segond fractures was 6% in the primary reconstruction group. The fracture fragment averaged 6.6 mm in height and 2.3 mm in width and was displaced a mean of 5.0 mm. The fracture fragment bed was localized at the tibial attachment site of the anterolateral ligament a mean 20.6 mm posterior to the Gerdy tubercle in nearly all patients. After ACL reconstruction, the Segond fracture healed in 90% of patients. The incidence of Segond fractures was 3 times as common in male patients ( P = .02); otherwise, its presence was not associated with any other demographic data, injury variables, or radiographic features ( P > .05). No patients undergoing revision surgery had a Segond fracture, and no patient with a Segond fracture had graft failure. Patients with a Segond fracture are at no higher risk to require revision ACL reconstruction compared with patients without a Segond fracture. This may be attributable to its high union rate. At the time of primary ACL reconstruction, if a Segond fracture is identified, it can be ignored (not repaired or reconstructed), and this approach does not appear to predispose to early ACL graft failure.


m6A and m5C modification of GPX4 facilitates anticancer immunity via STING activation.
Cancer immunotherapy is arguably the most rapidly advancing realm of cancer treatment. Glutathione peroxidase 4 (GPX4) has emerged as the vital enzyme to prevent lipid peroxidation and maintain cellular redox homeostasis. However, the mechanism of GPX4 in the regulation of cancer immunotherapy of colon adenocarcinoma (COAD) are incompletely understood. In pan-cancer analysis, we found that GPX4 showed remarkably upregulated expression and exhibited significant association with overall survival in multiple cancer types, especially COAD. Furthermore, upregulated GPX4 expression was positively correlated with increased immune cells infiltration and enhanced expression of immunomodulators. Mechanistically, RBM15B- and IGFBP2-mediated N6-methyladenosine (m6A) modification and NSUN5-mediated 5-methylcytosine (m5C) modification of GPX4 facilitated anticancer immunity via activation of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) signaling by maintaining redox homeostasis in COAD. The risk model and nomogram model constructed based on the GPX4-derived genes further confirmed the prognostic and treatment-guiding value of GPX4. In all, our study demonstrated that m6A and m5C modification of GPX4 may be a promising target for cancer immunotherapy via activating the cGAS-STING signaling pathway in COAD.


Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation.
The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it. In keeping with this dynamic perspective, research on episodic memory (and the hippocampus) has infiltrated domains, from perception to language and from empathy to problem solving, that were once considered outside its boundaries. Using the component process model as a framework, and focusing on the hippocampus, its subfields, and specialization along its longitudinal axis, along with its interaction with other brain regions, we consider these new developments and their implications for the organization of episodic memory and its contribution to functions in other domains.


Annotated genes and nonannotated genomes: cross-species use of Gene Ontology in ecology and evolution research.
Recent advances in molecular technologies have opened up unprecedented opportunities for molecular ecologists to better understand the molecular basis of traits of ecological and evolutionary importance in almost any organism. Nevertheless, reliable and systematic inference of functionally relevant information from these masses of data remains challenging. The aim of this review is to highlight how the Gene Ontology (GO) database can be of use in resolving this challenge. The GO provides a largely species-neutral source of information on the molecular function, biological role and cellular location of tens of thousands of gene products. As it is designed to be species-neutral, the GO is well suited for cross-species use, meaning that, functional annotation derived from model organisms can be transferred to inferred orthologues in newly sequenced species. In other words, the GO can provide gene annotation information for species with nonannotated genomes. In this review, we describe the GO database, how functional information is linked with genes/gene products in model organisms, and how molecular ecologists can utilize this information to annotate their own data. Then, we outline various applications of GO for enhancing the understanding of molecular basis of traits in ecologically relevant species. We also highlight potential pitfalls, provide step-by-step recommendations for conducting a sound study in nonmodel organisms, suggest avenues for future research and outline a strategy for maximizing the benefits of a more ecological and evolutionary genomics-oriented ontology by ensuring its compatibility with the GO.


Air pollution and cardiovascular disease: car sick.
The cardiovascular effects of inhaled particle matter (PM) are responsible for a substantial morbidity and mortality attributed to air pollution. Ultrafine particles, like those in diesel exhaust emissions, are a major source of nanoparticles in urban environments, and it is these particles that have the capacity to induce the most significant health effects. Research has shown that diesel exhaust exposure can have many detrimental effects on the cardiovascular system both acutely and chronically. This review provides an overview of the cardiovascular effects on PM in air pollution, with an emphasis on ultrafine particles in vehicle exhaust. We consider the biological mechanisms underlying these cardiovascular effects of PM and postulate that cardiovascular dysfunction may be implicated in the effects of PM in other organ systems. The employment of multiple strategies to tackle air pollution, and especially ultrafine particles from vehicles, is likely to be accompanied by improvements in cardiovascular health.


Production of anti-SAG1 IgY antibody against Toxoplasma gondii parasites and evaluation of antibody activity by ELISA method.
Chicken egg yolk antibody, also known as immunoglobulin Y (IgY), is the predominant class of serum immunoglobulin in birds. IgY has many advantages over mammalian antibodies, such as enhanced immunogenicity conserved mammalian proteins exhibited in birds due to their phylogenetic distance, non-invasive rapid, and economical collection system. However, there are limited studies about IgY production against Toxoplasma, which is a worldwide veterinary and public health problem. In this study, the production of specific IgY antibodies against the surface antigen 1 (SAG1) protein of Toxoplasma gondii and the determination of antibody activity via the enzyme-linked immunosorbent assay (ELISA) method were conducted. According to ELISA, Western blot, and NanoDrop results, specific and higher amounts of IgY antibody against SAG1 were obtained with this study. Considering the advantages of IgY and importance of SAG1 for the diagnosis of toxoplasmosis, it is expected that anti-SAG1 IgY will play an increasing role and gain commercial value in research, diagnostics, and immunotherapy against toxoplasmosis in the future.


Malpractice--the dentist's perspective.
A lawyer with more than twenty years of experience defending dentists in malpractice situations reflects on the attitudes he typically sees in dentist defendants. The "professional" orientation that patients should expect nothing more than that the dentist does his or her best, is often at odds with the patient plaintiff view that they will have their feelings recognized at almost any price. The lawyer's role is often one of education. As the facts and perspectives involved are revealed through disclosure, resolutions begin to emerge. The best approach is for dentists to learn to communicate with patients--from their perspectives.


Fcc vs. hcp competition in colloidal hard-sphere nucleation: on their relative stability, interfacial free energy and nucleation rate.
Hard-sphere crystallization has been widely investigated over the last six decades by means of colloidal suspensions and numerical methods. However, some aspects of its nucleation behaviour are still under debate. Here, we provide a detailed computational characterisation of the polymorphic nucleation competition between the face-centered cubic (fcc) and the hexagonal-close packed (hcp) hard-sphere crystal phases. By means of several state-of-the-art simulation techniques, we evaluate the melting pressure, chemical potential difference, interfacial free energy and nucleation rate of these two polymorphs, as well as of a random stacking mixture of both crystals. Our results highlight that, despite the fact that both polymorphs have very similar stability, the interfacial free energy of the hcp phase could be marginally higher than that of the fcc solid, which in consequence, mildly decreases its propensity to nucleate from the liquid compared to the fcc phase. Moreover, we analyse the abundance of each polymorph in grown crystals from different types of inserted nuclei: fcc, hcp and stacking disordered fcc/hcp seeds, as well as from those spontaneously emerged from brute force simulations. We find that post-critical crystals fundamentally grow maintaining the polymorphic structure of the critical nucleus, at least until moderately large sizes, since the only crystallographic orientation that allows stacking close-packed disorder is the fcc (111) plane, or equivalently the hcp (0001) one. Taken together, our results contribute with one more piece to the intricate puzzle of colloidal hard-sphere crystallization.


Are diagnostic criteria for eating disorders markers of medical severity?
The objective of this study was to compare the medical severity of adolescents who had eating disorders not otherwise specified (EDNOS) with those who had anorexia nervosa (AN) and bulimia nervosa (BN). Medical records of 1310 females aged 8 through 19 years and treated for AN, BN, or EDNOS were retrospectively reviewed. Patients with EDNOS were subcategorized into partial AN (pAN) and partial BN (pBN) when they met all Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria but 1 for AN or BN, respectively. Primary outcome variables were heart rate, systolic blood pressure, temperature, and QTc interval on electrocardiogram. Additional physiologically significant medical complications were also reviewed. A total of 25.2% of females had AN, 12.4% had BN, and 62.4% had EDNOS. The medical severity of patients with EDNOS was intermediate to that of patients with AN and BN in all primary outcomes. Patients with pAN had significantly higher heart rates, systolic blood pressures, and temperatures than those with AN; patients with pBN did not differ significantly from those with BN in any primary outcome variable; however, patients with pAN and pBN differed significantly from each other in all outcome variables. Patients with pBN and BN had longer QTc intervals and higher rates of additional medical complications reported at presentation than other groups. EDNOS is a medically heterogeneous category with serious physiologic sequelae in children and adolescents. Broadening AN and BN criteria in pediatric patients to include pAN and pBN may prove to be clinically useful.