Towards Enhancing Low Vision Usability of Data Charts on Smartphones.

The importance of data charts is self-evident, given their ability to express complex data in a simple format that facilitates quick and easy comparisons, analysis, and consumption. However, the inherent visual nature of the charts creates barriers for people with visual impairments to reap the associated benefts to the same extent as their sighted peers. While extant research has predominantly focused on understanding and addressing these barriers for blind screen reader users, the needs of low-vision screen magnifer users have been largely overlooked. In an interview study, almost all low-vision participants stated that it was challenging to interact with data charts on small screen devices such as smartphones and tablets, even though they could technically "see" the chart content. They ascribed these challenges mainly to the magnifcation-induced loss of visual context that connected data points with each other and also with chart annotations, e.g., axis values. In this paper, we present a method that addresses this problem by automatically transforming charts that are typically non-interactive images into personalizable interactive charts which allow selective viewing of desired data points and preserve visual context as much as possible under screen enlargement. We evaluated our method in a usability study with 26 low-vision participants, who all performed a set of representative chart-related tasks under different study conditions. In the study, we observed that our method signifcantly improved the usability of charts over both the status quo screen magnifer and a state-of-the-art space compaction-based solution.

Does Religion Mitigate the Effect of Neighborhood Disorder on Cognitive Decline?: Evidence from A National Longitudinal Study of US Older Adults.

OBJECTIVES: This paper examines whether perceived neighborhood disorder is associated with trajectories of cognitive functioning and whether religion mitigates this association among US older adults. METHODS: Data are drawn from the 2006-2016 Health and Retirement Study (N=12,669). Religious belief and religious attendance are assessed as potential moderators. Growth curve models are used to estimate trajectories of cognitive functioning over time. RESULTS: We find that perceived neighborhood disorder is associated with lower cognitive functioning at baseline; however, religious belief mitigates the impact of perceived neighborhood disorder on the level of cognitive functioning. For instance, individuals with high religious belief, despite experiencing high perceived neighborhood disorder, show better cognitive functioning at baseline compared to those with high disorder but low belief. While frequent religious attendance is associated with higher cognitive functioning at baseline, it does not moderate the impact of perceived neighborhood disorder on cognitive functioning. DISCUSSION: This study underscores the protective role of religious belief against cognitive aging in the face of neighborhood disorder, suggesting that personal faith may provide a cognitive reserve or coping mechanism. Our findings also imply that the absence of religious belief, combined with high perceived neighborhood disorder, may produce a compounded negative impact on cognitive aging.

Gut Microbiota Defines Functional Direction of Colonic Regulatory T Cells with Unique TCR Repertoires.

Intestinal microbiota and selected strains of commensal bacteria influence regulatory T (Treg) cell functionality in the colon. Nevertheless, whether and how microbiota changes the transcriptome profile and TCR specificities of colonic Tregs remain to be precisely defined. In this study, we have employed single-cell RNA sequencing and comparatively analyzed colonic Tregs from specific pathogen-free and germ-free (GF) mice. We found that microbiota shifts the activation trajectory of colonic Tregs toward a distinct phenotypic subset enriched in specific pathogen-free but not in GF mice. Moreover, microbiota induced the expansion of specific Treg clonotypes with shared transcriptional specificities. The microbiota-induced subset of colonic Tregs, identified as PD-1- CXCR3+ Tregs, displayed enhanced suppressive capabilities compared with colonic Tregs derived from GF mice, enhanced production of IL-10, and were the primary regulators of enteric inflammation in dextran sodium sulfate-induced colitis. These findings identify a hitherto unknown gut microbiota and immune cell interaction module that could contribute to the development of a therapeutic modality for intestinal inflammatory diseases.

Linking the 1940 US Census to the NSHAP: Novel Opportunity to Understand the Effects of Childhood Residential Environment on Cognitive Aging.

OBJECTIVE: The 1940 Census is a valuable resource for understanding various aspects of historical populations in the United States. Recently, the National Social Life, Health and Aging Project (NSHAP) integrated 1940 Census data into its extensive dataset, providing researchers with an opportunity to explore new avenues of life course investigation. We leverage the newly-introduced measures of childhood residential environment and evaluate their potential predictive utility in older adult cognitive functioning net of childhood and adulthood characteristics known to be key risk factors for poor cognition. METHOD: We analyzed 777 respondents who were children in 1940 (age<17) that have been linked to the 1940 U.S. Census. We used childhood geographic location, homeownership status, household composition, and parental nativity as predictors. Cognitive function was measured using the Montreal Cognitive Assessment. RESULTS: Regression analysis showed that growing up in an urban area was associated with better cognitive function, while being born in the South was linked to poorer cognitive function, even after controlling for childhood health, parental education, educational attainment, stroke, and smoking status. Additionally, childhood multigenerational household was associated with better cognitive function, and childhood family size was associated with poorer cognitive function. However, these associations became statistically insignificant with the inclusion of educational attainment. We did not find homeownership and parental nativity to be associated with cognitive function. DISCUSSION: The findings may shed light on the potential long-term effects of childhood circumstances on cognitive aging processes. Implications for current literature and directions for future research are discussed.

A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron.

Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8+ T cell response, and triggers macrophage 'nutritional immunity' to deploy the high-affinity iron transporter lipocalin-2 for capturing and sequestering iron in the tumor microenvironment. This process induces a cycle of tumor cell death, epitope expansion and subsequent tumor clearance. Together these data indicate that food commensals might be identified and developed into 'oncobiotics' for a multi-layered approach to cancer therapy.

Hip joint center lateralization minimally affects the biomechanics of patient-specific flanged acetabular components: A computational model.

Patient-specific flanged acetabular components are utilized to treat failed total hip arthroplasties with large acetabular defects. Previous clinical studies from our institution showed that these implants tend to lateralize the acetabular center of rotation. However, the clinical impact of lateralization on implant survivorship is debated. Our goal was to develop a finite element model to quantify how lateralization of the native hip center affects periprosthetic strain and implant-bone micromotion distributions in a static level gait loading condition. To build the model, we computationally created a superomedial acetabular defect in a computed tomography 3D reconstruction of a native pelvis and designed a flanged acetabular implant to address this simulated bone defect. We modeled two implants, one with ~1 cm and a second with ~2 cm of hip center lateralization. We applied the maximum hip contact force and corresponding abductor force observed during level gait. The resulting strains were compared to bone fatigue strength (0.3% strain) and the micromotions were compared to the threshold for bone ingrowth (20 µm). Overall, the model demonstrated that the additional lateralization only slightly increased the area of bone at risk of failure and decreased the areas compatible with bone ingrowth. This computational study of patient-specific acetabular implants establishes the utility of our modeling approach. Further refinement will yield a model that can explore a multitude of variables and could be used to develop a biomechanically-based acetabular bone loss classification system to guide the development of patient-specific implants in the treatment of large acetabular bone defects.

Race/ethnicity and the measurement of cognition in NSHAP: Recommendations for robustness.

OBJECTIVES: In this study, we examine the measurement of cognition in different racial/ethnic groups to move towards a less biased and more inclusive set of measures for capturing cognitive change and decline in older adulthood. METHODS: We use data from Round 2 (N=3377) and Round 3 (N=4777) of the National Social Life, Health, and Aging Project (NSHAP) and examine the study's Survey Adjusted version of the Montreal Cognitive Assessment (MoCA-SA). We employ exploratory factor analyses to explore configural invariance by racial/ethnic group. Using modification indexes, two-parameter item response theory models, and split-sample testing, we identify items that seem robust to bias by race. We test the predictive validity of the full (18-item) and short (4-item) MoCA-SAs using self-reported dementia diagnosis, instrumental activities of daily living (IADLs), proxy reports of dementia, proxy reports of dementia-related death, and National Death Index reports of dementia-related death. RESULTS: We found that four measures out of the 18 used in NSHAP's MoCA-SA formed a scale that was more robust to racial bias. The shortened form predicted consequential outcomes as well as NSHAP's full MoCA-SA. The short form was also moderately correlated with the full form. DISCUSSION: Although sophisticated structural equation modeling techniques would be preferrable for assuaging measurement invariance by race in NSHAP, the shortened form of the MoCA-SA provides a quick way for researchers to carry out robustness checks and to see if the disparities and associations by race they document are "real" or the product of artifactual bias.

Probiotic Consortium Confers Synergistic Anti-Inflammatory Effects in Inflammatory Disorders.

The composition and diversity of gut microbiota significantly influence the immune system and are linked to various diseases, including inflammatory and allergy disorders. While considerable research has focused on exploring single bacterial species or consortia, the optimal strategies for microbiota-based therapeutics remain underexplored. Specifically, the comparative effectiveness of bacterial consortia versus individual species warrants further investigation. In our study, we assessed the impact of the bacterial consortium MPRO, comprising Lactiplantibacillus plantarum HY7712, Bifidobacterium animalis ssp. lactis HY8002, and Lacticaseibacillus casei HY2782, in comparison to its individual components. The administration of MPRO demonstrated enhanced therapeutic efficacy in experimental models of atopic dermatitis and inflammatory colitis when compared to single strains. MPRO exhibited the ability to dampen inflammatory responses and alter the gut microbial landscape significantly. Notably, MPRO administration led to an increase in intestinal CD103+CD11b+ dendritic cells, promoting the induction of regulatory T cells and the robust suppression of inflammation in experimental disease settings. Our findings advocate the preference for bacterial consortia over single strains in the treatment of inflammatory disorders, carrying potential clinical relevance.

Childhood Adversity and Passive Suicidal Ideation in Later Life in the United States: Does Religious Attendance Matter?

This study examines whether adverse childhood experiences are associated with passive suicidal ideation in later life and whether religious attendance moderates this association among U.S. older adults. To this end, logistic regression analyses were conducted using data from the 2016 Health and Retirement Study. The results show that poor childhood health, lack of parental affection, and childhood trauma are all positively associated with passive suicidal ideation in later life. However, religious attendance modifies the association between childhood health and passive suicidal ideation. For instance, poor childhood health is associated with greater odds of passive suicidal ideation only for older adults who never attend religious services, while this is not the case for those who attend religious services. Yet, the associations of parental affection and childhood trauma with passive suicidal ideation do not appear to differ by religious attendance. We discuss the theoretical implications of these findings for views about childhood adversity, religion, and suicide risk in later life.

Cumulative exposure to extreme heat and trajectories of cognitive decline among older adults in the USA.

BACKGROUND: The projected increase in extreme heat days is a growing public health concern. While exposure to extreme heat has been shown to negatively affect mortality and physical health, very little is known about its long-term consequences for late-life cognitive function. We examined whether extreme heat exposure is associated with cognitive decline among older adults and whether this association differs by race/ethnicity and neighbourhood socioeconomic status. METHODS: Data were drawn from seven waves of the Health and Retirement Study (2006-2018) merged with historical temperature data. We used growth curve models to assess the role of extreme heat exposure on trajectories of cognitive function among US adults aged 52 years and older. RESULTS: We found that high exposure to extreme heat was associated with faster cognitive decline for blacks and residents of poor neighbourhoods, but not for whites, Hispanics or residents of wealthier neighbourhoods. CONCLUSION: Extreme heat exposure can disproportionately undermine cognitive health in later life for socially vulnerable populations. Our findings underscore the need for policy actions to identify and support high-risk communities for increasingly warming temperatures.

Living Alone, Environmental Hazards, and Falls Among U.S. Older Adults.

Background and Objectives: Physical conditions of living environments can affect the incidence of falls; however, prior work has focused typically on 1 domain at a time-either neighborhood or home, capturing limited environmental boundaries of older adults. We examined how neighborhood together with the home environment affect the incidence of falls over time and whether living arrangement modifies the influence of the environmental risks on falls. Research Design and Methods: Using the 2012-2020 waves of the Health and Retirement Study (HRS; N = 1,893), we fitted logistic regression to estimate the incidence of falls over an 8-year study period. We used the neighborhood and housing data that are collected systematically by trained observers in the HRS to assess environmental hazards. Sidewalk quality, neighborhood disorder, and the presence of green space were measured to capture outdoor environmental hazards. Indoor environmental hazards included the presence of housing decay and poorly maintained stairways. All models were stratified by living arrangement. Results: Neighborhood and housing environment were independently associated with the odds of falls net of demographic characteristics and preexisting health conditions, and effects were significant for people living alone only. The presence of green space and poorly maintained stairways were associated with greater odds of falling, net of covariates during 8 years of follow-up (odds ratios = 2.10 and 2.65, p < .05, respectively). None of the environmental risk factors were significant for those living with others. Discussion and Implications: Falls in old age may be determined in part by a combination of outdoor and indoor risk factors. More research is needed to understand pathways that lead to greater vulnerability among older adults living alone to environmental hazards.

Marchf6 E3 ubiquitin ligase critically regulates endoplasmic reticulum stress, ferroptosis, and metabolic homeostasis in POMC neurons.

The metabolic prohormone pro-opiomelanocortin (POMC) is generally translocated into the endoplasmic reticulum (ER) for entry into the secretory pathway. Patients with mutations within the signal peptide (SP) of POMC or its adjoining segment develop metabolic disorders. However, the existence, metabolic fate, and functional outcomes of cytosol-retained POMC remain unclear. Here, we show that SP-uncleaved POMC is produced in the cytosol of POMC neuronal cells, thus inducing ER stress and ferroptotic cell death. Mechanistically, the cytosol-retained POMC sequesters the chaperone Hspa5 and subsequently accelerates degradation of the glutathione peroxidase Gpx4, a core regulator of ferroptosis, via the chaperone-mediated autophagy. We also show that the Marchf6 E3 ubiquitin ligase mediates the degradation of cytosol-retained POMC, thereby preventing ER stress and ferroptosis. Furthermore, POMC-Cre-mediated Marchf6-deficient mice exhibit hyperphagia, reduced energy expenditure, and weight gain. These findings suggest that Marchf6 is a critical regulator of ER stress, ferroptosis, and metabolic homeostasis in POMC neurons.

Ability of a selfish B chromosome to evade genome elimination in the jewel wasp, Nasonia vitripennis.

B chromosomes are non-essential, extra chromosomes that can exhibit transmission-enhancing behaviors, including meiotic drive, mitotic drive, and induction of genome elimination, in plants and animals. A fundamental but poorly understood question is what characteristics allow B chromosomes to exhibit these extraordinary behaviors. The jewel wasp, Nasonia vitripennis, harbors a heterochromatic, paternally transmitted B chromosome known as paternal sex ratio (PSR), which causes complete elimination of the sperm-contributed half of the genome during the first mitotic division of fertilized embryos. This genome elimination event may result from specific, previously observed alterations of the paternal chromatin. Due to the haplo-diploid reproduction of the wasp, genome elimination by PSR causes female-destined embryos to develop as haploid males that transmit PSR. PSR does not undergo self-elimination despite its presence with the paternal chromatin until the elimination event. Here we performed fluorescence microscopic analyses aimed at understanding this unexplained property. Our results show that PSR, like the rest of the genome, participates in the histone-to-protamine transition, arguing that PSR does not avoid this transition to escape self-elimination. In addition, PSR partially escapes the chromatin-altering activity of the intracellular bacterium, Wolbachia, demonstrating that this ability to evade chromatin alteration is not limited to PSR's own activity. Finally, we observed that the rDNA locus and other unidentified heterochromatic regions of the wasp's genome also seem to evade chromatin disruption by PSR, suggesting that PSR's genome-eliminating activity does not affect heterochromatin. Thus, PSR may target an aspect of euchromatin to cause genome elimination.

Prophylactic cable prevents tapered titanium stem subsidence with 2 cm of stem-cortical engagement in a cadaveric model.

Aims: When performing revision total hip arthroplasty using diaphyseal-engaging titanium tapered stems (TTS), the recommended 3 to 4 cm of stem-cortical diaphyseal contact may not be available. In challenging cases such as these with only 2 cm of contact, can sufficient axial stability be achieved and what is the benefit of a prophylactic cable? This study sought to determine, first, whether a prophylactic cable allows for sufficient axial stability when the contact length is 2 cm, and second, if differing TTS taper angles (2° vs 3.5°) impact these results. Methods: A biomechanical matched-pair cadaveric study was designed using six matched pairs of human fresh cadaveric femora prepared so that 2 cm of diaphyseal bone engaged with 2° (right femora) or 3.5° (left femora) TTS. Before impaction, three matched pairs received a single 100 lb-tensioned prophylactic beaded cable; the remaining three matched pairs received no cable adjuncts. Specimens underwent stepwise axial loading to 2600 N or until failure, defined as stem subsidence > 5 mm. Results: All specimens without cable adjuncts (6/6 femora) failed during axial testing, while all specimens with a prophylactic cable (6/6) successfully resisted axial load, regardless of taper angle. In total, four of the failed specimens experienced proximal longitudinal fractures, three of which occurred with the higher 3.5° TTS. One fracture occurred in a 3.5° TTS with a prophylactic cable yet passed axial testing, subsiding < 5 mm. Among specimens with a prophylactic cable, the 3.5° TTS resulted in lower mean subsidence (0.5 mm (SD 0.8)) compared with the 2° TTS (2.4 mm (SD 1.8)). Conclusion: A single prophylactic beaded cable dramatically improved initial axial stability when stem-cortex contact length was 2 cm. All implants failed secondary to fracture or subsidence > 5 mm when a prophylactic cable was not used. A higher taper angle appears to decrease the magnitude of subsidence but increased the fracture risk. The fracture risk was mitigated by the use of a prophylactic cable.

Guided Autotransplantation of Impacted Canines Using a CAD/CAM Surgical Template.

Autotransplantation is a potential treatment alternative when orthodontic traction of an impacted tooth is difficult. In this article, we describe two cases of guided autotransplantation of an impacted canine using a computer-aided designed and manufactured surgical template. The impacted canine was segmented on preoperative cone-beam computed tomography images to ensure a sufficient periodontal ligament space and placement of the donor tooth with the least pressure on it. The canine was virtually transposed using a simulation program considering the adjacent teeth. The surgical template, which was connected to the occlusal stop on adjacent teeth, was designed and 3D-printed with polymer resin. The recipient site was prepared using the surgical template, followed by immediate transplantation of the surgically extracted canine into the socket. The transplanted donor tooth was positioned in planned infra-occlusion to prevent occlusal interference. It was then splinted with the adjacent teeth for initial stabilization. During follow-up, one transplanted tooth showed pulp canal obliteration and the other had suspected pulp necrosis; endodontic treatment was performed. One year after the procedure, the periradicular condition of both teeth was favorable.

Microbial Components and Effector Molecules in T Helper Cell Differentiation and Function.

The mammalian intestines harbor trillions of commensal microorganisms composed of thousands of species that are collectively called gut microbiota. Among the microbiota, bacteria are the predominant microorganism, with viruses, protozoa, and fungi (mycobiota) making up a relatively smaller population. The microbial communities play fundamental roles in the maturation and orchestration of the immune landscape in health and disease. Primarily, the gut microbiota modulates the immune system to maintain homeostasis and plays a crucial role in regulating the pathogenesis and pathophysiology of inflammatory, neuronal, and metabolic disorders. The microbiota modulates the host immune system through direct interactions with immune cells or indirect mechanisms such as producing short-chain acids and diverse metabolites. Numerous researchers have put extensive efforts into investigating the role of microbes in immune regulation, discovering novel immunomodulatory microbial species, identifying key effector molecules, and demonstrating how microbes and their key effector molecules mechanistically impact the host immune system. Consequently, recent studies suggest that several microbial species and their immunomodulatory molecules have therapeutic applicability in preclinical settings of multiple disorders. Nonetheless, it is still unclear why and how a handful of microorganisms and their key molecules affect the host immunity in diverse diseases. This review mainly discusses the role of microbes and their metabolites in T helper cell differentiation, immunomodulatory function, and their modes of action.

Synthesis of 1,4-Dialkoxynaphthalene-Based Imidazolium Salts and Their Cytotoxicity in Cancer Cell Lines.

In this study, we designed and synthesized novel 1,4-dialkoxynaphthalene-2-alkyl imidazolium salt (IMS) derivatives containing both 1,4-dialkoxynaphthalene and imidazole, which are well known as pharmacophores. The cytotoxicities of these newly synthesized IMS derivatives were investigated in order to explore the possibility of using them to develop anticancer drugs. It was found that some of the new IMS derivatives showed good cytotoxic activities. In addition, an initial, qualitative structure-activity relationship is presented on the basis of observations of activity changes corresponding to structural changes.

Childhood lead exposure is associated with lower cognitive functioning at older ages.

The Flint, Michigan water crisis renewed concern about lead toxicity in drinking water. While lead in drinking water has been shown to negatively affect cognition among children, much less is known about its long-term consequences for late-life cognition. Using a nationally representative sample of U.S. older adults linked to historical administrative data from 1940, we find that older adults who lived as children in cities with lead pipes and acidic or alkaline water-the conditions required for lead to leach into drinking water-had worse cognitive functioning but not steeper cognitive decline. About a quarter of the association between lead and late-life cognition was accounted for by educational attainment. Within the next 10 years, American children exposed to high levels of lead during the 1970s will enter older ages. Our evidence highlights the need for stronger actions to identify interventions to mitigate long-term damage among people at high risk.

Do social determinants of health explain racial/ethnic disparities in COVID-19 infection?

Racial/ethnic minorities have experienced higher COVID-19 infection rates than whites, but it is unclear how individual-level housing, occupational, behavioral, and socioeconomic conditions contribute to these disparities in a nationally representative sample. In this study, we assess the extent to which social determinants of health contribute to racial/ethnic differences in COVID-19 infection. Data are from the Understanding America Study's Understanding Coronavirus in America survey (UAS COVID-19 waves 7-29). UAS COVID-19 is one of the only nationally representative longitudinal data sources that collects information on household, work, and social behavioral context during the pandemic. We analyze onset of COVID-19 cases, defined as a positive test or a diagnosis of COVID-19 from a healthcare provider since the previous survey wave, over a year of follow-up (June 2020-July 2021). We consider educational attainment, economic resources, work arrangements, household size, and social distancing as key social factors that may be structured by racism. Cox hazard models indicate that Hispanic people have 48% higher risk of experiencing a COVID-19 infection than whites after adjustment for age, sex, local infection rate, and comorbidities, but we do not observe a higher risk of COVID-19 among Black respondents. Controlling for engagement in any large or small social gathering increases the hazard ratio for Hispanics by 9%, suggesting that had Hispanics had the same social engagement patterns as whites, they may have had even higher risk of COVID-19. Other social determinants-lower educational attainment, working away from home, and number of coresidents-all independently predict higher risk of COVID-19, but do not explain why Hispanic Americans have higher COVID-19 infection risk than whites.

Effect of childhood proximity to lead mining on late life cognition.

INTRODUCTION: Lead exposure negatively affects cognitive functioning among children. However, there is limited evidence about whether exposure to lead in early life impairs later life cognitive functioning. METHODS: Participants in the prospective Wisconsin Longitudinal Study cohort (N = 8583) were linked to the 1940 Census, which was taken when they were young children. We estimated the effect of living near a lead mine in childhood on late life memory/attention and language/executive function in 2004 (mean age 64) and 2011 (mean age 71). RESULTS: Lead-exposed children had significantly steeper memory/attention decline between 2004 and 2011 and worse language/executive function at baseline in late life. These long-term effects of lead were not mediated through adolescent IQ or late life SES and health factors. DISCUSSION: Proximity to lead mining in childhood had long-term effects on late life memory/attention decline and language/executive function, reflecting a possible latent influence of lead exposure. More research is needed to understand behavioral and biological pathways underlying this relationship.