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Interleukin-10, a highly effective cytokine recognized for its anti-inflammatory properties, plays a critical role in the immune system. In addition to its well-documented capacity to mitigate inflammation, IL-10 can unexpectedly demonstrate pro-inflammatory characteristics under specific circumstances. The presence of both aspects emphasizes the vital need to identify the IL-10-induced peptide. To mitigate the drawbacks of manual identification, which include its high cost, this study introduces StackIL10, an ensemble learning model based on stacking, to identify IL-10-inducing peptides in a precise and efficient manner. Ten Amino-acid-composition-based Feature Extraction approaches are considered. The StackIL10, stacking ensemble, the model with five optimized Machine Learning Algorithm (specifically LGBM, RF, SVM, Decision Tree, KNN) as the base learners and a Logistic Regression as the meta learner was constructed, and the identification rate reached 91.7%, MCC of 0.833 with 0.9078 Specificity. Experiments were conducted to examine the impact of various enhancement techniques on the correctness of IL-10 Prediction. These experiments included comparisons between single models and various combinations of stacking-based ensemble models. It was demonstrated that the model proposed in this study was more effective than singular models and produced satisfactory results, thereby improving the identification of peptides that induce IL-10., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tuhin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Acute graft-versus-host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation (HCT). Although recent advancements in GVHD prophylaxis have resulted in successful HCT across HLA barriers and expanded access to HCT for racial minorities, less is known about how race affects the severity and outcomes of acute GVHD. This study examines differences in the clinical course of acute GVHD and the prognostic value of GVHD biomarkers for Black and White recipients. We conducted a retrospective analysis of patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) database who underwent HCT between 2014 and 2021 to describe the difference in clinical course of acute GVHD and significance of GVHD biomarkers between Black and White recipients. We used propensity score matching to generate a 1:3 matched cohort of 234 Black patients and 702 White patients with similar baseline characteristics. In the first year after HCT Black patients experienced a higher cumulative incidence of grade III-IV acute GVHD (17% versus 12%, P = 0.050), higher nonrelapse mortality (NRM; 18% versus 12%, P = .009), and lower overall survival that trended toward statistical significance (73% versus 79%, P = .071) compared to White patients. The difference in NRM in the first year was even greater among Black patients who developed GVHD than White patients (24% versus 14%, P = .041). The distribution of low, intermediate, and high MAGIC biomarker scores at the time of treatment was similar across racial groups (P = .847), however, Black patients with high biomarker scores experienced significantly worse NRM than White patients (71% versus 32%, P = .010). Our data indicate that Black patients are at a higher risk of NRM following HCT, primarily from a higher incidence of severe GVHD. Serum biomarkers at treatment initiation can stratify patients for risk of NRM across races, however Black patients with high biomarker scores had a significantly greater NRM risk. These results suggest a need for strategies that mitigate the higher risk for poor GVHD outcomes among Black patients., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: Rheumatoid arthritis (RA) poses significant healthcare challenges in Latin America (LA) due to its high prevalence and unique healthcare dynamics. Despite global advancements, LA faces specific hurdles in effectively managing RA., Areas Covered: This review examines RA epidemiology, treatment strategies, and clinical challenges in LA. RA prevalence varies, with higher rates among indigenous populations. While conventional disease-modifying antirheumatic drugs (csDMARDs) are recommended as first-line therapy, access remains inconsistent. Biologics and targeted synthetic DMARDs are available, but biosimilars have limited accessibility, with drug prices varying significantly. Key barriers include supply interruptions, diagnosis delays, and high non-adherence rates driven by socioeconomic factors. A severe shortage of rheumatologists, particularly in rural areas, affects patient care. Cardiovascular events, comorbidities, and endemic infections further complicate RA management., Expert Opinion: Although RA care in LA has improved through better use of csDMARDs and advanced treatments, major challenges persist, such as a shortage of specialists, limited medical education, and fragmented healthcare systems. Expanding training programs, enhancing telemedicine, and ensuring drug supply continuity are essential. Strengthening clinical research, improving access to affordable treatments, and developing comprehensive, region-specific strategies are crucial to closing the gap between LA and more developed regions in RA care..

Introduction Heart failure (HF) poses a substantial and escalating medical and economic challenge, marked by significant morbidity and mortality. It stands as the primary cause of hospital admissions among the elderly, contributing significantly to healthcare expenditures in developed nations. Evaluating cardiac and pulmonary function remains challenging, necessitating careful interpretation to mitigate misdiagnosis and inappropriate treatment. Remote monitoring has emerged as a preventive strategy to curb HF-related hospitalizations, emphasizing the importance of early detection of impending acute HF decompensation. Implantable cardiac defibrillators (ICDs) capture various parameters, including heart rhythm, pacing percentages, thoracic impedance, and physical activity. Objective In this study, we aim to investigate the effectiveness of HeartLogic (Boston Scientific, Marlborough, Massachusetts) parameters in accurately distinguishing HF patients from individuals with alternative diagnoses. Methods This cross-sectional study was conducted at Cabell Huntington Hospital, St. Mary's Medical Center in Huntington, West Virginia, between 2021 and 2022. The study involved a retrospective chart review of electronic medical records, approved by the institutional review board, encompassing patients aged >18 admitted with Heartlogic-capable devices. The analysis included demographic variables, admission and discharge diagnoses, length of hospital stays, health literacy index, and thoracic impedance. Results Of the initially included 26 patients, 19 met all inclusion criteria. The demographic profile highlighted a predominantly older population with a male preponderance and a notable incidence of congestive heart failure (CHF). Physiological changes, particularly in thoracic impedance and the HeartLogic Index, demonstrated significant alterations. Logistic regression analysis revealed that changes in health literacy index and thoracic impedance significantly contributed to predicting the change in CHF diagnosis. Conclusion This study, conducted in a rural setting, demonstrates the capability of the HeartLogic algorithm in predicting HF events, providing valuable insights into its utility in diverse clinical environments. The findings emphasize the potential of this technology to enhance diagnostic accuracy and improve patient outcomes. Despite inherent limitations, this analysis contributes unique perspectives, particularly in the context of a specific and underexplored rural population in West Virginia., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Marshall University Joan C. Edwards School of Medicine issued approval 2001324-1. This cross-sectional study was performed at Cabell Huntington Hospital, St. Mary’s Medical Center in Huntington, West Virginia (WV) between 2021 and 2022. The study methodology entailed a meticulous retrospective examination of patients' electronic medical records (EMR). Approval for this study protocol was secured from the institutional review board (IRB) of Marshall University Joan C. Edwards School of Medicine, Huntington, WV (IRB NO: 2001324-1), and a waiver was obtained for informed consent. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Zaheer et al.)

Genome size variation in eukaryotes has myriad effects on organismal biology from the genomic to whole-organism level. Large genome size may be associated with lower selection efficiency because lower effective population sizes allow fixation of deleterious mutations via genetic drift, increasing genome size and decreasing selection efficiency. Because of a hypothesized negative relationship between genome size and recombination rate per base pair, increased genome size could also increase the effect of linked selection in the genome, decreasing the efficiency with which natural selection can fix or remove mutations. We used a transcriptomic dataset of 15 and a subset of six Neotropical salamander species ranging in genome size from 12 to 87 pg to study the relationship between genome size and efficiency of selection. We estimated dN/dS of salamanders with small and large genomes and tested for relaxation of selection in the larger genomes. Contrary to our expectations, we did not find a significant relationship between genome size and selection efficiency or strong evidence for higher dN/dS values in species with larger genomes for either species set. We also found little evidence for relaxation of selection in species with larger genomes. A positive correlation between genome size and range size (a proxy of population size) in this group disagrees with predictions of stronger drift in species with larger genomes. Our results highlight the complex interactions between the many forces shaping genomic variation in organisms with genomic gigantism., (© 2024. The Author(s).)

The provision of Wireless Fidelity (Wi-Fi) service in an indoor environment is a crucial task and the decay in signal strength issues arises especially in indoor environments. The Line-of-Sight (LOS) is a path for signal propagation that commonly impedes innumerable indoor objects damage signals and also causes signal fading. In addition, the Signal decay (signal penetration), signal reflection, and long transmission distance between transceivers are the key concerns. The signals lose their power due to the existence of obstacles (path of signals) and hence destroy received signal strength (RSS) between different communicating nodes and ultimately cause loss of the packet. Thus, to solve this issue, herein we propose an advanced model to maximize the LOS in communicating nodes using a modern indoor environment. Our proposal comprised various components for instance signal enhancers, repeaters, reflectors,. these components are connected. The signal attenuation and calculation model comprises of power algorithm and hence it can quickly and efficiently find the walls and corridors as obstacles in an indoor environment. We compared our proposed model with state of the art model using Received Signal Strength (RSS) and Packet Delivery Ratio (PDR) (different scenario) and found that our proposed model is efficient. Our proposed model achieved high network throughput as compared to the state-of-the-art models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Waqas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Nanostructured lipid carriers (NLCs) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug, according to the Biopharmaceutical Classification System (BCS); it has a log P of 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study, we developed an NLC core consisting of a solid lipid (Crodamol TM CP), a lipophilic liquid with medium polarity (SR TM Lauryl lactate), and a hydrophilic excipient (SR TM DMI) that allowed the solubilization of 'brick dust' types of drugs, including butamben. In this study, starting from the NLC core formulation previously developed we carried out an optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (Crodasol TM HS HP, Synperonic TM PE/F68, and Croduret TM 40) were studied and, for each of them, a 2 3 factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI), and zeta potential (mV) as the response variables. Stable NLCs were obtained using Crodasol TM HS HP and Synperonic TM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SR TM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped in stabilizing the system and decreasing particle size. NLCs containing Crodasol TM HS HP and Synperonic TM PE/F68 presented particle size values in the nanometric scale, PDI values lower than 0.3, and zeta potentials above |10|mV. Concerning NLCs' stability, SBTB-NLC with Synperonic TM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in an aqueous medium.

Amiodarone is commonly used nowadays for the treatment of atrial fibrillation (AF). The wide use of this medication has led to the occurrence of adverse events, including pulmonary toxicity, hepatotoxicity, thyroid dysfunction, and many others. Higher doses of Amiodarone of ≥400 mg/day have been linked to increased complications. We present a case of a 70-year-old male with multivessel coronary artery disease (CAD) with ischemic cardiomyopathy and severe peripheral artery disease (PAD) who underwent an elective left femoral to posterior tibial bypass surgery followed by percutaneous coronary intervention (PCI) complicated by new-onset AF. The patient was loaded with 150 mg of intravenous (IV) Amiodarone followed by 360 mg infusion over six hours for chemical cardioversion. The patient was then maintained on oral Amiodarone 400 mg/day until the day of presentation when he complained of progressive dyspnea. Imaging was significant for diffuse ground glass opacities and interstitial thickening. The echocardiogram revealed an improved ejection fraction (EF) of 40% from 20%. The patient had worsening oxygenation despite adequate IV diuresis and developed severe acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV). A bronchoscopy with bronchoalveolar lavage (BAL) showed diffuse alveolar hemorrhage (DAH) with a high lymphocyte count and negative infectious disease testing. Lab tests revealed elevated liver enzyme levels. There were also changes in thyroid function from baseline with elevated free T4 at 1.83 ng/dL (0.8-1.4 ng/dL), suppressed thyroid stimulating hormone (TSH) at 0.109 mIU/mL (0.4-4 mIU/mL), negative anti-thyroglobulin (TG) antibodies, and anti-thyroid peroxidase (TPO) antibodies indicating a type 2 Amiodarone-induced thyrotoxicosis. Unfortunately, the patient's condition deteriorated further despite appropriate treatment, and it was ultimately followed by his demise. Severe, fatal cases of Amiodarone toxicity are scarce, but more reports are being seen. We strongly believe clinicians should have a high index of suspicion for Amiodarone-related adverse events in elderly males with cardiopulmonary comorbidities. It is imperative to have an increased understanding, greater vigilance, and closer monitoring of pulmonary function tests (PFTs), laboratory tests, and imaging studies., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Al-Hiari et al.)

Alzheimer's disease is the main cause of aging-associated dementia, for which there is no effective treatment. In this work, we reanalyze the information of a previous genome wide association study, using a new pipeline design to identify novel potential drugs. With this approach, ribonucleoside-diphosphate reductase gene (RRM2B) emerged as a candidate target and its inhibitor, 2', 2'-difluoro 2'deoxycytidine (gemcitabine), as a potential pharmaceutical drug against Alzheimer's disease. We functionally verified the effect of inhibiting the RRM2B homolog, rnr-2, in an Alzheimer's model of Caenorhabditis elegans, which accumulates human Aβ1-42 peptide to an irreversible paralysis. RNA interference against rnr-2 and also treatment with 200 ng/ml of gemcitabine, showed an improvement of the phenotype. Gemcitabine treatment increased the intracellular ATP level 3.03 times, which may point to its mechanism of action. Gemcitabine has been extensively used in humans for cancer treatment but at higher concentrations. The 200 ng/ml concentration did not exert a significant effect over cell cycle, or affected cell viability when assayed in the microglia N13 cell line. Thus, the inhibitory drug of the RRM2B activity could be of potential use to treat Alzheimer's disease and particularly gemcitabine might be considered as a promising candidate to be repurposed for its treatment., Competing Interests: Conflicts of interest AMBL, MSI, CV, JLR, and MJM signed as authors of a patent application P201830955. The other authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

The objective of this study was to develop a versatile lipid core for the 'brick-dust type of drugs' (poorly water-soluble and poorly lipid-soluble drugs). In the first step, excipients of different polarities were classified according to their behavior in aqueous solutions. Subsequently, binary mixtures were prepared with cetyl palmitate (Crodamol™ CP pharma, Campinas, São Paulo, Brazil) as the solid lipid, and its miscibility with other excipients was evaluated using Raman mapping and classical least squares (CLS). Based on the results, the excipients Crodamol™ CP pharma (hydrophobic), Super Refined™ DMI (dimethyl isosorbide; hydrophilic, Mill Hall, PA, USA), and Super Refined™ Lauryl Lactate (lauryl lactate, medium polarity, Mill Hall, PA, USA) were chosen to compose the lipid core. The ideal proportion of these excipients was determined using a mixture design and the standard deviation (STD) of image histograms as the response variables. After statistical evaluation of the DoE results, the final composition was determined, and drugs with different logP (0 to 10) and physicochemical characteristics were evaluated in the optimized mixture. The drugs butamben (Sigma-Aldrich Co., Spruce Street, St. Louis, MO, USA), tacrolimus (NutriFarm, São Paulo, Brazil), atorvastatin calcium, and resveratrol (Botica da Terra, Campinas, Brazil) presented a homogeneous distribution in the optimized lipid core, indicating that this is a promising system to be used in nanostructured lipid carrier (NLC) formulations of such types of drugs.

Genetic diversity is the raw material of evolution, yet the reasons why it varies among species remain poorly understood. While studies at deeper phylogenetic scales point to the influence of life history traits on genetic diversity, it appears to be more affected by population size but less predictable at shallower scales. We used proxies for population size, mutation rate, direct selection, and linked selection to test factors affecting genetic diversity within a diverse assemblage of Neotropical salamanders, which vary widely for these traits. We estimated genetic diversity of noncoding loci using ddRADseq and coding loci using RNAseq for an assemblage of Neotropical salamanders distributed from northern Mexico to Costa Rica. Using ddRADseq loci, we found no significant association with genetic diversity, while for RNAseq data we found that environmental heterogeneity and proxies of population size predict a substantial portion of the variance in genetic diversity across species. Our results indicate that diversity of coding loci may be more predictable than that of noncoding loci, which appears to be mostly unpredictable at shallower phylogenetic scales. Our results suggest that coding loci may be more appropriate for genetic diversity estimates used in conservation planning because of the lack of any association between the variables we used and genetic diversity of noncoding loci., Competing Interests: The authors have no conflict of interest to declare., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention for preventing malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance ( kdr ) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 ( Ace-1 ) and voltage-gated sodium channel ( VGSC ) genes are non-synonymous, resulting in a change in amino acid, leading to the non-binding of the insecticide. In the present study, we analyzed target-site resistance in Nyssorhynchus darlingi , the primary malaria vector in the Amazon, in multiple malaria endemic localities. We screened 988 wild-caught specimens of Ny. darlingi from three localities in Amazonian Peru and four in Amazonian Brazil. Collections were conducted between 2014 and 2021. The criteria were Amazonian localities with a recent history as malaria hotspots, primary transmission by Ny. darlingi , and the use of both IRS and LLINs as interventions. Fragments of Ace-1 (456 bp) and VGSC (228 bp) were amplified, sequenced, and aligned with Ny. darlingi sequences available in GenBank. We detected only synonymous mutations in the frequently reported Ace-1 codon 280 known to confer resistance to organophosphates and carbamates, but detected three non-synonymous mutations in other regions of the gene. Similarly, no mutations linked to insecticide resistance were detected in the frequently reported codon (995) at the S6 segment of domain II of VGSC . The lack of genotypic detection of insecticide resistance mutations by sequencing the Ace-1 and VGSC genes from multiple Ny. darlingi populations in Brazil and Peru could be associated with low-intensity resistance, or possibly the main resistance mechanism is metabolic.

Osteoporosis management has become more relevant as the life expectancy increases. In Ecuador, approximately 19% of adults over 65 years of age have been diagnosed with osteoporosis. There is no national consensus for the management and prevention of the disease being this proposal the first Ecuadorian consensus., Introduction: In Ecuador, it is estimated that around 19% of adults over 65 years of age have osteoporosis. Due to the increase in life expectancy in the world population, the evaluation and management of osteoporosis has become more relevant. Currently, there is no national consensus for the management and prevention of the disease. The Ecuadorian Society of Rheumatology presented the project for the elaboration of the first Ecuadorian consensus for the management and prevention of osteoporosis., Methods: A panel of experts in multiple areas and extensive experience was invited to participate. The consensus was carried out using the Delphi method. Six working dimensions were created: definition and epidemiology of osteoporosis, fracture risk prediction tools, non-pharmacological treatment, pharmacological treatment, calcium and vitamin D, and glucocorticoid-induced osteoporosis., Results: The first round was held in December 2021, followed by the second round in February 2022 and the third round in March 2022. The data was shared with the specialists at the end of each round. After three rounds of work, a consensus was reached for the management and prevention of osteoporosis., Conclusion: This is the first Ecuadorian consensus for the management and treatment of postmenopausal osteoporosis., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose: We aimed to describe the performance and evaluate the educational value of justifications provided by artificial intelligence chatbots, including GPT-3.5, GPT-4, Bard, Claude, and Bing, on the Peruvian National Medical Licensing Examination (P-NLME)., Methods: This was a cross-sectional analytical study. On July 25, 2023, each multiple-choice question (MCQ) from the P-NLME was entered into each chatbot (GPT-3, GPT-4, Bing, Bard, and Claude) 3 times. Then, 4 medical educators categorized the MCQs in terms of medical area, item type, and whether the MCQ required Peru-specific knowledge. They assessed the educational value of the justifications from the 2 top performers (GPT-4 and Bing)., Results: GPT-4 scored 86.7% and Bing scored 82.2%, followed by Bard and Claude, and the historical performance of Peruvian examinees was 55%. Among the factors associated with correct answers, only MCQs that required Peru-specific knowledge had lower odds (odds ratio, 0.23; 95% confidence interval, 0.09-0.61), whereas the remaining factors showed no associations. In assessing the educational value of justifications provided by GPT-4 and Bing, neither showed any significant differences in certainty, usefulness, or potential use in the classroom., Conclusion: Among chatbots, GPT-4 and Bing were the top performers, with Bing performing better at Peru-specific MCQs. Moreover, the educational value of justifications provided by the GPT-4 and Bing could be deemed appropriate. However, it is essential to start addressing the educational value of these chatbots, rather than merely their performance on examinations.

Foodservice businesses influence the sustainability of their natural environment by producing significant amounts of waste. Yet, research has, thus far, been dominated by studies that limit their scope to food waste alone. Few studies have taken a broader look at sustainable waste initiatives, including innovative waste processing techniques, with a view to constructing management indicators for foodservices. This study combines management innovation practices related to resource management, waste prevention, processing and disposal techniques, and stakeholder involvement to offer sustainable standards. It primarily adopts the Delphi technique to propose specific solutions pertaining to waste management. Experts from government, industry, and academia reveal that potential waste management initiatives comprise three facets - service, process (operational), and organisational practices and innovations, 15 sub-facets and 41 indicators. This study thus establishes a catalogue of solutions for food, packaging and other 'non-food' waste that foodservice establishments can implement. In addition to its practical implications, an important contribution is its focus on management systems to establish waste management standards for hospitality, food and beverage (F&B) services, restaurants, and non-commercial catering.

Silicon photonics is evolving from laboratory research to real-world applications with the potential to transform many technologies, including optical neural networks and quantum information processing. A key element for these applications is a reconfigurable switch operating at ultra-low programming energy-a challenging proposition for traditional thermo-optic or free carrier switches. Recent advances in non-volatile programmable silicon photonics based on phase-change materials (PCMs) provide an attractive solution to energy-efficient photonic switches with zero static power, but the programming energy density remains high (hundreds of attojoules per cubic nanometre). Here we demonstrate a non-volatile electrically reconfigurable silicon photonic platform leveraging a monolayer graphene heater with high energy efficiency and endurance. In particular, we show a broadband switch based on the technologically mature PCM Ge 2 Sb 2 Te 5 and a phase shifter employing the emerging low-loss PCM Sb 2 Se 3 . The graphene-assisted photonic switches exhibited an endurance of over 1,000 cycles and a programming energy density of 8.7 ± 1.4 aJ nm - 3 , that is, within an order of magnitude of the PCM thermodynamic switching energy limit (~1.2 aJ nm - 3 ) and at least a 20-fold reduction in switching energy compared with the state of the art. Our work shows that graphene is a reliable and energy-efficient heater compatible with dielectric platforms, including Si 3 N 4 , for technologically relevant non-volatile programmable silicon photonics., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Two emaciated male northern elephant seal (NES) Mirounga angustirostris pups were admitted to The Marine Mammal Center (Sausalito, California, USA) and treated for malnutrition. Complete blood counts showed a progressive moderate to marked leukocytosis characterized by a predominance of large monomorphic mononuclear cells of probable lymphoid origin, frequently with flower-shaped nuclei. Both seals were euthanized due to suspected lymphoid neoplasia. At necropsy, most lymph nodes in both pups were markedly enlarged, some with distinct white nodules, the spleens were diffusely enlarged, and the intestinal mucosae were thickened. Histopathologic features consistent with disseminated large cell lymphoma were identified to varying degrees of severity in lymph nodes, bone marrow, liver, tonsils, spleen, liver, intestines, kidneys, lower urinary tract, and several other organs. Immunohistochemical staining of neoplastic cells was most consistent with B lymphocyte origin, with most cells staining positively for Pax 5 and CD20 with admixed small CD3-positive T lymphocytes and CD204-positive macrophages. PCR and sequencing identified a novel gammaherpesvirus, herein called miroungine gammaherpesvirus 3, from affected tissues. This virus is in a clade outside of named genera that utilize hosts in the suborder Caniformia. The present study is the first description of diffuse large B cell lymphoma with leukemic manifestation and concomitant detection of a novel gammaherpesvirus in free-living NESs. Further research regarding the prevalence of this new gammaherpesvirus and its associated pathogenesis in this species is indicated.

Beta-2 Human papillomaviruses 38b, 107, and 122 have been frequently found in cervical cancer samples in western Mexico. Because their E6/E7 genes functions are not fully elucidated, we deepen into their transformation capabilities. To achieve this goal, primary human fibroblasts (FB) were transduced with E6/E7 genotype-specific viral particles. Additionally, E6/E7 from HPVs 16 and 18 were included as controls. All E6/E7-cell models increased their lifespan; however, it is important to highlight that FB-E6/E7-122 showed growth as accelerated as FB-E6/E7-16 and 18. Furthermore, both FB-E6/E7-38b and 122 exhibited abilities to migrate, and FB-E6/E7-122 presented high invasive capacity. On the other hand, ΔNp73 expression was found in all cell models, except for FB-pLVX (empty-vector). Finally, RNAseq found differentially expressed genes enriched in signaling pathways related to cell cycle, epithelial-mesenchymal transition, and cancer, among others. This study shows for the first time, the great transformative potential that genotypes of the Beta-2 also possess, especially HPV122. These Beta-2 HPVs can modulate some of the genes that are well known to be regulated by Alpha-HPVs, however, they also possess alternative strategies to modulate diverse signaling pathways. These data support the idea that Beta-2 HPVs should play an important role in co-infections with Alpha-HPV during carcinogenesis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The remedy of memory deficits has been inadequate, as all potential candidates studied thus far have shown limited to no effects and a search for an effective strategy is ongoing. Here, we show that an expression of RGS14414 in rat perirhinal cortex (PRh) produced long-lasting object recognition memory (ORM) enhancement and that this effect was mediated through the upregulation of 14-3-3ζ, which caused a boost in BDNF protein levels and increase in pyramidal neuron dendritic arborization and dendritic spine number. A knockdown of the 14-3-3ζ gene in rat or the deletion of the BDNF gene in mice caused complete loss in ORM enhancement and increase in BDNF protein levels and neuronal plasticity, indicating that 14-3-3ζ-BDNF pathway-mediated structural plasticity is an essential step in RGS14414-induced memory enhancement. We further observed that RGS14414 treatment was able to prevent deficits in recognition, spatial, and temporal memory, which are types of memory that are particularly affected in patients with memory dysfunctions, in rodent models of aging and Alzheimer's disease. These results suggest that 14-3-3ζ-BDNF pathway might play an important role in the maintenance of the synaptic structures in PRh that support memory functions and that RGS14414-mediated activation of this pathway could serve as a remedy to treat memory deficits., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

RNA interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing mechanism that responds to double-stranded RNA (dsRNA) by sequence-specific downregulation of target genes. The dsRNA-mediated RNAi technology has become one of the most widely used and powerful tools for functional genomic studies in diverse organisms. However, its application has been limited due to the technical difficulty of making RNAi constructs caused by the inverted repeat structure that is required for the formation of hairpin RNA. Here, we present a ligation-independent cloning-based dual vector-mediated RNAi system for silencing specific genes in plants. This approach is simple, efficient, and cost-effective and can be readily adapted to other binary vectors for functional analysis of target genes and the development of sustainable disease and pest control strategies in a broad range of plant species., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Severe focal to multifocal abscessation of the axillary and inguinal lymph nodes is an important cause of morbidity and mortality in stranded pup and yearling California sea lions ( Zalophus californianus ; CSLs) at The Marine Mammal Center (TMMC). A retrospective case review was conducted of all pup and yearling CSLs with axillary and/or inguinal lymph node abscesses admitted to this California rehabilitation center between January 2015 and December 2019 ( n = 162). Clinical data and cultured isolates were evaluated to (1) characterize the clinical syndrome, (2) report isolated pathogens, and (3) investigate factors associated with clinical outcome (survival to release versus death). Of the 162 CSLs admitted with at least one axillary or inguinal lymph node abscess, almost all were in poor body condition, and overall mortality rate was 63% (102 of 165). Mortality rate was lower for animals presenting with a single abscess and abscess(es) in the inguinal location only; odds of death were significantly lower for animals that had their abscesses surgically drained ( P = 0.029) and those that received antimicrobials ( P = 0.037). Hematology and serum chemistry parameters at the time of abscess diagnosis reflected inflammation and malnutrition. Radiographic findings associated with abscesses from 45 cases included soft tissue swelling ( n = 40), intralesional gas ( n = 19), and osteomyelitis ( n = 3). Ninety bacterial isolates were recovered from aerobic ( n = 48) and anaerobic cultures ( n = 17), 48.9% of which were gram negative. The most common gram-negative organisms were Escherichia coli ( n = 15), Proteus spp. ( n = 8), and Bacteroides ureolyticus ( n = 7), and the most common gram-positive organisms were Streptococcus phocae ( n = 10) and Staphylococcus spp. ( n = 9). Management of lymph node abscesses via surgical drainage and multimodal systemic antimicrobial therapy with a broad-spectrum of activity may be considered to improve survival of these cases.

Human malaria continues to be a public health problem and an important cause of morbidity and mortality in the world. Malaria control is achieved through both individual protection against mosquito bites and drug treatment, which is hampered by the spread of Plasmodium falciparum resistance to most antimalarials, including artemisinin derivatives. One of the key pharmacological strategies for controlling malaria is to block transmission of the parasites to their mosquito vectors. Following this rational, MEFAS, a synthetic hybrid salt derived from artesunate (AS) and mefloquine has been previously reported for its activity against asexual P. falciparum parasites in vitro, in addition to a pronounced reduction in the viability of mature gametocytes. Herein, MEFAS was tested against asexual forms of Plasmodium vivax and for its ability to block malaria transmission in Anopheles darlingi mosquitoes in a membrane feeding assay using P. vivax field isolates. MEFAS demonstrated high potency, with a IC50 of 6.5 nM against asexual forms of P. vivax. At 50 μM, MEFAS completely blocked oocyst formation in mosquitoes, regardless of the oocyst number in the control group. At lower doses, MEFAS reduced oocyst prevalence by greater than 20%. At equivalent doses, AS irregularly reduced oocyst formation and caused only slight inhibition of mosquito infections. These results highlight the potential of MEFAS as a novel transmission-blocking molecule, as well as its high blood schizonticidal activity against P. vivax and P. falciparum field isolates, representing a starting point for further development of a new drug with dual antimalarial activity., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit., Objective: To determine whether ivermectin is an efficacious treatment for mild COVID-19., Design, Setting, and Participants: Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020., Intervention: Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200)., Main Outcomes and Measures: Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected., Results: Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group)., Conclusion and Relevance: Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT04405843.

Rheumatoid Arthritis (RA) is a chronic inflammatory autoimmune systemic disease that preferentially affects small and large joints with a progressive course and can become deforming and disabling. In recent years, much progress has been made in the evaluation of inflammation and disease activity, however, there are other factors that have a high impact on the quality of life of these patients, such as depression, anxiety, fatigue, sleep disorders, suicidal behavior, fibromyalgia, sexual activity, sarcopenia, frailty, cachexia and obesity that are not always evaluated by rheumatologists. This review shows that the evaluation and timely detection of these aspects in patients with RA could interfere with the prognosis and improve their quality of life., Competing Interests: Dr Gustavo Citera report grants, personal fees from Pfizer, during the conduct of the study; grants, personal fees from Pfizer, outside the submitted work. The authors report no other conflicts of interests in this work., (© 2021 Espinoza et al.)

Monomethyl mercury (MeHg + ) from the diet can cause mild to severe neurotoxicosis in fish-eating mammals. Chronic and low-level in utero exposure also can be neurotoxic, as documented in laboratory animal studies and epidemiologic investigations. In free-ranging animals, it is challenging to study low-level exposure related neurotoxicosis, and few studies have investigated the relationship between mercury (Hg) and adverse outcomes in wild populations. Relative to Hg concentrations on admission we evaluated different types of behaviors for 267 Pacific harbor seal (HS; Phoca vitulina richardii) pups at The Marine Mammal Center from 2015 to 2019 during rehabilitation after stranding and maternal separation. Admitted HS pups underwent a clinical exam; including sex and weight determination, and hair (partly lanugo grown in utero) and blood samples were collected for total Hg concentration ([THg]) determination. All pups were monitored weekly (behavior assessments included response to tactile stimulation, movement, swimming, interactions with other seals, hand feeding, and feeding independently), and days in rehabilitation and survival were recorded. There was a significant negative correlation between [THg] and responses to tactile stimulation and movements, measured in both hair and whole blood (p < 0.05). This relationship was found both during the intensive care unit (ICU) stage, and during the pool stage of rehabilitation. Additionally, there was a significant association between greater [THg] and number of days spent in rehabilitation, although there was no relationship between [THg] and survival. There was a significant sex difference, with greater [THg] in female pups, which contrasts with previously published findings in juvenile and adult harbor seals. Our findings support small, but significant associations between gestational THg exposure and clinical effects for tactile sensory response and movement, and longer rehabilitation durations for HS pups, although there was considerable variability among animals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Active metasurfaces, whose optical properties can be modulated post-fabrication, have emerged as an intensively explored field in recent years. The efforts to date, however, still face major performance limitations in tuning range, optical quality, and efficiency, especially for non-mechanical actuation mechanisms. In this paper, we introduce an active metasurface platform combining phase tuning in the full 2π range and diffraction-limited performance using an all-dielectric, low-loss architecture based on optical phase change materials (O-PCMs). We present a generic design principle enabling binary switching of metasurfaces between arbitrary phase profiles and propose a new figure-of-merit (FOM) tailored for reconfigurable meta-optics. We implement the approach to realize a high-performance varifocal metalens operating at 5.2 μm wavelength. The reconfigurable metalens features a record large switching contrast ratio of 29.5 dB. We further validate aberration-free and multi-depth imaging using the metalens, which represents a key experimental demonstration of a non-mechanical tunable metalens with diffraction-limited performance.

Background/objective: Latin America has scarce information related to rheumatologist's education, working conditions, productivity, and job satisfaction. The purpose of this survey was to describe the training and clinical practice characteristics of the rheumatology community in Latin America., Methods: This is a cross-sectional study. A digital survey was created, approved, and endorsed by the scientific committee of the Pan-American League of Associations for Rheumatology (PANLAR) and later sent to the rheumatology associations of the region. The data was analyzed in the statistical program SPSS v.22., Results: We included 600 surveys of rheumatologists from 19 Latin American countries. The majority were females (53%) and mestizos (58%). The mean age was 46.8 ± 11.7 years. The most frequent workplace was public/government hospitals 33.5% followed by private practice 28.8%, private hospital 20.8%, and university hospital 15.5%. The average number of weekly working hours was 37.8 ± 17.7. 87.5% worked in adult rheumatology, 12.7% pediatric rheumatology, and 23.5% internal medicine. Average satisfaction with practice as a rheumatologist was 5.3/7, career options 4.3/7, location 4.7/7, income 3.5/7, job security 3.7/7, and colleagues and co-workers 4.5/7. Finally, 69.7% had an annual compensation of < 50,000 US dollars., Conclusions: The majority of the rheumatologists in the region who responded were women, worked in public hospitals, and were satisfied with their clinical practice. There was a low level of income for the region. Key Points • This is the first study that showed the demographic and clinical practice characteristics of rheumatologists in Latin America. • The challenges faced by Latin rheumatologists are like those faced by the region: ethnic diversity, gender differences, migration, difficult access to education, limited research, and low income. • Due to the high prevalence of rheumatic diseases and the shortage of professionals in this area, it is essential to analyze the current workforce and the projections of supply and demand in rheumatology that are expected in the future.

Introduction: Currently, there are no records of the current status of rheumatologists in Ecuador., Objective: The purpose of this study is to get to know the current status of rheumatologists in Ecuador, focusing on education, working conditions, productivity, distribution of time between work activities, and job satisfaction., Materials and Methods: A digital survey was created using the Google Forms platform. It was distributed to all rheumatologist members of the Ecuadorian Society of Rheumatology. The data analysis was carried out using the statistical program SPSS v.23®., Results: A total of 64 surveys were received. The response rate was 86.48%. 62.5% were men and 37.5% women, with an average age of 40.76 ± 9.18. The main workplace was state/public hospital (56.3%). The average working hours per week were 40.35 ± 25.72. Most rheumatologists in Ecuador (62.5%) received their training abroad. 79.7% of rheumatologists earn less than $ 49,000 annually. The mean retirement age was 66.51 ± 6.7, and 54.7% have a retirement plan. The average satisfaction of Ecuadorian rheumatologists was 5.4 ± 1.33 [0-7]; 17.2% are very dissatisfied with their annual income., Conclusions: This is the first recorded data on the characteristics of rheumatologists in Ecuador. Most rheumatologists obtained their specialist degree abroad. In general, rheumatologists in Ecuador are satisfied with their clinical practice and dissatisfied with their annual income and job security., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Genessis Maldonado et al.)

The Bombay (Oh) phenotype is a rare phenotype in which red blood cells lack the H antigen as a result of a point mutation in the H gene. Oh patients are a challenge in transfusion medicine. We present a case of a pediatric patient with the Bombay phenotype who was carried to the emergency department of the Hospital Universitario San Vicente Fundación in Medellín, Colombia. The patient presented gastrointestinal hemorrhage and required transfusion therapy. Pretransfusion and molecular immunohematological analyses identified the Bombay phenotype. The patient was transfused with Oh red blood cells imported to Colombia from the Hematology and Hemotherapy Center of Ceará (Hemoce) in Fortaleza, Brazil. This first case of an Oh individual in Colombia highlights the need to look for donors with rare phenotypes to fulfill the transfusion requirements of the population., Competing Interests: Declaration of Competing Interest The authors have disclosed no conflict of interest relevant to the manuscript submitted to Transfusion and Apheresis Science., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Currently, approximately more than one billion people around the world are considered to have deficient levels of vitamin D. International consensus recommends vitamin D supplementation to high-risk patients (advanced age, osteoporosis, liver failure, malabsorption syndromes, etc.) and those with levels below 30 ng/mL. There are several vitamin D formulations and dosages available, including megadoses. At the moment, there is no consensus on the definition of megadoses. The purpose of this review is to define what is a megadose and analyze its effectiveness in bone metabolism, risk of fractures and falls., Conclusion: The administration of doses higher than 100,000 IU of vitamin D is considered a megadose. It is evident that the use of megadoses increases serum concentrations of vitamin D; however, there has been no evidence of a decrease in the risk of falls, vertebral fractures or changes in bone mineral density., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Narvaez et al.)

Introduction: Disability in RA is associated with loss of workdays, greater use of health resources and a higher prevalence of depression. The purpose of this study was to determine the prevalence of functional disability and the factors associated with it., Methods: A cross-sectional study was carried out during January-June 2019 at a rheumatology clinic in the city of Guayaquil. Patients with pre-established RA were included. Functional disability was measured using the HAQ-DI. Data were analyzed using the statistical program SPSS v22. We compared characteristics between patients with and without disability using Student's t -test and chi-square. A multiple logistic regression model for functional disability was made., Results: We included 395 patients, 87.8% female and 12.2% male with a mean age of 51.4±12 years and mean duration of disease 13.8±7 years. Most patients had extra-articular manifestations (80.8%) and comorbidities (81.3%). The mean HAQ-DI was 0.8±0.9, with a prevalence of disability of 26.6%. We found a statistically significant relationship between disability and female sex (p=0.018), age (p=0.020), presence of extra-articular manifestations (p=0.008), myalgia (p<0.001) and fatigue (p<0.001). In addition, patients with disabilities had a lower employment rate (26.7%) compared to those without disability (45.5%, p=0.001). In the multivariate logistic analysis, only depression (p=0.029), diabetes (p=0.003), SJC (p=0.001) and VAS of pain (p=0.004) were significantly related to functional disability., Conclusion: Disability affects a quarter of patients with RA. Among the determinants of disability, we found female sex, older age, grade of pain, inflammatory markers and the level of disease activity., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Intriago et al.)

The affiliation of the second author (Kenneth S. Knox) should have been Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA instead of Department of Medicine, University of Arizona-Phoenix, Phoenix, AZ 85004, USA.

Virus-based microRNA silencing (VbMS) is a rapid and efficient tool for functional characterization of microRNAs (miRNAs) in plants. The VbMS system has been developed and applied for various plant species including Nicotiana benthamiana, tomato, Arabidopsis, cotton, and monocot plants such as wheat and maize. Here, we describe a detailed protocol using PVX-based VbMS vectors to silence endogenous miRNAs in potato. To knock down the expression of a specific miRNA, target mimic (TM) molecules of miRNA of interest are designed, integrated into plant virus vectors, and expressed in potato by Agrobacterium infiltration to bind directly to the endogenous miRNA of interest and block its function.

SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30-50,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.

Hypermucoviscous K. pneumoniae (HMV) are emergent zoonotic pathogens associated with increased invasiveness and pathogenicity in terrestrial and marine mammals. In this study, HMV and non-HMV isolates recovered from stranded pinnipeds were used to investigate: 1) their persistence in sea and fresh water microcosms at 10 and 20°C, 2) their capacity to form biofilms, and 3) the biocide efficacy of four disinfectants on their planktonic and biofilm phenotypes. Results indicated that although HMV isolates were significantly more mucoviscous, non-HMV isolates displayed significantly greater capacity to form biofilms (p < 0.05). Additionally, non-HMV isolates persisted in greater numbers in both sea- and freshwater, particularly at 20°C. These two phenomena could be associated with the greater growth observed for non-HMV isolates in in-vitro growth-curve assays (p < 0.05). Similar susceptibility to disinfectants was detected in HMV and non-HMV isolates when exposed for 24 h; however, the minimal biofilm disinfectant eradication concentration for HMV isolates was significantly higher than that for non-HMV when exposed to disinfectants for 0.5 h. This information should be taken into consideration when developing biosecurity protocols in facilities holding marine mammals in captivity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Dual-energy X-ray absorptiometry is recognized for measuring bone mineral density. The lack of knowledge can lead to errors both in the acquisition of information and in its analysis and subsequent interpretation. The main errors in Ecuadorian Centers were positioning of the patient to the equipment and incorrect analyzed area., Purpose/introduction: Dual-energy X-ray absorptiometry (DXA) is recognized as the gold standard for measuring bone mineral density (BMD) with acceptable errors, good precision, and reproducibility. However, the training of operators in different centers and countries is not standardized, and the lack of knowledge can lead to errors both in the acquisition of information and in its analysis and subsequent interpretation. The purpose was to determine the most common errors in the performance of bone densitometry from different imaging centers in Ecuador., Methods: Cross-sectional descriptive study. We collected DXA scans from different imaging centers in Ecuador. Data from the DXA scan included city of origin, type of specialist that requested it, and densitometry diagnosis. The DXA images provided were analyzed double blind by experts in the field from Argentina., Results: From a total of 141 patients with a mean age of 61 ± 10 years, 93.6% were women. About 78% of the DXA scans came from private imaging centers and 22% from public centers, 95% of all came from the city of Guayaquil. The machines used were Hologic 50.4% and Lunar 49.6%. The densitometric diagnosis was 16.3% normal, 46.1% osteoporosis, and 37.6% osteopenia. A total of 112 left hip and 49 right hip scans were analyzed from which 31.2% and 22.4% had errors in patient positioning, respectively, mainly internal or external rotation. About 140 lumbar scans were analyzed from which 21.4% had patient positioning errors (not centered or not straight). Also in 38.5% the vertebral area did not correspond to L1-L4. About 3.5% had artifacts such as a metal bar or implant. The region of interest was misplaced in 24.1% of the lumbar scans and 19.9% of the femur., Conclusions: DXA quality standards exist but are often not implemented in clinical practice. When studies are performed incorrectly, it can lead to important errors in diagnosis and therapy. Physicians interested in the management of osteoporosis, although not directly involved in the performance and interpretation of DXA, should be familiar with the protocols to minimize errors and allow the proper use of bone densitometry.

The original version of this article, unfortunately, contained an error. The first and family name of Loreto Massardo was interchanged and is now presented correctly in this article.

Mercury (Hg) poses a health risk to wildlife populations and has been documented at relatively high concentrations in many marine mammals, including wild-caught pinnipeds along the central California, US coast. We measured total Hg concentrations ([THg]) in hair and blood of live-stranded harbor seals (HS; Phoca vitulina ), California sea lions (CSL; Zalophus californianus ), and northern elephant seals (NES; Mirounga angustirostris ) in California to quantify species, temporal, and spatial variability in [THg] and assess the relationships between [THg] measured by different methods (blood vs. filter paper) and in different matrices (blood vs. hair). We compared [THg] with toxicologic thresholds of concern to aid in identification of at-risk individuals or groups and better understand how the use of different methods and matrices affects assumed toxicologic risk. There was a wide range of [THg] in blood (<0.01-1.13 μg/g) and hair (0.45-81.98 μg/g), and NES had higher [THg] compared with HS and CSL. All three species had individuals with [THg] that exceeded the lower threshold for one or both matrices, but only HS pups had [THg] exceeding upper thresholds. Spatial differences in [THg] were detected, with higher concentrations in HS pups from areas surrounding San Francisco Bay, but differences were dependent on sampling year and matrix. The relationship between [THg] in blood and filter paper ( r 2 =0.98) was strong, and differences had little influence on comparisons with toxicologic thresholds. Blood and hair [THg] were generally in agreement ( r 2 =0.72), but large mismatches for a few seals underscore the importance of combined sampling in adverse effects studies where accurate assessment of Hg exposure is crucial. The wide range of [THg] in stranded HS pups that exceeded published thresholds of concern makes them a promising candidate for adverse effects studies, particularly because different matrices represent Hg exposure across key developmental stages.

Objectives: To identify baseline predictors of remission and low disease activity (LDA) in early rheumatoid arthritis (RA) from the GLADAR (Grupo Latino Americano De estudio de la Artritis Reumatoide) cohort., Methods: Patients with 1- and 2-year follow-up visits were included. Remission and LDA were defined by DAS28-ESR (< 2.6 and ≤ 3.2, respectively). Baseline predictors examined were gender, ethnicity, age at diagnosis, socioeconomic status, symptoms' duration, DMARDs, RF, thrombocytosis, anemia, morning stiffness, DAS28-ESR (and its components), HAQ-DI, DMARDs and corticosteroid use, and Sharp-VDH score. Multivariable binary logistic regression models (excluding DAS28-ESR components to avoid over adjustment) were derived using a backward selection method (α-level set at 0.05)., Results: Four hundred ninety-eight patients were included. Remission and LDA/remission were met by 19.3% and 32.5% at the 1-year visit, respectively. For the 280 patients followed for 2 years, these outcomes were met by 24.3% and 38.9%, respectively. Predictors of remission at 1 year were a lower DAS28-ESR (OR 1.17; CI 1.07-1.27; p = 0.001) and HAQ-DI (OR 1.48; CI 1.04-2.10; p = 0.028). At 2 years, only DAS28-ESR (OR 1.40; CI 1.17-1.6; p < 0.001) was a predictor. Predictors of LDA/remission at 1 year were DAS28-ESR (OR 1.42; CI 1.26-1.61; p < 0.001), non-use of corticosteroid (OR 1.74; CI 1.11-2.44; p = 0.008), and male gender (OR 1.77; CI 1.2-2.63; p = 0.036). A lower baseline DAS28-ESR (OR 1.45; CI 1.23-1.70; p < 0.001) was the only predictor of LDA/remission at 2 years., Conclusions: A lower disease activity consistently predicted remission and LDA/remission at 1 and 2 years of follow-up in early RA patients from the GLADAR cohort. Key Points • In patients with early RA, a lower disease activity at first visit is a strong clinical predictor of achieving remission and LDA subsequently. • Other clinical predictors of remission and LDA to keep in mind in these patients are male gender, non-use of corticosteroids and low disability at baseline. • Not using corticosteroids at first visit is associated with a lower disease activity and predicts LDA/remission at 1 year in these patients.

Purpose: To evaluate quality of life in patients with established rheumatoid arthritis (RA) and identify the factors that negatively affect it., Methods: This was a cross-sectional study with patients with established RA from a rheumatology center in Ecuador. The RA Quality of Life (RAQoL) questionnaire was used to assess QoL and the Health Assessment Questionnaire - disability index (HAQ-DI) questionnaire for functional capacity. In addition, demographics, clinical characteristics, and markers of disease activity were included. Data were analyzed using SPSS 22., Results: Of 186 patients, 89.8% were women, with a mean age of 51 years, 86.6% had symmetrical polyarticular involvement, 40.3% erosions, 46.8% morning stiffness, 46.8% xerophthalmia, and 39.2% fatigue. Depression was the most frequent comorbidity - 42.5%. The mean HAQ-DI score was 0.8, and 26.9% had functional disability. The mean RAQoL score was 7.2. Xerophthalmia, xerostomia, fatigue, morning stiffness, and depression were related to higher scores in the RAQoL ( p <0.05). The mean RAQoL was higher in patients with more disease activity and comorbidities ( p <0.05). Likewise, patients with functional disability had a mean RAQoL score of 15.6 versus 4.1 in patients without disability ( p <0.05). There were positive correlations between RAQoL and ESR, CRP, painful-joint count, swollen-joint count, VAS of pain, and physician assessment ( p <0.05)., Conclusion: QoL is severely affected in patients with RA. Depression, fatigue, morning stiffness, pain, high disease activity, and disability have a negative effect on QoL in RA. Likewise, patients with more comorbidities and extraarticular manifestations show worse QoL., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Intriago et al.)

Introduction: The lack of highly-productive Nyssorhynchus darlingi laboratory colonies limits some studies. We report the first well-established laboratory colony of Ny. darlingi in Brazil., Methods: Mosquitoes were collected from Porto Velho and were reared at the Laboratory of Fiocruz/RO. After induced mating by light stimulation in the F1 to F6, the subsequent generations were free mating. Larvae were reared in distilled water and fed daily until pupation., Results: In 11 generations, the colony produced a high number of pupae after the F5 generation., Conclusions: These results demonstrate the potential for permanently establishing Ny. darlingi colonies for research purposes in Brazil.

The exoerythrocytic stage of Plasmodium infection is a critical window for prophylactic intervention. Using genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we show that the human mucosal immunity gene, mucin-13 (MUC13), is strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm MUC13 transcript increases in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, marking both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes. This data provides insights into host-parasite interactions in Plasmodium infection, and demonstrates that a component of host mucosal immunity is reprogrammed during the progression of infection.

Emergent hypermucoviscous (HMV) strains of Klebsiella pneumoniae have been reported in multiple marine mammal species; however, there is limited information regarding the epidemiology and pathogenesis of this infection in these species. We determined the prevalence of HMV K. pneumoniae in wild-caught and stranded marine mammal populations on the US Pacific Coast. Samples were collected from 270 free-ranging California sea lions (CSLs; Zalophus californianus) captured at three discrete sampling sites and from 336 stranded marine mammals of various species. We recovered HMV K. pneumoniae only from CSLs, with a prevalence of 1.5% (4 of 275) in stranded animals, compared with 1.1% (3 of 270) in wild-caught animals. We assessed the phenotypic and genotypic variability of recovered HMV K. pneumoniae isolates recovered from CSLs ( n=11) and of archival HMV and non-HMV isolates from stranded marine mammals ( n=19). All but two HMV isolates were of the K2 serotype, whereas none of the non-HMV isolates belonged to this serotype. Of the HMV isolates, 96% (24 of 25) were PCR positive for the HMV-associated gene p- rmpA, whereas 92% (23 of 25) were PCR positive for p- rmpA2. Genetic fingerprinting by repetitive extragenic palindromic PCR showed four discrete clusters, demonstrating genotypic variability that loosely correlated with phenotype. Antimicrobial susceptibility testing revealed all isolates from stranded CSLs were susceptible to ceftiofur, indicating this antimicrobial agent is an appropriate choice for treatment of HMV K. pneumoniae infections in stranded CSLs. Our culture assay could reliably detect HMV K. pneumoniae from concentrations as low as 10 2 colony-forming units per milligram of feces. We identified the presence of HMV K. pneumoniae in both wild-caught and stranded CSLs from the US Pacific Coast and highlight the need for further studies to evaluate the potential impact of this pathogen on marine mammal health.

Chronic use of statins may have anti-inflammatory action, promoting immunomodulation and survival in patients with sepsis. This study aimed to analyze the effects of pretreatment with simvastatin in lethal sepsis induced by cecal ligation and puncture (CLP). Male Swiss mice received prophylactic treatment with simvastatin or pyrogen-free water orally in a single daily dose for 30 days. After this period, the CLP was performed. Naïve and Sham groups were performed as non-infected controls. Animal survival was monitored for 60 h after the CLP. Half of mice were euthanized after 12 h to analyze colony-forming units (CFUs); hematological parameters; production of IL-10, IL-12, IL-6, TNF-α, IFN-γ, and MCP-1; cell counts on peritoneum, bronchoalveolar lavage (BAL), bone marrow, spleen, and mesenteric lymph node; immunephenotyping of T cells and antigen presenting cells and production of hydrogen peroxide (H 2 O 2 ). Simvastatin induced an increase in survival and a decrease in the CFU count on peritoneum and on BAL cells number, especially lymphocytes. There was an increase in the platelets and lymphocytes number in the Simvastatin group when compared to the CLP group. Simvastatin induced a greater activation and proliferation of CD4+ T cells, as well as an increase in IL-6 and MCP-1 production, in chemotaxis to the peritoneum and in H 2 O 2 secretion at this site. These data suggest that simvastatin has an impact on the survival of animals, as well as immunomodulatory effects in sepsis induced by CLP in mice.

There is growing evidence that a significant share of global food is thrown away, with concomitant detrimental repercussions for sustainability. Reducing food waste is a key sustainability challenge for the food service industry. Despite the significance of this issue to the global foodservice industry, the link between innovation practices and food waste management has received limited attention in the academic literature. This paper uses innovation management and social constructionism to investigate interrelationships of food service provisions and innovations in waste management. It is based on the evaluation of food waste solutions and innovations that combine strategic dimensions of waste management with practice-driven initiatives, including incremental (processes and technologies) and radical innovations. The paper presents a range of waste management initiatives, showing that their implementation in the foodservice sector varies depending on management's beliefs, knowledge, goals and actions. The concepts discussed here could help practitioners to become more aware of the factors that drive the adoption of food waste innovations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against Plasmodium vivax exoerythrocytic forms. However, a robust in vitro culture system for P. vivax is still lacking. Thus, to study exoerythrocytic forms, researchers must have simultaneous access to fresh, temperature-controlled patient blood samples, as well as an anopheline mosquito colony. In addition, researchers must rely on native mosquito species to avoid introducing a potentially dangerous invasive species into a malaria-endemic region. Here, we report an in vitro culture system carried out on site in a malaria-endemic region for liver stage parasites of P. vivax sporozoites obtained from An. darlingi, the main malaria vector in the Americas. P. vivax sporozoites were obtained by dissection of salivary glands from infected An. darlingi mosquitoes and purified by Accudenz density gradient centrifugation. HC04 liver cells were exposed to P. vivax sporozoites and cultured up to 9 days. To overcome low P. vivax patient parasitemias, potentially lower mosquito vectorial capacity, and humid, nonsterile environmental conditions, a new antibiotic cocktail was included in tissue culture to prevent contamination. Culturing conditions supported exoerythrocytic (EEF) P. vivax liver stage growth up to 9 days and allowed for maturation into intrahepatocyte merosomes. Some of the identified small forms were resistant to atovaquone (1 μM) but sensitive to the phosphatidylinositol 4-kinase inhibitor, KDU691 (1 μM). This study reports a field-accessible EEF production process for drug discovery in a malaria-endemic site in which viable P. vivax sporozoites are used for drug studies using hepatocyte infection. Our data demonstrate that the development of meaningful, field-based resources for P. vivax liver stage drug screening and liver stage human malaria experimentation in the Amazon region is feasible.