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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.
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Hierro , Microambiente Tumoral , Animales , Hierro/metabolismo , Ratones , Microambiente Tumoral/inmunología , Humanos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/inmunología , Ratones Endogámicos C57BL , Lipocalina 2/metabolismo , Lipocalina 2/inmunología , Femenino , Simbiosis/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Activación de Macrófagos/inmunología , Ratones NoqueadosRESUMEN
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.
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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.
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Cromosomas de Insectos , Genoma de los Insectos , Animales , Protaminas/genética , Protaminas/metabolismo , Histonas/genética , Histonas/metabolismo , Masculino , Femenino , Genes de ARNr , ADN Ribosómico/genética , ADN Ribosómico/metabolismo , Sitios GenéticosRESUMEN
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.
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Antineoplásicos , Neoplasias , Sales (Química)/farmacología , Sales (Química)/química , Línea Celular , Antineoplásicos/química , Relación Estructura-Actividad , Cloruro de Sodio , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular TumoralRESUMEN
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.
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Experiencias Adversas de la Infancia , Ideación Suicida , Humanos , Estados Unidos/epidemiología , Anciano , Religión , Factores de RiesgoRESUMEN
Objectives. To assess the association between individual-level adherence to social-distancing and personal hygiene behaviors recommended by public health experts and subsequent risk of COVID-19 diagnosis in the United States. Methods. Data are from waves 7 through 26 (June 10, 2020-April 26, 2021) of the Understanding America Study COVID-19 survey. We used Cox models to assess the relationship between engaging in behaviors considered high risk and risk of COVID-19 diagnosis. Results. Individuals engaging in behaviors indicating lack of adherence to social-distancing guidelines, especially those related to large gatherings or public interactions, had a significantly higher risk of COVID-19 diagnosis than did those who did not engage in these behaviors. Each additional risk behavior was associated with a 9% higher risk of COVID-19 diagnosis (hazard ratio [HR] = 1.09; 95% confidence interval [CI] = 1.05, 1.13). Results were similar after adjustment for sociodemographic characteristics and local infection rates. Conclusions. Personal mitigation behaviors appear to influence the risk of COVID-19, even in the presence of social factors related to infection risk. Public Health Implications. Our findings emphasize the importance of individual behaviors for preventing COVID-19, which may be relevant in contexts with low vaccination. (Am J Public Health. 2022;112(1):169-178. https://doi.org/10.2105/AJPH.2021.306565).
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COVID-19/diagnóstico , Conductas de Riesgo para la Salud , Higiene , Cooperación del Paciente/estadística & datos numéricos , Distanciamiento Físico , Adulto , Anciano , Control de Enfermedades Transmisibles/métodos , Femenino , Guías como Asunto , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: To examine whether neighborhood and household disorder matter for cognitive functioning among middle-aged and older adults and whether the disorder-cognition link is moderated by social network resources. METHOD: Data are drawn from National Social Life, Health, and Aging Project (NSHAP) Wave 2 (N = 3198). Both neighborhood and household were considered as key residential contexts that shape one's social life and health. Exposure to neighborhood and household disorder was measured using interviewer assessments of signs of disorder and decay, including the presence of disrepair, trash, noise, and unpleasant smells such as air pollution, in the buildings and streets in which the respondent lives. Cognitive function was measured using the survey-adapted Montreal Cognitive Assessment (MoCA-SA). Network size, network range, and frequency of interaction among network members were assessed as moderators. RESULTS: Neighborhood and household disorder were independently associated with cognitive function. However, disorder in the household appeared to have more direct associations with cognitive function than did the neighborhood when both were present. The association between household disorder and cognitive function was mitigated by network size, such that poor housing conditions were associated with lower cognitive function only for those with small social networks. CONCLUSION: This study suggests a larger network may play a role in minimizing the negative influence of household disorder on cognitive function for middle-aged and older adults. Social policy and intervention aimed at promoting network ties may help reduce further disparities in cognitive function, especially for those vulnerable groups living in a poor-quality household.
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Cognición , Características de la Residencia , Anciano , Envejecimiento/psicología , Composición Familiar , Humanos , Persona de Mediana Edad , Red SocialRESUMEN
We examine how labor together with social participation protects against cognitive impairment and depression, with a focus on gender differences. Data are drawn from four waves of the Korean Longitudinal Study of Aging (2006-2012). Both paid work and unpaid work are considered labor participation. Social participation includes the frequency of participation in formal social institutions, religious groups, grandparenting, and interactions with family and friends. Using growth curve models, we find that social and labor participation are independently associated with outcomes and effects vary by gender. Religious group activity was beneficial only for women, whereas inability to work was detrimental for men only. Informal social gatherings and labor participation, paid or unpaid, were beneficial for both genders. Findings on gender differences highlight how social identities can shape social roles and confine activity space, and productive engagement, affecting outcomes for mental health in later life.
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BACKGROUND: Prior work has demonstrated how neighborhood poverty and racial composition impact racial disparities in access to the deceased donor kidney transplant waitlist, both nationally and regionally. We examined the association between neighborhood characteristics and racial disparities in time to transplant waitlist in Chicago, a diverse city with continued neighborhood segregation. METHODS: Using data from the United States Renal Data System (USRDS) and the US Census, we investigated time from dialysis initiation to kidney transplant waitlisting for African American and white patients in Chicago using cause-specific proportional hazards analyses, adjusting for individual sociodemographic and clinical characteristics, as well as neighborhood poverty and racial composition. RESULTS: In Chicago, African Americans are significantly less likely than whites to appear on the renal transplant waitlist (HR 0.73, P < .05). Compared to whites in nonpoor neighborhoods, African Americans in poor neighborhoods are significantly less likely to appear on the transplant waitlist (HR 0.61, P < .05). Over 69% of African Americans with ESRD live in these neighborhoods. CONCLUSIONS: Consistent with national data, African Americans in Chicago have a lower likelihood of waitlisting than whites. This disparity is explained in part by neighborhood poverty, which impacts the majority of African American ESRD patients in Chicago.
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Disparidades en Atención de Salud/etnología , Disparidades en Atención de Salud/estadística & datos numéricos , Fallo Renal Crónico/cirugía , Trasplante de Riñón/estadística & datos numéricos , Grupos Raciales/estadística & datos numéricos , Listas de Espera , Adolescente , Adulto , Anciano , Chicago , Femenino , Estudios de Seguimiento , Geografía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Características de la Residencia , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: We examined the association of dialysis facility characteristics with payment reductions and change in clinical performance measures during the first year of the United States Centers for Medicare & Medicaid Services (CMS) End Stage Renal Disease Quality Incentive Plan (ESRD QIP) to determine its potential impact on quality and disparities in dialysis care. METHODS: We linked the 2012 ESRD QIP Facility Performance File to the 2007-2011 American Community Survey by zip code and dichotomized the QIP total performance scores-derived from percent of patients with urea reduction rate > 65, hemoglobin < 10 g/dL, and hemoglobin > 12 g/dL-as 'any' versus 'no' payment reduction. We characterized associations between payment reduction and dialysis facility characteristics and neighborhood demographics, and examined changes in facility outcomes between 2007 and 2010. RESULTS: In multivariable analysis, facilities with any payment reduction were more likely to have longer operation (OR 1.03 per year), a medium or large number of stations (OR 1.31 and OR 1.42, respectively), and a larger proportion of African Americans (OR 1.25, highest versus lowest quartile), all p < 0.05. Most improvement in clinical performance was due to reduced overtreatment of anemia, a decline in the percentage of patients with hemoglobin ≥ 12 g/dL; for-profits and facilities in African American neighborhoods had the greatest reduction. CONCLUSIONS: In the first year of CMS pay-for-performance, most clinical improvement was due to reduced overtreatment of anemia. Facilities in African American neighborhoods were more likely to receive a payment reduction, despite their large decline in anemia overtreatment.
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Disparidades en Atención de Salud/economía , Fallo Renal Crónico/terapia , Mejoramiento de la Calidad/economía , Reembolso de Incentivo , Diálisis Renal/economía , Negro o Afroamericano , Instituciones de Atención Ambulatoria/economía , Instituciones de Atención Ambulatoria/normas , Centers for Medicare and Medicaid Services, U.S. , Instituciones de Salud , Disparidades en Atención de Salud/etnología , Humanos , Fallo Renal Crónico/etnología , Análisis Multivariante , Calidad de la Atención de Salud , Diálisis Renal/normas , Características de la Residencia , Estados UnidosRESUMEN
BACKGROUND: In the United States, African Americans and whites differ in access to the deceased donor renal transplant waitlist. The extent to which racial disparities in waitlisting differ between United Network for Organ Sharing (UNOS) regions is understudied. METHODS: The US Renal Data System (USRDS) was linked with US census data to examine time from dialysis initiation to waitlisting for whites (n = 188,410) and African Americans (n = 144,335) using Cox proportional hazards across 11 UNOS regions, adjusting for potentially confounding individual, neighborhood, and state characteristics. RESULTS: Likelihood of waitlisting varies significantly by UNOS region, overall and by race. Additionally, African Americans face significantly lower likelihood of waitlisting compared to whites in all but two regions (1 and 6). Overall, 39% of African Americans with ESRD reside in Regions 3 and 4--regions with a large racial disparity and where African Americans comprise a large proportion of the ESRD population. In these regions, the African American-white disparity is an important contributor to their overall regional disparity. CONCLUSIONS: Race remains an important factor in time to transplant waitlist in the United States. Race contributes to overall regional disparities; however, the importance of race varies by UNOS region.
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Negro o Afroamericano , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Trasplante de Riñón/estadística & datos numéricos , Listas de Espera , Población Blanca , Adolescente , Adulto , Anciano , Femenino , Geografía , Disparidades en Atención de Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Tiempo , Estados Unidos , Adulto JovenRESUMEN
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.
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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.
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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.
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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.
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Bifidobacterium animalis , Dermatitis Atópica , Probióticos , Humanos , Inflamación , Probióticos/uso terapéutico , Probióticos/farmacología , Bifidobacterium animalis/fisiología , Bacterias , Antiinflamatorios/farmacologíaRESUMEN
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.
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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.
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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.
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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.
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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.