Retrieval Induced Forgetting (RIF) demonstrates that retrieval of information can lead to forgetting of related information. The standard RIF paradigm involves studying a certain number of category-exemplar pairs; thereafter, half of the exemplars from half of the categories are retrieved. Finally, all studied pairs are recalled. RIF is revealed when unretrieved exemplars from the retrieved categories are more poorly recalled than exemplars from the unretrieved categories. One explanation for RIF asserts that inhibition prevents interference from the exemplars of the same category during the interpolated retrieval practice phase, which leads to forgetting of these items at final recall. An ongoing debate concerns whether this inhibition requires executive control or whether it is automatic. If inhibition in RIF involves executive control, then a task that will exhaust this limited capacity should reduce or eliminate the RIF effect. The effects of concurrent tasks during the retrieval practice phase have been shown to reduce or eliminate RIF, however, to our knowledge, the effects of prior tasks on RIF has not been investigated. In the present study, in one condition, we conducted an exhaustive inhibition task before the retrieval practice phase and compared this condition to the one in which the prior task was non-exhaustive. Results showed that the RIF effect was eliminated when the prior task was exhaustive. The results supported the executive control view for the inhibition mechanism behind RIF and further showed that exhaustion of the executive control capacity can impair inhibition in subsequent tasks.As COVID-19 halted traditional neuropsychological assessment due to infection risk, neuropsychologists considered alternative practice models. Cognitive stabilization intervention (CSI) via telehealth, was developed to stabilize cognition in advance of neuropsychological assessment. It incorporates elements of evidence-based treatments, including cognitive training, sleep training, and medication adherence training within a motivational interview framework. Two case vignettes are described. One vignette describes an elder man who received CSI to manage sleep difficulties, forgetfulness, and mood symptoms. Another vignette describes a woman who completed CSI following an autoimmune disorder episode to improve sleep, organization, and attention. The benefits and limitations of CSI are discussed.In the last three decades, the increased use of plastics is rapidly becoming a global environmental issue, resulting in growing landfills, pollution of surrounding atmosphere, and possible greenhouse effect. The automotive industry, as a major demander of plastic materials, is starting to take responsibility on sustainable actions. Japan, as the world’s top tier car manufacturing and dealing country, has been taking attempts to the proper dealings of used auto-plastic. This research aims to find out current situation of auto-plastic recycling industry after these attempts. Furthermore, this research compares pros and cons of each treatment and methods under treatment environmentally as well as economically from the point of recycling operators using life cycle assessment. Bumper is chosen as the target to represent auto-plastic because of their homogeneity of composition and relatively large share of weight among all auto-plastic parts. The result shows that material recycling amount is decreasing along with recent promotion demonstration. Top reason is that material recycling even reduces carbon emissions, costs far more than energy recovery, and that subsidy is given to energy recovery but not material recycling worsens the situation. Besides that, lack of cooperation between stakeholders on the demand of secondary plastic is impeding material recycling. Also, better scheme on how to separate auto-plastic and what kind would be separated should be noticed by the policymaker.Lacrimal gland tumors (LGTs) in dogs and cats are rare neoplasms that can affect either the nictitans (NLG) or the main lacrimal gland (MLG). A consistent classification scheme for canine and feline LGTs is lacking; however, the importance of a classification scheme for LGTs has been emphasized in the human literature, and an update to the World Health Organization (WHO) classification has recently been published. The aim of this study was to investigate the occurrence of different subtypes of canine and feline LGTs in accordance with the human WHO classification system. Epithelial LGTs (n = 46 tumors; 38 dogs, 8 cats) were reviewed and immunophenotyping for p63, CK14, SMA, calponin, CKAE1/AE3, and CK19 was performed. Consistent with previous literature reports, lacrimal carcinomas outnumbered adenomas in dogs and cats. Based on the WHO classification of human LGTs, the most common subtypes identified in dogs were pleomorphic, ductal, adenoid cystic, and epithelial-myoepithelial carcinoma. In cats, a lower number of subtypes was observed, and adenocarcinoma „not otherwise specified” (NOS) was the most frequent diagnosis. An uncommon case of feline epithelial-myoepithelial carcinoma was also observed. The application of the human WHO-LGT classification scheme to canine and feline tumors increased the diversity of diagnoses and allowed for the identification of numerous subtypes. Further studies to identify possible correlations between pathological subtypes and prognosis are warranted.Objectives Older adults are one of the most vulnerable age groups to the social distance measures imposed by the COVID-19 pandemic. This study aimed to assess factors associated with depressive and anxiety symptoms in Brazilian older adults during the pandemic.Method This cross-sectional online study assessed 380 older adults (over 60 years of age) living in Brazil, from 26th May 2020 to 29th June 2020. A self-reported questionnaire included sociodemographic data, lifestyle, health characteristics, and the COVID-19 related variables. The Geriatric Depression Scale (GDS) and the Geriatric Anxiety Inventory (GAI) were also applied. Data were analyzed via logistic regression models, using a hierarchical approach.Results The prevalence of depressive symptoms according to GDS was 28.7% (95% CI = 24.4%, 33.4%) and the prevalence of anxiety symptoms according to GAI was 26.1% (95% CI = 21.9%, 30.7%). Physically inactive older adults, the ones who were in social isolation for more days, feel much vulnerable to contracting COVID-19, and never or almost never receive support from family/friends were more likely to have depressive symptoms. Being female, physically inactive or physically active 1-3 times/week, feel very vulnerable to contracting COVID-19 and never or almost never receive support from family/friends were associated with the anxiety symptoms.Conclusion A high prevalence of depressive and anxious symptoms was identified in Brazilian older adults. The data can help in planning interventions aimed at older adults, also including their families, health professionals, and the whole society.

Women experiencing homelessness are at increased risk of cervical cancer and have disproportionately low Pap screening behaviors compared to the general population. Prevalence of Pap refusals and multiple kinds of trauma, specifically sexual trauma, are high among homeless women. This qualitative study explored how trauma affects Pap screening experiences, behaviors, and provider practices in the context of homelessness.

We conducted 29 in-depth interviews with patients and providers from multiple sites of a Federally Qualified Health Center as part of a study on barriers and facilitators to cervical cancer screening among urban women experiencing homelessness. The Health Belief Model and trauma-informed frameworks guided the analysis.

Trauma histories were common among the 18 patients we interviewed. Many women also had strong physical and psychological reactions to screening, which influenced current behaviors and future intentions. Although most women had screened at least once in their lifetime, manproach to cervical cancer screening may help address complex barriers among women experiencing homelessness, with histories of sexual trauma, or others who avoid, delay, or refuse the exam.

The aim of this study was to investigate the relationship between the C-reactive protein/albumin ratio and the prognosis of hypertensive COVID-19 patients.

It was designed as a single center retrospective study. PCR positive COVID-19 patients who were followed up in the intensive care unit (ICU) and received antihypertensive treatment were included in the study. The patients were divided into two groups as survivor and non-survivor. C-reactive protein/albumin (CAR) ratios of the patients were compared. The cut-off value was determined as a mortality predictor. The effect of CAR on mortality was evaluated using Logistic Regression analysis.

281 patients were included in the study. Groups consisted of 135 (non-survivor) and 146 (survivor) patients. CAR was significantly higher in the non-survivor group (p<0.001). The area under the ROC curve for CAR for mortality was 0.807, with sensitivity of 0.71 and specificity of 0.71. The cut-off value for CAR was calculated as 56.62. In logistic regression analysis, CAR increases mortality 4.9 times compared to the cut-off value.

CAR is a powerful and independent prognostic marker for predicting mortality and disease progression in hypertensive COVID-19 patients.

CAR is a powerful and independent prognostic marker for predicting mortality and disease progression in hypertensive COVID-19 patients.Microbial infections caused by sessile microorganisms are known to be a more challenging issue than infections caused by the same microorganisms in the planktonic state. Pseudomonas aeruginosa is an opportunistic pathogen and biofilm-forming agent. This species presents intense cellular communication mediated by signaling molecules. This process is known as quorum sensing (QS) and induces the transcription of specific genes that favors cell density growth and three-dimensional bacterial grouping. In this context, the discovery of compounds capable of inhibiting the action of the QS signaling molecules seems to be a promising strategy against biofilms. This work aimed to evaluate the anti-biofilm action and the in vitro safety profile of a sulfamethoxazole-Ag complex. The results obtained indicate potential anti-biofilm activity through QS inhibition. In silico tests showed that the compound acts on the las and pqs systems, which are the main regulators of biofilm formation in P. aeruginosa. Additionally, the molecule proved to be safe for human peripheral blood mononuclear cells.A De Garengeot hernia is a rare type of femoral hernia that involves a vermiform appendix within a femoral hernia sac. Because of the rarity of this disease, a standard surgical procedure has not been established, and most cases are diagnosed intraoperatively. Preoperative diagnosis of a De Garengeot hernia is quite difficult. Computed tomography is the most sensitive and specific technique among the available imaging tests for preoperative diagnosis of a De Garengeot hernia. Although a standard surgical procedure is lacking, prompt surgery has become the consensus. The most common procedure is the open anterior approach; this allows exploration of the hernia sac and rapid treatment of its contents, routine appendectomy through a single incision, and preperitoneal repair of the femoral hernia.We examined the moderating role of social capital (SC) in the association of socioeconomic status (SES) and health literacy (HL) with oral health (OH) status and the intentions to use OH services (IUOHS) among older Ghanaians. Data were derived from a cross-sectional survey (n = 522) and analyzed using ordinal and binary logistic regressions. Bridging SC moderated the relationship between HL and oral health status (B = 0. 0.117, p less then .05) and the association of SES with IUOHS (adjusted odds ratio [AOR] = 1.144; 95% confidence interval [CI] = [1.027, 3.599]). Trust modified the association between HL and IUOHS (AOR = 1.051; 95% CI = [1.014, 3.789]). Bonding SC moderated the association between SES and oral health status (B = 0.180, p less then .05). However, bonding SC negatively modified the association between SES and IUOHS (AOR = 0.961; 95% CI = [0.727, 0.997]). Cognitive and structural SC modify the associations of SES and HL with OH and IUOHS.Biofilms are an important medical burden, notably for patients with orthopaedic device-related infections. When polymicrobial, these infections are more lethal and recalcitrant. Inter-kingdom biofilm infections are poorly understood and challenging to treat. Here, an in vitro three-species model including Staphylococcus aureus, Escherichia coli and Candida albicans was developed, to represent part of the diversity observed in orthopaedic infections or other clinical contexts. The importance of fungal hyphae for biofilm formation and virulence factor expression was explored. Two protocols were set up, allowing, or not, for hyphal formation. Culturable cells and biomass were characterised in both models, and biofilms were imaged in bright-field, confocal and electron microscopes. The expression of genes related to virulence, adhesion, exopolysaccharide synthesis and stress response was analysed in early-stage and mature biofilms. It was found that biofilms enriched in hyphae had larger biomass and showed higher expression levels of genes related to bacterial virulence or exopolysaccharides synthesis.While religiosity is usually associated with lower death anxiety, holding doubts about one’s faith are associated with higher death anxiety. Using longitudinal data from the Religion, Aging, and Health Study (2001-2004), this study examines within-individual changes in religious doubt and death anxiety. Results from lagged dependent variable models suggest that compared to older adults who did not experience any doubt about their faith, those holding consistently high doubt or increasing or decreasing doubt reported greater death anxiety. Lingering religious doubt was associated with higher death anxiety among weekly religious attenders. Taken together, our findings suggest that being more assured in one’s faith and spiritual understanding may lead to a more peaceful experience when confronting thoughts about one’s own mortality, especially for older adults holding a stronger religious identity. We situate our findings within the literature on the „dark side” of religion and well-being in later life.This study examined cultural differences in advance care planning (ACP) and various strategies that social workers use to initiate conversations on ACP. We conducted qualitative interviews with 12 social workers in South Korea and the US and a thematic content analysis of the transcribed data. Our findings show that different cultural norms and generational viewpoints surrounding death and health-related decision-making influence how people prepare for end-of-life care (EOLC). Whereas principles of self-determination and autonomy guide ACP practices in the US, decisions regarding EOLC are more often made in consultation with family members in Korean and Korean-American communities. Nevertheless, social workers in both countries identified relationship-building, empowerment, and individualized approaches as common strategies in initiating discussions on ACP.

We examined the association between multimorbidity and social participation and whether purpose in life and life satisfaction moderate this relationship.

Participants were 12,825 Health and Retirement Study adults. We used multiple linear regression to examine the association between a cumulative-updated multimorbidity-weighted index (MWI) and social participation.

Among adults with average purpose in life or life satisfaction, MWI was associated with lower social participation. For those with above average purpose in life, each 1-point increase in MWI was associated with a 0.11-point (95% confidence interval [CI] [0.07, 0.14]) better social participation score. Participants with above average life satisfaction experienced a 0.04-point (95% CI [0.02, 0.07]) better social participation score with each 1-point increase in MWI.

Multimorbidity was associated with worse social participation, but this was reversed by above average purpose in life and life satisfaction. Interventions that improve well-being should be assessed to enhance social participation among older adults with any degree of multimorbidity.

Multimorbidity was associated with worse social participation, but this was reversed by above average purpose in life and life satisfaction. Interventions that improve well-being should be assessed to enhance social participation among older adults with any degree of multimorbidity.The Colombian armed conflict has disproportionately affected minorities, especially afro-Colombian communities. However, there is a lack of evidence about mental health of victims. This study aims to describe the prevalence of mental illness and its associated factors in Afro-descendant violence survivors in Buenaventura and Quibdó, Colombia. A cross-sectional study was carried out using data from a previous trial which aimed to reduce mental health symptoms (ClinicalTrials.gov NCT01856673). Data of 710 adults identified through a snowball sampling technique was analysed. Diagnoses of depression, anxiety, post-traumatic stress disorder (PTSD), and dysfunction were established using adapted versions of the Hopkins Symptoms Checklist and the Harvard Trauma Questionnaire, plus variables identified in a qualitative study. Multivariate regressions were used to identify associated factors with these diagnoses. The prevalence of depression, anxiety and PTSD in both cities was 26.62% (95% confidence interval [95%CI] 20.30;23.89), 36.53% (95%CI 30.63;42.36), and 39.15% (95%CI 33.36;44.83), respectively. Being married and having registered with the government as victim of the conflict were found to be protective factors for depression and PTSD, respectively. Psychological trauma, unemployment, and traumatic experiences, amongst others, were found as risk factors. The Colombian armed conflict, plus disparities and social exclusion, may be associated with mental health morbidity.Most bacteria employ a two-step indirect tRNA aminoacylation pathway for the synthesis of aminoacylated tRNAGln and tRNAAsn. The heterotrimeric enzyme GatCAB performs a critical amidotransferase reaction in the second step of this pathway. We have previously demonstrated in mycobacteria that this two-step pathway is error prone and translational errors contribute to adaptive phenotypes such as antibiotic tolerance. Furthermore, we identified clinical isolates of the globally important pathogen Mycobacterium tuberculosis with partial loss-of-function mutations in gatA, and demonstrated that these mutations result in high, specific rates of translational error and increased rifampin tolerance. However, the mechanisms by which these clinically derived mutations in gatA impact GatCAB function were unknown. Here, we describe biochemical and biophysical characterization of M. tuberculosis GatCAB, containing either wild-type gatA or one of two gatA mutants from clinical strains. We show that these mutations have mine the critical enzyme of the Mycobacterium tuberculosis indirect pathway, GatCAB, as well as two mutant enzymes previously identified from clinical isolates that were associated with increased mistranslation. We show that the mutants dysregulate the pathway via destabilizing the enzyme complex. Importantly, increasing stability improves translational fidelity in both wild-type and mutant bacteria, demonstrating a mechanism by which mycobacteria may tune mistranslation rates.As access to high-throughput sequencing technology has increased, the bottleneck in biomedical research has shifted from data generation to data analysis. Here, we describe a modular and extensible framework for didactic instruction in bioinformatics using publicly available RNA sequencing data sets from infectious disease studies, with a focus on host-parasite interactions. We highlight lessons learned from adapting this course for virtual learners during the coronavirus disease 2019 (COVID-19) pandemic.Ebola virus (EBOV) VP24 protein is a nucleocapsid-associated protein that inhibits interferon (IFN) gene expression and counteracts the IFN-mediated antiviral response, preventing nuclear import of signal transducer and activator of transcription 1 (STAT1). Proteomic studies to identify additional EBOV VP24 partners have pointed to the nuclear membrane component emerin as a potential element of the VP24 cellular interactome. Here, we have further studied this interaction and its impact on cell biology. We demonstrate that VP24 interacts with emerin but also with other components of the inner nuclear membrane, such as lamin A/C and lamin B. We also show that VP24 diminishes the interaction between emerin and lamin A/C and compromises the integrity of the nuclear membrane. This disruption is associated with nuclear morphological abnormalities, activation of a DNA damage response, the phosphorylation of extracellular signal-regulated kinase (ERK), and the induction of interferon-stimulated gene 15 (ISG15). Interl abnormalities, activation of a DNA damage response, the phosphorylation of extracellular signal-regulated kinase (ERK), and the induction of interferon-stimulated gene 15 (ISG15). Interestingly, VP24 also promotes the cytoplasmic translocation and downmodulation of barrier-to-autointegration factor (BAF), leading to repression of the BAF-regulated CSF1 gene. Finally, we show that EBOV infection also results in the activation of pathways associated with nuclear envelope damage, consistent with our observations in cells expressing VP24. These results reveal novel activities of EBOV VP24 protein, resulting in a cell phenotype similar to that of most laminopathies, with potential impact on EBOV replication.Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID50], 1200 to 1850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc)4 spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. IMPORTANCE The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nnHTN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an ongoing global public crisis. Although viral RNA modification has been reported based on the transcriptome architecture, the types and functions of RNA modification are still unknown. In this study, we evaluated the roles of RNA N6-methyladenosine (m6A) modification in SARS-CoV-2. Our methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and Nanopore direct RNA sequencing (DRS) analysis showed that SARS-CoV-2 RNA contained m6A modification. Moreover, SARS-CoV-2 infection not only increased the expression of methyltransferase-like 3 (METTL3) but also altered its distribution. Modification of METTL3 expression by short hairpin RNA or plasmid transfection for knockdown or overexpression, respectively, affected viral replication. Furthermore, the viral key protein RdRp interacted with METTL3, and METTL3 was distributed in both the nucleus and cytoplasm in the presence of RdRp. RdRp appeared to moy the distribution but also the posttranslational modification of METTL3. Our study provided evidence that host m6A components interacted with viral proteins to modulate viral replication.Prime-boost vaccinations of humans with different H5 strains have generated broadly protective antibody levels. However, the effect of an individual’s H5 exposure history on antibody responses to subsequent H5 vaccination is poorly understood. To investigate this, we analyzed the IgG responses to H5 influenza A/Indonesia/5/2005 (Ind05) virus vaccination in three cohorts (i) a doubly primed group that had received two H5 virus vaccinations, namely, against influenza A/Vietnam/203/2004 (Vie04) virus 5 years prior and A/Hong Kong/156/1997 (HK97) 11 years prior to the Ind05 vaccination; (ii) a singly primed group that had received a vaccination against Vie04 virus 5 years prior to the Ind05 vaccination; and (iii) an H5-naive group that received two doses of the Ind05 vaccine 28 days apart. Hemagglutinin (HA)-reactive IgG levels were estimated by a multiplex assay against an HA panel that included 21 H5 strains and 9 other strains representing the H1, H3, H7, and H9 subtypes. Relative HA antibody landscapes were gons between antigenically similar influenza strains. To assist in such analyses, the influenza „antibody landscape” method has been used to analyze and visualize the relationship of antibody-mediated immunity to antigenic distances between influenza strains. In this study, we describe a „relative antibody landscape” method that calculates the antigenic distance between the vaccine influenza strain and other H5 strains and uses this relative antigenic distance to plot the anti-H5 IgG levels postvaccination. This new method quantitatively estimates and visualizes the correlation between the humoral response to a particular influenza strain and the antigenic distance from other strains. Our findings demonstrate the effect of a subject’s H5 exposure history on H5 vaccine responses quantified by the relative antibody landscape method.Candida auris is an emerging fungal pathogen that is thermotolerant and often resistant to standard antifungal treatments. To trace its evolutionary history, the Sanyal lab conducted a comparative genomic study focusing on the positions of centromeres in C. auris and eight other species from the Clavispora/Candida clade of yeasts (A. Narayanan et al., mBio 12e00905-12, 2021). These researchers discovered that these species possess small regional centromeres that are highly stable, having remained in the same syntenic positions for over 100 million years. This stability is remarkable, given the lack of a conserved sequence underlying the centromeres and the relative ease with which other yeasts form neocentromeres. Thus, this work provides an opportunity to investigate the molecular mechanism of centromere inheritance in a genetically tractable and medically important yeast.Pigeon pea, a legume crop native to India, is the primary source of protein for more than a billion people in developing countries. The plant can form symbioses with N2-fixing bacteria; however, reports of poor crop nodulation in agricultural soils abound. We report here a study of the bacterial community associated with pigeon pea, with a special focus on the symbiont population in different soils and vegetative and non-vegetative plant growth. Location with respect to the plant roots was determined to be the main factor controlling the bacterial community, followed by developmental stage and soil type. Plant genotype plays only a minor role. Pigeon pea roots have a reduced microbial diversity compared to the surrounding soil and select for Proteobacteria, especially for Rhizobium spp., during vegetative growth. While Bradyrhizobium, a native symbiont of pigeon pea, can be found associating with roots, its presence is dependent on plant variety and soil conditions. A combination of 16S rRNA gene amplicon sure Indian origin of this plant, pigeon pea nodulates only poorly in native soils. While there have been multiple attempts to select the best N2-fixing symbionts, there are no reliable strains available for geographically widespread use. In this article, using 16S rRNA gene amplicon, culturomics, and plant co-inoculation assays, we show that the native pigeon pea symbionts such as Bradyrhizobium spp. are able to nodulate their host, despite being poor competitors for colonizing roots. Hence, in this system, the establishment of effective symbiosis seems decoupled from microbial competition on plant roots. Thus, the effort of finding suitable symbionts should focus not only on their N2-fixing potential but also on their ability to colonize. Increasing pigeon pea yield is a low-hanging fruit to reduce world hunger and degradation of the environment through the overuse of synthetic fertilizers.Since its emergence in 2019, circulating populations of the new coronavirus (CoV) continuously acquired genetic diversity. At the end of 2020, a variant named 20I/501Y.V1 (lineage B.1.1.7) emerged and replaced other circulating strains in several regions. This phenomenon has been poorly associated with biological evidence that this variant and the original strain exhibit different phenotypic characteristics. Here, we analyze the replication ability of this new variant in different cellular models using for comparison an ancestral D614G European strain (lineage B1). Results from comparative replication kinetics experiments in vitro and in a human reconstituted bronchial epithelium showed no difference. However, when both viruses were put in competition in human reconstituted bronchial epithelium, the 20I/501Y.V1 variant outcompeted the ancestral strain. All together, these findings demonstrate that this new variant replicates more efficiently and may contribute to a better understanding of the progressive replacement of circulating strains by the severe acute respiratory CoV-2 (SARS-CoV-2) 20I/501Y.V1 variant. IMPORTANCE The emergence of several SARS-CoV-2 variants raised numerous questions concerning the future course of the pandemic. We are currently observing a replacement of the circulating viruses by the variant from the United Kingdom known as 20I/501Y.V1, from the B.1.1.7 lineage, but there is little biological evidence that this new variant exhibits a different phenotype. In the present study, we used different cellular models to assess the replication ability of the 20I/501Y.V1 variant. Our results showed that this variant replicates more efficiently in human reconstituted bronchial epithelium, which may explain why it spreads so rapidly in human populations.Mycobacterium tuberculosis (Mtb) causes one of the deadliest infectious diseases worldwide. Upon infection, Mtb is phagocytosed by macrophages and uses its virulence-associated ESX-1 secretion system to modulate the host cell. We showed previously that the ESX-1 secretion system perturbs the Mtb-containing phagosome, and a population (∼30%) of intracellular Mtb is tagged with ubiquitin and targeted to selective autophagy. However, our understanding of how macrophages sense and respond to damaged Mtb-containing phagosomes remains incomplete. Here, we demonstrate that several cytosolic glycan-binding proteins called galectins recognize Mtb-containing phagosomes; in macrophage cell lines and in primary macrophages, galectin-3, -8, and -9 are all recruited to the same Mtb population that colocalizes with selective autophagy markers (ubiquitin, p62, and LC3). To test whether galectins are required for controlling Mtb replication in macrophages, we generated CRISPR/Cas9 knockouts and found that galectin-8-/- and gaes are the first line of defense against Mtb infection and are typically incredibly efficient at destroying intracellular pathogens, but Mtb has evolved to survive and replicate in this harsh environment. Previous work has found that a portion of intracellular Mtb bacilli damage their phagosomes, leaving them vulnerable to detection by the host and delivery to an antibacterial pathway called selective autophagy. Here, we show that in macrophages, galectin-8 recognizes damaged Mtb-containing phagosomes and targets Mtb to selective autophagy; we found that galectin-8, unlike other highly similar and closely related galectins, is required for targeting and controlling Mtb in macrophages. The specific role for galectin-8 appears to stem from its interaction with TAX1BP1, a selective autophagy adapter protein. Interestingly, overexpressing galectin-8 helps macrophages target and control Mtb, highlighting the importance of galectin-8 in the innate immune response to Mtb.Bloodstream infections (BSI) are a major public health burden due to high mortality rates and the cost of treatment. The impact of BSI is further compounded by a rise in antibiotic resistance among Gram-negative species associated with these infections. Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Enterobacter hormaechei, Citrobacter freundii, and Acinetobacter baumannii are all common causes of BSI, which can be recapitulated in a murine model. The objective of this study was to characterize infection kinetics and bacterial replication rates during bacteremia for these six pathogens to gain a better understanding of bacterial physiology during infection. Temporal observations of bacterial burdens of the tested species demonstrated varied abilities to establish colonization in the spleen, liver, or kidney. K. pneumoniae and S. marcescens expanded rapidly in the liver and kidney, respectively. Other organisms, such as C. freundii and E. hormaechei, were steadily cleared from all three target oajor organs is likely determined by a balance between replication rates and the ability of the host to clear bacteria. We selected a cohort of six species from three families that represent common causative agents of bloodstream infections in humans and determined their replication rates in a murine bacteremia model. We found that the bacteria grow rapidly in the spleen, demonstrating that they can obtain the necessary nutrients for growth in this environment. However, the overall number of bacteria decreased in most cases, suggesting that killing of bacteria outpaces their growth. Through a better understanding of how bacteria replicate during bloodstream infections, we aim to gain insight into future means of combating these infections.The function of the mammalian orthoreovirus (reovirus) σNS nonstructural protein is enigmatic. σNS is an RNA-binding protein that forms oligomers and enhances the stability of bound RNAs, but the mechanisms by which it contributes to reovirus replication are unknown. To determine the function of σNS-RNA binding in reovirus replication, we engineered σNS mutants deficient in RNA-binding capacity. We found that alanine substitutions of positively charged residues in a predicted RNA-binding domain decrease RNA-dependent oligomerization. To define steps in reovirus replication facilitated by the RNA-binding property of σNS, we established a complementation system in which wild-type or mutant forms of σNS could be tested for the capacity to overcome inhibition of σNS expression. Mutations in σNS that disrupt RNA binding also diminish viral replication and σNS distribution to viral factories. Moreover, viral mRNAs only incorporate into viral factories or factory-like structures (formed following expression of nonsthanisms of viral factory formation will help identify new targets for antiviral therapeutics that disrupt assembly of these structures and inform the use of nonpathogenic viruses for biotechnological applications.Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat deposition in the liver unrelated to alcohol consumption, is highly prevalent worldwide. However, effective therapeutic agents approved for NAFLD treatment are lacking. An ileal bile acid transporter inhibitor (IBATi), which represents a new mode of treatment of chronic idiopathic constipation, leads to increased delivery of bile acids to the colon. We investigated the effect of IBATi against NAFLD through modification of the gut microbiota in mice. IBATi treatment significantly suppressed body weight gain, liver dysfunction, and serum low-density lipoprotein levels and significantly decreased NAFLD activity scores in high-fat diet (HFD) mice. Treatment with IBATi ameliorated the decreased hepatic cholesterol 7-a-monooxygenase (Cyp7a1) and increased ileal fibroblast growth factor 15 (Fgf15) mRNA expression in HFD mice. Further, IBATi treatment changed the α-diversity in the gut microbiota reduced by HFD, which was analyzed in feces usingudy investigated the influence of the gut microbiota and the effect of an IBATi on NAFLD using a murine model. Treatment with IBATi significantly improved NAFLD in HFD mice. Further, fecal microbiome transplantation using stool from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. Our study makes a significant contribution to the literature because the study findings suggest a potential treatment strategy for NAFLD patients by ameliorating gut microbiota dysbiosis.Despite our extensive knowledge of the genetic regulation of heat shock proteins (HSPs), the evolutionary routes that allow bacteria to adaptively tune their HSP levels and corresponding proteostatic robustness have been explored less. In this report, directed evolution experiments using the Escherichia coli model system unexpectedly revealed that seemingly random single mutations in its tnaA gene can confer significant heat resistance. Closer examination, however, indicated that these mutations create folding-deficient and aggregation-prone TnaA variants that in turn can endogenously and preemptively trigger HSP expression to cause heat resistance. These findings, importantly, demonstrate that even erosive mutations with disruptive effects on protein structure and functionality can still yield true gain-of-function alleles with a selective advantage in adaptive evolution.The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 5 acyl sarcosines and 9 sarcosinate salts as used in cosmetics; all of these ingredients are reported to function in cosmetics as hair conditioning agents and most also can function as surfactants-cleansing agents. The ingredients reviewed in this assessment are composed of an amide comprising a fatty acyl residue and sarcosine and are either free acids or simple salts thereof. The Panel relied on relevant new data, including concentration of use, and considered data from the previous Panel report, such as the reaction of sarcosine with oxidizing materials possibly resulting in nitrosation and the formation of N-nitrososarcosine. The Panel concluded that these ingredients are safe as used in cosmetics when formulated to be non-irritating, but these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed.

Diabetes technologies, such as insulin pumps and continuous glucose monitors (CGM), have been associated with improved glycemic control and increased quality of life for young people with type 1 diabetes (T1D); however, few young people use these devices, especially those from minority ethnic groups. Current literature predominantly focuses on white patients with private insurance and does not report experiences of diverse pediatric patients with limited resources.

To explore potential differences between Latinx and non-Latinx patients, English- and Spanish-speaking young people with T1D (

 = 173, ages 11-25 years) were surveyed to assess attitudes about and barriers to diabetes technologies using the Technology Use Attitudes and Barriers to Device Use questionnaires.

Both English- and Spanish-speaking participants who identified as Latinx were more likely to have public insurance (

 = .0001). English-speaking Latinx participants reported higher Hemoglobin A1c values (

 = .003), less CGM use (

 = .0verse ethnic and language backgrounds.

Biofortified staples have been promoted widely in sub-Saharan Africa to combat micronutrient deficiencies. Contemporary projects are increasingly using elementary schools to target households with these foods.

This study assessed the effects of integrated nutrition education approaches, targeting preschoolers and their caregivers, on retention of orange-fleshed sweetpotato (OFSP) on farms in the second season after lapse of free vine dissemination initiatives.

Rural farming households, with preschoolers and no prior engagement with OFSP, were targeted. A multistage sample of 431 preschooler-caregiver pairs was recruited for a cluster-randomized controlled trial. After issuing routine OFSP promotion activities, 15 village-level clusters of the pairs were randomized into 1 control group (3 villages) and 3 treatment arms (4 villages each) for the interventions. Baseline and follow-up household-level survey data were collected from the caregivers. The interventions included (1) OFSP-branded exercise books, posters, and a poem to preschoolers only; (2) OFSP-oriented mobile phone-mediated text messages to caregivers only; and (3) both 1 and 2 provided to individual households concurrently. Interventions 1 and 2 were single-channeled, while 3 was multichanneled. We estimated the intention-to-treat (ITT) and treatment-on-the-treated (TOT) effects using a binary logit model and a special regressor method, respectively.

Only the multichanneled nutrition education approach had significant effects (ITT = 0.167, P = .001; TOT = .243, P = .007) on the caregivers’ likelihood to retain OFSP on their farms.

The finding implies that multichanneled agriculture-nutrition education interventions through Early Childhood Development institutions can be effective in ensuring sustainable adoption of OFSP.

The finding implies that multichanneled agriculture-nutrition education interventions through Early Childhood Development institutions can be effective in ensuring sustainable adoption of OFSP.Chimeric antigen receptor (CAR) T cell therapy mediates unprecedented benefit in certain leukemias and lymphomas, but has yet to achieve similar success in combating solid tumors. A substantial body of work indicates that the accumulation of adenosine in the solid tumor microenvironment (TME) plays a crucial role in abrogating immunotherapies. Adenosine deaminase 1 (ADA) catabolizes adenosine into inosine and is indispensable for a functional immune system. We have, for the first time, engineered CAR T cells to overexpress ADA. To potentially improve the pharmacokinetic profile of ADA, we have modified the overexpressed ADA in two ways, through the incorporation of a (1) albumin-binding domain or (2) collagen-binding domain. ADA and modified ADA were successfully expressed by CAR T cells and augmented CAR T cell exhaustion resistance. In a preclinical engineered ovarian carcinoma xenograft model, ADA and collagen-binding ADA overexpression significantly enhanced CAR T cell expansion, tumor tissue infiltration, tumor growth control, and overall survival, whereas albumin-binding ADA overexpression did not. Furthermore, in a syngeneic colon cancer solid tumor model, the overexpression of mouse ADA by cancer cells significantly reduced tumor burden and remodeled the TME to favor antitumor immunity. The overexpression of ADA for enhanced cell therapy is a safe, straightforward, reproducible genetic modification that can be utilized in current CAR T cell constructs to result in an armored CAR T product with superior therapeutic potential.Background Some papillary thyroid microcarcinomas (PTMCs) may progress with tumor enlargement or development of new lymph node (LN) metastasis during active surveillance (AS). This study evaluated the relevant predictors of disease progression, especially new cervical LN metastasis. Methods This was a long-term follow-up study conducted using a previous multicenter cohort of AS in Korea. After excluding 54 (14.2%) patients with a short follow-up duration, 326 PTMC patients were evaluated for tumor kinetics, including changes in tumor volume (TV) and TV doubling time (TVDT). Results During a median follow-up duration of 4.9 years, 17 (5.2%, 95% confidence intervals [CI] 2.7-7.6%) patients showed a maximal diameter increase of ≥3 mm after a median of 4.0 years follow-up, while 9 (2.8%, CI 1.0-4.5%) developed new LN metastasis after a median of 2.2 years follow-up. New cervical LN metastasis occurred exclusively of a maximal diameter increase of ≥3 mm. The prevalence of new development of LN metastasis was higher in patients with TVDT less then 5 years (7.4%) than in those with TV ≥50% (3.2%). Furthermore, only TVDT less then 5 years was significantly associated with LN metastasis (p = 0.002). In univariate and multivariate analyses, TVDT less then 5 years was an independent risk factor for disease progression with respect to new development of LN metastasis (hazard ratio [HR] = 6.51, CI 1.73-24.50; p = 0.002) and tumor enlargement (HR = 20.89, CI 5.78-75.48; p  less then  0.001). Finally, 86 (22.6%) patients underwent delayed surgery, and the most common reason was patient anxiety. Conclusions TVDT less then 5 years is a predictor of disease progression during AS in terms of new LN metastasis development as well as tumor enlargement. Determination of TVDT in the early phase of AS could help in predicting disease progression, tailoring follow-up intensity of AS and in determining if early surgical intervention is needed.The soluble form of the suppression of tumorigenicity-2 (sST2) is a biomarker for risk classification and prognosis of heart failure, and its production and secretion in the alveolar epithelium are significantly correlated with the inflammation-inducing in pulmonary diseases. However, the predictive value of sST2 in pulmonary disease had not been widely studied. This study investigated the potential value in prognosis and risk classification of sST2 in patients with community-acquired pneumonia. Clinical data of ninety-three CAP inpatients were retrieved and their sST2 and other clinical indices were studied. Cox regression models were constructed to probe the sST2’s predictive value for patients’ restoring clinical stability and its additive effect on pneumonia severity index and CURB-65 scores. Patients who did not reach clinical stability within the defined time (30 days from hospitalization) have had significantly higher levels of sST2 at admission (P  less then  0.05). In univariate and multivariate Cox regression analysis, a high sST2 level (≥72.8 ng/mL) was an independent reverse predictor of clinical stability (P  less then  0.05). The Cox regression model combined with sST2 and CURB-65 (AUC 0.96) provided a more accurate risk classification than CURB-65 (AUC0.89) alone (NRI 1.18, IDI 0.16, P  less then  0.05). The Cox regression model combined with sST2 and pneumonia severity index (AUC 0.96) also provided a more accurate risk classification than pneumonia severity index (AUC0.93) alone (NRI 0.06; IDI 0.06, P  less then  0.05). sST2 at admission can be used as an independent early prognostic indicator for CAP patients. Moreover, it can improve the predictive power of CURB-65 and pneumonia severity index score.Aim This study examines the effect of guideline-directed medical therapy (GDMT) on healthcare utilization in patients with heart failure with reduced ejection fraction from Optum® Integrated File from 1 January 2007 to 30 June 2020. Materials & methods Patients with both a beta blocker and either an ACE inhibitor (ACE-I), angiotensin receptor blocker (ARB) or angiotensin receptor neprilysin inhibitor were assigned to the GDMT cohort. All others were not on GDMT. Results Estimated annual all cause hospitalizations and emergency department visits per 100 patients was 29% (80 vs 62 patients) and 26% higher (54 vs 43 patients; p less then 0.0001) and annualized hospital days were longer (1.88 vs 1.64; p = 0.0020) for patients not on GDMT. Conclusion In a real-world population, heart failure with reduced ejection fraction, patients not optimally managed on GDMT had higher annualized healthcare utilization when compared with patients on GDMT.[Figure see text].[Figure see text].Preeclampsia, characterized by the onset of hypertension with significant proteinuria after 20 weeks’ gestation, is one of the leading causes of maternal and perinatal morbidity and mortality. Prophylactic low-dose aspirin treatment reduces the rate of preterm preeclampsia in high-risk women, but a significant proportion still develops preeclampsia. The mechanism of the prophylactic response is unknown. Here, the untargeted metabolomics analysis of 144 plasma samples from high-risk pregnant women before (11-13 weeks) and after (20-23 weeks) aspirin/placebo treatment elucidated metabolic effects of aspirin and metabolic differences potentially associated with the variation of the treatment response. We demonstrated that aspirin treatment resulted in a strong drug-associated metabolomics signature and that the preeclamptic or nonpreeclamptic outcome in response to treatment was significantly associated with the level of internal aspirin exposure ascertained from metabolomics data (t test, P=0.0083). Comparing women with and without preeclampsia after aspirin treatment, differences in 73 metabolites were detected, some of which involve pathways whose regulation is of importance in pregnancy and placental functions, such as glycerophospholipids metabolism, polyunsaturated fatty acid metabolism, and steroid hormone biosynthesis. To further examine the hypothesis that aspirin delays gestational age advancement and thus the onset of preeclampsia, we constructed a metabolic clock on pretreatment and placebo-treated samples that estimated gestational age with high accuracy and found that aspirin significantly decelerated metabolic gestational age by 1.27 weeks (95% CI, 0.66-1.88 weeks), and partially reversed one-fourth of the metabolites changed over gestational age advancement, suggesting that aspirin treatment slowed down the metabolic clock of gestation.